Common line selector valve for a system

Abstract

This application relates to common line selector valve for systems. A system can include a flow cell that supports an analyte of interest, a selector valve coupled to the flow cell to select a flow path through the flow cell from a plurality of flow paths, a pump coupled to the flow cell to displace fluid through the selected flow path during an analysis operation, and a control circuit coupled to the selector valve to command the selector valve to select the selected flow path.

Description

[0001] This application is a divisional application of the application filed on December 21, 2017, with application number 201780038470.9 and invention title "Common Pipeline Selector Valve for Systems".

[0002] Cross-reference of related applications This application claims priority to U.S. Patent Application No. 15 / 841,095, filed December 13, 2017, which claims priority to U.S. Patent Application No. 62 / 442,677, filed January 5, 2017, and to UK (GB) Patent Application No. 1704761.4, filed March 24, 2017, which also claims priority to U.S. Patent Application No. 62 / 442,677, all of which are hereby incorporated herein by reference in their entirety. background Instruments for sequencing molecules of interest (specifically, DNA, RNA, and other biological samples) have been developed and are constantly evolving. Before sequencing, a sample of the molecules of interest is prepared to form a library that will be mixed with reagents and ultimately introduced into a flow cell, where individual molecules attach to sites and are amplified to enhance detectability. The sequencing operation then involves a cycle of repeating the following steps: binding molecules at sites, labeling the bound components, imaging the components at sites, and processing the resulting image data.

[0003] In such sequencing systems, a fluid system (or subsystem) provides the flow of substances (e.g., reagents) under the control of a control system, such as a programmable computer and appropriate interfaces. Overview Details of one or more embodiments of the subject matter described in this specification are set forth in the accompanying drawings and the following description. Other features, aspects, and advantages will become apparent from the description, drawings, and claims.

[0004] In some embodiments, a system may be provided comprising: a plurality of flow paths fluidly connected to a flow cell when the flow cell is installed in the system to support an analyte of interest; a flow path selector valve coupled to the flow paths for selecting between the flow paths; a pump fluidly connected to the flow cell when the flow cell is installed in the system and for displacing fluid through one of the flow paths selected by the flow path selector valve during analytical operations; and control circuitry operatively coupled to the flow path selector valve, the control circuitry having one or more processors and a memory storing computer-executable instructions that, when executed by the one or more processors, control the one or more processors to command the flow path selector valve to select the selected flow path.

[0005] In some embodiments of the system, the plurality of flow paths may include: a first flow path for providing fluid flow through a first channel of the flow pool; and a second flow path for providing fluid flow through a second channel of the flow pool, wherein the second flow path is different from the first flow path.

[0006] In some implementations of the system, the plurality of flow paths may include a third flow path, which includes both the first flow path and the second flow path.

[0007] In some embodiments of the system, the flow path selector valve may be further fluidly coupled to a bypass line that bypasses the flow pool when the flow pool is installed in the system, and the flow path selector valve may also be controllable to select the bypass line instead of the flow path.

[0008] In some implementations of the system, the control circuit can automatically command the flow path selector valve to select the chosen flow path based on the analysis protocol during the analysis operation.

[0009] In some embodiments of the system, the system may further include a reagent selector valve positioned upstream of the flow path selector valve in the fluid direction, the reagent selector valve being used to select a reagent from a variety of reagents and direct the selected reagent to the inlet of the flow path selector valve.

[0010] In some embodiments of the system, the system may include one or more manifolds for fluidly connecting the flow pool to the flow path selector valve when the flow pool is installed in the system, and the one or more manifolds may be fluidly inserted between the flow path selector valve and the flow pool when the flow pool is installed in the system.

[0011] In some embodiments of the system, the pump may include an injection pump located downstream of the flow pool in the fluid direction.

[0012] In some embodiments, a system may be provided comprising: a reagent selector valve for selecting a reagent from a plurality of reagents according to an analytical protocol; a flow cell for supporting an analyte of interest; a flow path selector valve fluidly inserted between the reagent selector valve and the flow cell, the flow path selector valve being configured to select a flow path through the flow cell from a plurality of flow paths through the flow cell according to the analytical protocol and to guide the selected reagent through the selected flow path; a pump fluidly connected to the flow cell, the pump being configured to displace the selected reagent through the selected flow path according to the analytical protocol; and control circuitry operatively coupled to the flow path selector valve, the control circuitry having one or more processors and a memory storing computer-executable instructions, which, when executed by the one or more processors, control the one or more processors to cause the flow path selector valve to select the selected flow path.

[0013] In some implementations of the system, the plurality of flow paths may include a first flow path passing through a channel of the flow pool and a second flow path passing through a second channel of the flow pool, wherein the second flow path is different from the first flow path.

[0014] In some implementations of the system, the plurality of flow paths may include a third flow path, which includes both the first flow path and the second flow path.

[0015] In some embodiments of the system, the flow path selector valve may be further fluidly connected to a bypass line that bypasses the flow pool, and the flow path selector valve may be further controllable to select the bypass line instead of the flow path through the flow pool.

[0016] In some embodiments of the system, the system may include one or more manifolds that are fluidly coupled between the selector valve and the flow cell when the flow cell is installed in the sequencing system, so that the flow cell engages with the selector valve.

[0017] In some embodiments, a method may be provided comprising: controlling a flow path selector valve located upstream of a flow cell in the fluid direction to select a flow path through the flow cell from a plurality of flow paths through the flow cell according to an analytical protocol and to displace a reagent through the selected flow path, wherein the plurality of flow paths includes a first flow path through a channel of the flow cell, a second flow path through a second channel of the flow cell, and a third flow path including both the first flow path and the second flow path, wherein the second flow path is different from the first flow path.

[0018] In some embodiments of the method, the method may further include controlling a reagent selector valve fluidly connected to the flow path selector valve, the reagent selector valve being used to select different reagents from a variety of reagents for displacement through the flow path selector valve and the flow cell according to the analysis protocol, wherein the flow path selector valve is fluidly inserted between the reagent selector valve and the flow cell.

[0019] In some embodiments of the method, the method may further include commanding a change in the position of the flow path selector valve, the reagent selector valve, or both the flow path selector valve and the reagent selector valve during continuous cycles of the analysis protocol.

[0020] In some embodiments of the method, the method may further include instructing the flow path selector valve to select a bypass line that bypasses the flow pool rather than a flow path that passes through the flow pool.

[0021] In some embodiments of the method, the method may further include installing the flow cell into the sequencing system such that the flow cell is fluidly connected to a plurality of manifolds fluidly inserted between the flow path selector valve and the flow cell such that the flow cell is fluidly connected to the flow path selector valve, wherein the installation of the flow cell is performed prior to the transfer of the reagent.

[0022] In some embodiments of the method, the reagent can be displaced through the selected flow path by a pump located downstream of the flow cell.

[0023] In some of these embodiments of the system, the pump may include or may be an injection pump.

[0024] Details of one or more embodiments of the subject matter described in this specification are set forth in the accompanying drawings and the following description. Other features, aspects, and advantages will become apparent from the description, drawings, and claims. It should be noted that the relative dimensions in the following figures may not be drawn to scale. Brief description of the attached diagram These and other features, aspects, and advantages of this disclosure will become better understood when the accompanying drawings are read in detail, wherein similar characters throughout the drawings denote similar parts, wherein: Figure 1 It is a graphical overview of an example sequencing system that can use the disclosed technology; Figure 2 yes Figure 1 A graphical overview of an implementation of the fluid system of an example sequencing system; Figure 3 yes Figure 1 A graphical overview of the instance processing and control system of the instance sequencing system; Figure 4 It is used for Figure 1 A graphical overview of another implementation of a fluid system component of an example sequencing system; Figure 5 It is used for Figure 1 A schematic exploded view of an implementation scheme for a shared pipeline selector valve in a sequencing system; Figure 6 It is an explanation by means of Figure 1 A schematic diagram of an example port combination implemented by a shared pipeline selector valve in a sequencing system; Figure 7A and Figure 7B yes Figure 1 Cross-sectional front views of different configurations of the common pipeline selector valve implementation of the sequencing system and examples depicting the manner in which fluid can flow through the valve; Figures 8A to 8F yes Figure 1 Cross-sectional plan views of different configurations of the common pipeline selector valve implementation scheme for the sequencing system, which show different combinations of valve ports; Figures 9A to 9D Is it through Figure 1 A graphical overview of the various flow paths in the flow cell of the sequencing system, which are selected by a common pipeline selector valve. Figure 10 It is a fluid filling system without drawing fluid into it. Figure 1 Description of example methods in the flow cell of the sequencing system; Figure 11 It is used with Figure 1 A perspective view of an implementation scheme for a manifold assembly that interfaces with a sequencing system, the manifold assembly having a reagent selector valve, a common line selector valve, nozzles, and various fluid channels; Figure 12 It is an operation Figure 1 A flowchart of the implementation scheme for the sequencing system method; and Figure 13 It is used for Figure 1A schematic overview of another embodiment of the sequencing system and a fluid system having an additional common pipeline selector valve for selecting and combining various reagents. Detailed description Figure 1 This describes an embodiment of a sequencing system 10 configured to process molecular samples, which can be sequenced to determine their components, component ordering, and substantially the structure of the sample. The system includes instruments 12 for receiving and processing biological samples. A sample source 14 provides a sample 16 that, in many cases, will include tissue samples. For example, the sample source may include a person or individual, such as a human, animal, microorganism, plant, or other donor (including environmental samples), or any other individual containing the organic molecule of interest whose sequence will be determined. Of course, the system can be used with samples other than those obtained from organisms (including synthetic molecules). In many cases, the molecules will include DNA, RNA, or other molecules with base pairs whose sequences can define genes and variants with a specific function of ultimate interest.

[0025] Sample 16 is introduced into sample / library preparation system 18. This system can isolate, split, and otherwise prepare the sample for analysis. The resulting library contains molecules of interest of a length conducive to the sequencing operation. The resulting library is then provided to instrument 12, where sequencing is performed. In practice, the library, sometimes referred to as a template, is combined with reagents in an automated or semi-automated process and then introduced into a flow cell prior to sequencing.

[0026] exist Figure 1 In the embodiments described herein, the instrument includes a flow cell or array 20 for receiving a sample library. The flow cell includes one or more fluid channels that allow sequencing chemistry reactions to occur, including the attachment of molecules from the library and amplification at sites or locations detectable during sequencing operations. For example, the flow cell / array 20 may include a sequencing template fixed to one or more surfaces at the site or location. A “flow cell” may include a patterned array, such as a microarray, nanoarray, etc. In practice, the site or location may be positioned on one or more surfaces of a support in a regular repeating pattern, a complex non-repetitive pattern, or a random configuration. To enable sequencing chemistry reactions to occur, the flow cell also allows the introduction of substances for reactions, rinsing, etc., such as various reagents, buffers, and other reaction media. The substances flow through the flow cell and can contact the molecules of interest at various sites.

[0027] In the instrument, flow cell 20 is mounted on a movable stage 22, which in this embodiment is movable in one or more directions as indicated by reference numeral 24. For example, flow cell 20 may be provided as a removable and replaceable cartridge that can dock with a port on the movable stage 22 or other components of the system to allow delivery of reagents and other fluids to or from the flow cell. The stage is associated with an optical detection system 26 that directs radiation or light 28 to the flow cell during sequencing. The optical detection system may use various methods, such as fluorescence microscopy, to detect analytes positioned at sites in the flow cell. By way of non-limiting examples, optical detection system 26 may use confocal line scanning to generate progressively pixelated image data, which can be analyzed to locate individual sites in the flow cell and determine the type of nucleotide most recently attached or bound to each site. Other imaging techniques may also be suitably used, such as techniques that scan one or more radiation points along the sample, or techniques using a "step and shoot" imaging method. The optical inspection system 26 and the stage 22 can cooperate to maintain a static relationship between the flow cell and the inspection system while acquiring a regional image (or, as mentioned, scanning the flow cell in any suitable mode (e.g., point scan, line scan, “step-through” scan)).

[0028] While many different techniques can be used for imaging or, more generally, for detecting molecules at sites, the embodiments covered here utilize confocal optical imaging at the wavelength that induces excited fluorescent labeling. The label, excited by its absorption spectrum, transmits a fluorescent signal back by its emission spectrum. Optical detection system 26 is configured to capture such signals to allow for resolution processing of pixelated image data for analysis of the signal emission sites, and to process and store the resulting image data (or data derived therefrom).

[0029] In sequencing operations, the cycling process or procedure is performed automatically or semi-automatically, promoting reactions (e.g., by mononucleotides or oligonucleotides), followed by rinsing, imaging, and unpacking to prepare for subsequent cycles. The library may undergo several such cycles before all useful information can be extracted from the sample library, which is prepared for sequencing and immobilized on the flow cell. An optical detection system can generate image data by scanning the flow cell (and its sites) during each cycle of the sequencing operation using electronic detection circuitry (e.g., a camera or imaging electronics or a chip). The resulting image data can then be analyzed to locate individual sites in the image data and to analyze and characterize the molecules present at those sites, such as by referencing the specific color or wavelength of light detected at a particular site (characteristic emission spectra of specific fluorescent labels), as indicated by groups or clusters of pixels in the image data at that site. For example, in DNA or RNA sequencing applications, four common nucleotides can be represented by distinguishable fluorescence emission spectra (wavelengths or wavelength ranges of light). Each emission spectrum can then be assigned a value corresponding to that nucleotide. Based on this analysis, and by tracking the cycle value determined for each point, the individual nucleotides and their order can be determined for each point. These sequences can then be further processed to assemble longer fragments, including genes, chromosomes, etc. As used in this disclosure, the terms "automatic" and "semi-automatic" mean that once the operation begins, or once the program including the operation begins, the operation is performed by a system program or configuration with little or no human interaction.

[0030] In the illustrated embodiment, reagent 30 is drawn or aspirated into the flow cell via valve 32. The valve may be located via, for example, a pipette or suction tube. Figure 1 (Not shown) Reagents are drawn from a container or vessel containing the reagents. Valve 32 allows selection of reagents based on a prescribed sequence of operations. The valve may further receive a command to direct the reagents into the flow cell 20 via flow path 34. The used reagents are directed out of or through flow path 36. In the illustrated embodiment, pump 38 is used to move reagents through the system. The pump may also provide other useful functions, such as measuring reagents or other fluids passing through the system, drawing air or other fluids, etc. An additional valve 40 downstream of pump 38 allows the used reagents to be properly directed to disposal vessels or containers 42.

[0031] The instrument further includes a series of circuits that assist in commanding the operation of various system components, monitor component operation via feedback from sensors, collect image data, and at least partially process the image data. Figure 1In the implementation described herein, the control / monitoring system 44 includes a control system 46 and a data acquisition and analysis system 48. Both systems will include one or more processors (e.g., digital processing circuitry such as microprocessors, multi-core processors, FPGAs, or any other suitable processing circuitry) and associated memory circuitry 50 (e.g., solid-state memory devices, dynamic memory devices, onboard and / or offboard memory devices, etc.), which may store machine-executable instructions for controlling, for example, one or more computers, processors, or other similar logic devices to provide certain functionalities. A dedicated or general-purpose computer may at least partially constitute the control system and the data acquisition and analysis system. The control system may include circuitry configured (e.g., programmed) to process commands for fluid dynamics, optics, stage control, and any other useful functions of the instrument. The data acquisition and analysis system 48 interfaces with the optical inspection system to command the movement of the optical inspection system or the stage, or both, the emission of light for cyclic inspection, the reception and processing of returned signals, etc. The instrument may also include various interfaces, such as those indicated by reference numeral 52, such as operator interfaces that allow control and monitoring of the instrument, sample transfer, initiation of automated or semi-automated sequencing operations, and report generation. Finally, Figure 1 In one implementation, an external network or system 54 may be coupled to and cooperate with the instrument, for example, for analysis, control, monitoring, servicing and other operations.

[0032] It should be noted that, although in Figure 1 The description refers to a single flow cell and fluidic pathway, as well as a single optical detection system; however, some instruments may accommodate more than one flow cell and fluidic pathway. For example, in the currently covered implementation, two such configurations are provided to enhance sequencing and yield. In practice, any number of flow cells and pathways can be provided. These flow cells and pathways may utilize the same or different reagent receiving containers, disposal receiving containers, control systems, image analysis systems, etc. In the case of multiple fluidic systems, these multiple fluidic systems may be controlled individually or in a coordinated manner.

[0033] Figure 2 illustrate Figure 1An example fluid system for a sequencing system. In the illustrated embodiment, flow cell 20 includes a series of channels or pathways 56A and 56B that can be grouped in pairs for receiving fluid substances (e.g., reagents, buffers, reaction media) during an analytical (e.g., including sequencing) operation. Pathway 56A is coupled to a common line 58 (first common line), while path 56B is coupled to a second common line 60. A bypass line 62 is also provided to allow fluid to bypass the flow cell without entering it. As mentioned above, a series of dishes or containers 64 allow for the storage of reagents and other fluids that can be used during the analytical operation. A reagent selector valve (RSV) 66 is coupled to a motor or actuator (not shown) to allow selection of one or more reagents to be introduced into the flow cell. The selected reagent then proceeds to a common line selector valve (CLSV) 68, which similarly includes a motor (not shown). The common line selector valve can be commanded to select one or more or two common lines 58 and 60 to allow reagent 64 to flow in a controlled manner to passages 56A and / or 56B, or to select bypass line 62 to allow one or more reagents to flow through the bypass line.

[0034] The used reagent exits the flow cell via a line coupled between the flow cell and pump 38. In the illustrated embodiment, the pump includes a syringe pump with a pair of syringes 70, which are controlled and moved by actuator 72 to aspirate and eject reagents and other fluids during different operations in a test, validation, and analysis (e.g., sequencing) cycle. The pump assembly may include various other parts and components, including valves, instruments, actuators, etc. (not shown). In the illustrated embodiment, pressure sensors 74A and 74B sense the pressure on the pump inlet line, while pressure sensor 74C senses the pressure output from the syringe pump.

[0035] Fluid used by the system is pumped into the used reagent selector valve 76. This valve allows selection of one of several flow paths for used reagents and other fluids. In the illustrated embodiment, a first flow path leads to a first used reagent receiving container 78, while a second flow path leads to a second used reagent receiving container 82 via a flow meter 80. Depending on the reagent used, it may be advantageous to collect the reagent or some of it in a separate container for disposal, and the used reagent selector valve 76 allows for this control.

[0036] It should be noted that the valves within the pump assembly allow various fluids, including reagents, solvents, cleaning agents, air, etc., to be drawn by the pump and injected or circulated via one or more of a common line, bypass line, and flow tank. Furthermore, as mentioned above, in the currently covered embodiments, under common control... Figure 2The paper presents two parallel implementations of a fluid dynamics system. Each component of the fluid dynamics system can be part of a single analytical instrument and can perform sequencing operations on different flow cells and sample libraries in parallel.

[0037] The fluid dynamics system operates according to commands from a control system 46 that implements a defined protocol for testing, validation, analysis (e.g., including sequencing), etc. The defined protocol is pre-established and includes a series of events or operations for the activity, such as aspirating reagents, aspirating air, aspirating other fluids, spraying such reagents, air, and fluids, etc. This protocol will allow coordination of such fluid operations with other instrument operations, such as reactions occurring in the flow cell, imaging of the flow cell and its sites, etc. In the illustrated embodiment, the control system 46 uses one or more valve interfaces 84 and a pump interface 86, the valve interfaces being configured to provide command signals to valves, and the pump interface being configured to command the operation of pump actuators. Various input / output circuits 88 may also be provided for receiving and processing feedback, such as from pressure sensors 74A to 74C and flow meters 80.

[0038] Figure 3 This describes certain functional components of the control / monitoring system 44. As described, the memory circuit 50 stores prescribed routines executed during testing, debugging, fault diagnosis, service, and analysis operations. Many such protocols and routines can be implemented and stored in the memory circuit, and these protocols and routines can be updated or modified from time to time. Figure 3 As described herein, these protocols and routines may include fluid control protocol 90, which controls various valves, pumps, and any other fluid actuators, and receives and processes feedback from fluid sensors such as valves, as well as flow and pressure sensors. Stage control protocol 92 allows, for example, the movement of the flow cell as needed during imaging. Optical component control protocol 94 allows commands to be issued to the imaging assembly to illuminate portions of the flow cell and to receive return signals for processing. Image acquisition and processing protocol 96 allows image data to be processed, at least partially, for the extraction of useful data for analysis. Other protocols and routines may be provided in the same or different memory circuitry as indicated by reference numeral 98. In practice, the memory circuitry may be provided as one or more memory devices, such as both volatile and non-volatile memory. This memory may be located within the instrument, and some memory may be external.

[0039] One or more processors 100 access and implement the stored protocol on the instrument. As mentioned above, the processing circuitry can be part of a dedicated computer, a general-purpose computer, or any suitable hardware, firmware, and software platform. The processors and the operation of the instrument can be commanded by a human operator via operator interface 101. The operator interface allows for testing, debugging, troubleshooting, and servicing, as well as reporting any problems that may occur in the instrument. The operator interface also allows for initiating and monitoring analysis operations.

[0040] Figure 4 This describes a portion of the fluid system 120 used in an embodiment of instrument 12, where arrows indicate the ability to flow substances (e.g., reagents, buffers, analytes) through various illustrated flow paths during sample analysis. For Figure 4 In the embodiment described herein, flow pool 20 includes two pathway groups, denoted as pathway group A and pathway group B. Other embodiments of flow pool 20 may include a different number of pathway groups, such as more than two pathway groups. In yet another embodiment, flow pool 20 may include only one pathway group. Flow pool 20 may be a removable and / or replaceable component of the analysis system.

[0041] Each of the two described pathway groups A and B includes Figure 4 The pathways are represented as L1, L2, L3, and L4, respectively. In this regard, pathway groups A and B can be referred to as "pathway pairs" because each pathway group comprises two corresponding pathways. For the illustrated embodiment, flow cell 20 is designed to operate such that material (e.g., fluid) can be induced to flow through pathway groups A and B in the directions indicated by the arrows during the analytical protocol. Other protocols used for testing, etc., may allow certain substances to flow in different directions.

[0042] in addition, Figure 4 The pump 38 of the fluid system described herein includes a plurality of syringe pumps 124 (e.g., syringe pumps 124A and 124B). As described, each syringe pump 124 includes one or more corresponding syringes 126 (e.g., syringe 126A corresponding to passage group A and syringe 126B corresponding to passage group B) actuated by actuators 128 (e.g., actuators 128A and 128B), respectively. The described syringe pump 124 also includes valves 130 (e.g., valves 130A and 130B), which enable the syringe pump to push fluid into and withdraw fluid from different orifices or ports of the pump 124.

[0043] The fluid flow through the flow cell 20 is coordinated, either entirely or partially, via the control of syringe pumps 124, RSV 66, and CLSV 68. (As mentioned above...) Figure 2As described, RSV 66 is fluidly coupled to various reagent sources and allows selective fluid coupling between the reagent source and CLSV 68. As an example, RSV to CLSV common line 140 allows the reagent outlet port of RSV 66 to be fluidly coupled to the common line inlet port of CLSV 68, and RSV to CLSV common line 140 is designed to allow various fluids (e.g., reagents) to flow between RSV 66 and CLSV 68.

[0044] As discussed in further detail herein, CLSV 68 allows selective fluid coupling between a reagent selected at RSV 66 (e.g., via a selected reagent port) and various flow paths within flow cell 20. In this manner, CLSV 68 is coupled to flow cell 20 to select a flow path from a plurality of flow paths for fluid to pass through flow cell 20, including a first flow path through a channel of flow cell and a second flow path through a second channel of flow cell, the second flow path being different from the first flow path. In some embodiments, the plurality of flow paths includes a third flow path that includes both the first and second flow paths. In the illustrated embodiments, this means, among other things, that CLSV 68 is also configured to allow selected fluid coupling between RSV 66 and either or both of pathway group A and pathway group B (the first and second pathway groups, respectively) (and in some embodiments, other flow paths). In this manner, CLSV 68 allows for individual addressing of each pathway group or pathway pair of flow cell 20. CLSV 68 also allows for selective fluid coupling between RSV 66 and bypass line 142, which can be used to fill reagents without aspirating fluid into flow cell 20, for use in certain testing protocols and others. As used herein, the term "fluid coupling" is intended to indicate coupling between flow paths to allow fluid flow between those flow paths. Thus, selected or selective fluid coupling indicates the ability to selectively couple flow paths to allow fluid flow therebetween, which flow paths are also (when not fluidly coupled) fluidly isolated from each other (fluid cannot flow therebetween). During analytical operation, control circuitry automatically commands CLSV 68 (e.g., via a motor) to select a selected flow path based on the analytical protocol. For example, a flow cell may be installed in a sequencing system, and one or more manifolds (e.g., multiple manifolds) may engage flow cell 20 with CLSV 68 when flow cell 20 is properly installed. The control circuitry can perform certain diagnostics to ensure that proper fluid connections have been established, perform certain pre-analytical (e.g., predictive sequencing) operations including reagent filling of the fluid system 120, and then initiate various analytical (e.g., sequencing) protocols.

[0045] Selective fluid coupling using CLSV 68 as described above can be achieved using certain physical characteristics of valve 68. An embodiment of valve 68 is schematically illustrated in... Figure 5 As shown, CLSV 68 includes a stationary portion 150 and a movable portion 152, shown as separate from each other. When assembled, the stationary portion 150 and the movable portion 152 are positioned directly abutting each other in a manner that prevents fluid leakage between their respective fluid components (e.g., fluid ports, fluid channels). The movable portion 152 is configured to move (e.g., translate, rotate) relative to the stationary portion 150, as shown by arrow 154, to form various fluid connections between its respective fluid components. Whether the movable portion 152 translates, rotates, or performs both will depend on the specific geometry of CLSV 68 (e.g., elongated, annular, polygonal) and the nature of the various mechanical couplings 156 and fluid couplings 158 of valve 68. The mechanical couplings 156 of CLSV 68 may include couplings between valve 68 and other components of the sequencing system 10, such as housings including valves 66, 68 and various flow paths as described herein. Mechanical coupling 156 may also include coupling between the movable portion 152 and an actuator such as a motor, and between the movable portion 152 and the stationary portion 150.

[0046] Fluid coupling 158 can be dynamic because it can be adjusted, closed, opened, formed, blocked, etc. Fluid coupling 158 can include connections to, for example, common lines 58 and 60, and... Figure 4 The RSV to CLSV share 140 of various pipelines (e.g., Figure 2 The fluid coupling (flow path 34) may include one or more manifolds that operate to fluidly couple CLSV 68 to flow cell 20, for example, when flow cell 20 is mounted in the sequencing system.

[0047] According to the current implementation, the movement 154 of the movable part 152 relative to the stationary part 150 adjusts the overlap between the various channels 160 and the various ports 162 to generate various combinations of fluid coupling ports. These various combinations of fluid coupling ports are used to determine the flow path of the fluid through the flow pool 20.

[0048] In the illustrated embodiment, each channel 160 is part of the movable portion 152 (e.g., formed in the movable portion), and each port 162 is part of the stationary portion 150 (e.g., formed in the stationary portion). However, other embodiments of the CLSV 68 may have some or all of the respective ports 162 in the movable portion 152 and some or all of the respective channels 160 in the stationary portion 150. The respective channels 160 and ports 162 can be formed in their respective portions, for example, by subtractive manufacturing (e.g., etching, machining, and photolithography) or by additive manufacturing. One or more materials of the CLSV 68 may be selected or designed to withstand the influence of the system 10 ( Figure 1 The fluids typically used during the analysis and testing protocols of CLSV68 are designed to prevent the material from adsorbing into the reagent and to prevent breakage or other chemically induced degradation. Additionally, one or more materials of CLSV68 may be selected to have a certain coefficient of friction between the movable portion 152 and the stationary portion 150 to provide sufficient resistance to accidental movement of the movable portion 152, while still allowing the movable portion 152 to move freely under a certain amount of force applied by the actuator or user.

[0049] As shown, the movable portion 152 and the stationary portion 150 include annular geometry that overlaps in the axial direction 164. In the illustrated embodiment, the overlap is such that the center point 166 of the movable portion 152 and the center point 168 of the stationary portion 150 are substantially aligned in the axial direction 164. Other embodiments of the valve 68 may have a configuration in which the center points 166, 168 are offset from each other, for example, due to spatial constraints within the housing including the valve 68, certain design considerations, etc. In practice, the movable portion 152 and the stationary portion 150 may not be the same size (e.g., have the same perimeter, length, or depth) and may have different geometries (different shapes). For example, although the movable portion 152 is in Figure 5 The schematic diagram shows the stationary portion 150 in a stacked relationship, but some embodiments of CLSV 68 may have a movable portion 152 nested within the stationary portion 150 (but also in a stacked relationship).

[0050] To create fluid coupling using CLSV 68, some of the ports 162 extending through a thickness 170 of the stationary portion 150 (e.g., between parallel flat surfaces 172, 174) are aligned axially in the direction 164 with certain internal channels 160. Each port 162 extends from surface 172 through the stationary portion 150 to surface 174, where surface 172 is a first surface of the stationary portion 150 facing away from the movable portion 152, and surface 174 is a second surface of the stationary portion 150 facing and directly adjacent to the movable portion 152. The ports 162 are separated and distinct from each other within the stationary portion 150 and are available for delivering or receiving fluid depending on the configuration of the fluid coupling 158.

[0051] According to this embodiment, each channel 160 has a geometry that allows different combinations of each port 162 to be coupled to each other. This is schematically shown in Figure 6 middle, Figure 6 This includes different instance port combinations for CLSV 68. As shown, the CLSV 68 implementation includes five different ports, but other numbers of ports may be included in other implementations.

[0052] As depicted by example valve configuration 68A, the first fluid passage 160A of valve 68 is fluidly coupled to ports 1, 2, and 3. As an example, port 2 can be an inlet, and ports 1 and 3 can be outlets (leading to the pathway group). This configuration may be referred to as a high-yield configuration, where parallel operations (e.g., sequencing operations) are performed, for example, in parallel pathway groups A and B. In some testing protocols, such as pressure testing protocols, certain fluids may flow in different directions, that is, starting from pathway groups A and B and returning through valve 68 and common line 140.

[0053] In example valve configuration 68B, the second fluid passage 160B of valve 68 is fluidly coupled to ports 2 and 3 only. In an implementation where 2 is a fluid inlet and 3 is a fluid outlet, CLSV 68 therefore selects a single flow path group through flow pool 20. In valve configuration 68C, the third fluid passage 160C is fluidly coupled to ports 2 and 5. In this configuration, CLSV 68 only allows fluid to flow between these ports, and when port 5 is fluidly coupled to a line other than the flow path group (e.g., a bypass line), flow to the flow pool 20 is not permitted and instead bypasses the flow path group. The fluid coupling of the various ports of CLSV 68 can produce, except... Figure 6 The combinations shown are not limited to those presented in the diagram, and in fact, any one or a combination of ports can be selected using the CLSV 68 implementation.

[0054] Furthermore, different fluid coupling port combinations can be generated by moving the movable portion 152 of the CLSV 68 relative to the stationary portion 150, allowing various combinations of the different channels 160 of the movable portion 152 to be aligned with the various ports 162 of the stationary portion 150. See the cross-sectional front view of an embodiment of the CLSV 68. Figure 7A and Figure 7B Further understanding is needed regarding how channel 160 can be used to fluidly couple port 162. Figure 7A and Figure 7B In the implementation described herein, some ports in port 162 (e.g., bypass line ports and air inlet ports) are not shown in the figures for clarity. However, it should be understood that such ports may exist in different zones of valve 68.

[0055] exist Figure 7A and Figure 7B In this embodiment, the movable portion 152 is nested within the receiving area 180 of the stationary portion 150 and is rotatable relative to the stationary portion 150. In the depicted embodiment, the first channel 160A axially overlaps with the first port (channel group A port 162A), the second port (channel group B port 162B), and the third port (RSV port 162C) to fluidly couple the ports to each other. According to this embodiment and as shown, the channel 160 extends only partially through the thickness 182 of the movable portion 152 (as determined by the distance between parallel surfaces 184, 186, where surface 184 is adjacent to surface 174 of the stationary portion 150 and surface 186 faces away from the stationary portion 150).

[0056] Because the movable portion 152 is tightly sealed against the stationary portion 150, fluid only flows between ports 162A, 162B, and 162C. When material advances into the flow cell 20, for example during a portion of the sequencing protocol... Figure 4 In this configuration, the fluid can flow only in the manner depicted by the arrows extending from port 162C to ports 162A and 162B, a manner determined by the shape of the first channel 160A. Additionally, as the movable portion 152 is relative to... Figure 7A The rotation produces the orientation of CLSV 68. Figure 7B As shown, the movable portion 152 (its main body) is firmly sealed against port 162A of the passage group A, preventing fluid from leaving port 162A. This differs from the first channel 160A, as... Figure 7A Align the middle with the port, in Figure 7BIn this configuration, the second channel 160B is aligned with ports 162B and 162C. This second channel fluidly connects the two ports and allows fluid to flow through each port and out of CLSV 68. As fluid advances into flow cell 20, for example during a sequencing protocol, the fluid can flow from RSV 66, through RSV port 162C, through the second channel 160B, out of pathway group B port 162B, and into pathway group B (e.g., via...). Figure 2 and Figure 4 Pipeline 60).

[0057] Several other fluid combinations and flow directions can be achieved by adjusting the position of the movable portion 152 relative to the stationary portion 150 and by using the pump 38 for appropriate suction. In embodiments where both the movable portion 152 and the stationary portion 150 are annular, rotation of the movable portion 152 is then used to align a specific one of the arcuate channels 160 and one or more ports 162 located at different circumferential positions on the stationary portion 150. The channels 160 will have different geometries, generally indicating different shapes but sharing certain common parameters (e.g., channel depth determined by the size of the thickness 182 of the channel 160 along the movable portion 152, and channel width determined by the size of the channel 160 in the radial direction of the movable portion). Different geometries allow for different fluid connections.

[0058] An embodiment of the CLSV68, having ports for RSV 66, for pathway groups A and B, for bypass line 142, and for air, is shown. Figures 8A to 8F These diagrams are graphic plan views of the CLSV 68 in various locations or orientations. Different shading or hashes are used to distinguish port 162 of the CLSV 68. It should be understood that... Figures 8A to 8F The series of positions of CLSV68 described herein can be commanded by the control circuitry of the sequencing system to correspond, for example, to certain test operations, prediction operations, or sequencing operations.

[0059] Figures 8A to 8F The CLSV 68 described herein has a movable portion 152 that rotates about an axial direction 164 and includes various internal channels 160. Again, the movable portion 152 abuts against port 162 and is securely sealed, preventing fluid from leaving port 162 unless the channels 160 are properly aligned to allow flow to another port 162. For example, Figure 8AThe embodiment of the CLSV68 described herein, hereinafter referred to as "RSV to Path Groups A and B" using a first channel 160A, fluidly couples RSV port 162C to both path group A port 162A and path group B port 162B. This first channel is geometrically designed to axially overlap with ports 162A, 162B, and 162C to fluidly couple these ports together. It should be noted that... Figure 8A The remaining channel 160 of CLSV 68 in the position shown is positioned and geometrically designed so that it does not couple the other ports 162 of CLSV 68 together.

[0060] The clockwise rotation of the movable part 152 relative to the stationary part 150 about the axial direction 164 transforms the CLSV 68 to Figure 8B The location shown in the diagram, where an embodiment of the second channel 160B creates fluid coupling between port 162A of pathway group A and port 162C of RSV, is hereinafter referred to as the "RSV to pathway group A" location. The second channel is geometrically designed to axially overlap with ports 162A and 162C to fluidly couple these ports together. As shown, in Figure 8B The remaining channel 160 of CLSV 68 in the position shown is positioned and geometrically designed so that it does not couple the other ports 162 of CLSV 68 together. Therefore, although the first channel 160A is fluidly coupled to the channel group B port 162B, the channel group B port 162B remains fluidly isolated from the other ports because the channels 160 are fluidly isolated from each other.

[0061] Continue rotating clockwise, and CLSV 68 will transform to Figure 8C The configuration shown in the diagram, in which RSV port 162C is fluidly coupled to channel group B port 162B using a second channel 160B, hereinafter referred to as the "RSV to channel group B" location. Because the size of the second channel 160B is appropriately configured to couple only two adjacent ports 162, it can be used in several different locations to couple adjacent ports 162. Therefore, according to the current embodiment, one of the channels 160 can be used to create more than one combination of fluid couplings between ports 162. Here, due to the positioning and geometry of the channels 160 combined with the corresponding positions of the ports 162, the remaining ports 162 are again isolated from the other ports 162.

[0062] Figures 8A to 8C The orientation described in the text makes Figure 4The embodiment of fluid system 120 described herein can operate as described above to guide fluid received from RSV 66 through a single path group (e.g., path group A or B) or simultaneously through both path groups A and B. Additionally, although described in the case of clockwise rotation, CLSV 68 may also be rotated counterclockwise depending on the current position of channel 160 and the desired port combination. For example, from Figure 8A The orientation shown in the figure begins, and the movable part 152 can rotate counterclockwise to produce... Figure 8D The orientation shown in the document.

[0063] Figure 8D The orientation described herein enables the fluid system 120 to flow between RSV 66 and bypass line 142, and this orientation is hereinafter referred to as the "RSV to Bypass" position. In this position, the third channel 160C embodiment fluidly couples RSV port 162C to bypass port 162D. In the described position, the third channel 160C is geometrically designed and positioned to fluidly couple RSV port 162C and bypass port 162D only, while maintaining fluid isolation of the remaining port 162.

[0064] As described above, the CLSV 68 also includes an air inlet port 162E, which allows air to be drawn into the fluid system 120 and can be used for diagnostic or other purposes. Figure 8E The orientation described herein (e.g., by the movable part 152 from) Figure 8D The orientation created by counterclockwise rotation (e.g., hereinafter referred to as the "air to passage groups A and B" position) fluidly couples the air inlet port 162E to both passage group A port 162A and passage group B port 162B using the fourth channel 160D. The illustrated orientation can be used to dry passage groups A and B prior to pressure testing or other protocols.

[0065] Figure 8F The orientation of the position, referred to below as the "air to bypass" position, as described herein, can be produced by further rotation of the movable portion 152. In this configuration, the first channel 160A fluidly couples the air inlet port 162E to the bypass port 162D, which can be used to allow air to be introduced into the fluid system 120 during certain pressure tests. It should be noted that the second channel 160B can also create this fluid coupling.

[0066] Figures 8A to 8FThe orientation of CLSV 68 and other possible locations described herein can also be used for diagnostic purposes to enable processor 100 to isolate, prepare, and test various flow paths of the fluid system. Example fluid flow paths through fluid system 120 generated by certain locations of CLSV 68 described above (specifically, those involving RSV 66) are depicted in… Figures 9A to 9D middle.

[0067] exist Figure 9A In the implementation scheme described herein, CLSV 68 is in relation to Figure 8A In the described "RSV to pathway groups A and B" location. Therefore, during operation, RSV 66 selects reagent 64, which proceeds to CLSV 68 via RSV to CLSV common line 140. Because RSV port 162C is fluidly coupled to pathway group A port 162A and pathway group B port 162B via CLSV 68, the reagent flows through CLSV 68 and flows to pathway groups A and B respectively via common lines 58 and 60. Figure 9A In this implementation, this is illustrated by shading pathway groups A and B, along with bold arrows indicating the flow of fluid through flow cell 20 and to syringe pump 124. This configuration can be considered as representing the highest level of sequencing yield of flow cell 20.

[0068] exist Figure 9B In the implementation scheme described herein, CLSV 68 is in relation to Figure 8B In the described “RSV to Pathway Group A” location. Therefore, during operation, RSV 66 selects reagent 64, which proceeds via common line 140 to CLSV 68. Because RSV port 162C is fluidly coupled only to pathway group A port 162A via CLSV 68, the reagent flows through CLSV 68 and via common line 58 to pathway group A (pathways 1 and 2, L1 and L2). Figure 9B In this implementation, this scenario is shown as only pathway group A being shaded, along with a bold arrow on line 58 indicating the flow of fluid through flow cell 20 to the corresponding syringe pump 124A. This scenario allows for separate and distinct sequencing operations in pathway group A from those performed in pathway group B, and allows the parameters of the sequencing operations to be controlled independently between pathway groups A and B.

[0069] exist Figure 9C In the implementation scheme described herein, CLSV 68 is in relation to Figure 8CIn the described "RSV to Pathway Group B" location. Therefore, during operation and under the command of the control circuit, RSV 66 selects reagent 64, which proceeds via common line 140 to CLSV 68. Because RSV port 162C is fluidly coupled only to pathway group B port 162B via CLSV 68, the reagent flows through CLSV 68 and via common line 58 to pathway group B (pathways 3 and 4, L3 and L4). Figure 9B In the implementation scheme, this situation is shown as only the pathway group B being shaded, along with the bold arrows on the pipeline 58 indicating the fluid advancing through the flow pool 20 and to the corresponding injection pump 124B.

[0070] As described above, in some implementations, it may be necessary to isolate pathway groups from the output of CLSV 68 while still allowing certain reagents to flow through CLSV 68 for example, to fill the fluidic system 120 for introducing new reagents during sequencing. For example, during some protocols, it may be necessary to fill the fluidic element extending from RSV 66 and through CLSV 68 with reagents to be used. In these implementations, CLSV 68 may be positioned regarding... Figure 8D In the described “RSV to Bypass” location, in the illustrated embodiment, CLSV 68 is positioned such that RSV port 162C is fluidly coupled only to bypass port 162D, thereby allowing fluid to flow between bypass line 142 and CLSV 68 but not between CLSV 68 and access groups A and / or B. This is illustrated by a bold arrow from CLSV 68 through bypass line 142 and leading to syringe pump 124A. It should be noted that either or both of syringe pumps 124A and 124B can be used in conjunction with bypass line 142, but in a particular embodiment, bypass line 142 is used only in conjunction with syringe pump 124A.

[0071] The instance operation sequence using bypass port 162D is described in Figure 10 In this example, the operational sequence is a method 200 of filling a portion of the fluid system 120 without aspirating fluid through the flow cell 20. It should be noted that this filling is often critical in sequencing operations, utilizing approximately a few microliters of fluid. Therefore, any material remaining within the fluid line can cause measurement inaccuracies, variations in relative reagent volumes, etc.

[0072] To begin the filling sequence and as first shown at 202, CLSV 68 is in the first position, in this case, the "high output" position indicated above as "RSV to pathway groups A and B". In this position, fluid system 120 may have been protocol-completed to prepare flow cell 20 for the introduction of one or more of reagents 64.

[0073] To prepare the fluid system 120 for receiving and using new reagents, the CLSV 68 can be moved (e.g., by means of a motor and associated controller) to the position shown at 204. Figure 9D The second position of the "RSV to Bypass" position discussed. Again, in this position, the bypass port 162D is fluidly connected to the RSV port 162C. As shown in the transition from 202 to 204, the CLSV 68 can be displaced from the first position to the second position by the counterclockwise movement of the movable portion 152 relative to the stationary portion 150. This displacement moves the third channel 160C to a position where the RSV port 162C is fluidly coupled to the bypass port 162D.

[0074] RSV 66 is also controllably positioned (e.g., by means of a motor and associated controller) to select the desired reagent, as shown at 206. RSV 66 may have several different positions corresponding to various available reagents, and when appropriately selected, the reagent can then be aspirated through RSV 66 and toward CLSV 68 into common line 140. As shown at 208, this aspiration can be achieved using one or more of syringe pumps 124. In the illustrated embodiment, syringe pump 124 is fluidly connected to bypass line 142, which is fluidly coupled to bypass loop 210, which can act as a reservoir for substances to be used for filling and / or flushing fluid system 120. The diameter or width of bypass loop 210 may be larger than the diameter or width of common lines 58, 60, for example, to achieve the storage of appropriate amounts of buffers, reagents, etc. According to the described implementation scheme, reagent 64 is selected to be drawn into the bypass loop 210 without entering the bypass line 142.

[0075] Once the reagent has been properly aspirated into bypass loop 210, it can be dispensed directly into the auxiliary waste port of RSV 66 or into the syringe pump waste. This can be performed, for example, as shown at 212, by switching RSV 66 to its waste port and pressurizing the bypass line 142 and bypass loop 210 with syringe pump 124 to flow the reagent in the opposite direction to the aspiration actuation performed at 208. As shown at 214, the previously mentioned procedure can be performed for each reagent to be filled, after which CLSV 68 is switched back to the appropriate sequencing location (e.g., RSV to pathway groups A and B).

[0076] See also Figure 11 To further understand the properties of the various connectors, fluid pipelines, etc., with the various features described in this article, Figure 11This is a perspective view of a manifold assembly 220 having RSV 66, CLSV 68, bypass loop 210, and various fluid connections. In some embodiments, manifold assembly 220 may be considered as a pipette manifold assembly configured to dock with various reagent reservoirs to allow RSV 66 to select reagents from sources for final delivery to flow cell 20.

[0077] The manifold assembly 220 includes channels formed to define flow paths for reagents and other fluids. For example... Figure 11 As can be seen, valves 66 and 68 are driven and controlled by motors 222 and 224. One or more motor interfaces or connectors 226 provide power and, when needed, signals to and from the motors. As mentioned above, the motors (and thus the valves) are controlled by control circuitry during testing, commissioning, and servicing, as well as during sequencing operations.

[0078] The reagent and fluid channels within the manifold assembly 220 are coupled to a pipette 228, which, during operation, draws reagents and other fluids from a corresponding container (not shown). Figure 11 The flow path for reagents and fluids, generally indicated by reference numeral 230, may be formed in the body 232 (e.g., a monolithic structure) of the manifold assembly 220 by molding, etching, or any other suitable process to allow reagents and fluids to move from the pipette to the valve when the pump discussed above is commanded to aspirate reagents and fluids. At least one of the pipettes is configured as a nozzle pipette 234 to assist in mixing reagents during sequencing operations (e.g., prior to reaction and imaging). Figure 11 The document also describes a bypass loop 210 in which reagents and fluids can be drawn and moved for mixing (e.g., thereby serving as a mixing volume) and, where appropriate, to fill the fluid system 120. In embodiments where the bypass loop or bypass line serves as the mixing volume, the mixing volume can be part or all of the bypass line 62 or bypass loop 210. For example, reagents can be drawn into the bypass loop or line in the desired sequence such that the reagents do not traverse the entire length of the bypass loop or line (which could result in the reagents being dispensed for disposal). Once the bypass line (or part of the mixing volume) has been loaded with the desired sequence of reagents, a valve can be used to switch the end of the bypass line through which the reagents are introduced to fluidly connect to a flow path leading to, for example, a destination container, so that the entire set of reagents loaded into the bypass line can then be discharged back from the bypass line to the destination container. For example, the destination container can be a reservoir, line, or other vessel designed to contain reagents. For example, a destination container can serve as a temporary working volume to which reagents and / or other materials can be transferred, for example by mixing, to prepare the reagents and / or other materials for delivery to a flow cell. Thus, once prepared in the destination container, the reagents and other fluids can be transferred from the destination container to the flow cell.

[0079] It should be understood that the term "fluidly connected" or similar terms may be used herein to describe a connection between two or more components that enables fluid communication between such components; similarly, "electrically connected" may be used to describe an electrical connection between two or more components. The term "fluidly inserted" may, for example, describe a particular arrangement of components. For instance, if component B is fluidly inserted between component A and component C, then fluid flowing from component A to component C will flow through component B before reaching component C.

[0080] Various methods for operating the sequencing system can be performed according to the implementation scheme described herein. As an example, Figure 12 An embodiment of method 240 for operating a sequencing system with CLSV 68 to, for example, address pathway groups of flow cell 20 separately is described. Method 240 may be performed, in whole or in part, based on instructions executed by control circuitry, for example, during a sequencing protocol, testing protocol, or similar protocol. It should also be noted that some actions described herein may be performed in a different order than those presented, or some actions may be omitted entirely, and other operations may be included in method 240 where appropriate.

[0081] As mentioned above, certain components of the sequencing system can be removable, replaceable, or disposable. In some embodiments, flow cell 20 may be, for example, part of a disposable cartridge or a similar structure configured to interface with various connectors of the sequencing system. Therefore, method 240 includes, for example, fluidly engaging flow cell 20 with one or more manifolds (block 242) between CLSV 68 and flow cell 20 when the control circuitry determines that flow cell 20 has been installed into the sequencing system. This fluid engagement causes flow cell 20 to engage with CLSV 68, which occurs prior to reagent displacement from RSV 66 and CLSV 68.

[0082] Method 240 also includes control (block 244) of CLSSV 68 (e.g., its location) to select a flow path through the flow pool 20 from a plurality of flow paths through the flow pool 20. For example, selecting a flow path through the flow pool 20 may include selecting which pathways the fluid will flow through within the flow pool 20. See [link / reference] Figures 9A to 9C For example, the control circuit can flow only through the first flow path of the path group A (e.g., as...). Figure 9B (as shown in the image) a second flow path that flows only through pathway group B (e.g., as shown in the image) Figure 9C (as shown in the diagram) or a third flow path including both the first and second flow paths (e.g., as shown in the diagram) Figure 9A Choose between the options shown in the image.

[0083] The selection of an appropriate flow path for a reagent can be performed in accordance with the selection of an appropriate reagent for flow cell 20. Therefore, method 240 may include control (block 246) of RSV 66 located upstream of CLSV 68 in the fluid direction to select different reagents from a variety of reagents for translocation through CLSV 68 and flow cell 20 according to the sequencing protocol.

[0084] Method 240 then includes shifting reagents (block 248) through a selected flow path according to the sequencing protocol. For example, control circuitry may cause pump 38 to draw selected reagents through RSV 66, through RSV to CLSV common tubing 140, through CLSV 66, and through the selected flow path (through flow cell 20).

[0085] During various sequencing operations, various reagents can be used, meaning that various positions of CLSV 68 and / or RSV 66 can be selected to make appropriate transitions between reagents. Therefore, method 240 includes commanding (block 250) position changes of CLSV 68 and / or RSV 66 during continuous cycles of the sequencing protocol. A continuous cycle can be a cycle in which reagents are introduced into flow cell 20, or an entire cycle of the sequencing reaction sequence, or both. For example, changes in the positions of RSV 66 and CLSV 68 can be made as per [the relevant information]. Figure 10 Perform as described to make a change between reagents. In practice, this change may involve instructing CLSV 68 to select a bypass line instead of the flow path through flow cell 20, for example, to perform reagent filling of certain fluid structures of manifold assembly 220.

[0086] It should be understood that the CLSV 68 described herein can be used, either additionally or alternatively, to select and / or combine different common conduits. For example, in one embodiment and as... Figure 13 The diagram schematically illustrates that an additional CLSV 260 can be positioned upstream of CLSV 68, which is positioned between RSV 66 and flow cell 20. The additional CLSV 260 can be used to select between ports, for example, leading to various reagents, so that reagents can be drawn into the additional CLSV 260 and subsequent fluid elements in various combinations. As an example, the additional CLSV 260 can be commanded by control circuitry to switch to a position fluidly coupled to ports leading to the first reagent source 262 and the second reagent source 264. By fluidly coupling the ports together in this manner, the additional CLSV 260 allows, for example, the simultaneous drawing of the first and second reagents into the fluid system 120 by the action of pump 38. Ports of RSV 66 corresponding to combinations from the additional CLSV 260 can be selected to allow fluid coupling to CLSV 68 and subsequently to flow cell 20.

[0087] As an example, this configuration is particularly suitable for avoiding the packaging and transport of large volumes of substances that can be further diluted with a liquid sourced locally. In the case of buffers (e.g., the first reagent source 262 may be a concentrated buffer solution), and the second reagent source 264 may be a diluent such as water. In some situations, as shown, fluidly coupling the first reagent source 262 and the second reagent source 264 so that the concentrated buffer solution is diluted to an appropriate extent can be useful. Currently, the use of additional valves can be adapted to further control the relative mixing amounts of the different reagents (e.g., to control the relative flow rates).

[0088] If present, the use of ordinal indicators such as (a), (b), (c)... or similar thereof in this disclosure and claims, unless explicitly indicated in a particular order or sequence, shall be understood not to convey any such order or sequence. For example, if there are three steps indicated as (i), (ii), and (iii), it shall be understood that, unless otherwise indicated, these steps may be performed in any order (or even simultaneously if not otherwise prohibited). For example, if step (ii) involves disposing of an element produced in step (i), then step (ii) may be considered to occur at a point after step (i). Similarly, if step (i) involves disposing of an element produced in step (ii), the reverse shall be understood.

[0089] It should also be understood that the use of “for” (e.g., “a valve for switching between two flow paths”) can be replaced by language such as “configured to” (e.g., “a valve configured to switch between two flow paths”) or similar terms.

[0090] When used for reference quantities or similar quantifiable properties, unless otherwise indicated, terms such as “about,” “approximately,” “substantially,” “nominal,” or the like shall be understood to include values ​​within ±10% of the specified value.

[0091] In addition to the claims listed in this disclosure, the following additional embodiments should also be understood to be within the scope of this disclosure: Implementation Scheme 1: A system includes: a flow cell supporting the analyte of interest; a selector valve coupled to the flow cell to select a flow path through the flow cell from a plurality of flow paths; a pump coupled to the flow cell to displace fluid through the selected flow path during an analytical operation; and control circuitry coupled to the selector valve to command the selector valve to select the selected flow path.

[0092] Implementation Scheme 2: The system of Implementation Scheme 1, wherein the plurality of flow paths includes a first flow path passing through a channel of the flow pool and a second flow path passing through a second channel of the flow pool, the second flow path being different from the first flow path.

[0093] Implementation Scheme 3: The system of Implementation Scheme 2, wherein the plurality of flow paths includes a third flow path, which includes both the first flow path and the second flow path.

[0094] Implementation Scheme 4: The system of Implementation Scheme 1, wherein the selector valve is coupled to a bypass line that bypasses the flow pool, and wherein the selector valve is also controllable to select the bypass line instead of the flow path through the flow pool.

[0095] Implementation Scheme 5: The system of Implementation Scheme 1, wherein during the analysis operation, the control circuit automatically commands the selector valve to select the selected flow path based on the analysis protocol.

[0096] Implementation Scheme 6: The system of Implementation Scheme 1 includes a reagent selector valve located upstream of the selector valve in the fluid direction to select a reagent from a variety of reagents and to direct the selected reagent to the inlet of the selector valve.

[0097] Implementation Scheme 7: The system of Implementation Scheme 1 includes a plurality of manifolds that are fluidly coupled between the selector valve and the flow cell when the flow cell is installed in the sequencing system, so that the flow cell engages with the selector valve.

[0098] Implementation Scheme 8: The system of Implementation Scheme 1, wherein the pump includes an injection pump located downstream of the flow pool in the fluid direction.

[0099] Implementation Scheme 9: A system comprising: a reagent selector valve for selecting a reagent from a plurality of reagents according to an analytical protocol; a flow cell for supporting an analyte of interest; a selector valve coupled between the reagent selector valve and the flow cell to select a flow path through the flow cell from a plurality of flow paths according to the analytical protocol and to guide the selected reagent through the selected flow path; a pump coupled to the flow cell to displace the selected reagent through the selected flow path according to the analytical protocol; and control circuitry coupled to the selector valve to command the selector valve to select the selected flow path.

[0100] Implementation Scheme 10: The system of Implementation Scheme 9, wherein the plurality of flow paths includes a first flow path passing through a channel of the flow pool and a second flow path passing through a second channel of the flow pool, the second flow path being different from the first flow path.

[0101] Implementation Scheme 11: The system of Implementation Scheme 10, wherein the plurality of flow paths includes a third flow path, the third flow path including both the first flow path and the second flow path.

[0102] Implementation Scheme 12: The system of Implementation Scheme 9, wherein the selector valve is coupled to a bypass line that bypasses the flow pool, and wherein the selector valve is also controllable to select the bypass line instead of a flow path through the flow pool.

[0103] Implementation Scheme 13: A system as described in Implementation Scheme 9, comprising a plurality of manifolds that are fluidly coupled between the selector valve and the flow cell when the flow cell is installed in the sequencing system, thereby engaging the flow cell with the selector valve.

[0104] Implementation Scheme 14: A method comprising: controlling a selector valve located upstream of a flow cell in a fluid direction to select a flow path through the flow cell from a plurality of flow paths through the flow cell; displacing a reagent through the selected flow path according to an analytical protocol; wherein the plurality of flow paths includes a first flow path through a channel of the flow cell, a second flow path through a second channel of the flow cell, and a third flow path including both the first flow path and the second flow path, the second flow path being different from the first flow path.

[0105] Implementation Scheme 15: The method of Implementation Scheme 14, comprising controlling a reagent selector valve located upstream of the selector valve in the fluid direction to select different reagents from a variety of reagents for displacement through the selector valve and the flow cell according to the analysis protocol.

[0106] Implementation Scheme 16: The method of Implementation Scheme 15, which includes commanding the position of the selector valve and / or the reagent selector valve to change during continuous cycles of the analytical protocol.

[0107] Implementation Scheme 17: The method of Implementation Scheme 14 includes instructing the selector valve to select a bypass line instead of a flow path through the flow pool.

[0108] Implementation Scheme 18: The method of Implementation Scheme 14, comprising fluidly coupling the flow cell to a plurality of manifolds when the flow cell is installed in the sequencing system and before the reagent is displaced, such that the flow cell engages with the selector valve, the plurality of manifolds being between the selector valve and the flow cell.

[0109] Implementation Scheme 19: The method of Implementation Scheme 14, wherein the reagent is displaced through the selected flow path by a pump located downstream of the flow pool in the fluid direction.

[0110] Implementation Scheme 20: The method of Implementation Scheme 19, wherein the pump includes an injection pump.

[0111] It should be understood that all combinations of the foregoing concepts (assuming such concepts are not inconsistent with each other) are contemplated as part of the subject matter of the invention disclosed herein. All combinations of the claimed subject matter appearing at the end of this disclosure are contemplated as part of the subject matter of the invention disclosed herein. It should also be understood that terms expressly used herein that may also appear in any disclosure incorporated by reference should be interpreted in a manner substantially consistent with the meanings of the specific concepts disclosed herein.

Claims

1. A system comprising: Multiple flow paths, which are fluidly connected to the flow cell when the flow cell is installed in the system, to support the analyte of interest; A flow path selector valve, coupled to the flow path, for selecting between the flow paths; A pump, which is fluidly connected to the flow cell when the flow cell is installed in the system, and which, during analytical operations, displaces fluid through one of the flow paths selected by the flow path selector valve; and A control circuit, operatively coupled to the flow path selector valve, the control circuit having one or more processors and a memory storing computer-executable instructions, which, when executed by the one or more processors, control the one or more processors to command the flow path selector valve to select the selected flow path.

2. The system as claimed in claim 1, wherein, The plurality of flow paths include: a first flow path that provides fluid flow through a first channel of the flow pool; and a second flow path that provides fluid flow through a second channel of the flow pool, the second flow path being different from the first flow path.

3. The system as described in claim 2, wherein, The plurality of flow paths includes a third flow path, which includes both the first flow path and the second flow path.

4. The system as claimed in claim 1, wherein, The flow path selector valve is further fluidly coupled to a bypass line that bypasses the flow pool when the flow pool is installed in the system, and the flow path selector valve can also controllably select the bypass line instead of the flow path.

5. The system as claimed in claim 1, wherein, During the analysis operation, the control circuit automatically commands the flow path selector valve to select the chosen flow path based on the analysis protocol.

6. The system of claim 1, further comprising a reagent selector valve positioned upstream of the flow path selector valve in the fluid direction and for selecting a reagent from a plurality of reagents and directing the selected reagent to the inlet of the flow path selector valve.

7. The system of claim 1, further comprising one or more manifolds for fluidly connecting the flow pool to the flow path selector valve when the flow pool is installed in the system, wherein, The one or more manifolds are fluidly inserted between the flow path selector valve and the flow pool when the flow pool is installed in the system.

8. The system of claim 1, wherein, The pump includes an injection pump located downstream of the flow pool in the fluid direction.

9. A system comprising: A reagent selector valve that selects a reagent from a variety of reagents according to the analytical protocol; A flow cell, which supports the analyte of interest; A flow path selector valve, fluidly inserted between the reagent selector valve and the flow cell, the flow path selector valve being used to select a flow path through the flow cell from a plurality of flow paths through the flow cell and to guide the selected reagent through the selected flow path according to the analytical protocol; A pump, fluidly connected to the flow cell, is used to displace the selected reagent through the selected flow path according to the analytical protocol; and A control circuit, operatively coupled to the flow path selector valve, the control circuit having one or more processors and a memory storing computer-executable instructions, which, when executed by the one or more processors, control the one or more processors to cause the flow path selector valve to select the selected flow path.

10. The system of claim 9, wherein, The plurality of flow paths include a first flow path passing through a channel of the flow pool and a second flow path passing through a second channel of the flow pool, the second flow path being different from the first flow path.

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