Liquid path system and gene sequencer

Abstract

The utility model provides a liquid path system and a gene sequencer, the liquid path system comprises a rotary valve, a multi-way valve, a first electromagnetic valve, an injection pump and a waste liquid barrel, the injection pump is communicated with a first public port of the first electromagnetic valve, and when the first public port is selectively communicated with a first normally open port, the injection pump is communicated with the first normally open port; the injection pump is used for sucking a reagent and temporarily storing the reagent into the injection pump, and is used for reversely pushing the reagent temporarily stored in the injection pump into the kit so as to clean a pipeline between the first liquid inlet port and the kit. Based on the sequencing system provided by the embodiment, each group of sequencing chips can form an independent liquid path. Compared with the prior art, a three-way valve does not need to be additionally arranged between the multi-way valve and the rotary valve, and each group of chips has an independent liquid path, so that the shooting time of an optical machine can be efficiently utilized, and the sequencing efficiency is improved. Furthermore, the liquid path system provided by the utility model can realize automatic cleaning of the liquid path passage and the reagent pipeline.

Description

Technical Field

[0001] The present application belongs to the technical field of in vitro diagnostic instruments, and specifically relates to a liquid circuit system and a gene sequencer. Background Art

[0002] As an instrument for gene sequencing, a gene sequencer is usually equipped with a reagent kit, a carrier, and an optical machine. The reagent kit is used to store reagents, and the carrier has a temperature control function. The sequencing chip is placed on the carrier and connected by pipes to form a liquid path. The sequencing process requires the addition of multiple reagents to perform biochemical reactions on the surface of the sequencing chip to generate sequencing clusters, and then the sequencing clusters are photographed using an optical machine and the obtained photos are analyzed.

[0003] Since the ambient temperatures required for biochemical reactions and photographing processes are different, for example, the temperature range for biochemical reactions needs to be controlled at 50±0.5°, and the temperature range for photographing processes needs to be controlled at 20±0.5°, in order to improve the utilization efficiency of the optical machine, at least two groups of chips are provided, in which one group of chips performs biochemical reactions while the other group of chips can independently perform photographing processes.

[0004] In order to achieve the above purpose, the conventional method of the existing liquid path is to only set a rotary valve at the starting end of the liquid path, and the liquid outlet end of the rotary valve is connected to a three-way valve, and the three-way valve has two liquid outlet ports, which are respectively connected to two groups of chips. Since each group of chips is provided with at least two flow channels, a multi-way valve is provided between the chip and the three-way valve, and the multi-way valve has multiple liquid outlet ports, which are respectively connected to multiple flow channels of each group of chips. However, this solution uses more parts, is more complicated, and leads to higher costs. Utility Model Content

[0005] The present application provides a liquid circuit system and a gene sequencer to solve the problems of complex liquid circuits and high costs in the prior art.

[0006] In a first aspect of the present application, a fluid circuit system is provided, comprising:

[0007] A rotary valve having a first liquid outlet port and a plurality of first liquid inlet ports, wherein the first liquid inlet ports are connected to a reagent box, and the reagent box is used to store reagents;

[0008] a multi-way valve, having a second liquid inlet port and a plurality of second liquid outlet ports, wherein the second liquid inlet port is in communication with the first liquid outlet port, and one of the second liquid outlet ports is in communication with one of the flow channels of the sequencing chip;

[0009] A first solenoid valve, comprising a first common port, a first normally open port and a first normally closed port, wherein the first normally open port is connected to one of the flow channels of the sequencing chip;

[0010] a syringe pump connected to the first common port, and when the first common port is connected to the first normally open port, the syringe pump is used to absorb the reagent and temporarily store it inside the syringe pump, and to push the reagent temporarily stored inside the syringe pump back to the reagent box, so as to clean the pipeline between the first liquid inlet port and the reagent box;

[0011] The waste liquid barrel is connected to the first normally closed port. When the first common port is connected to the first normally closed port, the waste liquid barrel is used to receive the reagent discharged by the injection pump.

[0012] Optionally, a pressure sensor or a bubble sensor is provided on the passage between the first solenoid valve and the sequencing chip.

[0013] Optionally, a second solenoid valve is further arranged between the first solenoid valve and the injection pump, the second solenoid valve having a second common port, a second normally open port and a second normally closed port, the second common port is connected to the injection pump, the second normally open port is connected to the first common port, and the second normally closed port is connected to the reagent box, and when the second normally closed port is connected to the second common port, the second solenoid valve is used to quickly aspirate the reagent into the injection pump.

[0014] Optionally, a third solenoid valve is provided between the rotary valve and the sequencing chip, and a fourth solenoid valve is provided between the first solenoid valve and the sequencing chip;

[0015] 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 communicated with the first liquid outlet port, the third normally open port is communicated with the second liquid inlet port, and the third normally closed port is communicated with the fourth solenoid valve;

[0016] The fourth solenoid valve has a fourth common port, a fourth normally open port and a fourth normally closed port, the fourth common port is in communication with the first normally open port, the fourth normally open port is in communication with a flow channel of the sequencing chip, and the fourth normally closed port is in communication with the third normally closed port;

[0017] When the third common port is connected to the third normally closed port, the fourth normally closed port is connected to the fourth common port, and the first normally open port is connected to the first common port, the syringe pump is used to draw the reagent so as to exhaust the air;

[0018] When the third common port is connected to the third normally open port, the fourth normally open port is connected to the fourth common port, and the first normally open port is connected to the first common port, the injection pump is used to absorb or push back the reagent.

[0019] Optionally, the number of the first solenoid valves is equal to the sum of the number of flow channels of multiple groups of sequencing chips, and the number of the third solenoid valves and the fourth solenoid valves are respectively the same as the number of groups of sequencing chips.

[0020] Optionally, a fifth solenoid valve is provided between the rotary valve and the sequencing chip, and a sixth solenoid valve and a seventh solenoid valve are provided between the first solenoid valve and the sequencing chip;

[0021] The fifth solenoid valve has a fifth common port, a fifth normally open port and a fifth normally closed port, the fifth common port is communicated with the first liquid outlet port, the fifth normally open port is communicated with the second liquid inlet port, and the fifth normally closed port is communicated with the seventh solenoid valve;

[0022] The sixth solenoid valve has a sixth common port, a sixth normally open port and a sixth normally closed port, the sixth common port is connected to the seventh solenoid valve, and the sixth normally open port and the sixth normally closed port are respectively used to select and connect to one of the groups of chips;

[0023] The seventh solenoid valve has a seventh common port, a seventh normally open port and a seventh normally closed port, the seventh common port is connected to the first normally open port, the seventh normally open port is connected to the sixth common port, and the seventh normally closed port is connected to the fifth normally closed port;

[0024] When the fifth common port is connected to the fifth normally closed port, the seventh normally closed port is connected to the seventh common port, and the first normally open port is connected to the first common port, the syringe pump is used to draw the reagent so as to exhaust the air;

[0025] When the fifth common port is connected to the fifth normally open port, the sixth normally open port or the sixth normally closed port is connected to the sixth common port, the seventh normally open port is connected to the seventh common port, and the first normally open port is connected to the first common port, the injection pump is used to absorb or push back the reagent.

[0026] Optionally, when the sequencing chip is a dual-channel chip, the number of the first solenoid valve, the fifth solenoid valve, the sixth solenoid valve and the seventh solenoid valve is two respectively.

[0027] 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.

[0028] It can be seen from the above technical solutions that, based on the sequencing system provided in this embodiment, each group of sequencing chips can form an independent liquid path. Compared with the prior art, there is no need to set an additional three-way valve between the multi-way valve and the rotary valve, and each group of chips has an independent liquid path, which can achieve efficient use of the optical machine photography time and improve the sequencing efficiency. Furthermore, the rotary valve is used to select the connection of the cleaning reagent, so that the cleaning reagent flows to the injection pump through the sequencing chip and the first solenoid valve; then the first liquid inlet port of the rotary valve is adjusted to the reagent port used in the sequencing reaction, and the cleaning reagent temporarily stored in the injection pump is pushed back to the rotary valve, and then pushed back from the reagent port to the reagent box, so that the automatic cleaning of the liquid path and the reagent pipeline can be achieved. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 A schematic diagram of the structure of a fluid circuit system provided in the first embodiment of the present application;

[0030] Figure 2 A schematic diagram of the structure of a fluid circuit system provided in the second embodiment of the present application;

[0031] Figure 3 A schematic diagram of the structure of a fluid circuit system provided in the third embodiment of the present application;

[0032] Figure 4 A schematic structural diagram of a fluid circuit system provided in the fourth embodiment of the present application.

[0033] Figure numerals: 1-rotary valve; 11-first liquid inlet port; 12-first liquid outlet port; 2-multi-way valve; 21-second liquid inlet port; 22-second liquid outlet port; 3-first solenoid valve; 31-first common port; 32-first normally open port; 33-first normally closed port; 4-syringe pump; 5-second solenoid valve; 51-second common port; 52-second normally open port; 53-second normally closed port; 6-third solenoid valve; 61-third common port; 62-third normally open port ;63-third normally closed port;7-fourth solenoid valve;71-fourth common port;72-fourth normally open port;73-fourth normally closed port;8-fifth solenoid valve;81-fifth common port;82-fifth normally open port;83-fifth normally closed port;9-sixth solenoid valve;91-sixth common port;92-sixth normally open port;93-sixth normally closed port;10-seventh solenoid valve;101-seventh common port;102-seventh normally open port;103-seventh normally closed port. DETAILED DESCRIPTION

[0034] 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.

[0035] Reference Figure 1 The schematic diagram of the liquid circuit structure shown in the figure, the first embodiment of the present application provides a liquid circuit system, including: a rotary valve 1, having a first liquid outlet port 12 and a plurality of first liquid inlet ports 11, the first liquid inlet port 11 is connected to a reagent box, and the reagent box is used to store reagents; a multi-way valve 2, having a second liquid inlet port 21 and a plurality of second liquid outlet ports 22, the second liquid inlet port 21 is connected to the first liquid outlet port 12, and one of the second liquid outlet ports 22 is connected to one of the flow channels of the sequencing chip; a first solenoid valve 3, having a first common port 31, a first normally open port 32 and a first normally closed port 33, the first The normally open port 32 is connected to one of the flow channels of the sequencing chip; the injection pump 4 is connected to the first common port 31, and when the first common port is connected to the first normally open port, the injection pump is used to absorb the reagent and temporarily store it inside the injection pump 4, and to push the reagent temporarily stored inside the injection pump 4 back to the reagent box to clean the pipeline between the first liquid inlet port 11 and the reagent box; the waste liquid barrel (not numbered in the figure) is connected to the first normally closed port 33, and when the first common port is connected to the first normally closed port, the waste liquid barrel is used to receive the reagent discharged by the injection pump 4.

[0036] In this embodiment, a plurality of rotary valves 1 are provided, and each rotary valve 1 supplies liquid to a plurality of flow channels of a group of chips at the same time. Since the rotary valve is provided with only one first liquid outlet port 12, in order to supply liquid to a plurality of flow channels at the same time, a multi-way valve 2 is provided between the rotary valve 1 and the sequencing chip.

[0037] The solenoid valve is an industrial device controlled by electromagnetics. The first solenoid valve 3 can be a two-position three-way solenoid valve. The two-position three-way solenoid valve corresponds to different passages in the two states of power on and power off, thereby realizing different selections of liquid passages.

[0038] The multi-way valve is 1-way N-port, and the number of corresponding multi-way valve diversion channels is designed according to the number of chip channels. In one feasible way, the sequencing chip is a dual-channel chip, in which case the multi-way valve 2 can be a Y-type liquid path port, which has a simple structure and low cost. In the case of a dual-channel chip, two first solenoid valves 3 need to be set for each group of chips. In order to achieve synchronous liquid inlet, the injection pump 4 can use a double injection pump.

[0039] In order to improve the sequencing efficiency, at least two groups of sequencing chips are provided, one group of sequencing chips is used for biochemical reactions, and the other group of sequencing chips is used for taking pictures. Based on the sequencing system provided in this embodiment, each group of sequencing chips can form an independent liquid path. In the case of a double flow channel, this embodiment is provided with four rotary valves 1, two multi-way valves 2, four first solenoid valves 3, and two double injection pumps. Compared with the prior art, there is no need to additionally provide a three-way valve between the multi-way valve 2 and the rotary valve 1, and each group of chips has an independent liquid path, which can achieve efficient use of the optical machine photography time and improve the sequencing efficiency.

[0040] In this embodiment, the reagent box stores a plurality of reagents, and also stores a cleaning reagent. Furthermore, the cleaning reagent can be stored in a cleaning liquid box, and the cleaning liquid box and the reagent box are stored together in the reagent compartment. A reagent needle (not numbered in the figure) is provided above the reagent compartment, and the first liquid inlet port 11 of the rotary valve 1 is connected to the reagent needle through a pipeline, and the end of the reagent needle extends to the reagent box, which can be used to connect the reagent box to absorb the reagent in the reagent box.

[0041] After the sequencing reaction is completed, the rotary valve 1 is used to select and connect the cleaning reagent, so that the cleaning reagent flows to the injection pump 4 through the sequencing chip and the first solenoid valve 3; then the first liquid inlet port 11 of the rotary valve 1 is adjusted to the reagent port used in the sequencing reaction, and the cleaning reagent temporarily stored in the injection pump 4 is pushed back to the rotary valve 1, and then pushed back from the reagent port to the reagent kit, thereby realizing automatic cleaning of the liquid path and the reagent pipeline.

[0042] In order to monitor whether the liquid path is blocked or leaking during use, a pressure sensor or a bubble sensor is provided in the path between the first solenoid valve 3 and the sequencing chip in this embodiment. The detection principles of the pressure sensor and the bubble sensor are different, and they are described separately below.

[0043] The pressure sensor detects the fluid pressure when the fluid flows through the pipeline. If the pipeline is blocked, the pressure will not rebound to the atmospheric pressure of 103kpa (or nearby), resulting in a vacuum in the pipeline, which indicates that the liquid suction is abnormal; if there is a disconnection or leakage in the pipeline, the liquid will not be sucked in, or bubbles will be sucked at intervals, and the pressure data is also abnormal. Based on this, the following rules can be set to judge the abnormality: when the injection pump draws reagents, obtain the current pressure measurement value, and judge whether the current pressure measurement value is within the preset threshold interval; if the current pressure measurement value is greater than the upper limit 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 of the threshold interval, it is determined that the current pipeline has a blockage abnormality. Among them, the threshold interval is determined based on experimental measurements and is not specifically limited here.

[0044] The bubble sensor directly detects bubbles. During the operation of the liquid path, if the bubble sensor detects bubbles, it means there is an abnormality.

[0045] It should be noted that in the initial stage of the operation of the liquid circuit, since there is air in the pipeline itself, it is normal for the measured values ​​of the pressure sensor or bubble sensor to be abnormal. Under normal circumstances, no alarm or abnormal processing is performed for the abnormalities in the initial stage.

[0046] Reference Figure 2 As shown in the structural schematic diagram, in the second embodiment of the present application, a second solenoid valve 5 is also arranged between the first solenoid valve 3 and the injection pump 4, and the second solenoid valve 5 has a second common port 51, a second normally open port 52 and a second normally closed port 53, the second common port 51 is connected with the injection pump 4, the second normally open port 52 is connected with the first common port 31, and the second normally closed port 53 is connected with the reagent box, and when the second normally closed port 53 is connected with the second common port 51, the second solenoid valve 5 is used to quickly suck the reagent into the injection pump 4.

[0047] In the first embodiment of the present application, the cleaning reagent needs to be sucked first during the cleaning phase. Since the cleaning reagent passes through the sequencing chip, in order to avoid damaging the sequencing chip, the cleaning reagent needs to be kept within a lower flow rate range when sucking it, resulting in a longer cleaning time. In order to improve this problem, in the solution provided in the second embodiment of the present application, the cleaning reagent can be directly sucked into the injection pump 4 from the bypass where the second solenoid valve 5 is located, and then pushed back to the liquid path where the sequencing chip is located.

[0048] In the second embodiment, a three-way tube is arranged between the test kit and the second solenoid valve 5, the first port of the three-way tube is connected to the reagent needle, the second port is connected to the second solenoid valve 5, and the third port is connected to the first liquid inlet port 11 of the rotary valve 1. The three-way tube forms two branches, namely a first branch formed by the connection between the first port and the second port, and a second branch formed by the connection between the first port and the third port.

[0049] Under the action of the syringe pump, the cleaning reagent stored in the reagent kit enters the syringe pump through the reagent needle, the first branch of the three-way pipe, and the second solenoid valve. This process does not need to pass through the sequencing chip, and the path is relatively shortened, so it can enter the syringe pump at a faster flow rate. In other embodiments, since the cleaning reagent needs to pass through the sequencing chip, the sequencing chip is prone to rupture under greater pressure, and therefore, it is necessary to control the flow rate through the sequencing chip.

[0050] In this embodiment, automatic cleaning can be performed by combining conventional cleaning and rapid cleaning. In conventional cleaning, the cleaning reagent enters the injection pump through the reagent needle, the second branch of the three-way pipe, the rotary valve 1, the multi-way valve 2, the sequencing chip, the first solenoid valve 3, and the second solenoid valve 5. At this time, the injection pump and each pipeline can be cleaned. In rapid cleaning, the cleaning reagent is quickly absorbed through the second solenoid valve 5, and then pushed back into the front end pipeline of the rotary valve to quickly complete the cleaning process.

[0051] On the basis of the first embodiment, an emptying bypass is added to obtain the third embodiment of the present application. Figure 3 As shown in the structural diagram, a third solenoid valve 6 is arranged between the rotary valve 1 and the sequencing chip, and a fourth solenoid valve 7 is arranged between the first solenoid valve 3 and the sequencing chip.

[0052] The third solenoid valve 6 has a third common port 61 , a third normally open port 62 and a third normally closed port 63 . The third common port 61 is connected to the first liquid outlet port 12 , the third normally open port 62 is connected to the second liquid inlet port 21 , and the third normally closed port 63 is connected to the fourth solenoid valve 7 .

[0053] The fourth solenoid valve 7 has a fourth common port 71, a fourth normally open port 72 and a fourth normally closed port 73. The fourth common port 71 is connected to the first normally open port 32, the fourth normally open port 72 is connected to a flow channel of the sequencing chip, and the fourth normally closed port 73 is connected to the third normally closed port 63.

[0054] When the third common port 61 is connected to the third normally closed port 63 , the fourth normally closed port 73 is connected to the fourth common port 71 , and the first normally open port 32 is connected to the first common port 31 , the syringe pump 4 is used to suck the reagent to exhaust the air.

[0055] When the third common port 61 is connected to the third normally open port 63 , the fourth normally open port 72 is connected to the fourth common port 71 , and the first normally open port 32 is connected to the first common port 31 , the syringe pump 4 is used to absorb or push back the reagent.

[0056] In the embodiment of the present application, a bypass composed of a third solenoid valve and a fourth solenoid valve is used to exhaust the air from the reagent needle to the rotary valve component and the pipeline used in this stage in the initial stage.

[0057] In the third embodiment, the number of the first solenoid valves 3 is equal to the sum of the number of flow channels of multiple groups of sequencing chips, and the number of the third solenoid valves 6 and the fourth solenoid valves 7 are respectively the same as the number of groups of sequencing chips. In an achievable manner, two sequencing chips are provided, each group of sequencing chips is provided with two flow channels, the number of the first solenoid valves 3 is four, and the number of the third solenoid valves 6 and the fourth solenoid valves 7 are respectively two.

[0058] Compared with the first embodiment, the third embodiment adds a bypass for exhausting air, and the liquid circuit is more complicated. However, the first embodiment of the present application does not need to exhaust air through a bypass, and the design is relatively simple. Regarding the air in the reagent needle to the rotary valve components and the pipeline used in this stage, the first embodiment directly draws specific reagents, and the reagents flow through the sequencing chip, directly exhausting the air without staying on the surface of the sequencing chip. This solution has a small number of components, and accuracy, stability, etc. can be guaranteed.

[0059] Further optimization based on the third embodiment, refer to Figure 4 In the structural schematic diagram of the fourth embodiment shown in the figure, a fifth solenoid valve 8 is arranged between the rotary valve 1 and the sequencing chip, and a sixth solenoid valve 9 and a seventh solenoid valve 10 are arranged between the first solenoid valve 3 and the sequencing chip;

[0060] The fifth solenoid valve 8 has a fifth common port 81, a fifth normally open port 82 and a fifth normally closed port 83, the fifth common port 81 is connected to the first liquid outlet port 12, the fifth normally open port 82 is connected to the second liquid inlet port 21, and the fifth normally closed port 83 is connected to the seventh solenoid valve 10;

[0061] The sixth solenoid valve 9 has a sixth common port 91, a sixth normally open port 92 and a sixth normally closed port 93, the sixth common port 91 is connected to the seventh solenoid valve 10, and the sixth normally open port 92 and the sixth normally closed port 93 are respectively used to select and connect to one of the chips;

[0062] The seventh solenoid valve 10 has a seventh common port 101, a seventh normally open port 102 and a seventh normally closed port 103, the seventh common port 101 is connected to the first normally open port 32, the seventh normally open port 102 is connected to the sixth common port 91, and the seventh normally closed port 103 is connected to the fifth normally closed port 83;

[0063] When the fifth common port 81 is connected to the fifth normally closed port 83, the seventh normally closed port 103 is connected to the seventh common port 101, and the first normally open port 32 is connected to the first common port 31, the syringe pump 4 is used to suck the reagent so as to exhaust the air;

[0064] When the fifth common port 81 is connected with the fifth normally open port 82, the sixth normally open port 92 or the sixth normally closed port 93 is connected with the sixth common port 91, the seventh normally open port 102 is connected with the seventh common port 101, and the first normally open port 32 is connected with the first common port 31, the injection pump 4 is used to absorb or push back the reagent.

[0065] In this embodiment, when the sequencing chip is a dual-channel chip, the number of the first solenoid valve 3, the fifth solenoid valve 8, the sixth solenoid valve 9 and the seventh solenoid valve 10 are two respectively.

[0066] In this embodiment, the number of the first solenoid valves 3 is two, and only one set of double syringe pumps is needed to achieve the connection of the entire liquid path. For example, when chip A needs to aspirate liquid, the sixth normally open port 92 is connected to the sixth common port 91, the seventh normally open port 102 is connected to the seventh common port 101, and the first normally open port 32 is connected to the first common port 31. Compared with the third embodiment, this embodiment can save a double syringe pump and two solenoid valves, saving costs; however, due to the need to select chips back and forth, the operation is relatively cumbersome.

[0067] It can be seen that the four different embodiments provided in this application correspond to four different combinations. In practical applications, it is necessary to select the appropriate liquid path according to the situation. The solution provided in this application is not limited to the dual-channel chip. If the chip is changed to a four-channel / eight-channel, and the dual-injector is changed to a four-injector / eight-injector, the liquid inlet solution of other numbers of channels can be achieved by adding solenoid valves.

[0068] The present application also provides a method for controlling a fluid circuit system, comprising the following steps:

[0069] Step 100, controlling the first liquid inlet port of the rotary valve to select and connect to a first type of reagent in a reagent kit, wherein the first type of reagent is used for sequencing reaction.

[0070] Step 200: Control the first common port and the first normally open port of the first solenoid valve to be connected.

[0071] Step 300, control the injection pump to absorb the first type of reagent, so that the first type of reagent flows into the injection pump through the first liquid outlet port of the rotary valve, the second liquid inlet port of the multi-way valve, one of the second liquid outlet ports of the multi-way valve, the sequencing chip, and the first liquid path formed by the first solenoid valve.

[0072] Step 400, after sequencing is completed, the first common port and the first normally closed port of the first solenoid valve are controlled to be connected, so that the syringe pump pushes the temporarily stored first type of reagent into the waste liquid bucket.

[0073] Step 500, controlling the first liquid inlet port of the rotary valve to select a second type of reagent in the reagent kit, wherein the second type of reagent is used for cleaning the pipeline.

[0074] Step 600, controlling the syringe pump to absorb the second type of reagent, so that the second type of reagent flows into the syringe pump through the first liquid path.

[0075] Step 700, control the first liquid inlet port of the rotary valve to select the first type of reagent connected to the test kit again, and control the injection pump to push the temporarily stored second type of reagent from the first liquid path back to the test kit, so as to clean the first liquid path and the pipeline between the first liquid inlet port and the test kit.

[0076] During the sequencing process, different reagents need to be continuously added to the chip for biochemical reactions. Different reagents have different properties, such as high-salt solutions, acidic and alkaline solutions, high-viscosity solutions, protease-containing nucleic acid reagents, etc. After the experiment, all components that come into contact with the reagents need to be cleaned, otherwise the above solution may be contaminated by laboratory fungi to produce fungal substances, or precipitate crystals, or protein adhesion, etc., which may cause pipeline blockage. In addition, due to improper flow channel processing and design, some liquid path joints, corners, and reducers may have liquid path dead zones. The reagent fluid exchange efficiency in the dead zone is low or even no flow, and deposition and adhesion may occur in the dead zone, which in turn affects the cleanliness of the pipeline and the repeatability of the experiment.

[0077] In order to solve the above problems, in a control method for a liquid path system provided in this embodiment, in step 700, in addition to the conventional cleaning process, a reciprocating oscillation cleaning mode is added during the cleaning process, that is, a syringe pump is used to cyclically pump a micro volume (> the internal volume of the rotary valve) to form a pulsating fluid. The turbulence formed in the dead zone is more conducive to breaking the static boundary layer of the dead zone fluid, thereby increasing the fluid exchange efficiency in the dead zone; at the same time, the reciprocating motion of the fluid can enhance the shear force, which is more conducive to removing biological molecules attached to the inside of the pipeline.

[0078] This cleaning solution uses a reciprocating oscillation method to use shear force to disperse larger biomolecules and tube wall attachments; improve the dead zone fluid replacement efficiency and reduce the risk of cross-contamination of reagents. Furthermore, after the cleaning reagent is pushed back into the reagent box, the reagent needle is immersed in the cleaning reagent. Since the cleaning reagent is stirred in multiple cycles, the outer wall of the reagent needle is cleaned.

[0079] Optionally, after step 100, the method further includes:

[0080] Obtain the pressure measurement value of the pressure sensor; determine whether the pipeline where the pressure sensor is located is abnormal based on the relationship between the pressure measurement value and the preset threshold interval, wherein, when the injection pump draws the reagent, if the current pressure measurement value is greater than the upper limit value of the current threshold interval, it is determined that the current pipeline has an air leakage abnormality; if the current pressure measurement value is less than the lower limit value of the current threshold interval, it is determined that the current pipeline has a blockage abnormality;

[0081] Alternatively, a bubble detection result of the bubble sensor is obtained; and based on the bubble detection result, whether the pipeline where the bubble sensor is located is abnormal is determined, wherein if the bubble detection result shows that there are bubbles, the pipeline is abnormal.

[0082] Another embodiment of the present application further 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.

[0083] 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: A rotary valve having a first liquid outlet port and a plurality of first liquid inlet ports, wherein the first liquid inlet ports are connected to a reagent box, and the reagent box is used to store reagents; a multi-way valve, having a second liquid inlet port and a plurality of second liquid outlet ports, wherein the second liquid inlet port is in communication with the first liquid outlet port, and one of the second liquid outlet ports is in communication with one of the flow channels of the sequencing chip; A first solenoid valve, comprising a first common port, a first normally open port and a first normally closed port, wherein the first normally open port is connected to one of the flow channels of the sequencing chip; a syringe pump connected to the first common port, and when the first common port is connected to the first normally open port, the syringe pump is used to absorb the reagent and temporarily store it inside the syringe pump, and to push the reagent temporarily stored inside the syringe pump back to the reagent box, so as to clean the pipeline between the first liquid inlet port and the reagent box; The waste liquid barrel is connected to the first normally closed port. When the first common port is connected to the first normally closed port, the waste liquid barrel is used to receive the reagent discharged by the injection pump.

2. A fluid path system according to claim 1, characterized in that: A pressure sensor or a bubble sensor is provided on the passage between the first solenoid valve and the sequencing chip.

3. A liquid circuit system according to claim 1 or 2, characterized in that: A second solenoid valve is also arranged between the first solenoid valve and the injection pump, the second solenoid valve having a second common port, a second normally open port and a second normally closed port, the second common port being connected to the injection pump, the second normally open port being connected to the first common port, and the second normally closed port being connected to the reagent kit, and when the second normally closed port is connected to the second common port, the second solenoid valve is used to quickly aspirate the reagent into the injection pump.

4. A fluid path system according to claim 1, characterized in that: A third solenoid valve is provided between the rotary valve and the sequencing chip, and a fourth solenoid valve is provided between the first solenoid valve and the sequencing chip; 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 communicated with the first liquid outlet port, the third normally open port is communicated with the second liquid inlet port, and the third normally closed port is communicated with the fourth solenoid valve; The fourth solenoid valve has a fourth common port, a fourth normally open port and a fourth normally closed port, the fourth common port is in communication with the first normally open port, the fourth normally open port is in communication with a flow channel of the sequencing chip, and the fourth normally closed port is in communication with the third normally closed port; When the third common port is connected to the third normally closed port, the fourth normally closed port is connected to the fourth common port, and the first normally open port is connected to the first common port, the syringe pump is used to draw the reagent so as to exhaust the air; When the third common port is connected to the third normally open port, the fourth normally open port is connected to the fourth common port, and the first normally open port is connected to the first common port, the injection pump is used to absorb or push back the reagent.

5. A fluid path system according to claim 4, characterized in that: The number of the first solenoid valves is equal to the sum of the number of flow channels of multiple groups of sequencing chips, and the number of the third solenoid valves and the fourth solenoid valves are respectively the same as the number of groups of sequencing chips.

6. A fluid path system according to claim 1, characterized in that: A fifth solenoid valve is provided between the rotary valve and the sequencing chip, and a sixth solenoid valve and a seventh solenoid valve are provided between the first solenoid valve and the sequencing chip; The fifth solenoid valve has a fifth common port, a fifth normally open port and a fifth normally closed port, the fifth common port is communicated with the first liquid outlet port, the fifth normally open port is communicated with the second liquid inlet port, and the fifth normally closed port is communicated with the seventh solenoid valve; The sixth solenoid valve has a sixth common port, a sixth normally open port and a sixth normally closed port, the sixth common port is connected to the seventh solenoid valve, and the sixth normally open port and the sixth normally closed port are respectively used to select and connect to one of the groups of chips; The seventh solenoid valve has a seventh common port, a seventh normally open port and a seventh normally closed port, the seventh common port is connected to the first normally open port, the seventh normally open port is connected to the sixth common port, and the seventh normally closed port is connected to the fifth normally closed port; When the fifth common port is connected to the fifth normally closed port, the seventh normally closed port is connected to the seventh common port, and the first normally open port is connected to the first common port, the syringe pump is used to draw the reagent so as to exhaust the air; When the fifth common port is connected to the fifth normally open port, the sixth normally open port or the sixth normally closed port is connected to the sixth common port, the seventh normally open port is connected to the seventh common port, and the first normally open port is connected to the first common port, the injection pump is used to absorb or push back the reagent.

7. A fluid path system according to claim 6, characterized in that: When the sequencing chip is a dual-channel chip, the number of the first solenoid valve, the fifth solenoid valve, the sixth solenoid valve and the seventh solenoid valve are two respectively.

8. A gene sequencer, characterized in that: A fluid path system comprising any one of claims 1 to 7.

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