Multi-valve fluidic cartridge

By using a multi-valve fluid box design, high efficiency and low cross-contamination of fluid operation in the microfluidic box are achieved. By selectively connecting the fluid well and the loop through the rotary valve body, the problems of low fluid operation efficiency and cross-contamination in the prior art are solved.

CN114623269BActive Publication Date: 2026-04-07ILLUMINA INC
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2019-10-08
Publication Date
2026-04-07

AI Technical Summary

Technical Problem

Existing microfluidic cartridges have low fluid handling efficiency, requiring multiple fluid transfers to move the desired volume, which increases the time cycle and poses a risk of unintended cross-contamination between fluids.

Method used

The system employs a multi-valve fluid box design, including a fluid circuit, a bypass fluid circuit, first and second sets of fluid wells, and first and second valves. By rotating the valve body, selective connection and diversion of fluid are achieved, which are used for high-frequency and low-frequency fluid operations respectively, reducing the number of fluid transfers per operation.

Benefits of technology

It improves the efficiency of fluid handling, reduces the time cycle of each operation, and reduces the risk of cross-contamination between fluids through the separation valve.

✦ Generated by Eureka AI based on patent content.

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Abstract

This application relates to a multi-valve fluid cartridge. An apparatus includes a fluid circuit, a bypass fluid circuit, a first set of fluid wells, a second set of fluid wells, a first valve, and a second valve. The first valve is operatively associated with the first set of fluid wells such that it selectively fluidly connects any one of the first set of fluid wells to the outlet of the first valve. The second valve is operatively associated with the fluid circuit, the bypass fluid circuit, the outlet of the first valve, and the second set of fluid wells such that it selectively fluidly connects either the outlet of the second set of fluid wells and the outlet of the first valve to the fluid circuit, or fluidly connects the outlet of the first valve to the bypass fluid circuit.
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Description

[0001] This application is a divisional application of the application filed on October 8, 2019, with application number 201910951162.6 and invention title "Multi-valve Fluid Box".

[0002] Cross-reference to related applications

[0003] This application claims the benefit of the filing dates of provisional patent application No. 62 / 741,785, filed on October 5, 2018, and Dutch application No. 2021969, filed on November 9, 2018, pursuant to 35 U.SC §119(e), the disclosures of which are incorporated herein by reference. background

[0004] Due to factors such as limited space availability, the need for various types of fluid perfusion and sequencing for different fluid operations on a microfluidic cartridge can be problematic. Some microfluidic systems contain various types of fluids remotely from the region of interest (e.g., flow cells, mixing reservoirs) and have a single flow control valve operably associated with each type of fluid, such that the flow control valve selects one of the fluids for a specific fluid operation and directs the selected fluid to the region of interest for processing. Each fluid operation of a microfluidic cartridge involves moving the selected fluid from the flow control valve a common distance to the inlet of the region of interest, which limits the volume of fluid that can be delivered at each step of the operation. Therefore, each operation typically requires multiple fluid deliveries to move the desired total volume of fluid, thus increasing the time cycle of each fluid operation.

[0005] Overview

[0006] The following is a simplified overview to provide a basic understanding of some of the aspects described herein. This overview is not a comprehensive summary of the claimed subject matter. It is neither intended to identify key or essential elements of the claimed subject matter nor to describe its scope. Its sole purpose is to present some ideas in a simplified form as a prelude to a more detailed description to follow.

[0007] This disclosure includes an apparatus comprising: a fluid circuit; a bypass fluid circuit; a first set of fluid wells; a second set of fluid wells; a first valve having a first valve outlet and a plurality of first well ports operatively associated with the first set of fluid wells; and a second valve having a second valve outlet, a bypass selector channel, and a plurality of second well ports. In some examples, the first valve selectively fluidly connects a first well of the first set of fluid wells to the first valve outlet when in a first position, and selectively fluidly connects a second well of the first set of fluid wells to the first valve outlet when in a second position. In some examples, the second valve outlet is operatively associated with the fluid circuit, and the bypass selector channel is operatively associated with the bypass fluid circuit and the first valve outlet, such that the second valve selectively fluidly connects a first well of the second set of fluid wells to the fluid circuit when in the first well position, and selectively fluidly connects the bypass selector channel to the bypass fluid circuit when in the bypass position.

[0008] This disclosure includes an apparatus comprising:

[0009] Fluid circuit;

[0010] Bypass fluid loop;

[0011] First group of fluid wells;

[0012] The second group of fluid wells;

[0013] A first valve has a first valve outlet port and a plurality of first well ports operably associated with a first set of fluid wells. The first valve selectively fluidly connects a first well of the first set of fluid wells to the first valve outlet port when in a first position, and selectively fluidly connects a second well of the first set of fluid wells to the first valve outlet port when in a second position.

[0014] A second valve has a second valve outlet port, a bypass selector channel, and a plurality of second well ports operably associated with the second set of fluid wells. The second valve outlet port is operably associated with the fluid circuit, and the bypass selector channel is operably associated with the bypass fluid circuit and the first valve outlet port. The second valve selectively fluidly connects the first well of the second set of fluid wells to the fluid circuit in the first well position to allow fluid to flow from the first well of the second set of fluid wells to the fluid circuit, and selectively fluidly connects the bypass selector channel to the bypass fluid circuit in the bypass position.

[0015] A common passage that fluidly connects the outlet port of the first valve to the second valve;

[0016] The outlet channel, which is fluidly connected to the waste outlet; and

[0017] A valve array comprising one or more valves arranged along the outlet channel to selectively control at least one of the following: flow between the bypass fluid circuit and the pump, flow between the fluid circuit and the pump, and flow between the outlet channel and the waste outlet.

[0018] In some implementations, the second valve is rotatable between multiple positions.

[0019] In some implementations, the second valve selectively fluidly connects the outlet port of the first valve to the fluid circuit when the first valve is in the first valve position.

[0020] In some implementations, the second valve selectively connects the second well of the second set of fluid wells to the fluid circuit when the second well is in the second well position.

[0021] In some implementations, the first valve is rotatable between multiple positions.

[0022] In some embodiments, the bypass fluid circuit includes a bypass reservoir to contain a first predetermined volume of fluid.

[0023] In some embodiments, the fluid circuit includes a fluid device and a fluid storage tank, the fluid storage tank being downstream of the fluid device to contain a second predetermined volume of fluid.

[0024] In some embodiments, the fluid loop is fluidly connected to a flow pool; the bypass fluid loop includes a bypass channel; wherein the first well ports of the plurality of first well ports are operatively associated with the first wells of the first set of fluid wells, such that the first valve selectively allows flow from the first wells of the first set of fluid wells to the first valve outlet port; and wherein the second valve outlet port of the second valve is fluidly connected to the fluid loop, and the second valve includes: a bypass port fluidly connected to the bypass channel, a second valve inlet port fluidly connected to the first valve outlet port, a second well port of the plurality of second well ports fluidly connected to the first well of the second set of fluid wells, and a second valve rotator that rotates to a plurality of second valve positions, such that the second valve selectively allows flow from a selected one of the second well ports of the plurality of second well ports and the second valve inlet port to the second valve outlet port, or from the second valve inlet port to the bypass port.

[0025] In some embodiments, the bypass port, the second valve inlet port, and the plurality of second well ports are arranged in a circumferential pattern, and the second valve rotator includes: a second valve selector channel that fluidly connects the second valve outlet port to the second valve inlet port or one of the plurality of second well ports; and the bypass selector channel that fluidly connects the second valve inlet port to the bypass port when the second valve rotator is in a bypass position.

[0026] In some embodiments, the first valve includes a first valve rotator for rotating to a plurality of first valve positions such that the first valve selectively controls flow from a selected one of the plurality of first well ports to the first valve outlet port; and wherein the first valve rotator includes a first valve selector channel that fluidly connects a selected one of the plurality of first well ports to the first valve outlet port.

[0027] This disclosure includes a method comprising: selecting a first fluid stored in a first fluid well operatively associated with a first valve by setting a first valve from a block position to a first fluid well position; moving at least a portion of the selected first fluid from the first valve to a bypass passage operatively associated with the second valve by setting a second valve to a bypass position; selecting a second fluid stored in a second fluid well operatively associated with the second valve by setting the second valve to a second fluid well position; and moving at least a portion of the selected second fluid into a fluid loop while a portion of the selected first fluid is in the bypass passage.

[0028] This disclosure includes an apparatus comprising: a fluid loop fluidly connected to a flow pool; a bypass passage; a first fluid well; a second fluid well; a first valve including a first valve outlet port and a plurality of first well ports, the first well ports being operatively associated with the first fluid well such that the first valve selectively allows flow from the first fluid well to the outlet port; and a second valve including: a second valve outlet port fluidly connected to the fluid loop, a bypass port fluidly connected to the bypass passage, a second valve inlet port fluidly connected to the first valve outlet port, a second fluid well port fluidly connected to the second fluid well; and a second valve rotator that rotates to a plurality of second valve positions such that the second valve selectively allows flow from a selected one of the second fluid well ports and the second valve inlet ports to the second valve outlet port or from the second valve inlet port to the bypass port.

[0029] This disclosure includes an apparatus comprising:

[0030] A fluid loop that is fluidly connected to a flow pool;

[0031] Bypass lane;

[0032] First fluid well;

[0033] Second fluid well;

[0034] A first valve includes a first valve outlet port and a plurality of first valve ports, wherein a first valve port of the plurality of first valve ports is operatively associated with the first fluid well, such that the first valve selectively allows flow from the first fluid well to the first valve outlet port; and

[0035] The second valve includes:

[0036] The second valve outlet port is fluidly connected to the fluid circuit;

[0037] A bypass port, which is fluidly connected to the bypass channel;

[0038] The inlet port of the second valve is fluidly connected to the outlet port of the first valve.

[0039] A second fluid well port, fluidly connected to the second fluid well; and

[0040] The second valve rotator rotates to a plurality of second valve positions such that the second valve selectively allows flow from a selected one of the second fluid well port and the second valve inlet port to the second valve outlet port or from the second valve inlet port to the bypass port.

[0041] In some embodiments, the bypass port, the second valve inlet port, and the second fluid well port are arranged in a circular pattern, and the second valve rotator includes: a second valve selector channel that fluidly connects the second valve outlet port to one of the second valve inlet port or the second fluid well port, and a bypass selector channel that fluidly connects the second valve inlet port to the bypass port when the second valve rotator is in the bypass position.

[0042] In some embodiments, the first valve includes a first valve rotator for rotating to a plurality of first valve positions such that the first valve selectively controls flow from a selected one of the plurality of first valve ports to a first valve outlet port; and wherein the first valve rotator includes a first valve selector channel that fluidly connects a selected one of the plurality of first valve ports to the first valve outlet port.

[0043] This disclosure includes a method comprising:

[0044] A first fluid stored in a first set of fluid wells is selected by setting the first valve from a base position to a first fluid well position, the first set of fluid wells being operatively associated with the first valve;

[0045] At least a portion of the selected first fluid is moved from the first valve into a bypass passage operably associated with the second valve by setting the second valve to the bypass position;

[0046] The second fluid stored in a second set of fluid wells is selected by setting the second valve to the position of the second fluid well, the second set of fluid wells being operatively associated with the second valve;

[0047] When the selected first fluid is in the bypass channel, at least a portion of the selected second fluid is moved into the fluid loop.

[0048] In some embodiments, the method further includes moving at least a portion of the selected first fluid from the bypass channel to the fluid loop.

[0049] In some embodiments, the method further includes moving at least a portion of the selected second fluid from the fluid loop to the outlet line.

[0050] In some embodiments, the method further includes: selecting a second fluid stored in a second fluid well of the first set of fluid wells operably associated with the first valve; and moving at least a portion of the selected second fluid into the fluid circuit by setting the second valve to a first valve position.

[0051] In some embodiments, the method further includes introducing a volume of air into the bypass channel by setting the first valve to the cleaning position and the second valve to the bypass position.

[0052] In some implementations, the method further includes preventing first fluid stored in the first set of fluid wells from moving to the second valve by setting the first valve to the base position.

[0053] Other features and characteristics of the subject matter of this disclosure, as well as the function of related elements and combinations of components of the method of operation and the economy of manufacture, will become more apparent when considering the following description and the appended claims, all of which form part of this specification, wherein similar reference numerals denote corresponding components in the various figures. Attached Figure Description

[0054] The accompanying drawings, which are incorporated herein and form part of the specification, illustrate various examples of the subject matter of this disclosure. In the drawings, similar reference numerals indicate the same or functionally similar elements.

[0055] Figure 1 It is a schematic diagram of a device for guiding fluid from any well in the first group of wells into a fluid circuit or bypass circuit and for guiding fluid from any well in the second group of wells into a fluid circuit.

[0056] Figure 2 This is a schematic diagram of an exemplary first valve and an exemplary second valve with a bypass circuit.

[0057] Figure 3 This is a schematic diagram of an exemplary device configured in a first fluid processing mode.

[0058] Figure 4 This is a schematic diagram of an exemplary device configured in bypass mode.

[0059] Figure 5 This is a schematic diagram of an exemplary device configured in a second fluid processing mode.

[0060] Figure 6 This is a schematic diagram of an exemplary device set in waste mode.

[0061] Figure 7 This is a schematic diagram of an exemplary valve array arranged on an outlet channel that is fluidly connected to a fluid circuit, a bypass fluid circuit, a pump, and a waste outlet.

[0062] Figure 8 This is a table indicating various operating modes of an exemplary valve array.

[0063] Figure 9 This is a flowchart of an exemplary method for directing fluid flow from either a first set of wells or a second set of wells into a fluid loop or bypass loop.

[0064] Figure 10 This is a schematic diagram of the fluid cartridge incorporated into the processing instrument. Detailed description

[0065] While aspects of the subject matter of this disclosure may be embodied in various forms, the following description and accompanying drawings are merely intended to disclose some of these forms as specific examples of the subject matter. Therefore, the subject matter of this disclosure is not intended to be limited to the forms or examples thus described and shown.

[0066] Unless otherwise specified, all technical terms, symbols, and other technical terms or expressions used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains. All patents, applications, published applications, and other publications mentioned herein are incorporated herein by reference in their entirety. Where a definition set forth in this section is contrary to or otherwise inconsistent with the definitions set forth in the patents, applications, published applications, and other publications incorporated herein by reference, the definitions set forth in this section shall prevail over those incorporated herein by reference.

[0067] Unless otherwise indicated or the context suggests otherwise, as used herein, “a” or “an” means “at least one” or “one or more”.

[0068] This description may use relative spatial and / or directional terms when describing the location and / or orientation of components, devices, positions, features, or a portion thereof. Unless specifically stated or otherwise determined by the context of this description, such terms (including without limitation top, bottom, above, below, under, on top of, upper, lower, to the left, to the right, in front, behind, beside, adjacent, between, horizontal, vertical, diagonal, longitudinal, transverse, radial, axial, etc.) are used for convenience when referring to such components, devices, positions, features, or a portion thereof in the accompanying drawings and are not intended to be limiting.

[0069] Furthermore, unless otherwise stated, any particular size mentioned in this description represents only exemplary embodiments of the device embodying aspects of this disclosure and is not intended to be limiting.

[0070] The term “approximately” applies to all numerical values ​​specified herein, whether or not explicitly indicated. This term generally refers to a range of numbers that a person skilled in the art would consider, within the context of this disclosure, a reasonable amount of deviation from the listed numerical values ​​(i.e., having an equivalent function or result). For example, and not intended to be limiting, the term can be interpreted to include a deviation of ±10% from a given numerical value, assuming that such deviation does not alter the final function or result of the value. Thus, in some cases, as a person skilled in the art will recognize, a value of approximately 1% can be interpreted as a range from 0.9% to 1.1%.

[0071] As used herein, the term "adjacent" means close to or adjacent to each other. Adjacent objects may be spaced apart from each other, or may be in actual or direct contact with each other. In some instances, adjacent objects may be connected to each other or may be integrally formed with each other.

[0072] As used herein, the terms “substantially” and “basic” refer to a considerable degree or extent. When used in conjunction with, for example, an event, environment, characteristic, or attribute, the terms may refer to instances where the event, environment, characteristic, or attribute occurs precisely, or instances where the event, environment, characteristic, or attribute occurs very approximately (e.g., considering the general tolerance level or variability of the examples described herein).

[0073] As used herein, the terms “optional” and “optionally” mean that the components, structures, elements, events, environments, characteristics, attributes, etc., subsequently described may or may not be included or appear, and that the description includes instances where components, structures, elements, events, environments, characteristics, attributes, etc. are included or appear, as well as instances where they are not included or appear.

[0074] According to various examples, components and devices as described herein can be used in conjunction with fluid cartridges that may include one or more fluid handling passages, such as channels, branch channels, valves, splitters, vents, ports, access areas, through-holes, beads, reagent-containing beads, capping layers, reaction components, any combination thereof, and one or more of the like. Any element may be in fluid communication with another element.

[0075] All possible combinations of elements and components described in the specification or listed in the claims are contemplated and considered as part of this disclosure. It should be understood that all combinations of the foregoing concepts and other concepts discussed in more detail below (assuming such concepts are not inconsistent with each other) are contemplated as part of the inventive subject matter disclosed herein. In particular, all combinations of the claimed subject matter appearing in this disclosure are contemplated as part of the inventive subject matter disclosed herein.

[0076] In the appended claims, the term "comprising" is used as the concise English equivalent of the corresponding term "comprising". The terms "comprising" and "comprising" are defined herein as open-ended, encompassing not only the listed elements but also any additional elements. Furthermore, in the appended claims, the terms "first," "second," and "third," etc., are used merely as labels and are not intended to impose numerical requirements on their objects.

[0077] The term "fluid connectivity" means direct fluid connectivity, such as two areas being fluidly connected to each other via an unobstructed fluid handling passage connecting the two areas, or possibly being fluidly connected, for example, when two areas are connected via a fluid handling passage, they may be fluidly connected to each other, the fluid handling passage may include valves disposed therein, wherein fluid connectivity between the two areas may be established upon valve activation, for example by dissolving a soluble valve, causing a burstable valve to burst, or otherwise opening a valve disposed in the fluid handling passage.

[0078] Fluid box

[0079] There is a need for improved fluid cartridge devices and methods that allow more than one fluid operation to occur at a time. These fluid operations can occur independently of each other on the fluid cartridge to reduce the cumulative time of the fluid process. Furthermore, there is a need for improved fluid cartridge devices and methods that can isolate the fluids processed on the fluid cartridge by providing dedicated valve passages for each type of fluid operation to prevent unintended cross-contamination between fluids.

[0080] According to various examples, an apparatus includes a fluid cartridge configured to contain various types of fluids (e.g., reagents, buffer solutions, reaction media) and selectively move these fluid types through two or more independent fluid operations (e.g., mixing, incubation, or delivery of fluids). The fluid cartridge includes a first set of wells configured to contain one or more types of fluids associated with a first fluid processing operation and a second set of wells configured to contain one or more types of fluids associated with a second fluid processing operation. The fluid cartridge includes a fluid circuit and a bypass fluid circuit for independent fluid operations. A first valve is operably associated with the first set of wells such that it can selectively allow fluid to flow from any one of the wells in the first set of wells. A second valve is operably associated with the first valve, the fluid circuit, the bypass fluid circuit, and any one of the wells in the second set of wells to selectively allow fluid to flow from one of the wells in the second set of fluids to the fluid circuit, from the first valve to the fluid circuit, or from the first valve to the bypass fluid circuit. In some instances, the second valve can also be advantageously used for frequent fluid operations (e.g., repetitive sequencing operations), while the first valve can be used for less frequent fluid operations (e.g., paired-end or amplification operations). Separating the valves in this way can result in reduced space requirements for each valve and optimization of each valve to perform high-frequency and low-frequency operations.

[0081] like Figure 1As shown, the example apparatus includes a fluid cartridge 100 for containing various types of fluids and selectively sequencing these fluids through two or more independent fluid operations. In some examples, the fluid cartridge 100 includes a fluid loop 110, a bypass fluid loop 120, a first set of wells 130, a second set of wells 140, a first valve 150, a second valve 160, a common channel 105, an outlet channel 170, and a valve array 180. In some examples, the fluid cartridge 100 includes a substrate (not shown) supporting the various components of the cartridge (e.g., the first set of wells 130, the second set of wells 140, the first valve 150, the second valve 160, and the valve array 180), but one or more components of the cartridge may not be supported on a common substrate or other support structure. In some examples, fluid circuit 110, bypass fluid circuit 120, and outlet channel 170 include one or more fluid channels or conduits disposed on or within the base of fluid box 100 to transfer fluid within fluid box 100 and to transfer fluid within fluid box 100 to other devices fluidly connected to fluid box 100.

[0082] like Figure 1 As shown, the fluid circuit 110 includes a fluid device 112 (e.g., a flow cell) and two or more fluid channels 111, 115, which fluidly connect the fluid device 112 to a second valve 160 and an outlet channel 170, respectively. In one example, the fluid device 112 is a flow cell comprising a first glass layer (not shown) and a second glass layer (not shown) fixed together and defining one or more channels (not shown) therein. In various examples, the fluid device 112 may include a fluid inlet 113, a fluid outlet 114, and one or more fluid channels (not shown) fluidly connected to the fluid inlet 113 and the fluid outlet 114 to allow fluid processing (e.g., chemical or biochemical assays or other reactions) to occur. In various examples, the fluid device 112 is configured to allow the introduction of various types of fluids (e.g., reagents, buffers, reaction media) into the fluid inlet 113 to undergo fluid processing within one or more fluid channels. In various examples, the fluid device 112 is also configured to allow various types of fluids to exit through the fluid outlet 114 from one or more fluid channels.

[0083] exist Figure 1In the example shown, channel 111 is a fluid inlet 113 of fluid device 112 fluidly connected to the inlet channel of the second valve 160, while channel 115 is a post-line channel that fluid outlet 114 of fluid device 112 fluidly connected to outlet channel 170 (two channels are shown in the example, although in other examples fluid circuit 110 may include more than two channels). In some examples, fluid circuit 110 includes a reservoir 116 aligned with post-line channel 115, the reservoir 116 being configured to contain a volume of fluid passing through fluid device 112 such that fluid leaving fluid device 112 can be temporarily contained before being directed to outlet channel 170. Reservoir 116 is configured to allow bidirectional fluid flow such that reservoir 116 can also contain fluid directed from outlet channel 170 and allow fluid to flow to fluid device 112.

[0084] In some examples, the fluid device 112 is an integral part of the housing 100. In other examples, the fluid device 112 is removably attached or coupled to the housing 100, for example, via a fluid connector that connects the fluid inlet 113 and the fluid outlet 114 to the inlet channel 111 and the downstream pipeline channel 115, respectively.

[0085] exist Figure 1 In the illustrated example, the bypass fluid circuit 120 includes a bypass fluid passage 121 fluidly connecting the second valve 160 to the outlet passage 170 (one passage is shown in the illustrated example, but in other examples the bypass fluid circuit 120 may include two or more passages). The bypass fluid passage 121 is configured to allow fluid to flow from the second valve 160 to the outlet passage 170 without flowing through the fluid device 112. In some examples, the bypass fluid circuit 120 includes a reservoir 122 aligned with the bypass fluid passage 121, the reservoir 122 being configured to contain a volume of fluid supplied from the second valve 160, such that the fluid can be temporarily contained before being directed to the outlet passage 170. The reservoir 122 is configured to allow bidirectional fluid flow, such that the reservoir 122 can also contain fluid directed from the outlet passage 170 and allow fluid to flow to the second valve 160.

[0086] exist Figure 1 In the example shown, the common channel 105 connects the first valve 150 and the second valve 160.

[0087] like Figure 1 and Figure 2As shown, the first group of wells 130 includes two or more first fluid wells 131 connected to a first valve 150 for fluid connection. In the example shown, nineteen first fluid wells 131 are connected to the first valve 150, but any number of two or more first fluid wells are contemplated in this disclosure. The different fluid wells 131 of the first group of wells 130 may have the same or different dimensions (i.e., volumes). For example, all fluid wells 131 may have the same volume, all fluid wells 131 may have different volumes, or a subset of fluid wells 131 may have the same volume, and a subset of wells 131 may have different volumes, depending on the required storage volume of the reagent or other fluid to be stored in each first fluid well 131.

[0088] like Figure 1 and Figure 2 As shown, the second set of wells 140 includes two or more second fluid wells 141 connected to a second valve 160 for fluid connection. In the example shown, five second fluid wells 141 are connected to the second valve 160, but any number of two or more second fluid wells are contemplated in this disclosure. The different fluid wells 141 of the second set of wells 140 may have the same or different dimensions (i.e., volumes). For example, all fluid wells 141 may have the same volume, all fluid wells 141 may have different volumes, or a subset of fluid wells 141 may have the same volume, and a subset of wells 141 may have different volumes, depending on the required storage volume of the reagent, buffer solution, or other fluid to be stored in each second fluid well 141.

[0089] The first valve 150 is configured and arranged to selectively connect one of the first fluid wells 131 of the first set of wells 130 to the common passage 105, and thus to the second valve 160. Figure 1 and 2 In the example shown, the first valve 150 is a rotary valve including a first rotating body 151 rotatably mounted within the fluid cartridge 100. In some examples, the first rotating body 151 includes a disc (not shown) made of a rigid plastic material (e.g., polypropylene) and a disc made of an elastomeric material (e.g.,... A cap (not shown) made of silicone resin. In various examples, the first valve 150 includes a plurality of first well ports 155, each first well port being associated with one of the first fluid wells 131 of a first set of wells 130. Figure 1 and 2In the example shown, the group of first well ports 155 are arranged in a circumferential pattern around the first rotating body 151, such that each first well port 155 is located at the same radial distance from the center of the first rotating body 151. In other examples (not shown), the group of first well ports 155 may be arranged in a different configuration to fluidly connect the first valve 150 to the first group of wells 130. In some examples, each first well port 155 is fluidly connected to its associated first fluid well 131 via a fluid passage.

[0090] refer to Figure 2 The first valve 150 includes a first valve outlet, such as a first valve outlet port 154, fluidly connected to the second valve 160 via a common fluid passage 105, which extends from the first valve outlet port 154 of the first valve 150 to a second valve inlet port 166 of the second valve 160. In some examples, the outlet port 154 may be arranged around the center of the first rotating body 151. In the illustrated example, a portion of the common fluid passage 105 extending from the first valve outlet port 154 is shown in dashed lines, overlapping the rotating body 151, for example, extending below the first rotating body 151.

[0091] exist Figure 1 and 2 In the example shown, the first rotating body 151 includes a first valve selector channel 152 that extends radially from the first valve outlet port 154 toward the circumferential edge of the rotating body 151.

[0092] In various examples, the rotating body 151 is configured to rotate between multiple angular positions such that the first valve selector channel 152 can fluidly connect any of the first fluid wells 131 to the first valve outlet port 154 via a corresponding first well port 155 of each well. When the rotating body 151 is rotated to an angular position such that the first valve selector channel 152 is aligned with one of the first well ports 155, fluid can flow through the valve selector channel 152 from the selected first fluid well 131 and into the first valve outlet port 154.

[0093] In some examples, the first valve 150 may include a hard stop (not shown) to restrict rotation of the rotating body 151 in a blocked position, where the first valve selector channel 152 is not aligned with any of the first well ports 155. In some examples, the hard stop includes a protrusion extending from the circumferential edge of the first rotating body 151 and a post extending from the stator component (not shown) of the first valve 150, whereby the protrusion engages the post when the first rotating body 151 is positioned in the blocked position.

[0094] In various examples, when the first rotating body 151 is positioned at the blocking position, the first valve 150 is configured to prevent fluid from flowing from the first set of wells 130 to the second valve 160. In some examples, the first rotating body 151 is configured to rotate in a first direction from the blocking position to any of a plurality of first fluid positions to selectively allow flow from any of a plurality of first well ports 155 and any of the associated first fluid wells 131 to the first valve outlet port 154. In other examples, the first rotating body 151 is configured to rotate bidirectionally from the blocking position to any of a plurality of first fluid positions connecting one of the first well ports 155 and one of the associated first fluid wells 131 to the first valve outlet port 154.

[0095] In some examples, the first rotating body 151 can be set to a cleaning position (not shown) such that the first valve 150 allows fluid flow from an air source to separate aliquots of fluid passing through the common fluid channel 105 by means of air bubbles.

[0096] The second valve 160 is configured and arranged to selectively fluidly connect one of the second fluid wells 141 of the second set of wells 140 to the inlet passage 111 of the fluid circuit 110, connect the common passage 105 and the first valve 150 to the inlet passage 111 of the fluid circuit 110, or connect the common passage 105 and the first valve 150 to the bypass passage 121 of the bypass fluid circuit 120. Figure 1 and Figure 2 In the example shown, the second valve 160 is a rotary valve, which includes a second rotating body 161 rotatably mounted within the fluid cartridge 100, such that the second rotating body 161 is configured to rotate between a plurality of angular positions. In some examples, the second rotating body 161 includes a disc (not shown) made of a rigid plastic material (e.g., polypropylene) and an elastomer material (e.g., A cap (not shown) made of silicone resin. In various examples, the second valve 160 includes a second valve outlet (e.g., second valve outlet port 164) fluidly connected to an inlet passage 111 of the fluid circuit 110, a bypass port 165 fluidly connected to a bypass passage 121 of the bypass circuit 120, a second valve inlet port 166 fluidly connected to a common passage 105 and the first valve 150, and a plurality of second well ports 167, each second well port 167 being associated with one of the second fluid wells 141 of the second set of wells 140.

[0097] exist Figure 1 and Figure 2In the example shown, bypass port 165, second valve inlet port 166, and multiple second well ports 167 are arranged in a circular pattern around the second rotating body 161. In other examples (not shown), bypass port 165, second valve inlet port 166, and multiple second well ports 167 may be arranged to fluidly connect second valve 160 to bypass loop 120, first valve 150, and second set of wells 140 in other arrangements. In some examples, each second well port 167 is fluidly connected to its associated second fluid well 141 via a fluid passage.

[0098] refer to Figure 2 The second valve outlet port 164 is fluidly connected to the inlet passage 111 extending from the second valve 160 to the fluid device 112. In some examples, the second valve outlet port 164 is arranged around the center of the second rotating body 161 such that the bypass port 165, the second valve inlet port 166, and the set of second well ports 167 are located at the same radial distance from the second valve outlet port 164. In the example shown, a portion of the inlet passage 111 extending from the second valve outlet port 164 is shown in dashed lines, overlapping the rotating body 151, for example, extending below the second rotating body 161.

[0099] exist Figure 1 and Figure 2 In the example shown, the second rotating body 161 includes a second valve selector channel 162 that extends radially from the second valve outlet port 164 toward the circumferential edge of the second rotating body 161.

[0100] exist Figure 1-7 In the example shown, the second rotating body 161 also includes a bypass selector channel 163 disposed near the circumferential edge of the second rotating body 161. In some examples, the bypass selector channel 163 includes... Figure 3 The first end 163A is shown to be substantially radially aligned with the second valve selector channel 162, and the second end 163B is shown to be offset from the second valve selector channel 162. (Reference) Figure 4When the second rotating body 161 is positioned in the bypass position, the first end 163A of the bypass selector channel 163 is configured to be fluidly connected to the second valve inlet port 166, and the second end 163B of the bypass selector channel 163 is configured to be fluidly connected to the bypass port 165. In the bypass position, the second valve selector channel 162 is not aligned with any of the second well ports 167, such that the second selector valve channel 162 is not fluidly connected to any of the second fluid wells 141. In some embodiments, when the second rotating body 161 is positioned in the bypass position, the second valve selector channel 162 may be fluidly connected to the second fluid well 141, such that the second valve inlet port 166 is fluidly connected to the bypass port 165, while the selected second fluid well 141 is fluidly connected to the second valve outlet port 164.

[0101] In various examples, the second rotating body 161 is configured to rotate between multiple angular positions such that the second valve 160 allows fluid to flow (i) from one of the second fluid wells 141 of the second set of wells 140 to the inlet passage 111, (ii) from the common passage 105 and the first valve 150 to the inlet passage 111, or (iii) from the common passage 105 and the first valve to the bypass passage 121.

[0102] Rotation of the second rotating body 161 to an angular position where the second valve selector channel 162 is fluidly connected to one of the second well ports 167 allows fluid to flow from the selected corresponding second fluid well 141 through the second valve selector channel 162, through the second valve outlet port 164, and into the inlet channel 111. When the second valve selector channel 162 is fluidly connected to one of the second well ports 167, the first end 163A and the second end 163B of the bypass selector channel 163 are displaced from the second valve inlet port 166 and the bypass port 165, so that the bypass selector channel 163 is not in fluid communication with the second valve inlet port 166 and the bypass port 165.

[0103] Rotation of the second rotating body 161 to an angular position where the second valve selector channel 162 is fluidly connected to the second valve inlet port 166 allows fluid to flow from the common fluid channel 105 and the first valve 150 through the second valve selector channel 162, through the second valve outlet port 164, and into the inlet channel 111. When the second valve selector channel 162 is fluidly connected to the second valve inlet port 166, the first end 163A and the second end 163B of the bypass selector channel 163 are displaced from the second valve inlet port 166 and the bypass port 165, so that the bypass selector channel 163 is not in fluid communication with the second valve inlet port 166 and the bypass port 165.

[0104] In some examples, the second valve 160 may include a hard stop similar to the example described above with respect to the first valve 150 to restrict rotation of the second rotating body 161 in a blocked position, in which the second valve selector channel 162 is not aligned with any of the second well ports 167. When the second rotating body 161 is in the blocked position, the second valve 160 prevents fluid from flowing from the first valve 150 and / or any of the second set of wells 140 to the second valve outlet port 164, and prevents fluid from flowing from the first valve 150 to the bypass port 165.

[0105] In some examples, the second rotating body 161 is configured to rotate from a blocking position to a first valve position in a first direction, wherein the second valve selector channel 162 is aligned with the second valve inlet port 166, such that the second valve 160 allows fluid to flow between the second valve inlet port 166 and the second valve outlet port 164. When the second rotating body 161 is positioned in the first valve position, the valve selector channel 162 is aligned with the second valve inlet port 166, such that the second valve selector channel 162 is fluidly connected to the second valve inlet port 166, and the bypass selector channel 163 is not fluidly connected to either port. In some embodiments, the bypass selector channel 163 can fluidly connect the second well port 167 to another second well port 167 and / or bypass port 165.

[0106] In some examples, the second rotating body 161 is configured to rotate in a first direction from a blocking position to one or more second well positions, such that the second valve 160 allows fluid to flow between a selected second well port 167 and a second valve outlet port 164. When the second rotating body 161 is positioned at any of the second well positions, the inlet end of the second valve selector channel 162 is fluidly connected to the selected second well port 167, and the bypass valve channel 163 is not fluidly connected to either port.

[0107] In various examples of the first valve 150 and the second valve 160, automatic control and monitoring of the angular positions of the first rotating body 151 and the second rotating body 161 can be provided. Each rotating body can be connected to a motor or other power unit, for example, via gears, belts, pulleys, drive shafts, etc., to provide automatic, on-demand powered rotation of the rotating body. Angular position control and monitoring of the rotating body can be provided by rotary position sensors (e.g., encoders and / or stepper motors).

[0108] refer to Figure 1In the example shown, fluid cartridge 100 includes a waste outlet 191 fluidly connected to outlet channel 170, and pump 190 may be fluidly connected to outlet channel 170. In various examples, pump 190 is configured to apply a pressure differential between outlet channel 170 and either fluid circuit 110 and / or bypass fluid circuit 120 to propel fluid flow bidirectionally along either fluid circuit 110 and / or bypass fluid circuit 120. Pump 190 may include an injection pump having an actuator (not shown) operatively associated with a syringe. In various examples, the actuator is configured to move the plunger of the syringe in a first direction to generate a negative pressure differential to draw fluid toward the syringe barrel through fluid circuit 110 and / or bypass fluid circuit 120 (and possibly draw fluid into the syringe barrel). The actuator is also configured to move the plunger in a second direction opposite to the first direction to generate a positive pressure differential and discharge fluid away from the syringe (and possibly discharge fluid from the syringe) and into either fluid circuit 110 and / or bypass fluid circuit 120. In other examples (not shown), pump 190 may include any other pressure differential generating mechanism capable of reversing the flow direction.

[0109] In some examples, when the plunger of the syringe pump 190 changes direction, there may be a hysteresis (e.g., delay) in the pressure generated by the plunger. The operation of the syringe pump 190 can compensate for this hysteresis by first changing a portion of the stroke of the plunger in the opposite direction and then completing the stroke of the plunger in the opposite direction after waiting for a predetermined amount of time. In one example, the plunger 190 may move in a first direction to draw fluid into fluid circuit 110 or bypass fluid circuit 120, and then move in a second direction to distribute fluid into fluid circuit 110 or bypass fluid circuit 120. The process of distributing fluid into fluid circuit 110 or bypass fluid circuit 120 can be performed by first reversing the direction of the plunger in the second direction by a portion of the stroke to eliminate any hysteresis in the pressure generated by the syringe pump 190. After moving the plunger a portion of the stroke in the second direction, the stroke of the plunger in the second direction can be completed to ensure that the desired volume of fluid is distributed into fluid circuit 110 or bypass fluid circuit 120.

[0110] In various examples, the fluid cartridge 100 includes a valve array 180, which includes one or more control valves 181-183 arranged along an outlet passage 170 to selectively control flow between the fluid circuit 110, the bypass circuit 120, the pump 190, and the waste outlet 191. The control valves 181-183 include a first control valve 181 located at the junction between the downstream line 115 and the outlet passage 170, a second control valve 182 located at the junction between the bypass fluid passage 121 and the outlet passage 170, and a third control valve 183 located at the junction between the waste outlet 191 and the outlet passage 170.

[0111] In some examples, the third control valve 183 is closer to the pump 190 than the waste outlet 191 to facilitate the removal of bubbles from the pump 190. The proximity of the third control valve 183 relative to the pump 190 reduces the likelihood that bubbles output from the pump 190 will become trapped in the outlet passage 170, thereby allowing bubbles to be effectively removed from the fluid cartridge 100.

[0112] In various examples, the control valves 181-183 can be pinch valves consisting of small rounded dips, which can be compressed with external clamps to seal their respective passages. In various examples, the material bonded to the passages should be sufficiently flexible to enable the use of this pinch valve mechanism. Flow is allowed only in passages with open valves, thus creating a specific flow of selective fluid to its respective passage.

[0113] like Figure 1 As shown, pressure sensor 202 (e.g., a pressure gauge) can be connected to outlet channel 170 to monitor the pressure of the fluid flowing through it. In some examples, pressure sensor 202 is configured to generate a signal indicating a pressure measurement of the fluid flowing through outlet channel 170, and the operation of pump 190 and valve array 180 can be based on the pressure measurement of outlet channel 170.

[0114] refer to Figure 7 and Figure 8 In various examples, valve array 180 can operate in various modes, wherein specific control valves 181-183 are set to open or closed positions to selectively control flow between fluid circuit 110, bypass circuit 120, pump 190, and waste outlet 191. Reference Figure 8In some examples, as shown in Table 1, valve array 180 can be configured in a fully open mode, where all control valves 181-183 are set to the open position indicated by "O" in the table. In the fully open position, valve array 180 allows fluid to flow from fluid circuit 110 and bypass fluid circuit 120 to outlet passage 170, and allows fluid to flow from outlet passage 170 to waste outlet 191.

[0115] refer to Figure 8 As shown in Table 1, in some examples, valve array 180 can be configured in either a fluid loop or flow pool mode, wherein the first control valve 181 is set to the open position, and the second control valve 182 and the third control valve 183 are set to the closed position indicated by "X" in the table. In fluid loop mode, valve array 180 allows fluid flow between fluid loop 110 and pump 190, while preventing fluid flow between bypass fluid loop 120 and outlet channel 170 and preventing fluid flow between outlet channel 170 and waste outlet 191. Thus, in fluid loop mode, fluid from either the first set of wells 130 or the second set of wells 140 can be directed to fluid loop 110, reservoir 116, outlet channel 170, and / or pump 190, and fluid can be reversed to flow back from pump 190, outlet channel 170, and / or reservoir 116 to fluid loop 110.

[0116] refer to Figure 8 As shown in Table 1, in some examples, valve array 180 can be configured in waste mode, where the third control valve 183 is set to the open position, and the first control valve 181 and the second control valve 182 are set to the closed position. In waste mode, valve array 180 allows fluid flow between pump 190 and waste outlet 191, while preventing fluid flow between bypass fluid circuit 120 and outlet passage 170 and preventing fluid flow between fluid circuit 110 and outlet passage 170. Therefore, in waste mode, fluid from pump 190 and / or outlet passage 170 can be directed to waste outlet 191.

[0117] refer to Figure 8As shown in Table 1, in some examples, valve array 180 can be configured in bypass mode, where the second control valve 182 is set to the open position, and the first control valve 181 and the third control valve 183 are set to the closed position. In bypass mode, valve array 180 allows fluid flow between bypass fluid circuit 120 and pump 190, while preventing fluid flow between fluid circuit 110 and outlet passage 170 and preventing fluid flow between outlet passage 170 and waste outlet 191. Therefore, in bypass mode, fluid from either the first set of wells 130 or the second set of wells 140 can be directed to bypass fluid circuit 120, outlet passage 170, and / or pump 190, and fluid can be reversed to flow from pump 190 and / or outlet passage 170 to bypass fluid circuit 120.

[0118] In various examples, valve array 180 is configured to minimize cross-contamination or volumetric inaccuracies that may occur during the transition between two operating modes. In various examples, fluid control valves 181-183 are positioned such that, in the event that both the first fluid control valve 181 and the second fluid control valve 182 are momentarily opened, fluid flow will be directed to waste outlet 191, reducing the risk of cross-contamination between two or more fluids in fluid device 112. In various examples, fluid control valves 181-183 are driven by cams (not shown) arranged in an instrument (not shown) configured to handle fluid cartridge 100. The interaction between fluid control valves 181-183 and the cams is configured to minimize the transition time between two operating modes, thereby reducing the likelihood of cross-contamination or volumetric inaccuracies.

[0119] Fluid box operation mode

[0120] In various examples, such as Figure 3-6 As shown, the fluid box 100 operates in various modes to selectively direct fluid from any of the first fluid wells 131 of the first set of wells 130 to the fluid circuit 110 or bypass circuit 120, or from any of the second fluid wells 141 of the second set of wells 140 to the fluid circuit 110.

[0121] refer to Figure 3The first valve 150 and the second valve 160 can be configured in a first fluid handling mode to allow fluid to flow from a selected first fluid well 131 of the first set of wells 130 to the fluid loop 110, and to block flow from the second set of wells 140. In the first fluid handling mode, the first rotating body 151 of the first valve 150 is configured to connect the first valve selector channel 152 to a selected first well port of the first well ports 155 to allow fluid to flow from the associated first well 131 to the first valve outlet port 154, and the second rotating body 161 of the second valve 160 is configured to connect the second valve selector channel 162 to the second valve inlet port 166 to allow fluid to flow between the second valve inlet port 166 and the second valve outlet port 164. Simultaneously, with valve 181 open and valves 182 and 183 closed, the valve array 180 is configured in a fluid loop mode to allow fluid to flow from the fluid loop 110 to the outlet channel 170 and the pump 190. Figure 3 As shown, an equal sample of the first fluid (indicated by a thick line) is guided from the selected first well 131 via a common fluid passage 105 to the second valve 160 and then through the fluid device 112 for fluid processing. After passing through the fluid device 112, the equal sample of the first fluid may be temporarily contained in a storage tank 116 or sent directly to the injection pump 190.

[0122] refer to Figure 4 First valve 150 and second valve 160 can be configured in bypass mode to allow fluid to flow from a selected first fluid well 131 of the first set of wells 130 to bypass fluid loop 120 and to block flow from the second set of wells 140. In bypass mode, the first rotating body 151 of the first valve 150 is configured to connect the first valve selector channel 152 to a selected first well port of the first well ports 155 to allow fluid to flow from the associated first well port 131 to the first valve outlet port 154, and the second rotating body 161 of the second valve 160 is configured to align the bypass selector channel 163 with the second valve inlet port 166 and the bypass port 165 to allow fluid flow between the second valve inlet port 166 and the bypass port 165. Simultaneously, with valve 182 open and valves 181 and 183 closed, valve array 180 is configured in bypass mode to allow fluid to flow from bypass fluid loop 120 to outlet channel 170 and pump 190. Figure 4 As shown, a fraction of the first fluid (indicated by a thick line) is guided from the selected first well 131 to the second valve 160 via the common fluid passage 105 and into the bypass passage 121, wherein the fraction of the first fluid may be temporarily contained in the storage reservoir 122 and / or sent directly to the injection pump 190.

[0123] refer to Figure 5First valve 150 and second valve 160 can be configured to a second fluid handling mode to allow fluid to flow from a selected second fluid well 141 of the second set of wells 140 to the fluid loop 110, and to block flow from the first set of wells 130. In the second fluid handling mode, first valve 150 is configured to a blocking position, wherein first valve selector channel 152 is not aligned with any of the first well ports 155 to block fluid from the first set of wells 130. Second valve 160 is configured to connect second valve selector channel 162 to a selected second well port of the second well ports 167 to allow fluid to flow from the associated second fluid well 141 to the second valve outlet port 164. Simultaneously, with valve 181 open and valves 182 and 183 closed, valve array 180 is configured in fluid loop mode to allow fluid to flow from the fluid loop 110 to the outlet channel 170 and pump 190. Figure 5 As shown, a fractional sample of the second fluid (indicated by a thick line) is guided from the selected second fluid well 141 via inlet channel 111 to fluid device 112 for fluid processing. After passing through fluid device 112, the fractional sample of the second fluid may be temporarily contained in storage tank 116 and / or sent directly to injection pump 190.

[0124] refer to Figure 6 Fluid cartridge 100 can be set to waste mode. In waste mode, the first valve 150 is set to a blocking position, wherein the first valve selector channel 152 is not aligned with any of the first well ports 155 to block fluid from the first set of wells 130, and with valve 183 open and valves 181 and 182 closed, valve array 180 is set in waste mode to allow fluid flow between pump 190 and waste outlet 191, and to block flow from fluid circuit 110 or bypass fluid circuit 120 to outlet channel 170. In waste mode, the second valve 160 can be set in any position without directing fluid flow to both fluid circuit 110 and bypass fluid circuit 120. Figure 6 As shown, the used fluid contained in the injection pump 190 or another reservoir can be emptied into the waste outlet 191 for disposal.

[0125] In some instances, according to the reagent reuse process described in U.S. Patent No. 9,410,977, "FLUIDIC SYSTEM FOR REAGENT DELIVERY TO A FLOW CELL," filed August 7, 2014, by Stone et al., a fraction of the first fluid or the second fluid temporarily contained in the storage reservoir 116 can be reintroduced into the fluid device 112.

[0126] In some instances, according to the mixing process described in U.S. Patent Publication No. 2018 / 0185842, filed December 13, 2017, entitled “REAGENT CHANNEL MIXING SYSTEM AND METHOD,” an aliquot of the first fluid temporarily contained in the storage reservoir 122 may be used to mix with other fluids, such as another reagent solution.

[0127] According to the examples described in this disclosure, fluid cartridge 100 allows a second type of fluid processing operation (e.g., fluid delivery, mixing, or infusion) to occur in a bypass fluid loop 120 completely independent of fluid device 112. For example, a first fluid may be stored in fluid device 112 for a first fluid processing operation (e.g., cultivation), while a second fluid may be directed via bypass fluid loop 120 to reservoir 122 and / or injection pump 190 to undergo a second fluid processing operation (e.g., infusion). By operating two independent fluid operations simultaneously, fluid cartridge 100 can reduce or shorten the cumulative time for completing multiple fluid processes through parallelization.

[0128] According to the examples described in this disclosure, fluid cartridge 100 allows certain fluids (which may be incompatible with each other or may otherwise preferably remain separate) to remain separate by containing a first set of fluids in a first set of wells 130 associated with a first valve 150 and a second set of fluids in a second set of wells 140 associated with a second valve 160. For example, a first set of fluids for aggregation and two-end perfusion (CPE) operations may be contained in the first set of wells 130 and processed through a bypass channel 163 of the first valve 150 and the second valve 160, and a second set of fluids for sequencing-by-synthesis (SBS) operations may be contained in the second set of wells 140 and processed through a second valve selector channel 161 of the second valve 160. The second valve 160 may be configured such that the bypass channel 163 does not pass over either of the second well ports 167, thereby preventing any unintended cross-contamination between the first set of fluids intended for CPE operations and the second set of fluids intended for SBS operations.

[0129] According to the examples described in this disclosure, the fluid cartridge 100 allows fluids to be arranged based on workflow and usage. For example, a second set of fluids intended for SBS operations is selected and moved more frequently during the sequencing process than a first set of fluids intended for CPE operations. Therefore, in various examples, the second set of fluids contained in the second set well 140 is handled only by the second valve 160, such that while the second set of fluids is selected and moved by the second valve 160, the first set of fluids contained in the first set well 130 can be selectively kept idle and protected by the first valve 150. The arrangement of the first set well 130 and the second set well 140 with the first valve 150 and the second valve 160 reduces the total distance that valves 150 and 160 must rotate during the sequencing process, thereby improving the overall reliability of the fluid cartridge 100.

[0130] Processing instruments

[0131] The fluid cartridge 100 can be removably coupled to a fluid handling instrument. For example, in Figure 10 As schematically shown, a removable fluid cartridge 100 can be operatively mounted into a processing instrument 50. As described above, the fluid cartridge 100 includes a first valve 150 connected to a second valve 160 via a common fluid passage 105. The fluid cartridge 100 also includes a bypass loop 120 connecting the second valve 160 to a valve array 180. A fluid device 112 can be operatively coupled to the instrument 50 and connected to the second valve 160 of the cartridge 100 via an inlet passage 111. The instrument 50 may also include a waste outlet 191 (and possibly a waste reservoir) and a pump 190, both of which are connected to the valve array 180 of the cartridge 100. A controller 200 (which may be part of the instrument 50 or a separate or remote computer resource operatively coupled to the instrument 50) controls the operation of the instrument 50 (e.g., the processing of the fluid device 112 and the operation of the pump 190) and the operation of the cartridge 100 (e.g., the operation of the first valve 150 and the second valve 160 and the operation of the valve array 180).

[0132] Hardware and software

[0133] This disclosure is implemented through control and computation hardware components, user-created software, data input components, and data output components. The hardware components include computation and control modules (e.g., system controllers), such as microprocessors and computers, configured to perform computational and / or control steps by receiving one or more input values, executing one or more algorithms stored on a non-transitory machine-readable medium (e.g., software), the algorithms providing instructions for manipulating or otherwise acting on the input values, and outputting one or more output values. Such outputs may be displayed or otherwise indicated to a user to provide information, such as information about the status of the instrument or the processes thereby performed, or such outputs may include input to other processes and / or control algorithms. Data input components include elements through which data is input for use by the control and computation hardware components. Such data input units may include position sensors, motor encoders, and manual input elements such as graphical user interfaces, keyboards, touchscreens, microphones, switches, manually operated scanners, voice-activated input units, etc. Data output components may include hard disk drives or other storage media, graphical user interfaces, monitors, printers, indicator lights, or audible signal elements (e.g., buzzers, horns, bells, etc.). Software includes instructions stored on a non-transitory computer-readable medium that, when executed by control and computing hardware, cause the control and computing hardware to perform one or more automated or semi-automated processes.

[0134] In some examples, the apparatus may include a control system, which includes a computer-controlled controller 200 (in... Figure 1 (Illustrated schematically). Controller 200 may be a control system or computer connected to fluid cartridge 100, or may include computer components integrated with fluid cartridge 100. These computer components may include one or more microprocessors, displays, keyboards (and / or other user input devices), memory components, printers, etc. Controller 200 may be configured to receive input (e.g., user input) from a user or feedback device (e.g., a pressure sensor, flow meter, etc.) and manage the performance of fluid operations of fluid cartridge 100. Controller 200 may include software algorithms that enable the user to input user-defined parameters related to fluid processing operations into fluid cartridge 100, schedule different fluid processing operations on fluid cartridge 100, and cause controller 200 to execute different steps associated with the fluid processing operations, monitor the performance of the fluid processing operations, and output results to the user (on a display, printed out, etc.).

[0135] In various examples, controller 200 is operatively linked to first valve 150, second valve 160, valve array 180, and pump 190 (communication lines are omitted from the figures), such that controller 200 can send instructions to different devices of fluid cartridge 100 to perform different steps associated with fluid handling operations (e.g., with...). Figure 3-6 and Figure 9 Related processes).

[0136] Method for guiding fluid contained in a fluid cartridge

[0137] Based on various examples, Figure 9 A method 900 is shown for directing fluid from either a first set of wells 130 or a second set of wells 140 to a fluid loop 110 or a bypass fluid loop 120.

[0138] like Figure 9 As shown, method 900 includes step 910: selecting a first fluid well 131 in a first set of wells 130 operably associated with the first valve 150 by setting the first valve 150 from a blocked position to a first fluid position, wherein a first valve selector channel 152 is connected to one of the first well ports 155 corresponding to the selected first fluid well 131. In some examples, step 910 further includes using a first actuator comprising a motor (not shown) operably connected to the first valve 150 to rotate the first valve body 151 from the blocked position to the first fluid position. In some examples, step 910 further includes using a controller 200 operably linked to the first actuator to command the first valve 150 to be reconfigured from the blocked position to the first fluid position.

[0139] like Figure 9 As shown, method 900 includes step 920: moving first fluid from a selected first fluid well 131 through the first valve 150 to a bypass passage 121 operably associated with the second valve 160 by setting the second valve 160 to a bypass position, wherein a first end 163A of the bypass selector passage 163 is aligned with the second valve inlet port 166, and a second end 163B of the bypass selector passage 163 is aligned with the bypass port 165. In some examples, step 920 further includes using a pump 190 to generate a pressure differential to drive fluid from the selected first fluid well 131 through the first valve 150 to the bypass passage 121. In some examples, step 920 includes using a second actuator comprising a motor (not shown) operably connected to the second valve 160 to rotate a second valve body 161 to be connected to the bypass passage 121. In some examples, step 920 also includes using a controller 200 operatively linked to the second actuator to command the second valve 160 to be reconfigured to the bypass position.

[0140] like Figure 9 As shown, method 900 includes step 930: selecting a second fluid well 141 of a second set of wells 140 operably associated with the second valve 160 by setting the second valve 160 to a second well position, wherein the second valve selector channel 162 is aligned with one of the second well ports 167 corresponding to the selected second fluid well 141. In some examples, step 930 includes using a second actuator to rotate the second valve body 161 to the second well position. In some examples, step 930 also includes using a controller 200 operably linked to the second actuator to command the second valve 160 to be reconfigured to the second well position. In some examples, step 930 also includes preventing fluid stored in the first set of wells 131 from moving through the first valve 150, the common channel 105, and into the second valve 160 by setting the first valve to a blocking position.

[0141] like Figure 9 As shown, method 900 includes step 940: moving a second fluid from a selected second fluid well 141 of the second set of wells 140 through a second valve 160 and into the fluid circuit 110, while the first fluid moved from the selected first fluid well 131 in step 920 is stored in a bypass passage 121. Step 940 may also include containing the selected first fluid in a storage tank 122 and moving the selected second fluid into a fluid device 112. In some examples, step 940 further includes using a pump 190 to generate a pressure differential to drive fluid from the selected second fluid well 141 through the second valve 160 and into the fluid circuit 110.

[0142] In some examples, method 900 includes step 950: selecting a first fluid well 131 of a first set of fluid wells 130 operably associated with the first valve 150 by setting the first valve 150 to a first fluid position. In some examples, step 950 includes selecting the first fluid well 131 selected in step 910. In some examples, step 950 includes selecting a first fluid well 131 not selected in step 910, which contains a third fluid different from the first fluid contained in the first fluid well 131 selected in step 910.

[0143] In some examples, method 900 includes step 960: moving fluid from a selected first fluid well 131 in the first set of wells 130 through a first valve 150, a common passage 105, a second valve 160, and a fluid loop 110 by setting a second valve 160 to a first valve position, wherein a second valve selector passage 162 is connected to a second valve inlet port 166. In some examples, step 960 includes using a second actuator to rotate the second valve 160 to the first valve position. In some examples, step 960 further includes using a controller 200 operatively linked to the second actuator to command the second valve 160 to be rotated to the first valve position.

[0144] In some examples, method 900 may include, after step 920, moving at least a portion of the selected first fluid from bypass channel 121 to outlet channel 170 and into syringe pump 190, and then discharging that portion of the selected first fluid contained in syringe pump 190 through outlet channel 170 and into fluid circuit 110. In some examples, the step of moving at least a portion of the selected first fluid from bypass channel 121 to outlet channel 170 includes using an actuator to move the plunger of syringe pump 190 in a first direction to generate a negative pressure differential. In some examples, the step of discharging that portion of the selected first fluid contained in syringe pump 190 through outlet channel 170 and into fluid circuit 110 includes using an actuator to move the plunger of syringe pump 190 in a second direction to generate a positive pressure differential. In some examples, the step of moving at least a portion of the selected first fluid from the bypass channel 121 to the outlet channel 170 includes opening the second control valve 182 to the open position by setting the valve array 180 to the bypass mode, and setting the first control valve 181 and the third control valve 183 to the closed position. In some examples, the step of discharging this portion of the selected first fluid from the syringe pump 190 into the outlet channel 170 and into the fluid circuit 110 includes opening the first control valve 181 to the open position by setting the valve array 180 to the flow pool mode, and setting the second control valve 182 and the third control valve 183 to the closed position.

[0145] In some embodiments, method 900 may include, after step 940, moving selected first fluid from bypass passage 121 into fluid loop 110 by setting a second valve 160 to a bypass supply position, wherein the second valve selector passage 162 is aligned with bypass port 165. In some examples, this step includes using a second actuator to rotate a second valve body 161 to the bypass supply position. In some examples, this step also includes using a controller 200 operatively linked to the second actuator to command the second valve 160 to be reconfigured to the bypass supply position. In some examples, this step also includes preventing fluid stored in the first set of wells 131 from moving through the first valve 150, common passage 105, and into the second valve 160 by setting a first valve to a blocking position.

[0146] In some examples, method 900 may include, after step 940, moving at least a portion of the selected second fluid from fluid circuit 110 to outlet channel 170 and into syringe pump 190. In some examples, the step of moving at least a portion of the selected second fluid from fluid circuit 110 to outlet channel 170 includes using an actuator to move the plunger of syringe pump 190 in a first direction to generate a negative pressure differential. In some examples, the step of moving at least a portion of the selected second fluid from fluid circuit 110 to outlet channel 170 includes: opening first control valve 181 to an open position by setting valve array 180 to flow pool mode, and setting second control valve 182 and third control valve 183 to a closed position.

[0147] In some examples, method 900 may include a process of introducing a volume of air into bypass channel 121 by connecting a first valve selector channel 152 to a source of air or other gas or liquid to a purge position and by connecting a second valve 160 to a bypass position by connecting a bypass selector channel 163 to a second valve inlet port 166 and a bypass port 165.

[0148] In some implementations, steps 910, 920, 930, 940, 950 and / or 960 of method 900 may be performed in any order, and are not limited to this. Figure 9 The specific order shown. Furthermore, any one of steps 910, 920, 930, 940, 950, and / or 960 of method 900 may be omitted.

[0149] It should be understood that all combinations of the foregoing concepts and other concepts discussed in more detail below (provided that such concepts are not inconsistent with each other) are contemplated as part of the inventive subject matter disclosed herein. In particular, all combinations of the claimed subject matter appearing in this disclosure are contemplated as part of the inventive subject matter disclosed herein. It should also be understood that terms expressly used herein, which may also appear in any disclosure incorporated by reference, should be given the meaning most consistent with the specific concept disclosed herein.

[0150] While the subject matter of this disclosure has been described and illustrated in considerable detail with reference to certain illustrative examples (including various combinations and sub-combinations of features), those skilled in the art will readily recognize other examples, variations and modifications thereof, that are included within the scope of this disclosure. Furthermore, the description of such examples, combinations and sub-combinations is not intended to convey that the claimed subject matter requires features or combinations of features other than those expressly listed in the claims. Therefore, the scope of this disclosure is intended to include all modifications and variations contained within the spirit and scope of the appended claims below.

Claims

1. A fluid cartridge device, comprising: A fluid loop that is fluidly connected to a flow pool; Bypass lane; First group of fluid wells; The second group of fluid wells; A first valve includes a first valve outlet port operably associated with a first fluid well in the first set of fluid wells, such that the first valve selectively allows flow from the first fluid well to the first valve outlet port; A second valve includes a second valve outlet port fluidly connected to the fluid circuit, the second valve being operatively associated with a second fluid well of the second set of fluid wells and the bypass passage, such that the second valve selectively allows flow from the second fluid well to the second valve outlet port or from the first valve outlet port to the bypass passage; An outlet channel that fluidly connects the bypass channel and the fluid loop to the pump; as well as A storage reservoir aligned with the bypass channel is configured to contain a volume of fluid already supplied from the second valve, such that the fluid can be temporarily contained before being directed to the outlet channel.

2. The fluid cartridge device according to claim 1, wherein, The second valve also selectively allows flow from the outlet port of the first valve to the outlet port of the second valve.

3. The fluid cartridge device according to claim 1, wherein, The first valve is a rotary valve.

4. The fluid cartridge device according to claim 1, wherein, The second valve is a rotary valve.

5. The fluid cartridge device according to claim 1, wherein, The second valve selectively connects the outlet port of the first valve to the fluid circuit when the first valve is in the first valve position.

6. The fluid cartridge device according to claim 1, wherein, The second valve selectively fluidly connects the second fluid well to the fluid circuit when one of the second valve positions is engaged.

7. The fluid cartridge device according to claim 1, wherein, The second fluid well includes one of a plurality of second fluid wells, and wherein the second valve includes a plurality of second fluid well ports, each second fluid well port being fluidly connected to one of the plurality of second fluid wells.

8. The fluid cartridge device according to claim 7, wherein, The outlet channel is fluidly connected to the waste outlet.

9. The fluid cartridge device of claim 8, further comprising a valve array including one or more valves disposed along the outlet passage for selectively controlling flow between the bypass passage, the fluid circuit, the pump, and the waste outlet.

10. A method for guiding fluid using the fluid cartridge device according to claim 1, the method comprising: The first fluid in the first fluid well stored in the first set of fluid wells is selected by setting the first valve to a first position, the first set of fluid wells being operatively associated with the first valve; At least a portion of the selected first fluid is moved from the first valve into the bypass passage operably associated with the second valve by setting the second valve to the bypass position; The second fluid stored in the second set of fluid wells is selected by setting the second valve to the position of the second fluid well, the second set of fluid wells being operatively associated with the second valve; At least a portion of the selected second fluid is moved into the fluid loop.

11. The method of claim 10, further comprising moving at least said portion of the selected first fluid from the bypass channel to the fluid loop.

12. The method of claim 10, further comprising moving at least said portion of the selected second fluid from the fluid loop to the outlet line.

13. The method of claim 11, further comprising moving at least said portion of the selected second fluid from the fluid loop to the outlet line.

14. The method of claim 10, further comprising: Select a second fluid stored in a second fluid well of the first set of fluid wells operably associated with the first valve; At least a portion of the second fluid selected in the second fluid well of the first set of fluid wells is moved into the fluid circuit by setting the second valve to the first valve position.

15. The method of claim 11, further comprising: Select a second fluid stored in a second fluid well of the first set of fluid wells operably associated with the first valve; At least a portion of the selected second fluid in the second fluid well of the first set of fluid wells is moved into the fluid circuit by setting the second valve to the first valve position.

16. The method of claim 12, further comprising: Select a second fluid stored in a second fluid well of the first set of fluid wells operably associated with the first valve; At least a portion of the selected second fluid in the second fluid well of the first set of fluid wells is moved into the fluid circuit by setting the second valve to the first valve position.

17. The method of claim 13, further comprising: Select a second fluid stored in a second fluid well of the first set of fluid wells operably associated with the first valve; At least a portion of the selected second fluid in the second fluid well of the first set of fluid wells is moved into the fluid circuit by setting the second valve to the first valve position.

18. The method according to any one of claims 10-17, further comprising introducing a volume of air into the bypass channel by setting the first valve to the cleaning position and the second valve to the bypass position.

19. The method according to any one of claims 10-17, further comprising preventing the first fluid stored in the first set of fluid wells from moving to the second valve by setting the first valve to a base position.

20. The method of claim 18, further comprising preventing the first fluid stored in the first set of fluid wells from moving to the second valve by setting the first valve to a base position.

Citation Information

Patent Citations

  • Reagent channel mixing system and method

    US20180185842A1

  • Fluidic system for reagent delivery to a flow cell

    US9410977B2

  • Processing of slide mounted material

    US5273905A