CN114688301A - Flow Path Selection Valve, Flow Cell Assembly, Fluid System and Sequencing System - Google Patents

Abstract

The application discloses a flow path selection valve, a flow cell assembly, a liquid path system and a sequencing system. The flow path selection valve is configured to switch between a first valve position and a second valve position, the flow path selection valve is provided with a common port, a plurality of first ports, a plurality of second ports, and a plurality of communication grooves that selectively communicate the common port and the first port or the first port and the second port, the first port and the second port communicate through the communication grooves in a case where the flow path selection valve is in the first valve position, and the first port and the common port communicate through the communication grooves in a case where the flow path selection valve is in the second valve position. As such, the flow path selection valve is made to have two or more passages; the flow path selector valve is applicable to any fluid path system requiring the use of three-way valves, particularly multiple three-way valves, for example those involving the need to change the direction of one or more flow paths and/or dispense multiple liquids/solutions.

Description

Flow Path Selection Valve, Flow Cell Assembly, Fluid System and Sequencing System

technical field

The present application relates to the technical fields of machinery and fluids, and more particularly, to a flow path selection valve, a flow cell assembly, a liquid circuit system, and a sequencing system.

Background technique

In the related art, nucleic acid detection is performed on a nucleic acid sample placed on a solid-phase substrate, for example, nucleic acid sequence determination (sequencing) based on chip detection usually includes what is generally called sample processing before loading and loading on the machine. The sample processing before loading the machine is to process the nucleic acid sample to be tested to meet the loading requirements, such as connecting the nucleic acid sample to be tested to the surface of the solid-phase substrate. Sequencing.

Current commercial sequencing platforms typically include two or more independent or functionally connected devices to achieve the above-described sample processing and sequencing. For a sequencing platform that includes two supporting devices, usually, one of the devices is used to process the nucleic acid sample to be tested, including connecting it to a reaction chamber (such as a flow cell or a chip), and the device is often referred to as a hybridizer. , sample injector, library building device, sample processor or sample preparation device; another device detects the chip output by the previous device that is connected to the nucleic acid sample to be tested, thereby realizing nucleic acid sequence determination. This device is the most important sequencing platform. hardware, commonly known as a sequencer.

In the current commercial sequencing platforms, these independent and functionally connected devices can be sold or purchased together, or sold or purchased separately/partly; the purchase of multiple associated devices is generally more expensive, and the purchase of one or part of the devices, such as Buying only one of the sequencers requires manual operation or selection of commercial sample processing services, which generally requires users to operate more or participate more.

With the development of related technologies such as sequencing technology and automation, as well as the market's expectations for simple operation, a sequencer that integrates at least a part of the pre-installation sample processing and sequencing functions is a development direction (hereinafter referred to as this kind of integrated function). The sequencer is an integrated sequencer or an integrated sequencing platform), especially an integrated sequencer whose performance is not weakened, the volume is comparable or smaller, and the operation is easier, compared with the sequencing platform before integration.

However, at least it is hindered by the following factors, there are currently few mature integrated sequencer products with integrated functions: the sample processing and sequencing before the machine generally includes multiple steps and multiple reactions, involving the switching of multiple reagents, multiple series connection. Or parallel inflow and outflow sequential control and microfluidic manipulation.

Therefore, how to build a system that integrates at least a part of sample processing and sequencing functions before being put on the machine, and the performance of the system or the integrated sequencer including the system is equivalent to or has a certain quality before integration The level and the cost are within a certain range, which are issues worthy of attention.

SUMMARY OF THE INVENTION

The inventors of the present application found in the process of designing and testing the integrated liquid circuit for sample processing before on-machine and on-board sequencing and testing that the integrated liquid circuit that can precisely control trace liquids, especially, can control multiple reactors independently or alternately ( Integrated liquid circuits for the reaction on the reaction chamber/flow cell), and/or controlling the liquid environment of the different stages of the reaction in different regions of a reactor, involving a considerable number of valve bodies, and thus the number of associated pipes is relatively large and relatively staggered It is complex, and the constructed integrated liquid circuit takes up a relatively large space. Moreover, when building a complete machine (integrated sequencer) with other functional modules or systems, it is difficult to achieve a good fit under the expected volume.

Therefore, the embodiments of the present application provide a flow path selection valve, a flow cell assembly, a liquid circuit system, and a sequencing system to solve at least a part of the above problems at least to a certain extent.

Embodiments of the present application provide a flow path selection valve configured to switch between a first valve position and a second valve position, the flow path selection valve being provided with a common port, a plurality of first valve positions a port, a plurality of second ports and a plurality of communication grooves, the communication grooves selectively communicating the common port and the first port or the first port and the second port,

When the flow path selection valve is in the first valve position, the first port and the second port communicate through the communication groove,

When the flow path selection valve is in the second valve position, the first port and the common port communicate through the communication groove.

The flow path selection valve can realize three-way control of multiple liquid paths (flow path/flow path), and is especially suitable for systems that contain multiple liquid paths and need to control multiple liquid paths independently or in parallel.

In certain embodiments, the flow path selection valve includes:

a manifold provided with the common port, the plurality of first ports and the plurality of second ports;

A first valve core, the first valve core is provided with a communication groove, and the first valve core can rotate or slide relative to the manifold so that the flow path selection valve is in the first valve position and the second valve position. Switch between two valve positions.

In certain embodiments, the flow path selection valve includes a second valve core provided on the manifold, the first valve core is provided on the second valve core, and the second valve core is provided There are a first channel, a second channel and a third channel, the first channel communicates with the first port, the second channel communicates with the second port, and the third channel communicates with the common port ,

When the flow path selection valve is in the first valve position, the communication groove communicates the first passage and the second passage to communicate the first port and the second port. When the flow path selection valve is in the second valve position, the communication groove communicates the first passage and the third passage to realize the communication between the first port and the common port.

In certain embodiments, the manifold is provided with a cavity in which the second spool is at least partially received.

In some embodiments, the bottom surface of the cavity is provided with a first connection port, a second connection port and a third connection port, and the first connection port communicates with the first port and the first channel, so The second connection port communicates with the second port and the second channel, and the third connection port communicates with the common port and the third channel.

In certain embodiments, at least two of the first port, the second port, and the common port are located on different sides of the manifold, respectively.

In some embodiments, the communication groove includes a first communication groove and a second communication groove spaced apart, and when the flow path selection valve is in the first valve position, the first port is connected to the The second port communicates through the first communication groove, and when the flow path selection valve is in the second valve position, the first port and the common port communicate through the second communication groove.

In some embodiments, the flow path selection valve includes a driving member for driving the first valve core to rotate or slide; optionally, the driving member provides electromagnetic driving.

In some embodiments, the flow path selection valve includes a slider connected to the first valve core, the slider is connected to the driving member, and the driving member drives the first through the slider Spool slides.

In certain embodiments, the flow path selection valve includes a housing detachably connected to the manifold, and the first spool and the slider are accommodated in the housing.

In some embodiments, the housing is provided with a guide groove, the slider includes a connecting portion and a guide rail portion connected with the connecting portion, the connecting portion is connected with the first valve core, and the guide rail is connected to the first valve core. The part cooperates with the guide groove to guide the slider to drive the first valve core to slide.

The flow cell assembly of the embodiment of the present application includes the flow path selection valve described in any of the above embodiments and a flow cell connected to the flow path selection valve, the flow cell includes a plurality of channels arranged in parallel, and the channels of the channels are One end communicates with the first port.

In certain embodiments, the flow cell assembly includes two of the flow path selection valves and one of the flow cells, and one end of the channel of the flow cell is in communication with the first port of one of the flow path selection valves, so The other end of the channel of the flow cell communicates with the first port of the other flow path selection valve.

In certain embodiments, one end or the other end of the channel is ductless connected to the first port.

The fluid circuit system of the embodiments of the present application includes: a plurality of flow paths fluidly connected to the flow cell to support the target analyte when the flow cell is installed in the fluid circuit system; a flow path selector valve connected to the flow path, the flow path selector valve selects between the flow paths; a pump connected to the flow cell when the flow cell is installed in the fluid circuit system fluidly connected and flow liquid through a flow path selected by the flow path selection valve during analytical operations; and a control circuit operatively coupled to the flow path selection valve, the control circuit having one or more processes and memory storing computer-executable instructions that, when executed by the processor, control the processor to instruct the flow path selection valve to select a designated flow path.

In certain embodiments, the fluidics system further includes a reagent selection valve and a flow cell, the flow path selection valve for selecting a flow path through the flow cell from a plurality of flow paths through the flow cell according to the assay protocol, and The selected reagents are directed through the flow cell. The pump flows the selected reagent through the selected flow path according to the assay protocol.

In certain embodiments, the flow cell includes a plurality of channels arranged in parallel, one end of the channels communicating with the first port.

In certain embodiments, one end of the channel is ductless connected to the first port.

In some embodiments, the liquid circuit system further includes a first memory and a second memory, the first memory stores a sample solution to be tested, the first memory is connected to the second port, the second memory A memory stores reaction reagents, and the second memory is connected to the common port.

The sequencing system of the embodiment of the present application includes the liquid circuit system described in any one of the above embodiments.

In the flow path selection valve of any one of the above embodiments, when the flow path selection valve is located at the first valve position, each first port communicates with the corresponding second port through the corresponding communication groove, and the flow path selection valve is located at the second valve position. In this case, each first port is communicated with the common port through a corresponding communication groove, so that the flow path selection valve has two or more passages; the flow path selection valve is suitable for any need to use a three-way valve In particular, fluidic systems with multiple three-way valves, for example, involve fluidic systems that need to change the direction of one or more flow paths and/or dispense multiple liquids/solutions. The application of the flow path selection valve to a liquid path system including multiple liquid paths/flow paths can realize independent or parallel three-way control of these multiple liquid paths, and can avoid setting multiple three-way connections in the liquid path system at the same time. Valves, thereby reducing the cost, volume, and reagent consumption of the liquid circuit system, improving reliability, and facilitating maintenance, repair and manipulation. The above-mentioned any one of the flow path selection valve and/or any liquid circuit system including the flow path selection valve is particularly suitable for systems that include multiple flow paths and have high precision requirements for fluid control and delivery, such as sequencing systems (nucleic acid). sequencer system). The sequencing system including any one of the flow path selection valves mentioned above can realize independent control of different reaction processes in different parts/regions of the flow cell, and the preparation cost is low.

Additional aspects and advantages of embodiments of the present application will be set forth, in part, in the following description, and in part will be apparent from the following description, or learned by practice of embodiments of the present application.

Description of drawings

The above and/or additional aspects and advantages of the present application will become apparent and readily understood from the following description of embodiments taken in conjunction with the accompanying drawings, wherein:

FIG. 1 is an exploded schematic diagram of a flow path selection valve according to an embodiment of the present application;

2 is a schematic structural diagram of a liquid circuit system according to an embodiment of the present application;

3 is a schematic perspective view of a flow path selection valve according to an embodiment of the present application;

4 is a schematic perspective view of a manifold according to an embodiment of the present application;

5 is a schematic side view of a manifold of an embodiment of the present application;

6 is a schematic cross-sectional view of the manifold of FIG. 5 along the A-A direction;

7 is a schematic plan view of a first valve core according to an embodiment of the present application;

8 is a schematic plan view of a second valve core according to an embodiment of the present application;

FIG. 9 is a schematic diagram of the first valve core and the second valve core being matched and located in a first position according to an embodiment of the present application;

FIG. 10 is a schematic diagram of the first valve core and the second valve core being matched and located at a second position according to an embodiment of the present application;

11 is a schematic perspective view of a slider according to an embodiment of the present application;

12 is a schematic structural diagram of a housing according to an embodiment of the present application;

13 is a schematic structural diagram of a flow cell assembly according to an embodiment of the present application;

14 is a schematic structural diagram of a liquid circuit system according to an embodiment of the present application;

15 is a schematic structural diagram of a system according to an embodiment of the present application;

16 is a schematic flowchart of a method of an embodiment of the present application;

17 is a schematic diagram of a module of a liquid circuit system according to an embodiment of the present application;

18 is a schematic flowchart of a method of an embodiment of the present application;

FIG. 19 is a schematic flowchart of a method according to an embodiment of the present application.

Description of main component symbols:

Flow path selection valve 10, hydraulic system 12, pump 14, common port 16, first port 18, second port 20, communication groove 21, first communication groove 22, manifold 24, first valve core 26, second Communication groove 23, second valve core 28, first passage 30, second passage 32, third passage 34, cavity 36, first connection port 38, second connection port 40, third connection port 42, fasteners 55. Drive member 56, slider 57, housing 58, guide groove 59, connecting portion 60, guide rail portion 61, flow cell assembly 101, multiple flow paths 102, flow cell 62, control circuit 63, memory 64, first Storage 66, Second Storage 68, First Flow Cell 70, Second Flow Cell 72, First Flow Path Selection Valve 74, Second Flow Path Selection Valve 76, First Reaction Zone 78, Second Reaction Zone 80, Reagent Selection Valve 84 , liquid inlet 86 , liquid outlet 88 , liquid collector 89 , sequencing system 90 .

Detailed ways

The embodiments of the present application will be further described below with reference to the accompanying drawings. The same or similar reference numbers refer to the same or similar elements or elements having the same or similar functions throughout the drawings.

In addition, the embodiments of the present application described below in conjunction with the accompanying drawings are exemplary, only used to explain the embodiments of the present application, and should not be construed as limitations on the present application.

In this application, "first", "second", "third", "fourth" and "fifth" are used for descriptive purposes only and should not be construed as indicating or implying relative importance, order or implication Indicates the number of technical features indicated. Thus, features defined as "first", "second", etc., may expressly or implicitly include one or more of the stated features. In the description of this application, unless otherwise defined, "plurality" means two or more.

In this application, unless otherwise expressly specified and limited, "installation" and "connection" should be understood in a broad sense, for example, it may be a fixed connection, a detachable connection, or an integral connection; it may be a mechanical connection, It can also be an electrical connection or can communicate with each other; it can be a direct connection or an indirect connection through an intermediate medium, and it can be the internal communication between the two elements or the interaction relationship between the two elements. For those of ordinary skill in the art, the specific meanings of the above terms in this application can be understood according to specific situations.

In this application, unless otherwise expressly stated and defined, a first feature "on" or "under" a second feature may be in direct contact with the first and second features, or the first and second features indirectly through an intermediary touch. Also, the first feature being "above", "over" and "above" the second feature may mean that the first feature is directly above or obliquely above the second feature, or simply means that the first feature is level higher than the second feature. The first feature being "below", "below" and "below" the second feature may mean that the first feature is directly below or obliquely below the second feature, or simply means that the first feature has a lower level than the second feature.

In this application, the so-called "nucleic acid sequence determination", "sequence determination" and "sequencing" are equivalent, including DNA sequencing and/or RNA sequencing, including long fragment sequencing and/or short fragment sequencing; the so-called "sequencing" Assay reaction" is the same as sequencing reaction. Generally, in nucleic acid sequence determination, one base/nucleotide on the template nucleic acid can be identified/determined by one round of sequencing reaction, and the base is selected from at least one of A, T, C, G and U. In sequencing by synthesis (SBS) and/or sequencing by ligation (SBL), a round of sequencing reactions includes extension reactions (base extension), signal detection (eg, photographing/image acquisition) and group excision (excision detectable groups and/or blocking groups). The so-called "nucleotide analogs" are substrates, also known as reversible terminators, which are analogs of A, T, C, G and/or U nucleotides and can follow the principle of base complementarity Pairs with a specific type of base while being able to block or inhibit nucleotide/substrate binding to the next nucleotide position on the template strand. A round of sequencing reactions consists of one or several repeated reactions consisting of extension reaction (base extension), signal detection, and group excision; for example, four nucleotide analogs with the same detectable label, such as with the same Fluorescent molecules, one round of sequencing reaction includes four repeated reactions performed sequentially, corresponding to four nucleotides; for another example, four nucleotide analogs have two detectable labels that are detectably distinguishable by two signals, and two Two nucleotides with the same detectable label, one round of sequencing reaction can include two repeated reactions, that is, two nucleotides with different detectable labels are subjected to extension reaction, signal detection and group excision in the same reaction system. One repeat reaction to achieve one round of sequencing reaction completes base-type identification at one position of the template; as another example, four nucleotide analogs with four detectable labels with signals detectably distinguishable, or four nucleotides Three of the analogs had three detectable labels with signals detectably distinguishable, and the other nucleotide analog had no detectable label, and a round of sequencing reactions included the four nucleotide analogs in the same A repeated reaction was carried out in the reaction system.

Referring to FIGS. 1 to 2 , an embodiment of the present application provides a flow path selection valve 10 , and the flow path selection valve 10 can be applied to the liquid circuit system 12 , or in other words, the liquid circuit system 12 includes the flow path selection valve 10 , which achieves Convergence, diversion, flow path switching and/or flow control.

Referring to FIGS. 1 and 3 , the flow path selection valve 10 of the embodiment of the present application is configured to switch between a first valve position and a second valve position, and the flow path selection valve 10 has a common port 16 , a plurality of first ports 18. A plurality of second ports 20 and a plurality of communication grooves 21. The communication groove 21 selectively communicates the common port 16 and the first port 18 or the first port 18 and the second port 20 .

When the flow path selection valve 10 is in the first valve position, the first port 18 and the second port 20 communicate through the communication groove 21 . When the flow path selection valve 10 is in the second valve position, the first port 18 communicates with the common port 16 through the communication groove 21 .

In the flow path selection valve 10 and the liquid path system 12 according to the embodiment of the present application, when the flow path selection valve 10 is in the first valve position, each first port 18 and the corresponding second port 20 pass through the corresponding communication groove 21 When the flow path selection valve 10 is in the second valve position, each first port 18 communicates with the common port 16 through the corresponding communication groove 21, so that the flow path selection valve 10 has two or more passages ; The flow path selection valve 10 is suitable for any liquid system that requires the use of a three-way valve, especially a plurality of three-way valves, for example, involving changing the direction of one or more flow paths and/or distributing various liquids/solutions hydraulic system. Applying the flow path selection valve to the liquid path system 12 including multiple liquid paths/flow paths can realize independent or parallel three-way control of these multiple liquid paths, and can avoid setting multiple liquid paths in the liquid path system 12 at the same time. The three-way valve reduces the cost, volume, and reagent consumption of the liquid circuit system 12, improves reliability, and facilitates maintenance and operation.

Specifically, the number of the common port 16 is one, and the common port 16 can be used as the liquid inlet or outlet of the flow path selection valve 10 . In other words, the liquid can enter or flow out of the flow path selection valve 10 from the common port 16, thereby achieving split flow or co-flow. Here, the common port 16 serves as a liquid inlet of the flow path selection valve 10 , and liquid can enter the flow path selection valve 10 from the common port 16 . The shape of the common port 16 may be a regular shape such as a circle or a polygon, or an irregular shape. In the embodiment of the present application, in order to facilitate the formation, manufacture and/or connection of the common port 16 with common pipes, the common port 16 is circular.

The plurality of second ports 20 are in one-to-one correspondence with the plurality of first ports 18 . The plurality of communication grooves 21 are in one-to-one correspondence with the plurality of first ports 18 . The number of first ports 18 may be 2, 3, 4, 5, 6, 7, 8 or more. In the embodiment shown in FIG. 1 , the number of first ports 18 is 8 to accommodate elements or devices upstream or downstream of the flow path selection valve 10 that contain 8 outlets or inlets.

As shown in FIG. 2, liquid can enter the flow path selector valve 10 from the common port 16, exit from the eight first ports 18, and then enter a flow cell 62 containing eight channels or eight reaction zones, and so on , the parallel control of the liquid feeding into the 8 channels or 8 reaction areas of the flow cell 62 can be realized. The shape of the first port 18 may be a regular shape such as a circle or a polygon, or an irregular shape. In the embodiment of the present application, the first port 18 is circular. The first port 18 can serve as the liquid outlet of the flow path selector valve 10, and can also serve as the inlet.

Similarly, the present application does not limit the number of second ports 20, and the number of second ports 20 may be 2, 3, 4, 5, 6, 7, 8 or more. In the embodiment shown in FIG. 3 , the number of the second ports 20 is 8, so as to adapt to the element or device including 8 outlets or inlets upstream or downstream of the flow path selection valve 10 , such as the one located in FIG. 2 . The flow cell 62 downstream of the flow path selection valve 10 includes 8 channels or 8 reaction areas, so as to realize the parallel control of the liquid feeding into the 8 channels or 8 reaction areas of the flow cell 62 . The number of second ports 20 is equal to the number of first ports 18 . The shape of the second port 20 may be a regular shape such as a circle or a polygon, or an irregular shape. In the embodiment of the present application, the second port 20 is circular. The second port 20 can be used as a liquid inlet of the flow path selection valve 10, and can also be used as an outlet. For manufacturing convenience, the size of the second port 20 may be the same as the size of the first port 18 .

The number of the communication grooves 21 is the same as the number of the first ports 18 and/or the second ports 20 . In the embodiment of the present application, the number of the communication grooves 21 is also eight. The shape of the communication groove 21 is not limited, as long as the flow path selection valve 10 is in the first valve position, the first port 18 and the second port 20 can be communicated.

To sum up, in the first valve position, each first port 18 communicates with a corresponding second port 20 . At this time, the liquid enters the flow path selection valve 10 from the second port 20 and flows from the corresponding first port 18 outflow. That is to say, the flow path selection valve 10 also has the function of simultaneously feeding liquid into multiple channels and simultaneously discharging liquid from multiple channels.

In the second valve position, the common port 16 is communicated with each first port 18 through a corresponding communication groove 21. At this time, the liquid can enter the flow path selection valve 10 from the common port 16, and after passing through the communication groove 21, the liquid can pass through the communication groove 21. A port 18 flows out. In other words, in the second valve position, the liquid enters the flow path selection valve 10 from one common port 16 and flows out from the plurality of first ports 18 . That is to say, the flow path selection valve 10 has the function of one channel for liquid inlet and multiple channels for liquid outlet.

In the embodiment of the present application, when the flow path selection valve 10 is in the first valve position, both the first port 18 and the second port 20 are isolated from the common port 16; when the flow path selection valve 10 is in the second valve position , the common port 16 and the first port 18 are both isolated from the second port 20 to form an independent first flow channel or a second flow channel. Both the first flow channel and the second flow channel are multiple. In this way, it is beneficial to realize the parallel control of the liquid in and out of the multiple reaction areas, and also to realize the independent control of the liquid in and out of different reaction processes in the reaction area.

In some embodiments, the flow path selector valve 10 may be in a third valve position, in which case the common port 16 , the plurality of first ports 18 and the plurality of second ports 20 are isolated from each other. In this way, when the flow path selection valve 10 is in the third valve position, the flow path selection valve 10 can also achieve the function of controlling the liquid blocking.

In this embodiment, the flow path selection valve 10 has three modes, that is, a mode in which the first port 18 and the second port 20 communicate when the flow path selection valve 10 is in the first valve position; In the second valve position, the mode in which the common port 16 and the first port 18 are communicated; when the flow path selection valve 10 is in the third valve position, the mode in which the common port 16, the first port 18 and the second port 20 are isolated from each other.

It should be pointed out that the “blocking” of multiple ports referred to in this application means that multiple ports cannot communicate with each other, or, in other words, liquid cannot enter from one or more designated ports, and cannot enter from one or more designated ports. outgoing ports.

Referring to FIGS. 1 and 3 , in some embodiments, the flow path selector valve 10 includes a manifold 24 and a first spool 26 . Referring to FIGS. 4-6 , the manifold 24 has a common port 16 , a plurality of first ports 18 and a plurality of second ports 20 . Referring to FIG. 7 , the first valve core 26 is provided with a communication groove 21 . The first spool 26 is rotatable or slidable relative to the manifold 24 to switch the flow path selector valve 10 between a first valve position and a second valve position.

In this way, during the rotation or sliding of the first spool 26, the communication groove 21 can communicate with the common port 16 and the first port 18, or can communicate with the first port 18 and the second port 20, so that the liquid can enter from the manifold 24 The flow path selection valve 10 is inside and out of the flow path selection valve 10 from the manifold 24 .

Specifically, the manifold 24 is a diversion or confluence module. The manifold 24 can divert the liquid entering from the common port 16 and then flow out from the plurality of first ports 18 , and can also divert the liquid entering from the second port 20 . Then it flows out from the corresponding first port 18 . It will be appreciated that the interior of the manifold 24 has flow passages that communicate with the various ports.

In the example of the present application, the first valve core 26 is in the shape of a block, and the first valve core 26 can slide relative to the manifold 24 . The communication groove 21 is linear, and the communication groove 21 may be in a bent shape, a curved shape, or the like, and the specific shape of the communication groove 21 is not limited herein.

Illustratively, the number of the communication grooves 21 is the same as the number of the first ports 18 . In the embodiment of the present application, the number of the communication grooves 21 is eight. Of course, in other embodiments, the number of the communication grooves 21 may be 2, 3, 4, 5, 6 and other numbers.

Referring to FIGS. 1 , 3 and 8 , in some embodiments, the flow path selector valve 10 includes a second spool 28 disposed on the manifold 24 , and the first spool 26 is disposed on the second spool 28 , the second valve core 28 is provided with a first channel 30, a second channel 32 and a third channel 34, the first channel 30 communicates with the first port 18, the second channel 32 communicates with the second port 20, and the third channel 34 communicates with public port 16 is connected,

When the flow path selection valve 10 is in the first valve position, the communication groove 21 communicates the first passage 30 and the second passage 32 to realize the communication between the first port 18 and the second port 20, and when the flow path selection valve 10 is in the second valve position In the case of the position, the communication groove 21 communicates the first channel 30 and the third channel 34 to realize the communication between the first port 18 and the common port 16 .

In this way, the first spool 26 selectively communicates the first port 18 with the common port 16 or the first port 18 and the second port 20 through the second spool 28, which facilitates the preparation of the flow through the selector valve.

Specifically, the second valve core 28 has a square shape, and the volumes of the first valve core 26 and the second valve core 28 are both smaller than the volume of the manifold 24 . Since the manifold 24 and the first spool 26 are manufactured separately, the precision of the two may not be able to make the manifold 24 and the first spool 26 meet the matching requirements, resulting in the phenomenon of liquid leakage. Since the shapes of the first valve core 26 and the second valve core 28 are relatively regular, they are easy to manufacture. Therefore, in the embodiment of the present application, the manifold 24 and the first valve core 26 are connected by the second valve core 28 , which can make the flow path selection valve 10 easier to manufacture and have better stability.

Of course, in other embodiments, the second valve core 28 may be omitted. At this time, the first valve core 26 is matched and connected with the manifold 24 .

In the embodiment of the present application, the first channel 30 , the second channel 32 and the third channel 34 are all independent channels, and each channel is provided in isolation. The first channel 30 , the second channel 32 and the third channel 34 are all linear, and pass through the second valve core 28 along the thickness direction of the second valve core 28 .

Of course, in other embodiments, at least one of the first channel 30 , the second channel 32 and the third channel 34 may be bent, curved or the like, and the first channel 30 and the second channel 32 are not limited here. and the specific shape of the third channel 34 .

In the example of the present application, the number of the first channels 30 is the same as the number of the first ports 18 , both being eight. The number of the second channels 32 is the same as the number of the second ports 20 , both being eight. The number of the third channels 34 is eight. Of course, in other embodiments, the number of the first channel 30 , the second channel 32 and the third channel 34 may be 2, 3, 4, 5, 6 and other numbers.

8, the first channel 30, the second channel 32 and the third channel 34 are arranged in a matrix, and the eight first channels 30, the eight second channels 32 and the eight third channels 34 are all along the The two valve cores 28 are arranged at intervals in the length direction, and the eight first passages 30 are arranged along the first straight line, the eight second passages 32 are arranged along the second straight line, and the eight third passages 34 are arranged along the third passage 34 cloth. Along the width direction of the second valve core 28 , the first passages 30 and the third passages 34 are aligned one-to-one, and the first passages 30 and the second passages 32 are staggered.

Of course, in other embodiments, the first channel 30 , the second channel 32 and the third channel 34 may be arranged in other ways, and the arrangement of the first channel 30 , the second channel 32 and the third channel 34 is not limited here. Way.

It should be noted that, in the embodiment of the present application, the second valve core 28 is fixedly arranged relative to the manifold 24 . The first spool 26 slides on the surface of the second spool 28 relative to the second spool 28 so that the first spool 26 can slide between the first position and the second position, so that the communication groove 21 can be selectively The first channel 30 and the second channel 32 or the first channel 30 and the third channel 34 are connected to each other.

Referring to FIGS. 3 and 4 , in some embodiments, the manifold 24 is provided with a cavity 36 , and the second valve core 28 is at least partially accommodated in the cavity 36 . In this way, the manifold 24 and the second valve core 28 are more compactly matched, so that the volume of the flow path selection valve 10 can be reduced, which is beneficial to the miniaturization of the flow path selection valve 10 .

Specifically, the shape of the cavity 36 is adapted to the shape of the second valve core 28 . In the embodiment of the present application, the shape of the cavity 36 is also a rectangular parallelepiped. As shown in FIG. 3 , the second valve core 28 is partially accommodated in the cavity 36 , or in other words, a part of the second valve core 28 protrudes from the cavity 36 .

Referring to FIG. 4 , in some embodiments, the bottom surface of the cavity 36 is provided with a first connection port 38 , a second connection port 40 and a third connection port 42 . The first connection port 38 communicates with the first port 18 and the first channel 30 . The second connection port 40 communicates the second port 20 and the second channel 32 . The third connection port 42 communicates the common port 16 and the third channel 34 .

In this way, the second valve core 28 communicates with the first port 18 , the second port 20 and the common port 16 through the connection port provided on the bottom surface of the cavity 36 , so that the contact area between the second valve core 28 and the cavity 36 can be increased, Prevent liquid leakage.

In order to make the first connection port 38 butt with the first channel 30, the second connection port 40 with the second channel 32, and the third connection port 42 with the third channel 34, the first connection port 38, the second connection port 40 and the The arrangement of the third connection port 42 is the same as the arrangement of the first passage 30 , the second passage 32 and the third passage 34 , and the first connection port 38 , the second connection port 40 and the third connection are not repeated here. The arrangement of the ports 42 .

4 and 5, in certain embodiments, at least two of the first port 18, the second port 20, and the common port 16 are located on different sides of the manifold 24, respectively. For example, the first port 18 and the second port 20 are located on the same side of the manifold 24 and the common port 16 is located on the other side of the manifold 24 . As another example, the first port 18 and the common port 16 are located on the same side of the manifold 24 and the second port 20 is located on the other side of the manifold 24 . As another example, the first port 18 , the second port 20 and the common port 16 are located on different sides of the manifold 24 .

5, the first port 18 is located on the left side of the manifold 24, the second port 20 is located on the bottom side of the manifold 24, and the common port 16 is located on the right side of the manifold 24. In this way, each port is arranged on different sides of the manifold 24, so that the space of the manifold 24 can be fully utilized, so that the manifold 24 can be more miniaturized, and the connection of the manifold 24 with other components can be facilitated.

Referring to FIG. 7 , in some embodiments, the communication groove 21 includes a first communication groove 22 and a second communication groove 23 arranged at intervals. When the flow path selection valve 10 is in the first valve position, the first port 18 communicates with the second port 20 through the first communication groove 22, as shown in FIG. 9 . When the flow path selection valve 10 is in the second valve position, the first port 18 communicates with the common port 16 through the second communication groove 23, as shown in FIG. 10 . In other words, the communication groove 21 includes two discontinuous parts, so that the communication between the first port 18 and the second port 20 and the communication between the first port 18 and the common port 16 can be easily controlled through the communication groove 21 .

The arrows in Figures 9 and 10 represent the flow direction of the liquid. As shown in FIG. 9 , after entering the flow path selection valve 10 from the second port 20 , the liquid flows out of the first port 18 through the second passage 32 , the first communication groove 22 and the first passage 30 in sequence.

In FIG. 10 , after entering the flow path selection valve 10 from the common port 16 , the liquid flows out from the first port 18 after passing through the third passage 34 , the second communication groove 34 and the first passage 30 in sequence.

In the example of FIG. 7 , in order to adapt to the arrangement of the first passage 30 , the second passage 32 and the third passage 34 , the first communication groove 22 is inclined and extends linearly with respect to the width direction of the first valve core 26 , and the second communication groove 23 extends linearly along the width direction of the first valve body 26 .

It can be understood that FIG. 7 is only an example of the first communication groove 22 and the second communication groove 23 . In other embodiments, the shapes of the first communication groove 22 and the second communication groove 23 may be other shapes such as an arc shape, a bent shape, and the like.

In addition, in other embodiments, one of the first communication groove 22 and the second communication groove 23 may be omitted, or in other words, the communication groove 21 is a groove with a continuous structure. At this time, in one example, the first channel 30 may be disposed between the second channel 32 and the third channel 34 , and the first channel 30 , the second channel 32 and the third channel 34 are arranged along the same straight line. The communication groove 21 has a linear shape. When the first valve core 26 is in the first position, one end of the communication groove 21 is connected to the first channel 30 and the other end is connected to the second channel 32, so that the first port 18 and the second port 20 are communicated; at the second valve core 28 In the second position, one end of the communication groove 21 communicates with the third channel 34 and the other end communicates with the first channel 30 , so that the common port 16 and the first port 18 communicate with each other.

Referring again to FIGS. 1 and 3 , in some embodiments, the flow path selection valve 10 includes a driving member 56 for driving the first valve core 26 to rotate or slide. In this way, the driving member 56 can move the first spool 26 so that the first spool 26 can be located in different positions, so that the flow path selection valve 10 can perform different functions.

Specifically, the drive member 56 may provide electromagnetic drive. For example, the driving member 56 may be a motor, and when the first valve core 26 slides relative to the manifold 24, the driving member 56 may be a motor with a screw structure, and when the first valve core 26 rotates relative to the manifold 24, the driving member 56 is driven Component 56 may have a motor with a rotating shaft.

Referring to FIGS. 1 , 3 and 11 , in some embodiments, the flow path selection valve 10 includes a slider 57 connected to the first valve core 26 , the slider 57 is connected to the driving part 56 , and the driving part 56 passes through the slider 57 drives the first valve core 26 to slide. In this way, it is favorable for the driving member 56 to drive the first valve core 26 to slide.

Specifically, the slider 57 is detachably connected to the first valve core 26 . For example, the slider 57 is connected with the first valve core 26 through the positioning pin 54 , after the slider 57 is driven by the driving member 56 , the slider 57 can drive the first valve core 26 to slide through the positioning pin. Of course, the sliding block 57 and the first valve core 26 may be connected by means of an engaging structure or the like, and the present application does not limit the specific connection method of the sliding block 57 and the first valve core 26 .

When the driving component 56 is a lead screw motor, the slider 57 can be sleeved on the lead screw of the lead screw motor. During the rotation of the screw rod, the slider 57 can move relative to the screw rod, thereby pushing the first valve core 26 to move.

Referring to FIGS. 1 and 3 , in some embodiments, the flow path selector valve 10 includes a housing 58 detachably connected to the manifold 24 , and the first valve core 26 and the slider 57 are accommodated in the housing 58 . In this way, the housing 58 can protect the first valve core 26 and the slider 57 , and provide a pressing force to the first valve core 26 and the second valve core 28 to prevent liquid leakage from the first valve core 26 and the second valve core 28 adverse phenomenon.

Specifically, the housing 58 may be connected to the manifold 24 by fasteners 55 . In one example, during the assembly process of the flow path selection valve 10, the second valve core 28 is first installed in the manifold 24, then the first valve core 26 is installed on the second valve core 28, and then the first valve core 28 is installed on the second valve core 28. The valve core 26 and the slider 57 are limited, and then the housing 58 is covered on the manifold 24, so that the slider 57 and the first valve core 26 are both located in the housing 58, and finally pass through the manifold 24 through the fastener 55 And screw with the housing 58 so that the housing 58 is fixed on the manifold 24 .

Referring to FIGS. 11 and 12 , in some embodiments, the housing 58 is provided with a guide groove 59 , and the slider 57 includes a connecting portion 60 and a guide rail portion 61 connected to the connecting portion 60 . The connection portion 60 is connected to the first valve body 26 . The guide rail portion 61 cooperates with the guide groove 59 to guide the slider 57 to drive the first valve core 26 to slide. In this way, the cooperation of the guide rail portion 61 and the guide groove 59 can make the slider 57 slide along the predetermined track, so as to drive the first valve core 26 to slide between the first position and the second position.

Specifically, the connecting portion 60 may be connected with the first valve core 26 through the positioning pin 54 . The contour of the connecting portion 60 may be adapted to the shape of the first valve core 26 to facilitate connection with the first valve core 26. The guide rail portion 61 protrudes from the surface of the connecting portion 60 . The cross-sectional area of the rail portion 61 is smaller than the cross-sectional area of the connecting portion 60 .

Referring to FIG. 13 , the flow cell assembly 101 of the embodiment of the present application includes the flow path selection valve 10 of any of the above embodiments and the flow cell 62 , and the flow cell 62 is connected to the flow path selection valve 10 . The flow cell 62 includes a plurality of channels 621 arranged in parallel, and one end of the channels 621 communicates with the first port 18 . In this manner, flow path selector valve 10 and flow cell 62 may form an integral module for ease of installation.

The flow cell 62 referred to in this application provides a biochemical reaction site, the flow cell 62 can be a chip specifically, and the flow cell 62 is detachably connected to the flow path selection valve 10 . Specifically, the flow cell 62 can be provided with a plug connector, the plug connector is formed with a channel 621 , and the plug connector can be inserted into the first port 18 , so that the channel 621 of the flow cell 62 is directly connected to the first port 18 . Of course, in other embodiments, the flow cell 62 and the flow path selector valve 10 may be in conduit communication.

In some embodiments, the flow cell assembly 101 includes two flow path selection valves 10 and one flow cell 62, one end of the passage 621 is in communication with the first port 18 of one of the flow path selection valves 10, and the other end of the passage 621 is in communication with the other. The first port 18 of a flow path selector valve 10 communicates.

In some embodiments, one end or the other end of the channel 621 is connected to the first port 18 without a duct. In this way, the flow cell 62 is directly connected to the flow path selection valve 10, and the connected piping can be omitted, thereby reducing the risk of liquid leakage.

Referring to FIG. 2 again, the liquid circuit system 12 according to one embodiment of the present application includes the flow path selection valve 10 , the pump 14 , the plurality of flow paths 102 and the control circuit 63 according to any of the above embodiments. The plurality of flow paths 102 are fluidly connected to the flow cell 62 when the flow cell 62 is installed in the fluidic system 12 to support target analytes.

The pump 14 is fluidly connected to the flow cell 62 when the flow cell 62 is installed in the fluidics system 12 and flows liquid through the flow path 102 selected by the flow path selection valve 10 during analytical operations.

Operationally coupled to the flow path selection valve 10 is a control circuit 63 having one or more processors and a memory storing computer executable instructions that, when executed by the processor, control the processor to command the flow path The selector valve 10 selects the designated flow path 102 .

In the liquid circuit system 12 of the embodiment of the present application, the flow path selection valve 10 can be used to independently or in parallel three-way control of the plurality of flow paths 102, which can avoid the simultaneous installation of multiple three-way valves in the liquid circuit system 12, so that the liquid The circuit system 12 is reduced in cost, volume, reagent consumption, reliability, and ease of maintenance and operation. The above-mentioned fluid circuit system 12 is particularly suitable for systems that require high precision in fluid control and delivery, such as sequencing systems.

Specifically, the pump 14 may power the fluidic system 12 so that the fluid may flow. The number of the pumps 14 may include multiple, for example two, one of the pumps 14 may be communicated with the common port 16, and the other pump 14 may be communicated with the second port 20 to achieve split or parallel flow. A pump in communication with the common port 16 can power the liquid from the common port 16 to the first port 18 , and a pump in communication with the second port 20 can power the liquid from the second port 20 to the first port 18 .

In a specific embodiment, the number of the first ports 18 is 8, and the pump 14 includes 8 pumps equal to the number of the first ports 18 , such as negative pressure octal pumps, and the negative pressure octal pumps are located in the liquid circuit system Downstream of 12 , specifically, downstream of flow cell 62 , the octal pump can independently provide negative pressure for the fluid after passing through the flow path selection valve 10 , so that the power of the fluid in each flow path in the multiple flow paths 102 is large. It can be controlled independently, which is beneficial to finely control the flow rate and/or flow rate of the fluid in each flow channel.

Referring to FIG. 2 , in the embodiment of the present application, the liquid circuit system 12 further includes a storage 64, and the storage 64 can store solutions. The solutions include a variety of solutions, including reaction solutions, buffer solutions, cleaning solutions, and/or purified water, etc. The fluidic system 12 comprising the pump 14 may allow one or more solutions to flow toward the flow cell 62 sequentially or simultaneously, including reagents for different reactions or for different steps of a reaction.

In certain embodiments, the reservoir 64 includes a first reservoir 66 carrying the biological sample solution and a second reservoir 68, the second reservoir 68 carrying the reaction solution. With the flow path selection valve 10 in the first valve position, the flow path selection valve 10 communicates the first reservoir 66 with the flow cell 62 towards which the pump 14 induces flow of the biological sample solution. With the flow path selection valve 10 in the second valve position, the flow path selection valve 10 communicates the second reservoir 68 and the flow cell 62, and the pump 14 induces the reaction liquid to flow toward the flow cell 62 through the second flow path.

That is, the flow path selection valve 10 can allow the reaction solution and the biological sample solution to enter the flow cell 62 independently and time-divisionally, so as to sequentially realize the corresponding reactions, such as sample loading reactions (immobilization and/or hybridization of nucleic acids) and Sequencing reactions.

Exemplarily, the first reaction is, for example, an immobilization and/or hybridization reaction, that is, the nucleic acid to be detected is immobilized or connected to the channel or reaction area of the flow cell 62, and the biological sample solution is a solution containing the nucleic acid to be detected, and the biological sample solution can be This first reaction is carried out through the second port 20 and the first port 18 into the flow cell 62 in sequence. In one example, the flow cell 62 is a sandwich-like structure with three upper, middle and lower layers, or a structure with two upper and lower layers, the upper layer (near the objective lens) is a light-transmitting glass layer, and the middle or lower layer is light-transmitting The glass layer is either an opaque base layer, and the middle or lower layer is provided with multiple channels arranged in an array. The channels can accommodate liquid and provide physical space for the reaction. Each channel has an independent liquid inlet and outlet. The number is equal to the number of the first ports 18, a plurality of biological sample solutions can simultaneously and fluidly independently enter a channel of the flow cell 62 through a second port 20 and a first port 18, thus, the flow path selection The valve 10 or the fluid path system 12 including the flow path selection valve 10 can realize the loading and detection analysis of various biological samples without combining with other means (eg, labeling different biological samples). Specifically, the flow cell 62 here is, for example, a solid-phase substrate with functional groups on the surface and/or a solid-phase substrate with probes connected on the surface, and a solid-phase substrate with functional groups on the surface and/or a solid-phase substrate with probes connected on the surface. The solid-phase substrate is also generally referred to as a chip or a microsphere, for example, the upper surface of the channel (the lower surface of the upper glass layer) and/or the lower surface of the channel (the upper surface of the middle layer or the lower structure) has functional groups or is attached to it. The probe (oligonucleotide), the so-called functional group can be connected to the nucleic acid to be tested, and/or at least a part of the probe can be complementary to the nucleic acid to be tested, so as to realize the immobilization or connection of the nucleic acid to be tested to the solid. The surface of the phase substrate is used for subsequent detection and analysis of the nucleic acid to be tested immobilized or connected on the surface of the solid phase substrate, for example, a sequencing reaction.

The second reaction is, for example, a sequencing reaction, that is, a nucleic acid sequence determination reaction, more specifically, a sequencing-by-synthesis reaction using a reversible terminator based on chip detection. Correspondingly, the so-called reaction solution includes one or more substrates containing (reversible terminator), polymerase catalysts, cleavage reagents (group excision reagents), imaging reagents, cleaning reagents and other reagents, various reagents/reaction solutions can enter the flow sequentially or simultaneously through the common port 16 and the first port 18 cell 62 to perform the second reaction, specifically, the corresponding reagents can flow to the flow cell 62 after passing through the flow path selection valve 10 in sequence or at the same time, so as to perform multiple reaction steps in the flow cell 62 to realize the so-called sequencing reaction; The so-called flow cell 62 is, for example, a solid-phase substrate with the nucleic acid to be tested connected on the surface, and the solid-phase substrate with the nucleic acid to be tested connected on the surface is, for example, a chip or a microsphere.

By controlling a flow path selection valve 10 to switch the flow channels, the above-mentioned first reaction and second reaction can be carried out in the flow cell 62, which can make the nucleic acid sequence determination system (integrated system) comprising the first reaction and the second reaction simpler Structure. In this way, there is no need to perform the first reaction and the second reaction in different systems/equipment/devices, and the user operation is easier. Moreover, the cost of building the integrated nucleic acid sequence determination system is much lower than that of building a nucleic acid that realizes the first reaction alone. The sum of the cost of the sequencing system (sample loading device) and the nucleic acid sequencing system that implements the second reaction alone.

The first reaction of the embodiments of the present application includes a reaction in which a biomolecule is attached to the flow cell 62, eg, including an immobilization, hybridization, or sampling reaction. The so-called biomolecules include DNA and/or RNA, etc., including ribonucleotides, deoxyribonucleotides and their analogs, including A, T, C, G and U and their analogs. Among them, C represents cytosine or cytosine analog, G represents guanine or guanine analog, A represents adenine or adenine analog, T represents thymine or thymine analog, U represents uracil or uracil analog thing.

The second reaction includes a reaction for detecting the biomolecules connected to the flow cell 62. For example, the biomolecules are nucleic acids, and the second reaction can be a sequence determination reaction, which is generally called sequencing, including a method for determining DNA or RNA, etc. Primary structure or sequence, including determining the nucleotide/base order of a given nucleic acid fragment. The second reaction may include one or more sub-reactions. In one example, the DNA is sequenced, and the second reaction is sequencing, based on sequencing by synthesis or sequencing by ligation, specifically, for example, based on chip detection, using engineered nucleotides with detectable labels, such as Sequencing-by-synthesis is performed using dNTPs or dNTP analogs with detection labels. The sequencing includes multiple sub-reactions, including base extension reaction, signal acquisition and detection group excision, to realize the base at a position on the nucleic acid sequence to be detected. type of assay; performing the multiple sub-reactions once can be referred to as performing one repeated reaction or one round of reactions, and sequencing includes multiple repeated reactions or multiple rounds of reactions, to measure and read the nucleosides of at least a sequence of nucleic acid molecules (templates). Acid/base order. The so-called modified nucleotides carry fluorescent molecules, which can be excited to fluoresce to be detected by an optical system under certain circumstances. After the modified nucleotide labels are bound to the nucleic acid to be tested, they can prevent the base/nucleoside The acid binds to the next position of the nucleic acid to be tested, such as a dNTP with a chemically cleavable moiety at the 3' hydroxyl end or a dNTP with a molecular conformation that prevents the next nucleotide from binding to the nucleic acid to be tested, dNTP or dNTP similar The compounds are four deoxyribonucleotides containing the bases A, T/U, C, and G, respectively.

For sequencing by synthesis (SBS) or sequencing by ligation (SBL) based on chip detection, under the action of polymerase or ligase, the base extension reaction includes on the flow cell 62 on which the nucleic acid molecule to be detected is immobilized, based on The principle of base complementarity enables nucleotides (including modified nucleotides) to bind to nucleic acid molecules to be detected, and to collect corresponding reaction signals. The engineered nucleotides may be nucleotides with a detectable label that allows the engineered nucleotides to be detected under certain circumstances, such as nucleotides with fluorescent molecular labels, under specific conditions. Under the excitation of laser light of wavelength, it will fluoresce; generally, for SBS, the modified nucleotide also has the function of inhibiting the binding of another nucleotide to the next position of the same nucleic acid molecule, such as with a blocking group , the blocking group can prevent other nucleotides from binding to the next position of the template, so that each extension reaction is a single-base extension reaction, so that the corresponding signal from the next single-base extension can be collected, blocking The breaking group is, for example, an engineered azide group ( _-N3 ) attached to the 3' position of the sugar group of the nucleotide.

For the detection and analysis of biomolecules, generally, the biomolecules are connected to the flow cell 62 first, and then the biomolecules connected to the flow cell 62 are detected; specifically, in any of the above-mentioned specific embodiments, the first reaction is performed first. The second reaction is then performed, that is, the sequencing reaction is performed after the nucleic acid to be detected is connected to the flow cell 62 . In this way, using the liquid circuit system 12, multiple types of reactions including sampling and sample detection can be performed in a nucleic acid sequence determination system.

In some specific embodiments, the first reaction is a sampling reaction, the second reaction is a sequencing reaction, the first reaction is performed first and then the second reaction is performed, and the nucleic acid molecules to be detected are contained in a trace amount of biological sample solution, for example, a microliter level , for example, 20 microliters; before the first reaction, the liquid circuit system 12 has been cleaned with a cleaning solution such as a solution that does not affect subsequent reactions, and the liquid circuit system 12 is filled with cleaning solution; before starting the first reaction , first inject a section of air to separate the subsequent inflow of the biological sample solution and the cleaning solution already in the liquid circuit system, so as to prevent the trace biological samples from being diffused and/or diluted, affecting the connection of the nucleic acid molecules to be tested to the flow cell 62 and The subsequent detection of nucleic acid molecules to be tested, and the separation of the subsequent inflow of the biological sample solution and the cleaning solution already in the liquid circuit system, is also conducive to observing the injection situation, and is conducive to observing whether the flow cell 62, for example, a chip containing multiple channels is not. Normal, whether the hydraulic system 12 is normal, etc.

The substrate can be any solid support that can be used to immobilize nucleic acid sequences, such as nylon membranes, glass slides, plastics, silicon wafers, magnetic beads, and the like. Probes may be randomly distributed on the surface of the substrate, and the probes may be a DNA and/or RNA sequence, etc. The probes may also be called primers, capture strands or immobilized strands. The first reaction can immobilize the attachment of the biomolecule to the probe, eg, based on the principle of base complementarity, to attach the biomolecule into the flow cell 62 .

Acquiring signals includes acquiring signals emitted by engineered nucleotides bound to nucleic acid molecules, such as using an optical imaging assembly/system to irradiate a specific region in the flow cell 62 after the base extension reaction, where the fluorescent molecules in the specific region are irradiated. The label is excited to fluoresce, and the area is photographed/imaged to record the biochemical reaction signal as image information. Sequence determination further includes converting image information obtained from multiple rounds/repeated reactions into sequence information, that is, determining base types based on image information, which is commonly referred to as base-calling.

Group excision involves removal of a detectable label and/or blocking group attached to an engineered nucleotide of a nucleic acid molecule following a base extension reaction to enable binding of other nucleotides, including engineered nucleotides To the next position of the nucleic acid molecule, the next repeated reaction or the next round of reactions is performed.

After the completion of the previous round or the previous sub-reaction or the previous step and before the start of the next round or the next sub-reaction or the next step, a cleaning reagent can also be introduced to remove residues in the flow cell 62 or the liquid circuit system 12 of unreacted substances, substances that interfere with the reaction or signal acquisition.

In certain embodiments, the flow path selector valve 10 is positioned upstream of the flow cell 62 . In this way, the flow path selection valve 10 can control the entry of the solution into the flow cell 62, and the liquid circuit system 12 only needs to use one power component (such as a pump) or only need to provide power in one direction to control the in and out of various solutions. A variety of reactions are realized, which is conducive to further reducing the volume of the liquid circuit system 12 and improving the degree of integration thereof, which is conducive to industrialization.

In certain embodiments, the pump 14 is positioned downstream of the flow cell 62 to provide negative pressure. In this way, the pump 14 can cause the flow cell 62 and elements such as the flow path selection valve 10 to form a negative pressure, thereby allowing the solution to enter the flow cell 62 . In addition, the negative pressure formed by the pump 14 can remove the air in the flow cell 62 to prevent the air from affecting the normal reaction of the flow cell 62 . The liquid circuit system 12 including the pump 14 located downstream of the flow cell 62 can provide a unified power direction for the incoming and outgoing liquids of various types of reactions, and is especially suitable for the liquid circuit system 12 containing pressure-sensitive components/components, If the flow cell 62 is a chip containing thin glass and a multi-layer sheet-like structure bonded by glue, the chip may also include multiple independent reaction areas/channels, and changes in the direction of power/pressure may easily deform the chip or cause liquid leakage. Liquid or cross-channel phenomenon.

14, in some embodiments, the flow cell 62 includes a first flow cell 70 and a second flow cell 72, and the flow path selection valve 10 includes a first flow path selection valve 74 and a second flow path selection valve 76, The first flow path selection valve 74 and the second flow path selection valve 76 communicate with the first flow cell 70 and the second flow cell 72, respectively. In this way, the first flow path selection valve 74 and the second flow path selection valve 76 can independently control the reactions of the first flow cell 70 and the second flow cell 72, which is beneficial to the staggered operation of the first flow cell 70 and the second flow cell 72. Different reactions or different steps/sub-reactions of the same reaction improve the reaction efficiency. In addition, the fluid circuit system 12 including the flow path selection valve 10, combined with the multiple flow cells 62 or the flow cells 62 with multiple independent reaction regions, is beneficial to improve the detection throughput and/or realize the detection of multiple samples at one time.

Specifically, the first flow cell 70 and the second flow cell 72 may be separate structures, or may be integrated structures. In the example shown in FIG. 14 , the first flow cell 70 and the second flow cell 72 are integral structures. The first flow cell 70 and/or the second flow cell 72 may include one or more reaction zones. Wherein, each reaction zone can realize the reaction, and the reaction zones can be intersecting, continuous or separate zones.

In the example of FIG. 14 , the first flow cell 70 includes eight first reaction zones 78 . The eight first reaction regions 78 are in one-to-one correspondence with the eight first ports 18 of the first flow path selection valve 74 . Eight first reaction zones 78 are arranged separately. Similarly, the second flow cell 72 includes eight second reaction zones 80 . The eight second reaction regions 80 are in one-to-one correspondence with the eight second ports of the second flow path selection valve 76 . Eight second reaction zones 80 are arranged separately.

It should be noted that the first flow path selection valve 74 and the second flow path selection valve 76 may work simultaneously, or may work independently or staggered, so that the reactions or steps on the first flow cell 70 and the second flow cell 72 can be It can be performed in a staggered manner or at the same time, which is beneficial to improve the reaction efficiency and save the consumption of detection reagents and/or time.

Referring to Figure 15, in some embodiments, the fluidics system 12 includes a reagent selection valve 84 and a flow cell 62, the reagent selection valve 84 selects a reagent from a variety of reagents according to an assay protocol. Flow path selection valve 10 is fluidly connected between reagent selection valve 84 and flow cell 62, and flow path selection valve 10 is used to select a flow path through flow cell 62 from among a plurality of flow paths through flow cell 62 in accordance with an analytical protocol , and directs the selected reagent through the flow cell 62 . The pump 14 flows the selected reagent through the selected flow path according to the assay protocol.

Specifically, the reagent selection valve 84 is provided with a plurality of liquid inlet ports 86 and one liquid outlet port 88 . The liquid outlet port 88 is selectively connected to one of the liquid inlet ports 86 , and the liquid inlet port 86 is communicated with the reagent selection valve 82 . As such, the multiple inlets 86 of the reagent selection valve 84 allow the flow cell to enter different liquids, thereby enabling multiple rounds/repetitions.

As shown in FIG. 15 , in certain embodiments, the fluidics system 12 includes a sump 89 that collects the fluid exiting the flow cell 62 . For example, the liquid collector 89 collects the liquid after the first reaction and the second reaction.

To sum up, in one embodiment of the present application, the liquid circuit system 12 includes the flow path selection valve 10 , the pump 14 , a plurality of flow paths 102 and the control circuit 63 . The flow path selector valve 10 includes a manifold 24 and a first spool 26 . The manifold 24 is provided with a common port 16 , a plurality of first ports 18 and a plurality of second ports 20 . The first valve body 26 is provided with a communication groove 21 . The first spool 26 is rotatable or slidable relative to the manifold 24 to switch the flow path selector valve 10 between a first valve position and a second valve position. When the flow path selection valve 10 is in the first valve position, the first port 18 and the second port 20 communicate through the communication groove 21 . When the flow path selection valve 10 is in the second valve position, the first port 18 communicates with the common port 16 through the communication groove 21 . The plurality of flow paths 102 are fluidly connected to the flow cell 62 when the flow cell 62 is installed in the fluidic system 12 to support target analytes. The pump 14 is fluidly connected to the flow cell 62 when the flow cell 62 is installed in the fluidic system 12 and flows liquid through the flow path 102 selected by the flow path selection valve 10 during analytical operations. Operatively coupled to the flow path selection valve 10 is a control circuit 63 having one or more processors and a memory storing computer-executable instructions that, when executed by the processor, control the processor to command the flow path The selector valve 10 selects the designated flow path 102 .

Referring to FIG. 15 , an embodiment of the present application further provides a sequencing system 90 . The sequencing system 90 is, for example, a nucleic acid measurement system. The sequencing system 90 includes the liquid circuit system 12 of any of the above embodiments.

In one example, the control circuit 63 is configured to control the rotation of the flow path selector valve 10 to a first valve position to communicate a first reservoir 66 with the flow cell 62, the first reservoir 66 carrying a first reaction solution containing nucleic acids molecules; and configured to, with the flow path selector valve 10 in the first valve position, pass a first reaction solution through the flow cell 62 to perform a first reaction, the first reaction comprising attaching at least a portion of the nucleic acid molecules to the flow cell 62 and be configured to rotate the flow path selector valve 10 to the second valve position to communicate the second storage 68 and the flow cell 62, the second storage 68 carrying a second reaction solution containing the components required for nucleic acid sequencing and is configured to make the second reaction liquid enter the flow cell 62 through the second flow channel to carry out the second reaction when the flow path selection valve 10 is in the second valve position, and the second reaction includes causing the first reaction to be carried out after the first reaction is carried out. The nucleic acid molecules in the flow cell 62 interact with the second reaction solution to generate a polymerization reaction and detect signals from the reaction, so as to realize the sequence determination of the nucleic acid molecules. The sequencing system 90 mentioned in this application is, for example, a machine such as a sequencer or a sequencing platform.

In one example, the first storage 66 carries a biological sample solution, the biological sample solution contains nucleic acid molecules, the second storage 68 carries a reaction solution, and the reaction solution includes components required to perform a polymerization reaction, and the control circuit 63 is configured as the flow path selection valve 10 such that the biological sample solution in the first reservoir 66 enters the flow cell 62 to perform a first reaction including at least a portion of the nucleic acid molecules connected to the flow cell 62, and the control circuit 63 is configured to control the flow after the first reaction is performed The path selection valve 10 allows the reaction solution in the second storage 68 to enter the flow cell 62 to perform a second reaction. The second reaction includes the interaction between the nucleic acid molecules in the flow cell 62 and the reaction solution to achieve a polymerization reaction.

Sequencing system 90 operates according to commands implementing prescribed protocols for testing, validation, analysis (eg, including sequencing), and the like. A prescribed protocol will be pre-established and include a series of events or operations for activities, such as aspirating reagents, aspirating air, aspirating other fluids, ejecting such reagents, air and fluids, and the like. This protocol will allow the coordination of such fluid manipulations with other manipulations of the instrument, such as the reactions taking place in the flow cell 62, imaging of the flow cell 62 and its sites, and the like.

The present application also provides a system, which includes the sequencing system 90 described in any of the above embodiments.

The present application also provides a method for controlling a system to implement sequencing. The system can be the above liquid circuit system 12. For example, the system includes multiple flow paths 102, a flow cell 62 connected to the multiple flow paths 102, and a flow path selection valve. 10. Pump 14, first storage 66, and second storage 68. The flow path selection valve 10 includes a manifold 24 and a first spool 26 . The manifold 24 is provided with a common port 16 , a plurality of first ports 18 and a plurality of second ports 20 . The first valve body 26 is provided with a communication groove 21 . The first spool 26 is rotatable or slidable relative to the manifold 24 so that the communication groove 21 selectively communicates the common port 16 and the first port 18 or the first port 18 and the second port 20 to select different flow paths. The first memory 66 is connected to the second port 18 . The second memory 68 is connected to the common port 16 . The first storage 66 carries the first reaction solution, and the first reaction solution contains nucleic acid molecules. The second storage 68 carries a second reaction solution containing components required for nucleic acid sequencing. The pump 14 is used to flow the liquid through the flow path selected by the flow path selection valve 10 .

Referring to FIG. 16 , the method includes: S110 , switching the flow path selection valve 10 to the first valve position, so that the communication groove 21 communicates with the first port 18 and the second port 20 to communicate with the first storage 66 and the flow cell 62 ; S120, when the flow path selection valve 10 is in the first valve position, control the pump 14 to work so that the first reaction solution enters the flow cell 62 to carry out the first reaction, the first reaction including connecting at least a portion of the nucleic acid molecules to the flow Pool 62; S130, switch the flow path selection valve 10 to the second valve position, so that the communication groove 21 communicates with the first port 18 and the common port 16 to communicate with the second reservoir 68 and the flow cell 62; S140, in the flow path selection valve When the 10 is in the second valve position, the pump 14 is controlled to work so that the second reaction solution enters the flow cell 62 to carry out the second reaction. The second reaction includes making the nucleic acid molecules in the flow cell 62 after the first reaction and the first reaction. The two reaction solutions interact with each other to generate a polymerization reaction and detect the signal from the reaction, so as to realize the sequence determination of the nucleic acid molecule.

The method realizes the first reaction and the second reaction by setting one flow path selection valve 10 in different valve positions to switch between different flow channels/reagents, and is especially suitable for operation control of highly integrated systems or equipment.

The current second-generation high-throughput sequencing platform or single-molecule sequencing platform generally needs to process the sample to be tested before sequencing on the machine. Sequencing the library of the platform and loading the library into a designated area such as the flow cell 62 to place the flow cell 62 containing the sample to be tested into the sequencer for automated sequencing. On current commercially available sequencing platforms, the processing of samples to be tested prior to on-board sequencing is generally separate from on-board sequencing, such as manual sample processing/library preparation in reagent tubes, or processing and loading of samples to be tested on sample processing equipment . The method can realize sample processing and sequencing before being put on the machine, and realize the switching and in-out control of different flow channels of various reagents by placing the flow path selection valve 10 in different valve positions, and is especially suitable for integrating the functions of sample processing and sequencing before being put on the machine. Integrated sequencing platform.

Please refer to FIG. 17 , in some embodiments, the system further includes a third storage 104, the third storage 104 is connected to the common port 16, the third storage 104 carries a third reaction solution, and the third reaction solution includes Amplify the desired components. The method further includes performing the following after performing step S120 and before performing step S140 (after performing the first reaction and before performing the second reaction): controlling the pump 14 to work so that the third reaction liquid in the third storage 104 enters the flow cell 62, so as to A third reaction is performed, and the third reaction includes making the nucleic acid molecules in the flow cell 62 after the first reaction interact with the third reaction solution to realize the amplification of the nucleic acid molecules.

The so-called "amplification" refers to the cloning of nucleic acid molecules, such as by polymerase chain reaction replicating the nucleic acid molecule into tens of thousands or even millions of copies, into a cluster (cluster), which is hundreds of thousands of copies. Any molecule in the millions of copies/clusters has the same sequence as the original nucleic acid molecule, so that the signal from the nucleic acid molecule can be amplified by increasing the number of molecules, which is convenient for the detection of the nucleic acid molecule; specifically, in subsequent sequencing, The signal emitted by the tens of millions of molecules (clusters) is equivalent to the signal from the single nucleic acid molecule, greatly enhancing the signal of the molecule, facilitating detection.

The second-generation high-throughput sequencing platforms currently on the market, such as the ILLUMINA sequencing platform, the Ion Torrent sequencing platform and the BGI sequencing platform, all require amplification such as bridge PCR or rolling circle amplification before sequencing. and so on to amplify the signal from the molecule to be detected, so as to obtain a stronger signal that is easy to identify and detect (or less susceptible to interference).

Please refer to FIG. 17 , in some embodiments, the system further includes a fourth storage 106 , the fourth storage 106 is connected to the common port 16 , and the fourth storage carries the washing solution. The method further includes, before performing step S120 (before performing the first reaction): in the case where the flow path selection valve 10 is in the first valve position, controlling the pump 14 to operate so that the washing solution in the fourth storage 106 enters the flow Pool 62. In this way, the washing solution can rinse the flow cell 62, which can prevent the subsequent first reaction solution from being polluted by the last residual substances and/or reduce the unnecessary loss of the first reaction solution such as a trace amount of biological sample solution (for example, filling in in the piping of the fluid system 12).

In some embodiments, the method further includes performing (before the first reaction) the following step before performing step S120: in the case where the flow path selection valve 10 is in the first valve position, controlling the pump 14 to work to send the flow cell to the flow cell 62 into the air. In this way, before starting the first reaction, a section of air is injected to separate the first reaction solution that flows in later and the cleaning solution already in the liquid circuit system, so as to prevent the trace biological samples from being diffused and/or diluted, affecting the waiting The nucleic acid molecules to be detected are connected to the flow cell 62 and the subsequent detection of the nucleic acid molecules to be detected.

In some embodiments, the method further includes performing the following step before performing step S120 and/or performing step S140 (before performing the first reaction and/or performing the second reaction): controlling the pump 14 to work to make the fourth The wash solution in reservoir 106 enters flow cell 62 . In this way, the washing solution can clean the flow cell 62, which can prevent the subsequent first reaction solution and/or the second reaction solution from being affected by the previous reaction or the residues of the previous step.

In certain embodiments, the flow cell 62 has a solid support surface on which a first sequencing primer is immobilized, and at least one end of the nucleic acid molecule comprises at least a portion of a sequence capable of complementary pairing with at least a portion of the first sequencing primer , the first reaction includes complementary pairing of at least a portion of the nucleic acid molecule with the first sequencing primer for ligation into the flow cell 62 .

The so-called "first sequencing primer" is an oligonucleotide (a short nucleic acid sequence with a known sequence), and the known sequence immobilized on the chip surface is often also called a "probe".

In some embodiments, the second reaction solution contains the first nucleotide, the first polymerase and the cleavage reagent, and step S140 includes: (a) controlling the pump 14 to work so that the first nucleotide and the first polymerase enter the Flow cell 62 and subjecting flow cell 62 to conditions suitable for a polymerization reaction to bind a first nucleotide, comprising a base, a sugar unit, a moiety, to a nucleic acid molecule by extending a first sequencing primer. Cleavage blocking group and detectable label; (b) exciting the detectable label and collecting the signal from the detectable label; (c) controlling the operation of the pump 14 to allow the cleavage reagent to enter the flow cell 62 to remove the first nucleotide A cleavable blocking group and a detectable label; (d) repeating (a)-(c) at least once.

Specifically, the so-called "placed under conditions suitable for the polymerization reaction" generally involves temperature conditions in addition to the components/reagents required for the polymerization reaction (eg, polymerase, reaction substrates, ie, nucleotides, and/or sequencing primers). For example, the nucleic acid sequence determination system 90 also includes a temperature control system for controlling the temperature of the flow cell 62/reaction chamber to achieve "conditions suitable for the polymerization reaction".

Detectable labels are, for example, optically detectable labels, such as fluorescent molecules. The cleavable blocking group can prevent/inhibit the binding of other nucleotides (first nucleotides) in the reaction system to the next position of the nucleic acid molecule to be tested, which can be a physical block such as the 3' band of the sugar group There is an azide group (-N ₃ ), and it can also be a non-physical block (virtual block). For example, the blocking group can form a spatial conformation that blocks the extension reaction in the extension reaction solution system.

In some embodiments, the second reaction solution further includes a second nucleotide, and step S140 further includes performing the following after (a): controlling the pump 14 to work so that the second nucleotide and the first polymerize Enzyme enters the flow cell and the flow cell is placed under conditions suitable for a polymerization reaction to bind the second nucleotide to the nucleic acid molecule by continuing to extend the product after (a), so The second nucleotide comprises a base, a sugar unit and a cleavable blocking group. Compared with the first nucleotide, the second nucleotide is a reversible terminator without a detectable label. For the same polymerase, the reaction efficiency of the second nucleotide is generally higher than that of the first nucleotide. High, the execution of this step is conducive to synchronizing the reactions of multiple nucleic acid molecules in a cluster, that is, it can eliminate or reduce the nucleic acid molecules that are prephasing or phasing in a cluster to a certain extent, which is conducive to sequencing. progress of the reaction.

Please refer to FIG. 19, in certain embodiments, the second reaction solution comprises a third nucleotide, a fourth nucleotide, a second polymerase, a third polymerase, a cleavage reagent and a second sequencing primer, and the nucleic acid molecules are At least one end contains at least a portion of a sequence capable of complementary pairing with at least a portion of the second sequencing primer, and controlling the pump 14 to work so that the second reaction solution enters the flow cell 62 through the second flow channel to perform the second reaction includes: (i) controlling The pump 14 operates to enter the third nucleotide and the second polymerase into the flow cell 62 and to place the flow cell 62 under conditions suitable for the polymerization reaction to bind the third nucleotide to the nucleic acid by extending the first sequencing primer Molecularly, a nascent strand is obtained, and the third nucleotide is a nucleotide with neither a cleavable blocking group nor a detectable label; (ii) control the pump 14 to work so that the fourth nucleotide , the third polymerase, and the second sequencing primer enter the flow cell 62, and the flow cell 62 is placed under conditions suitable for the polymerization reaction, so that the second sequencing primer binds to the nascent strand and causes the fourth core by extending the second sequencing primer. The nucleotide is bound to the nascent strand, and the fourth nucleotide comprises a base, a sugar unit, a cleavable blocking group, and a detectable label; (iii) excitation of the detectable label and collection of a signal from the detectable label; (iv) ) controlling pump 14 to operate to allow cleavage reagent to enter flow cell 62 to remove the cleavable blocking group and detectable label of the fourth nucleotide; (v) repeating (ii)-(iv) at least once. In this way, the second reaction can be achieved through the steps (ii)-step (v), and the determination of the sequence of the nucleic acid molecule can be achieved.

The third nucleotide can be, for example, a natural nucleotide; the fourth nucleotide can be the same as the first nucleotide; the first to third polymerases can be the same or different, such as different types of DNA polymerases or the same type Different mutants of DNA polymerase, each independently, can effectively catalyze the specified extension/polymerization reaction in combination with the specified nucleotide.

Compared with the sequencing method of the previous embodiment, this method can read the sequence of the other end of the nucleic acid molecule to be tested by synthesizing the complementary strand of the nucleic acid molecule to be tested, so as to realize the sequencing of the other end of the nucleic acid molecule to be tested.

Similarly, in some embodiments, the second reaction solution further comprises a fifth nucleotide, and the method further includes, after (ii), controlling the pump 14 to work so that the fifth nucleotide and the A third polymerase enters the flow cell and subjects the flow cell to conditions suitable for polymerization to bind the fifth nucleotide to the nascent strand by continuing to extend the product after (ii) above, the fifth nucleotide comprises a base, a sugar unit and a cleavable blocking group. The so-called fifth nucleotide is, for example, the same as the second nucleotide, which is a reversible terminator without a detectable label. The execution of this step is conducive to the synchronous reaction state of multiple nucleic acid molecules in a cluster, that is, a certain The degree of elimination or reduction of nucleic acid molecules that are prephasing or phasing in a cluster is beneficial to the progress of the sequencing reaction and the acquisition of longer reads.

It should be pointed out that the explanations on the technical features such as the structure, connection relationship and operation control of the flow path selection valve 10 and/or the liquid circuit system 12 in the above-mentioned embodiments are also applicable to the control system implementing any of these embodiments. The method for realizing sequencing, with regard to how to utilize the flow path selection valve 10 and related elements/structural components to realize the method for realizing sequencing in the control system of any of these embodiments, is not expanded here, and those skilled in the art use the flow path in the above-mentioned embodiments An example introduction of the structure, connection relationship, function and operation mode of the path selection valve 10 and/or the liquid circuit system 12 and an example description of the current sequencing method, it is possible to understand how to utilize and control the flow path selection valve 10 and/or in the above embodiment. Or the liquid circuit system 12 and/or the sequencing system 90 to implement the corresponding sequencing method.

The present application also provides a method, which includes the method for implementing sequencing by the control system described in any of the above embodiments.

In the description of this specification, reference is made to the terms "some embodiments," "one embodiment," "some embodiments," "exemplary embodiments," "examples," "specific examples," or "some examples." Described means that a particular feature, structure, material, or characteristic described in connection with the described embodiment or example is included in at least one embodiment or example of the present application. In this specification, schematic representations of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the particular features, structures, materials or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.

Logic and/or steps represented in flowcharts or otherwise described herein, for example, may be considered an ordered listing of executable instructions for implementing the logical functions, and may be embodied in any computer-readable storage medium , for use by an instruction execution system, apparatus, or device (such as a computer-based system, a system including a processor, or other system that can fetch and execute instructions from an instruction execution system, apparatus, or device), or in conjunction with these instruction execution systems, device or equipment. For the purposes of this specification, a "computer-readable storage medium" can be any device that can contain, store, communicate, propagate, or transmit a program for use by or in conjunction with an instruction execution system, apparatus, or apparatus .

In addition, each functional unit in each embodiment of the present invention may be integrated into one processing module, or each unit may exist physically alone, or two or more units may be integrated into one module. The above-mentioned integrated modules can be implemented in the form of hardware, and can also be implemented in the form of software function modules. If the integrated modules are implemented in the form of software functional modules and sold or used as independent products, they may also be stored in a computer-readable storage medium.

Although the embodiments of the present application have been shown and described above, it should be understood that the above embodiments are exemplary and should not be construed as limitations to the present application. Variations, modifications, substitutions, and alterations are made to the embodiments, and the scope of the present application is defined by the claims and their equivalents.

Claims (10)

1. A flow path selector valve configured to switch between a first valve position and a second valve position, the flow path selector valve being provided with a common port, a plurality of first ports, a plurality of second ports, and a plurality of communication grooves that selectively communicate the common port and the first port or the first port and the second port,

the first port and the second port communicate through the communication groove with the flow path selector valve in the first valve position,

the first port and the common port communicate through the communication groove with the flow path selector valve in the second valve position.

2. The flow path selector valve of claim 1, wherein the flow path selector valve comprises:

a manifold provided with the common port, the plurality of first ports, and the plurality of second ports;

a first spool provided with the communication groove, the first spool being rotatable or slidable relative to the manifold to switch the flow path selection valve between the first valve position and the second valve position; optionally, the flow path selector valve includes a second spool disposed on the manifold, the first spool disposed on the second spool, the second spool disposed with a first passage communicating with the first port, a second passage communicating with the second port, and a third passage communicating with the common port,

the communication groove communicates the first passage and the second passage to enable the first port and the second port to communicate with each other with the flow path selector valve in the first valve position,

the communication groove communicates the first passage and the third passage with the first port communicating with the common port with the flow path selector valve in the second valve position; optionally, the manifold is provided with a cavity, the second valve spool being at least partially received in the cavity; optionally, a first connection port, a second connection port and a third connection port are arranged on the bottom surface of the cavity, the first connection port is communicated with the first port and the first channel, the second connection port is communicated with the second port and the second channel, and the third connection port is communicated with the common port and the third channel; optionally, at least two of the first port, the second port and the common port are located on different sides of the manifold, respectively; optionally, the communication groove includes a first communication groove and a second communication groove which are provided at intervals, the first port and the second port communicate through the first communication groove with the flow path selector valve in the first valve position, and the first port and the common port communicate through the second communication groove with the flow path selector valve in the second valve position; optionally, the flow path selector valve comprises a drive member for driving the first spool to rotate or slide.

3. The flow path selector valve of claim 2, wherein the flow path selector valve includes a slider coupled to the first spool, the slider coupled to the drive member, the drive member driving the first spool to slide via the slider; optionally, the drive member provides an electromagnetic drive.

4. The flow path selector valve of claim 3, comprising a housing removably connected to the manifold, the first spool and the slider being housed in the housing; optionally, the housing is provided with a guide groove, the slider includes a connecting portion and a guide rail portion connected to the connecting portion, the connecting portion is connected to the first valve element, and the guide rail portion is matched with the guide groove to guide the slider to drive the first valve element to slide.

5. A flow cell assembly, comprising:

the flow path selector valve of any one of claims 1-4; and

a flow cell connected to the flow path selector valve, the flow cell including a plurality of channels arranged in parallel, one end of the channels communicating with the first port.

6. A flow cell assembly according to claim 5, comprising two said flow path selection valves and one said flow cell, one end of the channel of said flow cell being in communication with the first port of one of the flow path selection valves and the other end of the channel of said flow cell being in communication with the first port of the other flow path selection valve; optionally, one or the other end of the channel is in ductless connection with the first port.

7. A fluid path system, comprising:

a plurality of flow paths fluidly connected with the flow cell to support a target analyte when the flow cell is installed in the fluidic circuit system;

the flow path selector valve of any one of claims 1-4, connected to the flow paths, the flow path selector valve selecting between the flow paths;

a pump fluidly connected to the flow cell when the flow cell is installed in the fluid path system and flowing liquid through the flow path selected by the flow path selection valve during an analysis operation; and

a control circuit operatively coupled to the flow path selection valve, the control circuit having one or more processors and memory storing computer-executable instructions that, when executed by the processors, control the processors to command the flow path selection valve to select a specified flow path.

8. The fluid path system of claim 7, further comprising:

a reagent selection valve to select a reagent from a plurality of reagents according to an analysis protocol; and

a flow cell carrying a target analyte;

the flow path selection valve is fluidly connected between the reagent selection valve and the flow cell, the flow path selection valve selects a flow path of a flow-through flow cell from a plurality of flow paths through the flow cell according to an analytical protocol and directs the selected reagent through the flow cell, the pump flows the selected reagent through the selected flow path according to the analytical protocol; optionally, the flow cell comprises a plurality of channels arranged in parallel, one end of the channels communicating with the first port; optionally, one end of the channel is un-piped to the first port.

9. The fluid path system of any of claims 7-8, further comprising a first reservoir and a second reservoir,

the first memory stores a sample solution to be tested, the first memory is connected with the second port,

the second memory stores a reaction reagent, and the second memory is connected with the common port.

10. A sequencing system comprising the fluid path system of any one of claims 7-9.

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