Method for controlling liquid inlet of liquid path system, liquid path system, device, equipment and storage medium
By controlling the liquid circuit system with pump and valve components, flexible loading and mixing of test samples and reagents can be achieved, solving the problems of tag allocation errors and cross-contamination in high-throughput sequencing and improving sequencing efficiency and quality.
Patent Information
- Application Number
- CN202410607811.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-05-15
- Publication Date
- 2025-11-18
AI Technical Summary
In existing high-throughput sequencing technologies, multiplex sample analysis suffers from sequencing data errors due to incorrect label or index allocation. Furthermore, manual sample loading is cumbersome and prone to cross-contamination, affecting sequencing efficiency and quality.
The system employs a pump-valve assembly to control the liquid circuit, enabling flexible loading and mixing of test samples and reagents through fluid channels and buffer areas, thus avoiding cross-contamination and improving sequencing efficiency and quality.
It improves the flexibility of loading test samples, reduces cross-contamination, improves sequencing quality and efficiency, and simplifies the operation process.
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Figure CN120967073A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of gene sequencing, and more particularly to a method for controlling the inflow of liquid into a liquid system, a liquid system, a sequencing device, a computer device, and a computer storage medium. Background Technology
[0002] Gene sequencing technology refers to the technical means of obtaining the base sequence of DNA or RNA by detection. Currently, the dominant sequencing technology is high-throughput sequencing. In sequencing platforms based on sequencing-by-synthesis, the general process of gene sequencing includes: immobilizing the nucleic acid sample to be tested on a flow cell using methods such as hybridization; then using PCR amplification to form nucleic acid clusters; adding sequencing reagents, such as fluorescent bases, polymerases, and primers, to the flow cell; and finally, using the principle of complementary base pairing, binding the fluorescent bases to the bases on the nucleic acid sample; and finally, using an optical imaging system to excite the fluorescent bases to produce fluorescence and collecting the fluorescence to form an image. Base identification is then performed on the image to determine the base sequence of the nucleic acid sample.
[0003] In existing technologies, high-throughput sequencing can determine the nucleic acid sequences of multiple samples in the same flow cell. This can be achieved through multiple sample analysis, which adds a unique tag or index (index, barcode, or tag) to each nucleic acid fragment during library construction. This allows libraries from multiple samples to be mixed in a single reaction system for sequencing, and the sequencing data can then be allocated to the corresponding samples based on the tag or index, thus obtaining the sequencing data for each sample. However, allocation errors are often unavoidable between tags or indexes in multiple samples, causing sequencing data from sample A to be incorrectly allocated to sample B, resulting in false positives or false negatives.
[0004] Furthermore, high-throughput sequencing enables the sequencing of nucleic acid sequences from multiple samples within a single flow cell. This can also be achieved by loading multiple sample channels into the flow cell and then performing subsequent sequencing. For example, externally to the sequencer, multiple different samples can be manually loaded into different channels of the flow cell using tools such as pipettes, before the flow cell is placed into the sequencer for sequencing. This method avoids sequencing data allocation errors caused by incorrect label or index assignment. However, this method is cumbersome, increases sequencing time and cost, and is prone to cross-contamination between samples (e.g., due to human error or incomplete pipette cleaning). In addition, sample loading flexibility is low, sequencing time is long, and sequencing efficiency is low. Summary of the Invention
[0005] To at least solve one of the technical problems existing in the prior art, the present invention provides a method for controlling the liquid intake of a liquid circuit system, a liquid circuit system, a sequencing device, a computer device, and a computer storage medium.
[0006] This application provides a method for controlling liquid inlet to a liquid circuit system. The liquid circuit system includes a flow tank and a pump-valve assembly. The flow tank includes multiple fluid channels, each fluid channel having an inlet and an outlet. The method includes:
[0007] Multiple test samples are drawn from the sample box using a pump-valve assembly, and each test sample is pumped into the fluid channel from its corresponding outlet; or,
[0008] A single test sample is drawn from the sample box using a pump-valve assembly, and the single test sample is pumped into the fluid channel from the inlet of each fluid channel.
[0009] In this way, the pump-valve assembly can allow a single sample to enter the fluid channel from the inlet of each fluid channel, or allow each of multiple samples to enter the fluid channel from the outlet of its respective fluid channel. This allows for the selection of different injection methods based on the number of samples, improving the flexibility of sample loading. In addition, by allowing each of multiple samples to enter the fluid channel from the outlet of its respective fluid channel, cross-contamination between multiple samples is avoided, improving sequencing quality and sequencing efficiency.
[0010] In some implementations, the fluid system includes multiple buffer areas, each corresponding to a different fluid channel;
[0011] Each sample to be tested is pumped into the fluid channel from the outlet of its corresponding fluid channel, including:
[0012] Each sample to be tested is pumped into its corresponding buffer area, and the sample to be tested in each buffer area is pumped into the fluid channel from the outlet of the corresponding fluid channel.
[0013] In this way, each buffer region can store one of multiple test samples, allowing the pump valve assembly to pump each test sample through its corresponding buffer region from the outlet of the corresponding fluid channel into the fluid channel, realizing the reverse flow of the test samples in the fluid channel, increasing the flexibility of test sample loading, while avoiding cross-contamination between multiple test samples, and improving sequencing quality and sequencing efficiency.
[0014] In some implementations, the method further includes:
[0015] The reagent is drawn from the kit using a pump-valve assembly and pumped into each buffer zone, and the reagent in each buffer zone is pumped into the fluid channel from the outlet of the corresponding fluid channel.
[0016] In this way, the buffer area can store reagents, allowing the pump valve assembly to pump reagents through each buffer area from the outlet of the corresponding fluid channel into the fluid channel, realizing reverse flow of reagents in the fluid channel, increasing the flexibility of reagent loading, while reducing sequencing time and improving sequencing efficiency.
[0017] In some implementations, the pump-valve assembly pumps the sample and / or reagent to the buffer area in a negative pressure driven manner.
[0018] In this way, the pump valve assembly can generate negative pressure to drive the sample and / or reagent to be tested to move towards the buffer area, thereby realizing the transport of the sample and / or reagent.
[0019] In some implementations, the pump-valve assembly pumps the sample and / or reagent to be tested from the outlet of the fluid channel into the fluid channel in a positive pressure driven manner.
[0020] In this way, the pump-valve assembly can generate positive pressure to drive the sample and / or reagent to be tested from the buffer area to the fluid channel, thereby realizing the transport of the sample and / or reagent.
[0021] In some implementations, the method includes the following steps before drawing multiple test samples from a sample cassette using a pump-valve assembly:
[0022] The reagent is drawn from the kit using a pump valve assembly and pumped into the sample box to mix with each sample to be tested in the sample box.
[0023] This allows each sample to be mixed with the reagent in the sample box before entering the fluid channel, thus saving the time required for pre-processing the sample and facilitating industrialization.
[0024] In some implementations, a pump-valve assembly is used to aspirate multiple test samples from a sample box, including:
[0025] The pump valve assembly is used to draw the mixture of each test sample and reagent from the sample box.
[0026] In this way, the sample cartridge can store the mixture of the test sample and reagent, which makes it easier for the pump valve assembly to draw the test sample and / or the mixture of the test sample and reagent from the sample cartridge, thereby improving the utilization rate of the sample cartridge, reducing the container for storing the mixture of the test sample and reagent, reducing the size of the liquid circuit system, and thus saving space.
[0027] In some implementations, each sample to be tested is pumped into the fluid channel from the outlet of its corresponding fluid channel, including:
[0028] The mixture of each sample and reagent is pumped into the fluid channel from the outlet of the corresponding fluid channel.
[0029] In this way, the pump-valve assembly allows the mixture of each sample and reagent to enter the fluid channel from the outlet of a corresponding fluid channel. The reverse flow of the sample and reagent mixture in the fluid channel increases the flexibility of sample loading, while reducing sequencing time and improving sequencing efficiency.
[0030] In some implementations, the fluid system includes multiple buffer areas, each corresponding to a different fluid channel;
[0031] The reagent is drawn from the kit using a pump valve assembly and pumped into the sample cartridge for mixing with each sample in the cartridge, including:
[0032] The reagents are pumped to each buffer area using a pump-valve assembly, and the reagents from each buffer area are pumped into the sample box to mix with the corresponding test sample in the sample box.
[0033] In this way, the buffer area can store reagents, allowing the pump valve assembly to pump reagents from the reagent kit through each buffer area into the sample box.
[0034] In some embodiments, pumping the mixture of each sample and reagent into the fluid channel from the outlet of a corresponding fluid channel includes:
[0035] The mixture of each sample and reagent is pumped back to its corresponding buffer area, and the mixture of the sample and reagent in each buffer area is pumped into the fluid channel from the outlet of the corresponding fluid channel.
[0036] In this way, the buffer area can store the mixture of each sample and reagent separately, allowing the pump valve assembly to pump the mixture of each sample and reagent into the fluid channel from the outlet of the corresponding fluid channel through its respective buffer area. This achieves reverse flow of the mixture of sample and reagent in the fluid channel, increasing the flexibility of sample loading and avoiding cross-contamination between multiple mixtures of sample and reagent, thus improving sequencing quality and efficiency.
[0037] In some implementations, the pump-valve assembly pumps the mixture of the sample and reagent to a buffer area in a negative pressure driven manner.
[0038] In this way, the pump and valve assembly can generate negative pressure to drive the mixture of the test sample and reagent to move towards the buffer area, thereby realizing the transport of the mixture of the test sample and reagent.
[0039] In some implementations, the pump-valve assembly pumps the mixture of the test sample and reagent in the buffer area from the outlet of the fluid channel into the fluid channel in a positive pressure driven manner.
[0040] In this way, the pump and valve assembly can generate positive pressure to drive the mixture of the test sample and reagent from the buffer area to the fluid channel, thereby realizing the transport of the mixture of the test sample and reagent.
[0041] In some implementations, the method further includes:
[0042] The reagent is drawn from the kit using a pump-valve assembly and pumped into the fluid channel from the inlet of each fluid channel.
[0043] In this way, the pump-valve assembly can allow reagents to enter the fluid channel from either the outlet or the inlet. This bidirectional flow of reagents within the fluid channel increases the flexibility of reagent loading, while simultaneously reducing sequencing time and improving sequencing efficiency.
[0044] In some implementations, the pump-valve assembly pumps individual test samples and / or reagents from the inlet of each fluid channel into the fluid channel in a negative pressure driven manner.
[0045] In this way, the pump-valve assembly can generate negative pressure to drive individual test samples and / or reagents to move into each fluid channel, thereby enabling the transport of individual test samples and / or reagents.
[0046] In some embodiments, the pump-valve assembly includes a first flow path selection valve and a pump unit;
[0047] The first flow path selection valve and pump unit are both located downstream of the flow pool;
[0048] The first flow path selection valve is used to connect the pump assembly to the fluid channel, and / or to the pump assembly to the sample box;
[0049] Multiple test samples are drawn from the sample box through the first flow path selection valve and pump assembly, and each test sample enters the fluid channel from the outlet of its corresponding fluid channel.
[0050] In this way, the first flow path selection valve can connect the sample box and each fluid channel, thereby controlling the flow path of multiple samples to be tested.
[0051] In some embodiments, multiple buffer areas are provided between the first flow path selection valve and the pump assembly, and the multiple buffer areas are provided in a one-to-one correspondence with multiple fluid channels;
[0052] Multiple test samples are drawn from the sample box via a first flow path selection valve and pump assembly, and each test sample enters the fluid channel from the outlet of its corresponding fluid channel, including:
[0053] Each sample to be tested is pumped from the sample box to its corresponding buffer area via a pump unit through a first flow path selection valve, and the sample to be tested in each buffer area is pumped into the corresponding fluid channel from the outlet of the fluid channel via a first flow path selection valve.
[0054] In this way, the first flow path selection valve can select the sample box and fluid channel to connect with the buffer area, thereby controlling the switching of flow paths for multiple samples to be tested.
[0055] In some embodiments, the pump-valve assembly further includes a second flow path selection valve;
[0056] The second flow path selection valve is located upstream of the flow cell and is used to connect the reagent kit with the first flow path selection valve.
[0057] The reagent is drawn from the kit through the first flow path selection valve, the second flow path selection valve, and the pump assembly, and the reagent is brought into the fluid channel from the outlet of the fluid channel.
[0058] Thus, the reagent kit and the fluid channel can be connected through the first flow path selection valve and the second flow path selection valve, thereby controlling the flow path of the reagent.
[0059] In some embodiments, reagents are drawn from the kit via a first flow path selection valve, a second flow path selection valve, and a pump assembly, and the reagents are drawn from the outlet of the fluid channel into the fluid channel, including:
[0060] The reagents are pumped from the reagent kit to each buffer area via the second flow path selection valve and the first flow path selection valve through the pump assembly, and the reagents in each buffer area are pumped into the fluid channel from the outlet of the corresponding fluid channel via the first flow path selection valve.
[0061] In this way, the first flow path selection valve can select the second flow path selection valve and the fluid channel to connect with the buffer area, thereby controlling the flow path switching of reagents in the kit connected to the second flow path selection valve.
[0062] In some implementations, the pump assembly pumps the sample and / or reagent to be tested through a first flow path selection valve to a buffer area in a negative pressure driven manner.
[0063] In this way, the pump assembly can generate negative pressure to drive the sample and / or reagent to be tested to move towards the buffer area, thereby realizing the transport of the sample and / or reagent.
[0064] In some implementations, the pump unit pumps the sample to be tested and / or reagents in the buffer area into the fluid channel from the outlet of the fluid channel via a first flow path selection valve in a positive pressure driven manner.
[0065] In this way, the pump unit can generate positive pressure to drive the sample and / or reagent to be tested from the buffer area through the first flow path selection valve to the fluid channel, thereby realizing the transport of the sample and / or reagent.
[0066] In some embodiments, the pump-valve assembly further includes a second flow path selection valve;
[0067] The second flow path selection valve is located upstream of the flow cell and is used to connect the reagent kit with the first flow path selection valve.
[0068] Before drawing multiple test samples from the sample cassette via the first flow path selection valve and pump assembly, the method further includes:
[0069] The reagent is drawn from the reagent kit through the first flow path selection valve, the second flow path selection valve, and the pump assembly, and then pumped into the sample box to mix with the sample to be tested in the sample box.
[0070] Thus, the reagent kit and sample box can be connected through the first flow path selection valve and the second flow path selection valve, thereby controlling the reagent flow path.
[0071] In some embodiments, multiple buffer areas are provided between the first flow path selection valve and the pump assembly, and the multiple buffer areas are provided in a one-to-one correspondence with multiple fluid channels;
[0072] Reagents are drawn from the kit via a first flow path selection valve, a second flow path selection valve, and a pump assembly, and then pumped into the sample cartridge for mixing with the sample to be tested in the sample cartridge, including:
[0073] The reagents are pumped from the reagent kit into each buffer area via the first flow path selection valve and the second flow path selection valve. The reagents in each buffer area are then pumped into the sample box via the first flow path selection valve to mix with the corresponding test sample in the sample box.
[0074] In this way, the first flow path selection valve can select reagent kits and sample boxes to connect to each buffer area, thereby controlling the switching of reagent flow paths.
[0075] In some embodiments, multiple test samples are drawn from a sample box via a first flow path selection valve and a pump assembly, and each test sample enters the fluid channel from the outlet of its corresponding fluid channel, including:
[0076] The pump unit pumps the mixture of each sample and reagent to its corresponding buffer area through the first flow path selection valve, and pumps the mixture of the sample and reagent in each buffer area into the fluid channel from the outlet of the corresponding fluid channel through the first flow path selection valve.
[0077] In this way, the first flow path selection valve can select the sample box and fluid channel to connect with each buffer area, thereby controlling the flow path switching of each sample and reagent mixture.
[0078] In some implementations, the pump unit pumps the mixture of each sample and reagent to its respective buffer area via a first flow path selection valve in a negative pressure driven manner.
[0079] In this way, the pump assembly can generate negative pressure to drive the mixture of each test sample and reagent to move to the corresponding buffer area, thereby realizing the transport of multiple test sample and reagent mixtures.
[0080] In some implementations, the pump unit pumps the mixture of the test sample and reagent in each buffer zone into the fluid channel from the outlet of the corresponding fluid channel via a first flow path selection valve in a positive pressure driven manner.
[0081] In this way, the pump assembly can generate positive pressure to drive the mixture of each test sample and reagent from each buffer area to the corresponding fluid channel, thereby realizing the transport of multiple test sample and reagent mixtures.
[0082] In some embodiments, the pump valve assembly further includes a second flow path selection valve and a manifold assembly;
[0083] The second flow path selection valve and manifold assembly are located upstream of the flow cell. The second flow path selection valve is used to connect the reagent kit to the manifold assembly and / or connect the reagent kit to the first flow path selection valve. The manifold assembly connects to the fluid channel of the flow cell.
[0084] Individual test samples and / or reagents are drawn from sample cassettes and / or kits via a second flow path selection valve, manifold assembly, and pump assembly, and the individual test samples and / or reagents are introduced into the fluid channels from the inlet of each fluid channel.
[0085] Thus, the second flow path selection valve can connect the manifold assembly and the first flow path selection valve to the reagent kit, enabling control of reagent flow path switching. Additionally, the manifold assembly can split individual test samples and / or reagents, ensuring that test samples entering different fluid channels through the inlet of each fluid channel are the same test sample or the same reagent.
[0086] In some implementations, the pump assembly pumps individual test samples and / or reagents from the inlet of each fluid channel into the fluid channel in a negative pressure driven manner.
[0087] In this way, the pump assembly can generate negative pressure to drive individual test samples and / or reagents to move into each fluid channel, thereby achieving the transport of individual test samples and / or reagents.
[0088] In some implementations, the first flow path selection valve includes multiple sets of ports, each set of ports being used to control the inlet of a fluid channel;
[0089] Each set of ports includes a first port, a second port, a third port, and a fourth port. The first port is connected to the outlet of the fluid channel, the second port is connected to the buffer area, the third port is connected to the sample box, and the fourth port is connected to the reagent kit. Any one of the first, third, and fourth ports can be selectively connected to the second port.
[0090] Thus, the first flow path selection valve allows the buffer area to selectively connect to the outlet of the fluid channel, the sample cassette, and the reagent kit, enabling control over the switching of the flow path for the sample and / or reagent. Multiple ports can simultaneously control the inlet flow to multiple fluid channels, reducing the number of solenoid valves required and consequently reducing the cost and space occupied by the fluidization system.
[0091] In some embodiments, the fluid system includes a plurality of first pipelines, each corresponding to a plurality of first ports, with each end of the first pipeline connected to the outlet of a fluid channel and a first port, respectively.
[0092] In this way, the test samples and / or reagents in each buffer area can flow from the second port and the first port into the corresponding fluid channel through the first pipeline, thereby realizing the transport of the test samples and / or reagents.
[0093] In some embodiments, the liquid circuit system includes multiple second pipelines, each corresponding to a multiple third port. Each second pipeline is connected to a sample box and a third port at both ends. Each second pipeline is used to allow a sample to be tested in the sample box to pass through a first flow path selection valve into the corresponding buffer area.
[0094] In this way, the sample to be tested in the sample box can flow into multiple buffer areas from multiple first ports through multiple second pipes, thus realizing the transportation of the sample to be tested.
[0095] In some embodiments, the liquid circuit system includes a third line, which is configured to correspond one-to-one with a plurality of fourth ports. The two ends of the third line are respectively connected to the reagent kit and each of the fourth ports. The third line is used to allow the reagents in the reagent kit to enter each buffer area through a first flow path selection valve.
[0096] In this way, reagents in the kit can flow into multiple buffer areas from multiple fourth ports via the third tubing, thus realizing reagent transport.
[0097] In some embodiments, the first flow path selection valve includes a plurality of connecting slots, and the second port is connected to one of the first port, the third port, and the fourth port through the connecting slots.
[0098] In this way, the buffer area can be selectively connected to the outlet of the fluid channel, the sample box, and the reagent kit through the connecting slot, so as to control the flow path of the sample and / or reagent to be tested.
[0099] In some embodiments, the first flow path selection valve includes a stator and a rotor rotatably disposed with respect to the stator. The stator has multiple sets of ports, each set of ports including a first port, a second port, a third port, and a fourth port. The rotor has a connecting groove.
[0100] Thus, by rotating the rotor, the connecting groove can selectively connect the buffer area with the outlet of the fluid channel, the sample box, and the reagent kit, thereby controlling the switching of the flow path of the sample and / or reagent.
[0101] In some implementations, the first port, the second port, the third port and the fourth port are arranged at intervals along the circumferential direction of the stator.
[0102] Thus, the first port, the second port, the third port, and the fourth port are arranged at intervals along the circumference of the stator, such that the second port is connected to one of the first port, the third port, and the fourth port through a connecting slot.
[0103] In some embodiments, there are multiple connecting slots, which are arranged at intervals along the circumference of the rotor.
[0104] In this way, multiple connecting channels can simultaneously connect two adjacent ports in multiple sets of ports, allowing simultaneous control of multiple liquid circuits, reducing the number of solenoid valves used, thereby reducing the cost and space occupied by the liquid circuit system.
[0105] In some implementations, the second flow path selection valve includes a common port and at least one connection port, the common port being connected to one end of a third pipeline and the connection port being connected to the reagent kit.
[0106] In this way, the reagent kit can be connected to a third tubing through the common port and connection port, thereby controlling the reagent flow path.
[0107] This application provides a liquid circuit system, which includes a flow cell and a pump-valve assembly. The flow cell includes multiple fluid channels, each fluid channel having an inlet and an outlet. The pump-valve assembly is used to draw multiple test samples from a sample box and pump each test sample into the fluid channel from the outlet of its corresponding fluid channel; or, the pump-valve assembly is used to draw a single test sample from the sample box and pump the single test sample into the fluid channel from the inlet of each fluid channel.
[0108] This application provides a sequencing apparatus including the above-described liquid circuit system.
[0109] This application provides a computer device including a processor and a memory. The memory stores a computer program, which, when executed by the processor, causes the processor to implement the method for controlling the flow of liquid in a liquid circuit system as described in any of the above embodiments.
[0110] This application provides a computer storage medium that, when executed by a processor, enables the processor to implement the method for controlling the liquid intake of a liquid circuit system according to any of the above embodiments.
[0111] Additional aspects and advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. Attached Figure Description
[0112] The above and / or additional aspects and advantages of the present invention will become apparent and readily understood from the description of the embodiments taken in conjunction with the following drawings, in which:
[0113] Figure 1 This is a schematic diagram of the structure of the liquid circuit system according to an embodiment of the present invention;
[0114] Figure 2 This is a flowchart illustrating the method of an embodiment of the present invention;
[0115] Figure 3 This is a flowchart illustrating the method of an embodiment of the present invention;
[0116] Figure 4 This is a schematic diagram of the structure of the first flow path selection valve according to an embodiment of the present invention;
[0117] Figure 5 This is a schematic diagram of the structure of the first flow path selection valve according to an embodiment of the present invention.
[0118] Explanation of reference numerals in the attached drawings: 100, fluid system; 10, flow cell; 11, fluid channel; 12, inlet; 13, outlet; 20, pump and valve assembly; 21, first flow path selection valve; 211, first port; 212, second port; 213, third port; 214, fourth port; 215, connecting groove; 216, stator; 217, rotor; 218, plug; 22, pump assembly; 23, second flow path selection valve; 231, common port; 232, connection port; 24, manifold assembly; 30, sample box; 40, buffer area; 50, reagent kit; 60, waste bottle; 70, solenoid valve; 81, first pipeline; 82, second pipeline; 83, third pipeline; 831, inlet; 832, outlet. Detailed Implementation
[0119] Embodiments of the present invention are described in detail below, examples of which are shown in the accompanying drawings, wherein the same or similar reference numerals denote the same or similar elements or elements having the same or similar functions throughout. The embodiments described below with reference to the accompanying drawings are exemplary and are only used to explain the present invention, and should not be construed as limiting the present invention.
[0120] The following disclosure provides many different embodiments or examples for implementing various structures of the invention. To simplify the disclosure, specific examples of components and arrangements are described below. These are merely examples and are not intended to limit the invention. Furthermore, reference numerals and / or letters may be repeated in different examples; such repetition is for simplification and clarity and does not in itself indicate a relationship between the various embodiments and / or arrangements discussed. In addition, examples of various specific processes and materials are provided in this invention, but those skilled in the art will recognize the application of other processes and / or the use of other materials.
[0121] In this article, "sequencing" refers to nucleic acid sequencing, also known as "nucleic acid sequencing" or "gene sequencing," which involves determining the base sequence of the primary structure of nucleic acid molecules. This can be achieved using sequencing by synthesis (SBS), ligation sequencing (SBL), or hybridization sequencing (SBH). Sequencing by synthesis, as we understand it, includes not only SBS (typically ILLUMINA / Solexa technology), which uses polymerases to catalyze the incorporation of nucleotides into the sample (synthesis reaction) and detects the corresponding reaction signals to identify the type of incorporated nucleotides, but also sequencing similar to SBS, which uses polymerases or non-polymerases to controllably introduce or ligate nucleotides into the sample and directly or indirectly detects the corresponding signals to determine the type of ligated nucleotides.
[0122] Sequencing can include DNA sequencing and / or RNA sequencing. It includes long-fragment sequencing and / or short-fragment sequencing. The terms "long-fragment" and "short-fragment" are relative. For example, nucleic acid molecules longer than 1Kb, 2Kb, 5Kb, or 10Kb can be called long fragments, while those shorter than 1Kb or 800bp can be called short fragments. It can include paired-end sequencing, single-end sequencing, and / or paired-end sequencing, etc. Paired-end sequencing or paired-end sequencing can refer to the readout of any two segments or parts of the same nucleic acid molecule that do not completely overlap.
[0123] Sequencing can be performed using a sequencing platform. According to the embodiments of this application, the sequencing platforms that can be selected include, but are not limited to, Illumina's HiSeq, MiSeq, NextSeq, and Novaseq sequencing platforms, Thermo Fisher / Life Technologies' Ion Torrent platform, BGI Genomics' BGISEQ and MGISEQ / DNBSEQ platforms, and single-molecule sequencing platforms. The sequencing method can be selected as single-end sequencing, paired-end sequencing, or sequencing methods supported by the selected automated sequencing platform.
[0124] Sequencing generally includes: library preparation, PCR amplification (optional), sequencing, and data analysis. The sequence obtained from sequencing is called the sequencing sequence, also known as reads.
[0125] In some examples, sequencing-by-synthesis (SBS) is used to perform multiple rounds of sequencing to obtain sequencing sequences or reads. For instance, the sample to be tested is brought into contact with polymerase and modified nucleotides and placed under suitable conditions for polymerization. The modified nucleotides are controllably incorporated into the sample, or in other words, single-base extensions are controllably achieved. The corresponding reaction signals are detected, and the type of nucleotide incorporated into the sample in that reaction is determined based on these signals. This process of controllable single-base extensions and corresponding signal detection is repeated multiple times to detect the type of nucleotides or bases incorporated into the sample in multiple or multiple rounds of reactions based on the reaction signal information, thereby reading a portion of the sequence from the sample.
[0126] The test sample, also known as the test template or template, can be an unamplified single molecule or an amplified molecular cluster or long chain containing multiple identical polynucleotide molecules, such as the cloning clusters or DNA nanospheres (DNB) formed by bridge amplification or rolling circle amplification used by mainstream sequencing platforms. The test sample can be presented as a single-stranded, double-stranded, and / or hybridized complex with probes or primers.
[0127] The corresponding reaction signals can be, for example, fluorescence signals, or they can be converted into image data formed by collecting these fluorescence signals. These image data are then processed and analyzed to detect the nucleotides incorporated into the sample in each or each round of reaction, so as to determine a portion of the base sequence of the sample.
[0128] Specifically, in some examples, sequencing is achieved based on surface fluorescence imaging detection. The sample to be tested is attached to a solid surface. For example, the nucleotides can be modified to have fluorescent labels or be able to bind to them, as well as removable inhibitory groups that prevent other nucleotides from polymerizing and attaching to the next position of the sample to be tested (such modified nucleotides are also called reversible terminators). After each polymerization reaction or single-base extension reaction, the fluorescent label is excited to emit light, and these emission signals are acquired to obtain images of the sample to be tested at the specified surface position where the single-base extension reaction has occurred. Then, the inhibitory groups and fluorescent labels are removed to perform the next polymerization reaction and signal acquisition (photographing). This process is repeated multiple times to obtain image set information related to the nucleotides attached to the sample to be tested in each single-base extension reaction.
[0129] Understandably, when a sample undergoes a polymerization reaction at a designated location on the surface, it emits fluorescence, which typically appears as a bright spot or bright patch with a higher intensity than the background signal in the corresponding location of the image acquired during that reaction. Therefore, based on the information in these image sets, including the bright spots corresponding to specific chemical characteristics (samples undergoing polymerization), it is possible to determine whether a sample at a designated location has undergone a polymerization reaction. By combining this with a pre-defined, distinguishable fluorescence signal and the correspondence between nucleotide types, the type of nucleotide polymerized and linked to the sample can be detected, thereby determining at least a portion of the sample's sequence and obtaining the so-called read.
[0130] It should be noted that the term "nucleotide" includes ribonucleic acid or deoxyribonucleic acid, including natural nucleotides or their derivatives or modifications thereof (also known as modified nucleotides or altered nucleotides, etc.). In this document, the term "nucleotide" is sometimes used to refer to the bases contained in the nucleotide, which will be readily understood by those skilled in the art based on conventional knowledge and / or context.
[0131] Please see Figure 1 This application provides a method for controlling the inlet of a liquid circuit system 100. The liquid circuit system 100 includes a flow tank 10 and a pump-valve assembly 20. The flow tank 10 includes a plurality of fluid channels 11, each fluid channel 11 having an inlet 12 and an outlet 13. The method includes:
[0132] Multiple test samples are drawn from the sample box 30 using the pump valve assembly 20, and each test sample is pumped into the fluid channel 11 from its corresponding outlet 13; or,
[0133] A single test sample is drawn from the sample box 30 using the pump valve assembly 20, and the single test sample is pumped into the fluid channel 11 from the inlet 12 of each fluid channel 11.
[0134] This application provides a fluid system 100, which includes a flow tank 10 and a pump-valve assembly 20. The flow tank 10 includes a plurality of fluid channels 11, each fluid channel 11 having an inlet 12 and an outlet 13. The pump-valve assembly 20 is used to draw a plurality of test samples from a sample box 30 and pump each test sample into the fluid channel 11 from the outlet 13 of its corresponding fluid channel 11; or, the pump-valve assembly 20 is used to draw a single test sample from the sample box 30 and pump the single test sample into the fluid channel 11 from the inlet 12 of each fluid channel 11.
[0135] This application provides a computer device including a processor and a memory. The memory stores a computer program, which, when executed by the processor, causes the processor to implement the method for controlling the flow of liquid in a fluid system 100 as described in any of the above embodiments. For example, the processor is used to draw multiple test samples from a sample box 30 using a pump-valve assembly 20, and pump each test sample into a fluid channel 11 from its corresponding outlet 13; or it is used to draw a single test sample from the sample box 30 using the pump-valve assembly 20, and pump the single test sample into the fluid channel 11 from the inlet 12 of each fluid channel 11.
[0136] Thus, the pump-valve assembly 20 can allow a single sample to enter the fluid channel 11 from the inlet 12 of each fluid channel 11, or allow each sample to enter the fluid channel 11 from its corresponding outlet 13. This allows for the selection of different injection methods based on the number of samples, improving the flexibility of sample loading. Furthermore, by allowing each sample to enter the fluid channel 11 from its corresponding outlet 13, cross-contamination between multiple samples is avoided, improving sequencing quality and efficiency.
[0137] Specifically, the flow cell 10 provides a site for biochemical reactions during sequencing. The flow cell 10 can also be referred to as a chip, and it can be detachably connected to the pump-valve assembly 20. The fluid channel 11 has a liquid-containing space capable of holding the sample and reagents, allowing the sample to react with the reagents. The sample can be fixed on the inner surface of the fluid channel 11. Multiple fluid channels 11 in the flow cell 10 are arranged side-by-side. The number of fluid channels 11 can be three, four, five, six, etc., and each fluid channel 11 can be exactly the same size or different sizes. In some embodiments, the fluid channel 11 has a non-circular cross-section or an approximately rectangular cross-section, a width of at least 2 mm, about 4 mm, or about 7 mm, and a height of at least 0.8 mm or about 1.2 mm.
[0138] The sample to be tested includes at least one nucleic acid molecule, and the reagents include a polymerase and at least one nucleotide molecule. The polymerase is used to bind the nucleotide molecule to the nucleic acid molecule. The base types of the multiple nucleotide molecules can be the same or different. The nucleotide molecule carries a blocking group, which blocks the binding of more than one nucleotide to the nucleic acid molecule. The blocking group carries an optically detectable label, which allows the reaction between the nucleotide molecule and the nucleic acid molecule to be detected, thereby enabling the sequencing of the nucleic acid molecule.
[0139] The pump-valve assembly 20 includes at least one pump group 22 and at least one valve, and is used to control the flow direction of the sample to be tested. The sample box 30 can be selectively connected to the inlet 12 or the outlet 13 of the fluid channel 11 through the pump-valve assembly 20. When the sample box 30 is connected to the inlet 12 of the fluid channel 11, the pump-valve assembly 20 pumps a single sample to be tested from the sample box 30 into the fluid channel 11 from the inlet 12 of each fluid channel 11; when the sample box 30 is connected to the outlet 13 of the fluid channel 11, the pump-valve assembly 20 pumps multiple samples to be tested from the sample box 30 into the fluid channel 11 from the outlet 13 of their respective corresponding fluid channels 11.
[0140] The sample box 30 is used to store the sample to be tested. Furthermore, the sample box 30 can receive reagents or recovered samples.
[0141] Please see Figure 1 In some embodiments, the fluid system 100 includes a plurality of buffer areas 40, and the plurality of buffer areas 40 are configured in a one-to-one correspondence with a plurality of fluid channels 11;
[0142] Each sample to be tested is pumped into the fluid channel 11 from its corresponding outlet 13, including:
[0143] Each sample to be tested is pumped into its corresponding buffer area 40, and the sample to be tested in each buffer area 40 is pumped into the fluid channel 11 from the outlet 13 of the corresponding fluid channel 11.
[0144] In some embodiments, the pump-valve assembly 20 is used to pump each sample to be tested to its corresponding buffer region 40, and to pump the sample to be tested in each buffer region 40 from the outlet 13 of the corresponding fluid channel 11 into the fluid channel 11.
[0145] In some implementations, the processor is used to pump each sample under test to a corresponding buffer region 40 using the pump-valve assembly 20, and to pump the sample under test of each buffer region 40 from the outlet 13 of the corresponding fluid channel 11 into the fluid channel 11.
[0146] In this way, each buffer region 40 can store one of multiple test samples, allowing the pump valve assembly 20 to pump each test sample through its corresponding buffer region 40 from the outlet 13 of the corresponding fluid channel 11 into the fluid channel 11, realizing the reverse flow of the test samples in the fluid channel 11, increasing the flexibility of test sample loading, while avoiding cross-contamination between multiple test samples, and improving sequencing quality and sequencing efficiency.
[0147] Specifically, the buffer area 40 can be a tubing or a storage bottle. The buffer area 40 is selectively connected to the sample box 30 and the outlet 13 of the fluid channel 11. When the buffer area 40 is connected to the sample box 30, the pump valve assembly 20 pumps each sample to be tested in the sample box 30 to its corresponding buffer area 40. When the buffer area 40 is connected to the outlet 13 of the fluid channel 11, the pump valve assembly 20 pumps the sample to be tested in each buffer area 40 from the outlet 13 of the corresponding fluid channel 11 into the fluid channel 11.
[0148] In some implementations, the method further includes:
[0149] The reagent is drawn from the reagent kit 50 using the pump valve assembly 20 and pumped to each buffer area 40, and the reagent in each buffer area 40 is pumped into the fluid channel 11 from the outlet 13 of the corresponding fluid channel 11.
[0150] In some embodiments, the pump-valve assembly 20 is used to draw reagents from the reagent kit 50 and pump the reagents to each buffer zone 40, and to pump the reagents from each buffer zone 40 into the fluid channel 11 from the outlet 13 of the corresponding fluid channel 11.
[0151] In some implementations, the processor is used to draw reagents from the reagent kit 50 using the pump valve assembly 20, pump the reagents to each buffer area 40, and pump the reagents from each buffer area 40 into the fluid channel 11 from the outlet 13 of the corresponding fluid channel 11.
[0152] In this way, the buffer area 40 can store reagents, allowing the pump valve assembly 20 to pump reagents through each buffer area 40 from the outlet 13 of the corresponding fluid channel 11 into the fluid channel 11, realizing the reverse flow of reagents in the fluid channel 11, increasing the flexibility of reagent loading, while reducing sequencing time and improving sequencing efficiency.
[0153] Specifically, kit 50 is used to store reagents, including but not limited to DNA primers, DNA fragmentation enzymes, T4 DNA polymerase, Klenow enzyme, bases, ligases, DNA adapters, T4 polynucleotide kinases, washing solutions, and / or purified water. For example, the DNA primers in kit 50 are pumped into fluid channel 11, allowing the DNA primers to be covalently linked to flow cell 10.
[0154] The buffer area 40 is selectively connected to the reagent kit 50 and the outlet 13 of the fluid channel 11. When the buffer area 40 is connected to the reagent kit 50, the pump valve assembly 20 pumps the reagent in the reagent kit 50 to each buffer area 40. When the buffer area 40 is connected to the outlet 13 of the fluid channel 11, the pump valve assembly 20 pumps the reagent in each buffer area 40 from the outlet 13 of the corresponding fluid channel 11 into the fluid channel 11.
[0155] In some implementations, the pump-valve assembly 20 pumps the sample and / or reagent to be tested into the buffer area 40 in a negative pressure driven manner.
[0156] In this way, the pump valve assembly 20 can generate negative pressure to drive the sample and / or reagent to be tested to move towards the buffer area 40, thereby realizing the transport of the sample and / or reagent.
[0157] Specifically, the pump valve assembly 20 can pump the sample to be tested from the sample box 30 to the buffer area 40 in a negative pressure driven manner, the pump valve assembly 20 can also pump the reagent from the reagent kit 50 to the buffer area 40 in a negative pressure driven manner, and the pump valve assembly 20 can also pump both the sample to be tested and the reagent to the buffer area 40 in a negative pressure driven manner.
[0158] In some embodiments, the pump-valve assembly 20 pumps the sample to be tested and / or reagents in the buffer region 40 from the outlet 13 of the fluid channel 11 into the fluid channel 11 in a positive pressure driven manner.
[0159] Thus, the pump-valve assembly 20 can generate positive pressure to drive the sample and / or reagent to be tested from the buffer area 40 to the fluid channel 11, thereby realizing the transport of the sample and / or reagent.
[0160] Specifically, the pump valve assembly 20 can pump the sample to be tested from the outlet 13 of the fluid channel 11 into the fluid channel 11 in a positive pressure driven manner, or pump the reagent from the buffer area 40 from the outlet 13 of the fluid channel 11 into the fluid channel 11 in a positive pressure driven manner, or pump both the sample to be tested and the reagent from the buffer area 40 from the outlet 13 of the fluid channel 11 into the fluid channel 11 in a positive pressure driven manner.
[0161] Please see Figure 2 In some embodiments, the method includes, before aspirating multiple test samples from sample cassette 30 using pump valve assembly 20:
[0162] S10, the reagent is drawn from the reagent kit 50 using the pump valve assembly 20 and pumped into the sample box 30 to mix with each sample to be tested in the sample box 30.
[0163] In some implementations, the pump valve assembly 20 is used to draw reagents from the reagent kit 50 and pump the reagents into the sample cartridge 30 to mix with each sample to be tested in the sample cartridge 30.
[0164] In some implementations, the processor is used to draw reagents from the reagent kit 50 using the pump valve assembly 20 and pump the reagents into the sample cassette 30 to mix with each sample to be tested in the sample cassette 30.
[0165] This allows each sample to be mixed with the reagent in the sample box 30 before entering the fluid channel 11, thus saving the time required for pre-processing the sample and facilitating industrialization.
[0166] Specifically, reagents and test samples can be mixed using methods such as rotation mixing, finger-snap mixing, inverted mixing, pipette mixing, and stirring to ensure uniform mixing. For example, during library preparation, DNA fragmentation enzyme, T4 DNA polymerase, Klenow enzyme, A base, ligase, and DNA adapters are mixed with the test sample. The DNA fragmentation enzyme fragments the test sample, the T4 DNA polymerase fills in the ends of the DNA fragments, the Klenow enzyme adds an A base to the 3' end of the DNA fragment, and the ligase connects the DNA adapters to both ends of the DNA fragment.
[0167] Please see Figure 2 In some embodiments, the pump valve assembly 20 draws multiple test samples from the sample cassette 30, including:
[0168] S20, the pump valve assembly 20 draws the mixture of each test sample and reagent from the sample box 30.
[0169] In some embodiments, the pump valve assembly 20 is used to draw a mixture of each test sample and reagent from the sample cartridge 30.
[0170] In some implementations, the processor is used to draw a mixture of each test sample and reagent from the sample cassette 30 using the pump-valve assembly 20.
[0171] In this way, the sample box 30 can store the mixture of each sample and reagent, which makes it easier for the pump valve assembly 20 to draw the sample and / or the mixture of sample and reagent from the sample box 30, thereby improving the utilization rate of the sample box 30, reducing the container for storing the mixture of sample and reagent, reducing the size of the liquid circuit system 100, and thus saving space.
[0172] Specifically, the sample box 30 can store each test sample, or mix each test sample with reagents and store the mixed solution. The pump valve assembly 20 can draw each test sample from the sample box 30, or draw the mixture of each test sample and reagents.
[0173] Please see Figure 2 In some embodiments, each sample to be tested is pumped into the fluid channel 11 from its corresponding outlet 13, including:
[0174] S30, the pump valve assembly 20 is used to pump the mixture of each sample and reagent from the outlet 13 of the corresponding fluid channel 11 into the fluid channel 11.
[0175] In some embodiments, the pump-valve assembly 20 is used to pump the mixture of each sample and reagent from the outlet 13 of a corresponding fluid channel 11 into the fluid channel 11.
[0176] In some implementations, the processor is used to pump a mixture of each sample and reagent from the outlet 13 of a corresponding fluid channel 11 into the fluid channel 11 using the pump-valve assembly 20.
[0177] In this way, the pump valve assembly 20 can allow the mixture of each sample and reagent to enter the fluid channel 11 from the outlet 13 of the corresponding fluid channel 11. The reverse flow of the mixture of sample and reagent in the fluid channel 11 increases the flexibility of sample loading, while reducing sequencing time and improving sequencing efficiency.
[0178] Specifically, the pump valve assembly 20 can pump the mixture of the test sample and reagent from the outlet 13 of the fluid channel 11 into the fluid channel 11, and discharge the mixture of the test sample and reagent from the inlet 12 of the fluid channel 11.
[0179] Please see Figure 1 In some embodiments, the fluid system 100 includes a plurality of buffer areas 40, and the plurality of buffer areas 40 are configured in a one-to-one correspondence with a plurality of fluid channels 11;
[0180] The reagent is drawn from the reagent kit 50 using the pump valve assembly 20 and pumped into the sample cartridge 30 to mix with each sample to be tested in the sample cartridge 30, including:
[0181] The reagent is pumped to each buffer area 40 using the pump valve assembly 20, and the reagent in each buffer area 40 is pumped into the sample box 30 to be mixed with the corresponding test sample in the sample box 30.
[0182] In some embodiments, the pump valve assembly 20 is used to pump reagents to each buffer region 40 and to pump reagents from each buffer region 40 into the sample cassette 30 to mix with the corresponding test sample in the sample cassette 30.
[0183] In some implementations, the processor is used to pump reagents to each buffer region 40 using the pump-valve assembly 20, and to pump the reagents from each buffer region 40 into the sample cassette 30 to mix with the corresponding test sample in the sample cassette 30.
[0184] Thus, the buffer area 40 can store reagents, allowing the pump valve assembly 20 to pump reagents from the reagent kit 50 through each buffer area 40 into the sample box 30.
[0185] Specifically, the buffer area 40 is selectively connected to the reagent kit 50 and the sample box 30. When the buffer area 40 is connected to the reagent kit 50, the pump valve assembly 20 pumps the reagent in the reagent kit 50 to each buffer area 40. When the buffer area 40 is connected to the sample box 30, the pump valve assembly 20 pumps the reagent in each buffer area 40 into the sample box 30 and mixes it with the corresponding test sample in the sample box 30.
[0186] In some embodiments, pumping the mixture of each sample and reagent into the fluid channel 11 from the outlet 13 of a corresponding fluid channel 11 includes:
[0187] The mixture of each sample and reagent is pumped back to its corresponding buffer area 40, and the mixture of the sample and reagent in each buffer area 40 is pumped into the fluid channel 11 from the outlet 13 of the corresponding fluid channel 11.
[0188] In some embodiments, the pump-valve assembly 20 is used to pump the mixture of each sample and reagent back to its respective corresponding buffer area 40, and to pump the mixture of the sample and reagent in each buffer area 40 from the outlet 13 of the corresponding fluid channel 11 into the fluid channel 11.
[0189] In some implementations, the processor is used to pump the mixture of each sample and reagent back to its respective corresponding buffer area 40, and to pump the mixture of the sample and reagent in each buffer area 40 from the outlet 13 of the corresponding fluid channel 11 into the fluid channel 11.
[0190] In this way, the buffer area 40 can store the mixture of each sample and reagent separately, so that the pump valve assembly 20 can pump the mixture of each sample and reagent into the fluid channel 11 from the outlet 13 of the corresponding fluid channel 11 through its corresponding buffer area 40. This realizes the reverse flow of the mixture of sample and reagent in the fluid channel 11, which increases the flexibility of loading the sample and avoids cross-contamination between multiple mixtures of sample and reagent, thereby improving sequencing quality and sequencing efficiency.
[0191] Specifically, the buffer region 40 is selectively connected to the sample box 30 and the outlet 13 of the fluid channel 11. When the buffer region 40 is connected to the sample box 30, the pump valve assembly 20 pumps each mixture in the sample box 30 to each buffer region 40. When the buffer region 40 is connected to the outlet 13 of the fluid channel 11, the pump valve assembly 20 pumps the mixture in each buffer region 40 from the outlet 13 of the corresponding fluid channel 11 into the fluid channel 11.
[0192] In some embodiments, the pump-valve assembly 20 pumps the mixture of the sample and reagent to the buffer area 40 in a negative pressure driven manner.
[0193] In this way, the pump valve assembly 20 can generate negative pressure to drive the mixture of the test sample and reagent to move towards the buffer area 40, thereby realizing the transport of the mixture of the test sample and reagent.
[0194] In some embodiments, the pump-valve assembly 20 pumps the mixture of the test sample and reagent in the buffer region 40 from the outlet 13 of the fluid channel 11 into the fluid channel 11 in a positive pressure driven manner.
[0195] In this way, the pump valve assembly 20 can generate positive pressure to drive the mixture of the sample and reagent to move from the buffer area 40 to the fluid channel 11, thereby realizing the transport of the mixture of the sample and reagent.
[0196] Specifically, the pump valve assembly 20 can pump the reagent from the reagent kit 50 to the buffer area 40 in a negative pressure driven manner, and then pump the reagent in the buffer area 40 to the sample box 30 in a positive pressure driven manner to mix with the sample to be tested in the sample box 30. Then, the mixture of the sample to be tested and the reagent is pumped from the sample box 30 to the buffer area 40 in a negative pressure driven manner. Finally, the mixture of the sample to be tested and the reagent in the buffer area 40 is pumped from the outlet 13 of the fluid channel 11 into the fluid channel 11 in a positive pressure driven manner.
[0197] In some implementations, the method further includes:
[0198] The reagent is drawn from the reagent kit 50 using the pump valve assembly 20 and pumped into the fluid channel 11 from the inlet 12 of each fluid channel 11.
[0199] In some embodiments, the pump-valve assembly 20 is used to draw reagents from the reagent kit 50 and pump the reagents from the inlet 12 of each fluid channel 11 into the fluid channel 11.
[0200] In some implementations, the processor is used to draw reagents from the kit 50 using the pump-valve assembly 20 and pump the reagents from the inlet 12 of each fluid channel 11 into the fluid channel 11.
[0201] Thus, the pump valve assembly 20 can allow reagents to enter the fluid channel 11 from the outlet 13 of each fluid channel 11, or allow reagents to enter the fluid channel 11 from the inlet 12 of the fluid channel 11. The bidirectional flow of reagents in the fluid channel 11 increases the flexibility of reagent loading, while reducing sequencing time and improving sequencing efficiency.
[0202] Specifically, the reagent kit 50 can be selectively connected to the inlet 12 or the outlet 13 of the fluid channel 11 via the pump valve assembly 20. When the reagent kit 50 is connected to the inlet 12 of the fluid channel 11, the pump valve assembly 20 pumps the reagent in the reagent kit 50 from the inlet 12 into the fluid channel 11; when the reagent kit 50 is connected to the outlet 13 of the fluid channel 11, the pump valve assembly 20 pumps the reagent in the reagent kit 50 from the outlet 13 into the fluid channel 11.
[0203] In some implementations, the pump-valve assembly 20 pumps individual test samples and / or reagents from the inlet 12 of each fluid channel 11 into the fluid channel 11 in a negative pressure driven manner.
[0204] Thus, the pump-valve assembly 20 can generate negative pressure to drive individual test samples and / or reagents to move into each fluid channel 11, thereby enabling the transport of individual test samples and / or reagents.
[0205] Specifically, the pump valve assembly 20 can pump a single test sample from the sample box 30 into each fluid channel 11 from the inlet 12 of the fluid channel 11 in a negative pressure driven manner, or pump the reagent in the kit 50 into each fluid channel 11 from the inlet 12 of the fluid channel 11 in a negative pressure driven manner, or pump a single test sample and reagent into each fluid channel 11 from the inlet 12 of the fluid channel 11 in a negative pressure driven manner.
[0206] Please see Figure 1 In some embodiments, the pump valve assembly 20 includes a first flow path selection valve 21 and a pump assembly 22;
[0207] The first flow path selection valve 21 and the pump group 22 are both located downstream of the flow pool 10;
[0208] The first flow path selection valve 21 is used to connect the pump assembly 22 with the fluid channel 11, and / or connect the pump assembly 22 with the sample box 30;
[0209] Multiple test samples are drawn from the sample box 30 through the first flow path selection valve 21 and the pump group 22, and each test sample enters the fluid channel 11 from the outlet 13 of its corresponding fluid channel 11.
[0210] In some embodiments, the first flow path selection valve 21 and the pump assembly 22 are used to draw multiple test samples from the sample box 30 and to allow each test sample to enter the fluid channel 11 from the outlet 13 of its corresponding fluid channel 11.
[0211] In some implementations, the processor is used to draw multiple test samples from the sample box 30 through the first flow path selection valve 21 and the pump assembly 22, and to allow each test sample to enter the fluid channel 11 from the outlet 13 of its corresponding fluid channel 11.
[0212] Thus, the first flow path selection valve 21 can connect the sample box 30 and each fluid channel 11, thereby controlling the flow path of multiple samples to be tested.
[0213] Specifically, the first flow path selection valve 21 and the pump assembly 22 are connected to the outlet 13 of each fluid channel 11. For example... Figure 1As shown by the dashed lines, the first flow path selection valve 21 can connect the pump assembly 22 to the sample container 30, allowing the pump assembly 22 to draw multiple test samples from the sample container 30. The first flow path selection valve 21 can also connect the pump assembly 22 to the outlet 13 of each fluid channel 11, allowing the pump assembly 22 to drive each test sample into the fluid channel 11 from its corresponding outlet 13. The pump assembly 22 can be a peristaltic pump, plunger pump, syringe pump, gear pump, or diaphragm pump, etc., and can provide either negative or positive pressure. The pump assembly 22 includes multiple individual pumps, each corresponding one-to-one with a specific fluid channel 11.
[0214] Please see Figure 1 In some embodiments, multiple buffer areas 40 are provided between the first flow path selection valve 21 and the pump group 22, and the multiple buffer areas 40 are provided in a one-to-one correspondence with multiple fluid channels 11.
[0215] Multiple test samples are drawn from the sample box 30 through the first flow path selection valve 21 and the pump assembly 22, and each test sample enters the fluid channel 11 from the outlet 13 of its corresponding fluid channel 11, including:
[0216] The pump unit 22 pumps each sample to be tested from the sample box 30 to its corresponding buffer area 40 via the first flow path selection valve 21, and pumps the sample to be tested from the buffer area 40 into the corresponding fluid channel 11 from the outlet 13 via the first flow path selection valve 21.
[0217] In some embodiments, the pump assembly 22 is used to pump each sample to be tested from the sample box 30 to its corresponding buffer area 40 via the first flow path selection valve 21, and to pump the sample to be tested from the buffer area 40 into the corresponding fluid channel 11 from the outlet 13 via the first flow path selection valve 21.
[0218] In some embodiments, the processor is configured to pump each sample to be tested from the sample box 30 to a corresponding buffer area 40 via the pump assembly 22 through the first flow path selection valve 21, and to pump the sample to be tested from the buffer area 40 into the corresponding fluid channel 11 from the outlet 13 of the fluid channel 11 via the first flow path selection valve 21.
[0219] Thus, the first flow path selection valve 21 can select the sample box 30 and the fluid channel 11 to connect with the buffer area 40, thereby controlling the switching of the flow paths of multiple samples to be tested.
[0220] Specifically, the first flow path selection valve 21 can connect each buffer area 40 and the sample box 30, so that the pump group 22 pumps each of the multiple test samples from the sample box 30 to its corresponding buffer area 40 through the first flow path selection valve 21. The first flow path selection valve 21 can also connect each buffer area 40 to the outlet 13 of the corresponding fluid channel 11, so that the pump group 22 pumps the test sample of each buffer area 40 into the fluid channel 11 from the outlet 13 of the corresponding fluid channel 11 through the first flow path selection valve 21.
[0221] Please see Figure 1 In some embodiments, the pump valve assembly 20 further includes a second flow path selection valve 23;
[0222] The second flow path selection valve 23 is located upstream of the flow cell 10, and the second flow path selection valve 23 is used to connect the reagent kit 50 and the first flow path selection valve 21.
[0223] The reagent is drawn from the reagent kit 50 through the first flow path selection valve 21, the second flow path selection valve 23 and the pump assembly 22, and the reagent is brought into the fluid channel 11 from the outlet 13.
[0224] In some embodiments, the first flow path selection valve 21, the second flow path selection valve 23, and the pump assembly 22 are used to draw reagents from the reagent kit 50 and to allow the reagents to enter the fluid channel 11 from the outlet 13.
[0225] In some embodiments, the processor is used to draw reagents from the kit 50 through a first flow path selection valve 21, a second flow path selection valve 23 and a pump assembly 22, and to allow the reagents to enter the fluid channel 11 from the outlet 13.
[0226] Thus, the reagent kit 50 and the fluid channel 11 can be connected through the first flow path selection valve 21 and the second flow path selection valve 23, thereby controlling the flow path of the reagent.
[0227] Specifically, the second flow path selection valve 23 is connected to the reagent kit 50. For example... Figure 1 As shown by the dashed lines, the first flow path selection valve 21 can connect the pump assembly 22 and the second flow path selection valve 23, allowing the pump assembly 22 to draw reagents from the reagent kit 50. The first flow path selection valve 21 can also connect the pump assembly 22 and the outlet 13 of the fluid channel 11, allowing the pump assembly 22 to drive the reagents from the outlet 13 into the fluid channel 11. The second flow path selection valve 23 can be a rotary valve, pneumatic reversing valve, electro-hydraulic reversing valve, manual reversing valve, piezoelectric valve, pinch valve, or rotary cutter valve, etc.
[0228] In some embodiments, reagents are drawn from the reagent kit 50 via a first flow path selection valve 21, a second flow path selection valve 23, and a pump assembly 22, and the reagents are brought into the fluid channel 11 from the outlet 13, including:
[0229] The reagents are pumped from the reagent kit 50 to each buffer area 40 via the second flow path selection valve 23 and the first flow path selection valve 21 through the pump assembly 22, and the reagents in each buffer area 40 are pumped into the fluid channel 11 from the outlet 13 of the corresponding fluid channel 11 via the first flow path selection valve 21.
[0230] In some embodiments, the pump assembly 22 is used to pump reagents from the reagent kit 50 to each buffer area 40 via the second flow path selection valve 23 and the first flow path selection valve 21, and to pump reagents from each buffer area 40 into the fluid channel 11 from the outlet 13 of the corresponding fluid channel 11 via the first flow path selection valve 21.
[0231] In some embodiments, the processor is configured to pump reagents from reagent kit 50 to each buffer region 40 via pump assembly 22 through second flow path selection valve 23 and first flow path selection valve 21, and to pump reagents from each buffer region 40 into the fluid channel 11 from outlet 13 of the corresponding fluid channel 11 via first flow path selection valve 21.
[0232] Thus, the first flow path selection valve 21 can select the second flow path selection valve 23 and the fluid channel 11 to connect with the buffer area 40, thereby controlling the flow path switching of the reagents in the reagent kit 50 connected to the second flow path selection valve 23.
[0233] Specifically, the second flow path selection valve 23 connects the reagent kit 50 and the first flow path selection valve 21. The first flow path selection valve 21 can connect each buffer area 40 and the second flow path selection valve 23, so that the pump assembly 22 pumps the reagent from the reagent kit 50 through the second flow path selection valve 23 and the first flow path selection valve 21 to each buffer area 40. The first flow path selection valve 21 can also connect each buffer area 40 and the outlet 13 of the corresponding fluid channel 11, so that the pump assembly 22 pumps the reagent from each buffer area 40 into the corresponding fluid channel 11 through the outlet 13 of the corresponding fluid channel 11 via the first flow path selection valve 21.
[0234] In some embodiments, the pump assembly 22 pumps the sample and / or reagent to be tested through the first flow path selection valve 21 to the buffer area 40 in a negative pressure driven manner.
[0235] In this way, the pump unit 22 can generate negative pressure to drive the sample and / or reagent to be tested to move towards the buffer area 40, thereby realizing the transport of the sample and / or reagent.
[0236] Specifically, the pump assembly 22 can pump the sample to be tested from the sample box 30 to the buffer area 40 through the first flow path selection valve 21 in a negative pressure driven manner. The pump assembly 22 can also pump the reagent from the reagent kit 50 to the buffer area 40 through the second flow path selection valve 23 and the first flow path selection valve 21 in a negative pressure driven manner. The pump assembly 22 can also pump the sample to be tested and the reagent to the buffer area 40 through the first flow path selection valve 21 in a negative pressure driven manner.
[0237] In some embodiments, the pump assembly 22 pumps the sample to be tested and / or reagents in the buffer region 40 into the fluid channel 11 from the outlet 13 via the first flow path selection valve 21 in a positive pressure driven manner.
[0238] In this way, the pump unit 22 can generate positive pressure to drive the sample and / or reagent to be tested from the buffer area 40 through the first flow path selection valve 21 to the fluid channel 11, thereby realizing the transport of the sample and / or reagent.
[0239] Specifically, the pump unit 22 can pump the sample to be tested from the buffer area 40 into the fluid channel 11 through the first flow path selection valve 21 via the outlet 13 of the fluid channel 11 in a positive pressure driven manner; it can also pump the reagent from the buffer area 40 into the fluid channel 11 through the first flow path selection valve 21 via the outlet 13 of the fluid channel 11 in a positive pressure driven manner; and it can also pump both the sample to be tested and the reagent from the buffer area 40 into the fluid channel 11 through the outlet 13 of the fluid channel 11 via the first flow path selection valve 21 in a positive pressure driven manner.
[0240] Please see Figure 1 In some embodiments, the pump valve assembly 20 further includes a second flow path selection valve 23;
[0241] The second flow path selection valve 23 is located upstream of the flow cell 10, and the second flow path selection valve 23 is used to connect the reagent kit 50 and the first flow path selection valve 21.
[0242] Before drawing multiple test samples from the sample cassette 30 via the first flow path selection valve 21 and pump assembly 22, the method further includes:
[0243] The reagent is drawn from the reagent kit 50 through the first flow path selection valve 21, the second flow path selection valve 23 and the pump assembly 22, and then pumped into the sample box 30 to mix with the sample to be tested in the sample box 30.
[0244] In some embodiments, the first flow path selection valve 21, the second flow path selection valve 23, and the pump assembly 22 are used to draw reagents from the reagent kit 50 and pump the reagents into the sample box 30 to mix with the sample to be tested in the sample box 30.
[0245] In some embodiments, the processor is used to draw reagents from the reagent kit 50 through a first flow path selection valve 21, a second flow path selection valve 23 and a pump assembly 22, and pump the reagents into the sample cassette 30 to mix with the sample to be tested in the sample cassette 30.
[0246] Thus, the reagent kit 50 and the sample box 30 can be connected through the first flow path selection valve 21 and the second flow path selection valve 23, thereby controlling the reagent flow path.
[0247] Specifically, such as Figure 1 As shown by the dotted line, the second flow path selection valve 23 is connected to the reagent kit 50. The first flow path selection valve 21 can connect the pump group 22 and the second flow path selection valve 23, so that the pump group 22 draws reagents from the reagent kit 50. The first flow path selection valve 21 can also connect the pump group 22 and the sample box 30, so that the pump group 22 drives the reagents into the sample box 30 and mixes them with the test samples in the sample box 30.
[0248] Please see Figure 3 In some embodiments, multiple buffer areas 40 are provided between the first flow path selection valve 21 and the pump group 22, and the multiple buffer areas 40 are provided in a one-to-one correspondence with multiple fluid channels 11.
[0249] Reagents are drawn from reagent kit 50 through first flow path selection valve 21, second flow path selection valve 23, and pump assembly 22, and then pumped into sample cartridge 30 to mix with the sample to be tested in sample cartridge 30, including:
[0250] S11, the reagent is pumped from the reagent kit 50 into each buffer area 40 through the first flow path selection valve 21 and the second flow path selection valve 23 via the pump group 22, and the reagent in each buffer area 40 is pumped into the sample box 30 through the first flow path selection valve 21 to mix with the corresponding test sample in the sample box 30.
[0251] In some embodiments, the pump assembly 22 is used to pump reagents from the reagent kit 50 into each buffer area 40 via the first flow path selection valve 21 and the second flow path selection valve 23, and to pump the reagents from each buffer area 40 into the sample box 30 via the first flow path selection valve 21 to mix with the corresponding test sample in the sample box 30.
[0252] In some embodiments, the processor is used to pump reagents from the reagent kit 50 into each buffer region 40 via the pump assembly 22 through the first flow path selection valve 21 and the second flow path selection valve 23, and to pump the reagents from each buffer region 40 into the sample box 30 via the first flow path selection valve 21 to mix with the corresponding test sample in the sample box 30.
[0253] Thus, the first flow path selection valve 21 can select the reagent kit 50 and sample box 30 to connect with each buffer area 40, thereby controlling the switching of reagent flow paths.
[0254] Specifically, the second flow path selection valve 23 connects the reagent kit 50 and the first flow path selection valve 21. The first flow path selection valve 21 can connect each buffer area 40 to the second flow path selection valve 23, so that the pump assembly 22 pumps the reagent from the reagent kit 50 into each buffer area 40 through the second flow path selection valve 23 and the first flow path selection valve 21. The first flow path selection valve 21 can also connect the pump assembly 22 to the sample box 30, so that the pump assembly 22 pumps the reagent from each buffer area 40 into the sample box 30 through the first flow path selection valve 21 and mixes it with the corresponding test sample in the sample box 30.
[0255] Please see Figure 3 In some embodiments, multiple test samples are drawn from the sample box 30 via the first flow path selection valve 21 and the pump assembly 22, and each test sample enters the fluid channel 11 from the outlet 13 of its corresponding fluid channel 11, including:
[0256] S21, the mixture of each sample and reagent is pumped to its corresponding buffer area 40 by the pump group 22 through the first flow path selection valve 21, and the mixture of the sample and reagent in each buffer area 40 is pumped into the fluid channel 11 from the outlet 13 of the corresponding fluid channel 11 through the first flow path selection valve 21.
[0257] In some embodiments, the pump assembly 22 is used to pump the mixture of each sample to be tested and the reagent to their respective corresponding buffer areas 40 via the first flow path selection valve 21, and to pump the mixture of the sample to be tested and the reagent in each buffer area 40 from the outlet 13 of the corresponding fluid channel 11 into the fluid channel 11 via the first flow path selection valve 21.
[0258] In some embodiments, the processor is used to pump the mixture of each sample and reagent to its respective corresponding buffer area 40 via the pump assembly 22 through the first flow path selection valve 21, and to pump the mixture of the sample and reagent in each buffer area 40 from the outlet 13 of the corresponding fluid channel 11 into the fluid channel 11 via the first flow path selection valve 21.
[0259] Thus, the first flow path selection valve 21 can select the sample box 30 and the fluid channel 11 to connect with each buffer area 40, thereby controlling the flow path switching of each sample and reagent mixture.
[0260] Specifically, the first flow path selection valve 21 can connect each buffer area 40 and the sample box 30, so that the pump group 22 pumps the mixture of each sample to be tested and the reagent from the sample box 30 to each buffer area 40 through the first flow path selection valve 21. The first flow path selection valve 21 can also connect each buffer area 40 and the outlet 13 of the corresponding fluid channel 11, so that the pump group 22 pumps the mixture of the sample to be tested and the reagent from each buffer area 40 into the corresponding fluid channel 11 through the first flow path selection valve 21 from the outlet 13 of the corresponding fluid channel 11.
[0261] In some embodiments, the pump assembly 22 pumps the mixture of each sample and reagent to its respective buffer area 40 via the first flow path selection valve 21 in a negative pressure driven manner.
[0262] In this way, the pump unit 22 can generate negative pressure to drive the mixture of each sample and reagent to be tested to move to the corresponding buffer area 40, thereby realizing the transport of the mixture of multiple samples and reagents to be tested.
[0263] In some embodiments, the pump unit 22 pumps the mixture of the test sample and reagent in each buffer area 40 into the fluid channel 11 from the outlet 13 of the corresponding fluid channel 11 via the first flow path selection valve 21 in a positive pressure driven manner.
[0264] In this way, the pump unit 22 can generate positive pressure to drive the mixture of each test sample and reagent from each buffer area 40 to the corresponding fluid channel 11, thereby realizing the transport of the mixture of multiple test samples and reagents.
[0265] Specifically, the pump unit 22 can pump reagents from the reagent kit 50 to each buffer area 40 via the second flow path selection valve 23 and the first flow path selection valve 21 in a negative pressure driven manner. Then, in a positive pressure driven manner, the reagents in each buffer area 40 are pumped to the sample box 30 via the first flow path selection valve 21 to mix with the corresponding test sample in the sample box 30. Then, in a negative pressure driven manner, the mixture of each test sample and reagent is pumped from the sample box 30 to each buffer area 40 via the first flow path selection valve 21. Finally, in a positive pressure driven manner, the mixture of each test sample and reagent in each buffer area 40 is pumped into the fluid channel 11 from the outlet 13 of the corresponding fluid channel 11 via the first flow path selection valve 21.
[0266] Please see Figure 1 In some embodiments, the pump valve assembly 20 further includes a second flow path selection valve 23 and a manifold assembly 24;
[0267] The second flow path selection valve 23 and the manifold assembly 24 are located upstream of the flow cell 10. The second flow path selection valve 23 is used to connect the reagent kit 50 to the manifold assembly 24, and / or connect the reagent kit 50 to the first flow path selection valve 21. The manifold assembly 24 is connected to the fluid channel 11 of the flow cell 10.
[0268] Individual test samples and / or reagents are drawn from sample cassettes 30 and / or reagent kits 50 via a second flow path selection valve 23, manifold assembly 24 and pump assembly 22, and the individual test samples and / or reagents are brought into the fluid channel 11 from the inlet 12 of each fluid channel 11.
[0269] In some implementations, the second flow path selection valve 23, manifold assembly 24, and pump assembly 22 are used to draw individual test samples and / or reagents from sample cassette 30 and / or reagent kit 50, and to allow individual test samples and / or reagents to enter the fluid channel 11 from the inlet 12 of each fluid channel 11.
[0270] In some implementations, the processor is configured to draw individual test samples and / or reagents from sample cassettes 30 and / or reagent kits 50 via a second flow path selection valve 23, manifold assembly 24 and pump assembly 22, and to allow individual test samples and / or reagents to enter fluid channels 11 from inlet 12 of each fluid channel 11.
[0271] Thus, the second flow path selection valve 23 can connect the manifold assembly 24 and the first flow path selection valve 21 to the reagent kit 50, thereby controlling the switching of the reagent flow path. In addition, the manifold assembly 24 can split the flow of a single test sample and / or reagent, so that the test samples entering different fluid channels 11 through the inlet 12 of each fluid channel 11 are the same test sample or the same reagent.
[0272] Specifically, such as Figure 1 As shown by the double-dotted line, the manifold assembly 24 is connected to the inlet 12 of the fluid channel 11. The second flow path selection valve 23 can connect the reagent kit 50 and the manifold assembly 24, so that the pump unit 22 can pump the reagents of the reagent kit 50 into the fluid channel 11 through the second flow path selection valve 23 and the manifold assembly 24 from the inlet 12 of each fluid channel 11. The second flow path selection valve 23 can also connect the sample box 30 and the manifold assembly 24, so that the pump unit 22 can pump the sample to be tested from the sample box 30 into the fluid channel 11 through the second flow path selection valve 23 and the manifold assembly 24 from the inlet 12 of each fluid channel 11.
[0273] In one embodiment, the fluid system 100 includes a waste liquid bottle 60 connected to a manifold assembly 24 and a pump assembly 22. The waste liquid bottle 60 is used to store or discharge all or part of the waste liquid from the fluid system 100. The waste liquid bottle 60 can be connected to the inlet 12 of each fluid channel 11 via the manifold assembly 24, allowing waste liquid from reactions occurring within the fluid channels 11 to flow into the waste liquid bottle 60 from the inlet 12 of each fluid channel 11. The waste liquid bottle 60 can also be connected to the outlet 13 of each fluid channel 11 via the pump assembly 22, allowing waste liquid from reactions occurring within the fluid channels 11 to flow into the waste liquid bottle 60 from the outlet 13 of each fluid channel 11. A solenoid valve 70 can be installed between the waste liquid bottle 60 and the manifold assembly 24. When the solenoid valve 70 is energized, the pump assembly 22 can drive the waste liquid in each fluid channel 11 to flow from the inlet 12 of each fluid channel 11 through the manifold assembly 24 into the waste liquid bottle 60. When the solenoid valve 70 is de-energized, the pump assembly 22 can drive the waste liquid in each fluid channel 11 to flow from the outlet 13 of each fluid channel 11 through the pump assembly 22 into the waste liquid bottle 60.
[0274] In some embodiments, the pump assembly 22 pumps individual test samples and / or reagents from the inlet 12 of each fluid channel 11 into the fluid channel 11 in a negative pressure driven manner.
[0275] In this way, the pump assembly 22 can generate negative pressure to drive individual test samples and / or reagents to move to each fluid channel 11, thereby realizing the transport of individual test samples and / or reagents.
[0276] Specifically, the pump assembly 22 can pump a single test sample from the sample cassette 30 into each fluid channel 11 via the second flow path selection valve 23 and the manifold assembly 24 in a negative pressure driven manner. The pump assembly 22 can also pump reagents from the reagent kit 50 into each fluid channel 11 via the second flow path selection valve 23 and the manifold assembly 24 in a negative pressure driven manner. The pump assembly 22 can also pump a single test sample and reagents into each fluid channel 11 via the second flow path selection valve 23 and the manifold assembly 24 in a negative pressure driven manner.
[0277] Please see Figure 1 and Figure 4 In some embodiments, the first flow path selection valve 21 includes multiple sets of ports, each set of ports being used to control the inlet of a fluid channel 11. Each set of ports includes a first port 211, a second port 212, a third port 213, and a fourth port 214. The first port 211 is connected to the outlet 13 of the fluid channel 11, the second port 212 is connected to the buffer area 40, the third port 213 is connected to the sample cassette 30, and the fourth port 214 is connected to the reagent kit 50. Any one of the first port 211, the third port 213, and the fourth port 214 is selectively connected to the second port 212.
[0278] Thus, the first flow path selection valve 21 allows the buffer area 40 to selectively connect with the outlet 13 of the fluid channel 11, the sample cassette 30, and the reagent kit 50, enabling control of the flow path switching for the sample and / or reagent. Multiple ports can simultaneously control the inlet flow of multiple fluid channels 11, reducing the number of solenoid valves 70 required, thereby reducing the cost and space occupied by the liquid circuit system 100.
[0279] Specifically, the first port 211, the second port 212, and the third port 213 can serve as either the liquid outlet or the liquid inlet of the first flow path selection valve 21, and the fourth port 214 can serve as the liquid inlet of the first flow path selection valve 21. The number of ports can be two, three, four, five, six, or more groups, and the number of port groups can be consistent with the number of fluid channels 11. The spacing between multiple groups of ports can be consistent. In one embodiment, the number of fluid channels 11 is four, and the first flow path selection valve 21 includes four groups of ports. The four first ports 211 are respectively connected to the outlets 13 of the four fluid channels 11, and the flow path of the fluid in the four fluid channels 11 can be controlled simultaneously through the first flow path selection valve 21. The ports can be regular shapes such as circles or polygons, or irregular shapes. The shape of each port can be the same or different. In this embodiment, the ports are circular to facilitate port formation, manufacturing, and / or connection with common pipes.
[0280] Please see Figure 1 In some embodiments, the fluid system 100 includes a plurality of first pipes 81, which are configured one-to-one with a plurality of first ports 211. Each first pipe 81 is connected to the outlet of a fluid channel 11 and a first port 211 at both ends.
[0281] In this way, the test samples and / or reagents in each buffer area 40 can flow from the second port 212 and the first port 211 into the corresponding fluid channel 11 through the first pipe 81, thereby realizing the transport of the test samples and / or reagents.
[0282] Specifically, the first pipe 81 can be a pipe for transmitting fluid, including but not limited to gas, liquid, etc. The cross-sectional shape of the first pipe 81 can be circular, and the length and diameter of the first pipe 81 can be set according to actual needs. The number of first pipes 81 can be the same as the number of fluid channels 11, and multiple first pipes 81 are respectively connected to multiple fluid channels 11 and multiple first ports 211.
[0283] Please see Figure 1In some embodiments, the liquid circuit system 100 includes a plurality of second pipes 82, which are configured one-to-one with a plurality of third ports 213. Each second pipe 82 is connected to a sample box 30 and a third port 213 at both ends. Each second pipe 82 is used to allow a sample to be tested in the sample box 30 to enter the corresponding buffer area 40 through the first flow path selection valve 21.
[0284] In this way, the sample to be tested in the sample box 30 can flow from multiple first ports 211 into multiple buffer areas 40 through multiple second pipes 82, thereby realizing the transportation of the sample to be tested.
[0285] Specifically, the second conduit 82 can be a conduit for transmitting fluid, including but not limited to gas and liquid. The cross-sectional shape of the second conduit 82 can be circular, and its length and diameter can be set according to actual needs. The number of second conduits 82 can be the same as the number of fluid channels 11. Multiple second conduits 82 are connected one-to-one with multiple memories of the sample box 30, and each memory is used to store a single sample to be tested.
[0286] Please see Figure 1 In some embodiments, the liquid circuit system 100 includes a third pipeline 83, which is configured one-to-one with a plurality of fourth ports 214. The two ends of the third pipeline 83 are respectively connected to the reagent kit 50 and each fourth port 214. The third pipeline 83 is used to allow the reagents in the reagent kit 50 to enter each buffer area 40 through the first flow path selection valve 21.
[0287] In this way, the reagents of the reagent kit 50 can flow from multiple fourth ports 214 into multiple buffer areas 40 through the third tube 83, thereby realizing the transport of reagents.
[0288] Specifically, the third conduit 83 can be a conduit for transmitting fluid, including but not limited to gas and liquid. The cross-sectional shape of the third conduit 83 can be circular, and its length and diameter can be set according to actual needs. The third conduit 83 has one inlet 831 and multiple outlets 832. The number of outlets 832 can be the same as the number of fluid channels 11. The inlet 831 of the third conduit 83 is connected to the reagent kit 50, and the multiple outlets 832 of the third conduit 83 are respectively connected to multiple fourth ports 214 one by one.
[0289] Please see Figure 4 and Figure 5 In some embodiments, the first flow path selection valve 21 includes a plurality of communication slots 215, and the second port 212 is connected to one of the first port 211, the third port 213, and the fourth port 214 through the communication slots 215.
[0290] Thus, the buffer area 40 can be selectively connected to the outlet 13 of the fluid channel 11, the sample box 30 and the reagent kit 50 through the connecting groove 215, thereby controlling the flow path of the sample and / or reagent to be tested.
[0291] Specifically, the number of connecting slots 215 can be the same as the number of fluid channels 11. One connecting slot 215 corresponds to a set of ports to control the flow of fluid in one fluid channel 11. The number of connecting slots 215 can be four. The four connecting slots 215 can be connected to four second ports 212 and four first ports 211 respectively, or they can be connected to four second ports 212 and four third ports 213 respectively, or they can be connected to four second ports 212 and four fourth ports 214 respectively.
[0292] Please see Figure 4 and Figure 5 In some embodiments, the first flow path selection valve 21 includes a stator 216 and a rotor 217 rotatably disposed with respect to the stator 216. The stator 216 is provided with multiple sets of ports, each set of ports including a first port 211, a second port 212, a third port 213 and a fourth port 214. The rotor 217 is provided with a connecting groove 215.
[0293] Thus, by rotating the rotor 217, the connecting groove 215 can selectively connect the buffer area 40 with the outlet 13 of the fluid channel 11, the sample box 30, and the reagent kit 50, thereby controlling the switching of the flow path of the sample and / or reagent.
[0294] Specifically, the first port 211, the second port 212, the third port 213, and the fourth port 214 can be circular through holes, penetrating the stator 216 along its thickness direction. The stator 216 and the rotor 217 can be coaxially arranged, or in other words, the central axis of the stator 216 coincides with the central axis of the rotor 217. The connecting groove 215 can be bent, curved, or other shapes; the specific shape of the connecting groove 215 is not limited here.
[0295] Please see Figure 4 and Figure 5 In some embodiments, the first port 211, the second port 212, the third port 213 and the fourth port 214 are arranged at intervals along the circumference of the stator 216.
[0296] Thus, the first port 211, the second port 212, the third port 213 and the fourth port 214 are arranged circumferentially along the stator 216, such that the second port 212 is connected to one of the first port 211, the third port 213 and the fourth port 214 through the connecting slot 215.
[0297] Specifically, each group of ports may include a first port 211, two second ports 212, a third port 213, and a fourth port 214. The first port 211, the third port 213, and the fourth port 214 are respectively distributed on both sides of the two second ports 212. For example, one second port 212 is located between the first port 211 and the third port 213, and the other second port 212 is located between the third port 213 and the fourth port 214. That is, the first port 211, the second port 212, the third port 213, the second port 212, and the fourth port 214 are arranged sequentially in a clockwise or counterclockwise direction around the stator 216. In one embodiment, the two second ports 212 are connected to the same buffer area 40 outside the first flow path selection valve 21 via a Y-shaped pipe. By rotating the first flow path rotary valve 21, the connecting groove 215 connects one of the second ports 212 with the third port 213, or connects the other second port 212 with the fourth port 214. For example, through a Y-shaped conduit, reagents, test samples, or their mixtures can enter the buffer region 40 via the fourth port 214, the connecting channel 215, and the second port 212. The reagents, test samples, or their mixtures in the buffer region 40 can then enter the corresponding fluid channels via the second port 212, the connecting channel 215, and the first port 212. In one embodiment, a plug 218 is provided on the stator 216, located on both sides of each group of ports. When the connecting channel 215 connects the plug 218 and an adjacent port, fluid interruption control can be achieved.
[0298] Please see Figure 4 and Figure 5 In some embodiments, there are multiple connecting slots 215, which are arranged at intervals along the circumference of the rotor 217.
[0299] In this way, multiple connecting channels 215 can simultaneously connect two adjacent ports in multiple sets of ports, and multiple liquid circuits can be controlled at the same time, reducing the number of solenoid valves 70 used, thereby reducing the cost and space occupied by the liquid circuit system 100.
[0300] Specifically, the length of the connecting groove 215 can be the distance between two adjacent ports, allowing the connecting groove 215 to connect two adjacent ports. This ensures that fluid enters from one port and flows out from another, achieving accurate control of the fluid flow path, preventing fluid from entering or flowing out from multiple ports, reducing the risk of cross-contamination between different test samples, and improving sequencing quality. The spacing between two adjacent connecting grooves 215 is consistent, so that when one connecting groove 215 connects to the first port 211 and the second port 212, the other connecting grooves 215 can connect to the corresponding first port 211 and second port 212.
[0301] Please see Figure 1In some embodiments, the second flow path selection valve 23 includes a common port 231 and at least one connection port 232, the common port 231 being connected to one end of the third pipeline 83 and the connection port 232 being connected to the reagent kit 50.
[0302] Thus, the reagent kit 50 can be connected to the third tubing 83 through the common port 231 and the connection port 232, thereby controlling the reagent flow path.
[0303] Specifically, there can be two connection ports 232. One connection port 232 is connected to the reagent kit 50, and the other connection port 232 is connected to the sample box 30. The common port 231 is selectively connected to one of the connection ports 232, so that the common port 231 can selectively connect to the reagent kit 50 or the sample box 30. For example, when the first flow path selection valve 21 connects the buffer area 40 and the third pipeline 83, and the second flow path selection valve 23 connects the reagent kit 50 and the third pipeline 83, the reagent of the reagent kit 50 can flow from the third pipeline 83 into the buffer area 40 through the first flow path selection valve 21; when the first flow path selection valve 21 connects the buffer area 40 and the first pipeline 81, and the second flow path selection valve 23 connects the reagent kit 50 and the manifold assembly 24, the reagent of the reagent kit 50 can enter the fluid channel 11 from the inlet 12 of the fluid channel 11 through the manifold assembly 24; when the first flow path selection valve 21 connects the buffer area 40 and the first pipeline 81, and the second flow path selection valve 23 connects the sample box 30 and the manifold assembly 24, the sample to be tested in the sample box 30 can enter the fluid channel 11 from the inlet 12 of the fluid channel 11 through the manifold assembly 24.
[0304] This application provides a sequencing apparatus including a liquid flow system 100. Thus, the liquid flow system 100 can select different sample introduction methods according to the number of samples to be tested, improving the flexibility of sample loading while avoiding cross-contamination between multiple samples, thereby improving sequencing quality and efficiency.
[0305] This application provides a computer storage medium that, when executed by a processor, enables the processor to implement the method for controlling the liquid intake of the liquid circuit system 100 according to any of the above embodiments.
[0306] Specifically, in one embodiment, the processor can be a central processing unit (CPU). The processor can also be other general-purpose processors, digital signal processors (DSPs), application-specific integrated circuits (ASICs), field-programmable gate arrays (FPGAs), or other programmable logic devices, discrete gate or transistor logic devices, discrete hardware components, or combinations of the above types of chips.
[0307] Computer programs can be stored in memory. Memory, as a non-transitory computer-readable storage medium, can be used to store non-transitory software programs, non-transitory computer-executable programs, and modules, such as the program instructions / modules corresponding to the methods in the above method embodiments. The processor executes various functional applications and data processing by running the non-transitory software programs, instructions, and modules stored in memory, thereby implementing the control methods in the above method embodiments.
[0308] Storage media can include, but are not limited to: USB flash drives, read-only memory (ROM), random access memory (RAM), portable hard drives, magnetic disks, optical disks, and other media that can store computer programs.
[0309] In the description of this specification, the references to terms such as "one embodiment," "some embodiments," "illustrative embodiment," "example," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the invention. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples.
[0310] Although embodiments of the invention have been shown and described, those skilled in the art will understand that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the claims and their equivalents.
Claims
1. A method for controlling liquid inlet in a liquid circuit system, characterized in that, The fluid system includes a flow tank and a pump and valve assembly. The flow tank includes multiple fluid channels, each of which has an inlet and an outlet. The method includes: The pump-valve assembly is used to draw multiple test samples from the sample box, and each test sample is pumped into the fluid channel from the outlet of its corresponding fluid channel; or, The pump-valve assembly is used to draw a single sample from the sample box and pump the single sample into the fluid channel from the inlet of each fluid channel.
2. The method according to claim 1, characterized in that, The fluid system includes multiple buffer areas, and each of the multiple buffer areas is configured to correspond one-to-one with a multiple fluid channel; The step of pumping each of the test samples into the fluid channel from the outlet of its corresponding fluid channel includes: Each of the test samples is pumped into its corresponding buffer area, and the test samples in each buffer area are pumped into the fluid channel from the outlet of the corresponding fluid channel. Optionally, the method further includes: The reagent is drawn from the kit using the pump-valve assembly and pumped into each of the buffer areas, and the reagent in each of the buffer areas is pumped into the fluid channel from the outlet of the corresponding fluid channel; Optionally, the pump-valve assembly pumps the sample to be tested and / or the reagent to the buffer area in a negative pressure driven manner; Optionally, the pump-valve assembly pumps the test sample and / or the reagent in the buffer area from the outlet of the fluid channel into the fluid channel in a positive pressure driven manner; Optionally, before drawing multiple samples from the sample cassette using the pump-valve assembly, the method includes: The reagent is drawn from the reagent kit using the pump valve assembly and pumped into the sample box to mix with each of the test samples in the sample box; Optionally, the step of drawing multiple test samples from the sample box using the pump valve assembly includes: The pump valve assembly is used to draw a mixture of each sample to be tested and the reagent from the sample box; Optionally, pumping each of the test samples into the fluid channel from the outlet of its respective corresponding fluid channel includes: The mixture of each test sample and the reagent is pumped into the fluid channel from the outlet of the corresponding fluid channel; Optionally, the fluid system includes multiple buffer areas, and the multiple buffer areas are configured in a one-to-one correspondence with the multiple fluid channels; The step of drawing reagents from the kit using the pump valve assembly and pumping the reagents into the sample cassette to mix with each of the test samples in the sample cassette includes: The reagent is pumped to each of the buffer areas using the pump valve assembly, and the reagent in each of the buffer areas is pumped into the sample box to mix with the corresponding test sample in the sample box; Optionally, pumping the mixture of each test sample and the reagent into the fluid channel from the outlet of a corresponding fluid channel includes: The mixture of each test sample and the reagent is pumped back to its corresponding buffer area, and the mixture of the test sample and the reagent in each buffer area is pumped into the fluid channel from the outlet of the corresponding fluid channel. Optionally, the pump-valve assembly pumps the mixture of the test sample and the reagent to the buffer area in a negative pressure driven manner; Optionally, the pump-valve assembly pumps the mixture of the test sample and the reagent in the buffer area from the outlet of the fluid channel into the fluid channel in a positive pressure driven manner; Optionally, the method further includes: The reagent is drawn from the kit using the pump-valve assembly and the reagent is pumped into the fluid channel from the inlet of each of the fluid channels; Optionally, the pump-valve assembly pumps a single sample to be tested and / or the reagent into the fluid channel from the inlet of each fluid channel in a negative pressure driven manner.
3. The method according to claim 1 or 2, characterized in that, The pump-valve assembly includes a first flow path selection valve and a pump unit; The first flow path selection valve and the pump set are both located downstream of the flow pool; The first flow path selection valve is used to connect the pump assembly to the fluid channel, and / or to connect the pump assembly to the sample box; Multiple test samples are drawn from the sample box through the first flow path selection valve and the pump group, and each test sample enters the fluid channel from the outlet of its corresponding fluid channel. Optionally, multiple buffer areas are provided between the first flow path selection valve and the pump group, and the multiple buffer areas are provided in a one-to-one correspondence with the multiple fluid channels; The step of drawing multiple test samples from the sample box through the first flow path selection valve and the pump assembly, and causing each test sample to enter the fluid channel from the outlet of its corresponding fluid channel, includes: The pump unit pumps each of the test samples from the sample box to its corresponding buffer area via the first flow path selection valve, and pumps the test samples from each of the buffer areas into the fluid channel from the outlet of the corresponding fluid channel via the first flow path selection valve. Optionally, the pump valve assembly further includes a second flow path selection valve; The second flow path selection valve is located upstream of the flow cell, and the second flow path selection valve is used to connect the reagent kit and the first flow path selection valve; The reagent is drawn from the kit through the first flow path selection valve, the second flow path selection valve and the pump assembly, and the reagent is brought into the fluid channel from the outlet of the fluid channel; Optionally, the step of drawing reagents from the kit through the first flow path selection valve, the second flow path selection valve, and the pump assembly, and allowing the reagents to enter the fluid channel from the outlet of the fluid channel, includes: The reagent is pumped from the kit to each of the buffer areas via the pump assembly through the second flow path selection valve and the first flow path selection valve, and the reagent in each of the buffer areas is pumped into the fluid channel from the outlet of the corresponding fluid channel via the first flow path selection valve. Optionally, the pump assembly pumps the sample to be tested and / or the reagent to the buffer area via the first flow path selection valve in a negative pressure driven manner; Optionally, the pump assembly pumps the sample to be tested and / or the reagent in the buffer area into the fluid channel from the outlet of the fluid channel via the first flow path selection valve in a positive pressure driven manner; Optionally, the pump valve assembly further includes a second flow path selection valve; The second flow path selection valve is located upstream of the flow cell, and the second flow path selection valve is used to connect the reagent kit and the first flow path selection valve; Before drawing multiple test samples from the sample box through the first flow path selection valve and the pump assembly, the method further includes: The reagent is drawn from the kit through the first flow path selection valve, the second flow path selection valve and the pump assembly, and the reagent is pumped into the sample box to be mixed with the sample to be tested in the sample box. Optionally, multiple buffer areas are provided between the first flow path selection valve and the pump group, and the multiple buffer areas are provided in a one-to-one correspondence with the multiple fluid channels; The step of drawing reagents from the kit through the first flow path selection valve, the second flow path selection valve, and the pump assembly, and pumping the reagents into the sample box to mix with the sample to be tested in the sample box, includes: The reagent is pumped from the kit into each buffer area via the first flow path selection valve and the second flow path selection valve through the pump assembly, and the reagent in each buffer area is pumped into the sample box via the first flow path selection valve to mix with the corresponding test sample in the sample box. Optionally, the step of drawing multiple test samples from the sample box through the first flow path selection valve and the pump assembly, and causing each test sample to enter the fluid channel from the outlet of its corresponding fluid channel, includes: The pump assembly pumps the mixture of each sample to be tested and the reagent to their respective corresponding buffer areas via the first flow path selection valve, and pumps the mixture of the sample to be tested and the reagent in each buffer area into the fluid channel from the outlet of the corresponding fluid channel via the first flow path selection valve. Optionally, the pump assembly pumps each sample to be tested and the reagent mixture to its respective corresponding buffer area via the first flow path selection valve in a negative pressure driven manner; Optionally, the pump assembly pumps the mixture of the test sample and the reagent in each of the buffer areas into the fluid channel from the outlet of the corresponding fluid channel via the first flow path selection valve in a positive pressure driven manner; Optionally, the pump valve assembly further includes a second flow path selection valve and a manifold assembly; The second flow path selection valve and the manifold assembly are located upstream of the flow cell. The second flow path selection valve is used to connect the reagent kit to the manifold assembly and / or connect the reagent kit to the first flow path selection valve. The manifold assembly connects to the fluid channel of the flow cell. A single test sample and / or reagent is drawn from the sample cassette and / or reagent kit via the second flow path selection valve, the manifold assembly, and the pump assembly, and the single test sample and / or reagent is introduced into the fluid channel from the inlet of each fluid channel; Optionally, the pump assembly pumps a single sample to be tested and / or the reagent from the inlet of each fluid channel into the fluid channel in a negative pressure driven manner; Optionally, the first flow path selection valve includes multiple sets of ports, each set of ports being used to control the inlet of one of the fluid channels; Each set of ports includes a first port, a second port, a third port, and a fourth port. The first port is connected to the outlet of the fluid channel, the second port is connected to the buffer area, the third port is connected to the sample box, and the fourth port is connected to the reagent kit. Any one of the first port, the third port, and the fourth port is selectively connected to the second port.
4. A fluid circuit system, characterized in that, include: A flow cell, comprising multiple fluid channels, each having an inlet and an outlet. A pump valve assembly for drawing multiple test samples from a sample box and pumping each test sample into the fluid channel from the outlet of its corresponding fluid channel. or, The pump-valve assembly is used to draw a single test sample from the sample cassette and pump the single test sample into the fluid channel from the inlet of each of the fluid channels.
5. The fluid circuit system according to claim 4, characterized in that, The pump-valve assembly includes a first flow path selection valve and a pump assembly. Both the first flow path selection valve and the pump assembly are located downstream of the flow cell. The first flow path selection valve connects the pump assembly to the fluid channel and / or connects the pump assembly to the sample box. The first flow path selection valve and the pump assembly are used to draw multiple test samples from the sample box and to allow each test sample to enter the fluid channel from the outlet of its corresponding fluid channel. Optionally, the fluid system includes multiple buffer areas, each of which is configured to correspond one-to-one with a multiple fluid channel. The multiple buffer areas are connected to the first flow path selection valve and the pump group. The first flow path selection valve and the pump group pump each sample to be tested to one of its corresponding buffer areas and pump the sample to be tested in each buffer area from the outlet of the corresponding fluid channel into the fluid channel. Optionally, the first flow path selection valve is provided with a plurality of first ports and a plurality of second ports, each first port being selectively connected to a second port, the second port being connected to the buffer area, the fluid circuit system including a plurality of first pipelines, the plurality of first pipelines being configured one-to-one with the plurality of first ports, and the two ends of each first pipeline being connected to the outlet of a fluid channel and a first port respectively; Optionally, the first flow path selection valve is provided with a plurality of third ports, each of the third ports being selectively connected to a second port. The liquid circuit system includes a plurality of second pipelines, each of the second pipelines being configured in a one-to-one correspondence with the plurality of third ports. The two ends of each second pipeline are respectively connected to the sample box and a third port. Each second pipeline is used to allow a sample to be tested in the sample box to pass through the first flow path selection valve into the corresponding buffer area. Optionally, the first flow path selection valve is provided with a plurality of fourth ports, each of the fourth ports being selectively connected to a second port. The liquid circuit system includes a third pipeline, which is configured to correspond one-to-one with the plurality of fourth ports. The two ends of the third pipeline are respectively connected to the reagent kit and each of the fourth ports. The third pipeline is used to allow the reagents in the reagent kit to enter each of the buffer areas through the first flow path selection valve. Optionally, the first flow path selection valve includes a plurality of communication slots, and the second port is connected to one of the first port, the third port, and the fourth port through the communication slots; Optionally, the first flow path selection valve includes a stator and a rotor rotatably disposed with respect to the stator. The stator is provided with multiple sets of ports, each set of ports including a first port, a second port, a third port, and a fourth port. The rotor is provided with the communicating groove. Optionally, the first port, the second port, the third port, and the fourth port are arranged at intervals along the circumferential direction of the stator; Optionally, there are multiple connecting slots, which are arranged at intervals along the circumference of the rotor.
6. The hydraulic system according to claim 5, characterized in that, The pump-valve assembly includes a second flow path selection valve located upstream of the flow cell. The second flow path selection valve includes a common port and at least one connection port. The common port is connected to one end of the third pipeline, and the connection port is connected to the reagent kit. The second flow path selection valve is used by the pump-valve assembly to draw reagents from the reagent kit and pump the reagents to each of the buffer areas, and to pump the reagents from each of the buffer areas into the fluid channel from the outlet of the corresponding fluid channel. Optionally, the pump-valve assembly is used to pump the sample to be tested and / or the reagent to the buffer area in a negative pressure driven manner; Optionally, the pump-valve assembly is used to pump the test sample and / or the reagent in the buffer area from the outlet of the fluid channel into the fluid channel in a positive pressure driven manner; Optionally, the pump valve assembly includes a second flow path selection valve located upstream of the flow cell. The second flow path selection valve includes a common port and at least one connection port. The common port is connected to one end of the third tubing, and the connection port is connected to the reagent kit. The second flow path selection valve is used by the pump valve assembly to draw reagents from the reagent kit and pump the reagents into the sample cassette to mix with each of the test samples in the sample cassette. Optionally, the pump valve assembly is used to pump the reagent to each of the buffer areas and pump the reagent from each of the buffer areas into the sample box to mix with the corresponding test sample in the sample box; Optionally, the pump valve assembly is used to pump the mixture of each test sample and the reagent back to its respective corresponding buffer area, and to pump the mixture of the test sample and the reagent in each buffer area from the outlet of the corresponding fluid channel into the fluid channel; Optionally, the pump-valve assembly is used to pump the mixture of the test sample and the reagent to the buffer area in a negative pressure driven manner; Optionally, the pump-valve assembly is used to pump the mixture of the test sample and the reagent in the buffer region from the outlet of the fluid channel into the fluid channel in a positive pressure driven manner.
7. The fluid circuit system according to claim 6, characterized in that, The pump-valve assembly includes a manifold assembly located upstream of the flow cell. A second flow path selection valve connects the reagent kit to the manifold assembly and / or connects the reagent kit to the first flow path selection valve. The manifold assembly connects the common port to each fluid channel of the flow cell. The second flow path selection valve, the manifold assembly, and the pump assembly are used to draw a single test sample and / or reagent from the sample cassette and / or reagent kit and to allow the single test sample and / or reagent to enter the fluid channel from the inlet of each fluid channel.
8. A sequencing device, characterized in that, Includes the fluid circuit system as described in any one of claims 4-7.
9. A computer device, characterized in that, It includes a processor and a memory, the memory storing a computer program that, when executed by the processor, causes the processor to implement the method for controlling the flow of liquid in a fluid circuit system as described in any one of claims 1-3.
10. A computer storage medium, characterized in that, When the computer program is executed by the processor, the processor implements the method for controlling the inlet of a liquid circuit system as described in any one of claims 1-3.