RU2800868C2 - Multivalve fluid cartridge - Google Patents

Abstract

FIELD: microfluidic cartridges.

SUBSTANCE: cartridge contains 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 connected to the first set of fluid wells such that it is configured to selectively fluidly connect any of the wells of the first set of fluid wells to the outlet port of the first valve. The second valve is operatively connected to the fluid circuit, to the bypass fluid circuit, to the outlet port of the first valve, and to the second set of fluid wells, such that it is configured to selectively fluidly connect any of the wells of the second set of fluid wells and the outlet port of the first valve to the fluid circuit or outlet port of the first valve with a bypass fluid circuit.

EFFECT: reduced cycle time for each operation with fluid.

16 cl, 10 dwg

Description

State of the art

The need to prime and alternate different types of fluids for different fluid handling in a microfluidic (microfluidic) cartridge can be a problem, for example due to limited space available. Some microfluidic systems provide for the placement of different types of fluids away from the study area (e.g., flow cell, mixing tank), while the system has one flow control valve operatively associated with various types of fluids, so that the specified flow control valve selects one of fluids for a specific operation, and directs the selected fluid to the study area for processing. Each fluid operation of the microfluidic cartridge consists of moving the selected fluid a characteristic distance from the flow control valve to the entrance to the fluid examination area, which limits the volume of fluid that can be transferred at each stage of the operation. As a result, each operation typically requires multiple fluid transfers to move the total volume of fluid required, and thereby increases the cycle time of each fluid operation.

Disclosure of invention

Below, a brief summary will be presented to provide a basic understanding of some aspects of the described invention. This disclosure is not a detailed overview of the claimed subject matter. It is intended neither to identify key or critical elements of the claimed subject matter, nor to delineate the scope of the invention. The sole purpose is to present some of the ideas in a simplified form as an introduction to the more detailed description that will be presented below.

The present invention in one aspect provides 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 port, and a plurality of first well ports operatively associated with the first set of fluid wells , and a second valve comprising a second valve outlet port, a bypass selector port, and a plurality of second well ports. According to some examples, the first valve is configured to selectively fluidly connect the first well of the first set of fluid wells to the outlet port of the first valve when the first valve is in the first position, and selectively fluidly connect the second well of the first set of fluid wells to the outlet port of the first valve when the first the valve is in the second position. According to some examples, the outlet port of the second valve is operatively connected to the fluid circuit, wherein the bypass selector channel is operatively coupled to the bypass fluid circuit and to the outlet port of the first valve such that the second valve is configured to selectively fluidly connect the first well of the second set of fluid wells to the fluid loop when the second valve is set to the first well position, and selective fluid connection of the bypass selector channel to the bypass fluid loop when the second valve is set to the bypass position.

The present invention, in another aspect, provides a method comprising: selecting a first fluid stored in a first fluid well of a first set of fluid wells operatively associated with a first valve by setting the first valve from a blocking position to a first fluid well position; transferring at least a portion of the selected first fluid from the first valve to a bypass channel operatively associated with the second valve by placing the second valve in the bypass position; selecting a second liquid stored in the second liquid well of the second set of liquid wells operatively associated with the second valve by placing the second valve in the position of the second liquid well; and moving at least a portion of the selected second fluid into the fluid circuit while a portion of the selected first fluid is in the bypass.

The present invention, in yet another aspect, provides an apparatus comprising: a fluid circuit in fluid communication with a flow cell; passageway; first liquid well; second liquid well; a first valve comprising a first valve outlet port and a plurality of first well ports, wherein the first of said plurality of first well ports is operatively coupled to the first fluid well such that the first valve is configured to selectively allow fluid to flow from the first liquid well to the outlet port; and a second valve, comprising: an outlet port of the second valve having a fluid connection with the fluid circuit; a bypass port having a fluid connection with the bypass channel; an inlet port of a second valve in fluid communication with an outlet port of the first valve; a second liquid well port having a liquid connection with the second liquid well; and a rotary element of the second valve, configured to rotate to a plurality of positions of the second valve, so that the second valve is configured to selectively provide fluid flow from a selected one of the port of the second fluid well and the inlet port of the second valve to the outlet port of the second valve or from the inlet port of the second valve to the bypass port.

Other distinguishing features and characteristics of the subject matter of the present invention, methods of operation, functions of the respective structural elements and combination of parts, and manufacturing economics will become more apparent upon reading the following description and the appended claims with reference to the accompanying drawings, which together form a part of the present description, when In this case, in the various figures, the corresponding elements are assigned the same reference designations.

Brief description of the drawings

The accompanying drawings, which are included and form part of the description, illustrate various embodiments of the invention. In the drawings, like reference numbers designate identical or functionally similar elements.

Fig. 1 schematically depicts apparatus for directing liquid from any one of the first set of wells into the liquid loop or bypass loop, and from any one of the second set of wells into the liquid loop.

Fig. 2 schematically shows an example of a first valve and an example of a second valve with a bypass circuit.

Fig. 3 schematically shows an example of an apparatus set to a first mode of liquid handling.

4 schematically shows an example of an apparatus set to bypass mode.

Fig. 5. schematically depicts an example of an apparatus set to the second liquid handling mode.

Fig. 6 schematically shows an example of an apparatus set to drain mode.

Fig. 7 schematically depicts an example of a set of valves located downstream of the outlet port and in fluid communication with the fluid circuit, fluid bypass circuit, pump, and drain port.

Fig. 8 is a table defining the various modes of operation of the valve stack.

Fig. 9 is a flow diagram of an exemplary method for channeling fluid from a first set of fluid wells and a second set of fluid wells into a fluid loop or bypass loop.

Fig. 10 is a block diagram of a liquid cartridge built into a processing apparatus.

Implementation of the invention

Although the subject matter of the present invention may be embodied in various forms, the following description and accompanying drawings serve only to disclose some of these forms as specific examples. Accordingly, the subject matter of the invention is not intended to be limited to the forms or examples described and illustrated.

Unless otherwise stated, all technical terms, symbols and other technical terms or terminology used in the present description have the same meaning as generally accepted among specialists in the field to which the present invention relates.

Unless otherwise specified, or otherwise implied by the context, an element referred to in the singular means "at least one" or "one or more".

In the present description, terms describing the relative spatial position (position) and/or orientation can be used to characterize the position and/or orientation of a component, apparatus, location, design feature or part. Unless specifically stated or otherwise given by the context of the description, then, among other possibilities, such terms as top, bottom, above, below, under, above, top, bottom, left, right, front, behind, next, next to, between, horizontal, vertical, diagonal, longitudinal, transverse, radial, axial, and the like, are used for convenience in referring to such component, apparatus, location, feature or part in the drawings, and are not intended to limit the inventive concept.

In addition, unless otherwise noted, any specific dimensions mentioned in the description are given simply to provide an idea of an exemplary implementation of the device, i.e. implementation of aspects of the invention, and are not intended to limit the idea of the invention.

The term "approximately" applies to all numerical values given in the description, regardless of whether it is indicated explicitly or not. This term generally refers to a certain numerical range that a person skilled in the art would consider a reasonable amount of deviation from the mentioned numerical value (ie, a value that gives an equivalent result) in the context of the present invention. By way of example, which is not exhaustive, the term may be understood to include a deviation of ±10% from a given numerical value, provided that such deviation does not change the end result (or function) of that value. Therefore, under some circumstances, the specialist should be clear that approximately 1% can be understood as the range from 0.9% to 1.1%.

In the sense in which the term "adjacent" is used in the present description, it means "close" or "adjacent". Neighboring objects may be spaced apart from each other or may be in actual direct contact with each other. In some cases, neighboring objects may be connected to each other or may be integral with each other.

In the sense in which the terms "substantially" and "essential" are used in the present description, they characterize a significant measure or degree. When these terms are used, for example, in conjunction with an occurrence, circumstance, characteristic, or property, they may refer to situations in which the occurrence, circumstance, characteristic, or property occurs "exactly", as well as to situations in which the occurrence, circumstance, the characteristic or property takes place “with a reasonably good approximation”, for example, taking into account the tolerance or variability of the examples given in the description.

In the sense in which the terms "optional" and "optional" are used in the present description, they mean that the component, structure, element, event, circumstance, characteristic, property, etc. mentioned after them. may or may not be included, or may or may not occur, and that the description covers situations in which a component, construct, element, event, circumstance, characteristic, property, etc. . are included or occur, and situations in which they are not included or do not occur.

In accordance with various examples, assemblies and devices, as discussed in the description, can be used in combination with a fluid cartridge, which may contain one or more fluid processing passages, including one or more elements, for example, one or more channels, a side channel, a valve, a flow divider, a vent channel, a port, an access area, a transition, a drop, a drop containing a reagent, a coating layer, a reaction component, a combination of these elements, and the like. Any element can have fluid communication with another element.

All possible combinations of elements and components discussed in the description or mentioned in the claims are considered as part of the disclosure of the subject invention. It should be understood that all combinations of the above ideas and additional ideas, which will be discussed in more detail below, (provided that such ideas do not contradict each other), are considered as part of the subject matter disclosed in the present description. In particular, all combinations of the claimed subject matter that appear at the end of this description are considered to be part of the disclosed subject matter.

In the appended claims, the term "comprising" is used as equivalent to the corresponding term "comprising". The terms "comprising" and "including" mean an open form that covers not only the listed elements, but also any additional elements. In addition, in the claims, the terms "first", "second", "third", etc. are used simply as an explanatory designation, and are not intended to impose any numerical requirements on objects.

The term "fluid communication" means either direct fluid communication, for example, the two regions may be in fluid communication with each other through a fluid handling passage connecting the two said regions, or may be capable of fluid communication, for example, the two regions may be to fluid communication with each other when they are connected through a fluid handling passage, which may contain a valve located therein, and fluid communication can be established between these two areas by actuating the valve, for example, by dissolving a soluble shutter, destroying a collapsible shutter , or otherwise opening a valve located in the fluid handling passage.

Liquid cartridge

There is a need for improved liquid cartridge devices and methods that allow more than one liquid handling operation to be performed simultaneously. Such liquid handling operations can take place independently of each other in a liquid cartridge, thereby reducing the accumulated liquid handling time. In addition, there is a need for improved fluid cartridge devices and methods that isolate fluids processed in a fluid cartridge by providing a dedicated valve port for each type of fluid operation to prevent unintentional fluid cross-contamination.

According to various examples, the apparatus comprises a fluid cartridge that is configured to accommodate different types of fluids (e.g., reagents, buffer, reaction media), and selectively move different types of fluids through two or more independent fluid operations (e.g., mixing, incubating, or transferring fluids). ). The fluid cartridge comprises a first set of wells accommodating one or more types of fluids associated with the first fluid handling operation and a second set of wells accommodating one or more types of fluids associated with the second fluid handling operation. The fluid cartridge contains a fluid circuit and a bypass fluid circuit for independent fluid operations. The first valve is operatively associated with the first set of wells such that the first valve can selectively allow fluid to flow from any well of the first set. The second valve is operatively associated with the first valve, the fluid loop, the bypass fluid loop, and any one of the wells of the second set to selectively allow fluid to flow from one of the wells of the second set to the fluid loop, from the first valve to the fluid loop, or from the first valve to the bypass fluid contour. In some cases, the second valve can also be effectively used for frequent fluid operations (eg, repetitive sequencing operations), while the first valve can be used for less frequent fluid operations (eg, paired-end sequencing or amplification operations). Separating the valves in this way can result in a reduction in the space requirement for each valve, and an optimization of each valve for frequent operations and infrequent operations.

As shown in FIG. 1, an exemplary device includes a fluid cartridge 100 for accommodating different types of fluids, and selectively passing different types of fluids sequentially through two or more independent fluid operations. According to some examples, the fluid cartridge 100 includes a fluid circuit 110, a fluid bypass circuit 120, a first well set 130, a second well set 140, a first valve 150, a second valve 160, a common passage 105, an outlet passage 170, and a valve set 180. According to some examples, the liquid cartridge 100 includes a support (not shown) that carries various cartridge components such as a first well set 130, a second well set 140, a first valve 150, a second valve 160, and a valve set 180, although one or more cartridge components may not be supported by a common substrate or other supporting structure. In some examples, fluid circuit 110, bypass fluid circuit 120, and outlet 170 are one or more fluid channels or tubes located on or within the substrate of fluid cartridge 100 to convey fluid within fluid cartridge 100 or to other devices that fluidly connected to the fluid cartridge 100.

As shown in FIG. 1, fluid circuit 110 includes an inkjet device 112 (eg, a flow cell) and two or more fluid conduits 111, 115 that fluidly connect fluid device 112 to a second valve 160 and outlet conduit 170, respectively. According to one example, inkjet device 112 is a flow cell comprising a first layer of glass (not shown) and a second layer of glass (not shown) that are bonded together to form one or more channels (not shown) internally. In various examples, fluidic device 112 may include a fluid inlet 113, a fluid outlet 114, and one or more fluid channels (not shown) that communicate with fluid inlet 113 and fluid outlet 114 to allow fluid processing, such as chemical or biochemical analysis. or carrying out another reaction. According to various examples, fluidic device 112 is configured to introduce various types of fluids (eg, reagents, buffers, reaction media) into fluid inlet 113 to manipulate fluids within one or more fluid channels. According to various examples, the jet device 112 is further configured to flush various types of fluids from one or more fluid channels through fluid outlet 114. In the example depicted in FIG. 1, passage 111 is an inlet passage that connects fluid inlet 113 of inkjet device 112 to second valve 160, and passage 115 is an end line passage that connects fluid outlet 114 of inkjet device 112 to outlet passage 170 (two passages are shown by way of example). , although fluid loop 110 may comprise more than two channels in other examples). In some examples, fluid circuit 110 includes a buffer reservoir 116 in line with end channel 115 configured to hold some volume of fluid that has passed through jet device 112 so that fluid exiting jet device 112 can be delayed for a time before being will be directed toward outlet 170. Buffer reservoir 116 is configured to provide bi-directional fluid flow such that buffer reservoir 116 can also retain fluid directed from outlet 170 and allow it to flow toward jet device 112.

In some examples, inkjet device 112 is an integral part of cartridge 100. In other examples, inkjet device 112 is attached or attached to cartridge 100 in a releasable manner, i. through fluid connectors connecting fluid inlet 113 and fluid outlet 114 to inlet port 111 and end line port 115, respectively.

In the example shown in FIG. 1, fluid bypass circuit 120 includes fluid bypass passage 121 that connects second valve 160 to outlet passage 170 (a single passage is shown for illustration purposes, although in other examples, fluid bypass circuit 120 may include two or more passages). Bypass fluid circuit 120 is configured to allow fluid to flow from second valve 160 to outlet 170 without passing through fluidic device 112. According to some examples, bypass fluid circuit 120 includes a buffer reservoir 122 in line with bypass fluid channel 121, configured to retain some volume of liquid that has been supplied from the second valve 160 so that this liquid can be delayed for a while before being directed to the outlet channel 170. The buffer tank 122 is configured to provide a bidirectional fluid flow, so that the buffer tank 122 can also retain fluid directed from the outlet port and allow fluid to flow to second valve 160.

In the example shown in FIG. 1, a common passage 105 connects the first valve 150 to the second valve 160.

As shown in FIG. 1 and 2, the first set of wells 130 includes two or more fluid wells 131 that are connected to the first valve 150 in a fluid connection with the first valve 150. In the illustrated example, nineteen first fluid wells 131 are associated with the first valve 150, although the invention contemplates any number (two or more) of first fluid wells. The different fluid wells 131 of the first set of fluid wells 130 may have the same or different sizes (ie, volumes), for example, all fluid wells 131 may have the same volumes; all liquid wells 131 may have different volumes; or some subset of fluid wells 131 may have the same volumes, and some subset of fluid wells 131 may have different volumes, depending on the required storage volume of reagents or other liquid in each first fluid well 131.

As shown in FIG. 1 and 2, the second well set 140 comprises two or more fluid wells 141 that are connected to the second valve 160 in a fluid connection with the second valve 160. In the illustrated example, five second fluid wells 141 are associated with the second valve 160, although the invention contemplates any number (two or more) of second fluid wells. The different fluid wells 141 of the second fluid well set 140 may have the same or different sizes (ie, volumes), for example, all fluid wells 141 may have the same volumes; all liquid wells 141 may have different volumes; or some subset of fluid wells 141 may have the same volumes, and some subset of fluid wells 141 may have different volumes, depending on the required storage volume of reagents, buffer, or other liquid in every other fluid well 141.

The first valve 150 is designed and configured to selectively connect one of the first fluid wells 131 of the first set of wells 130 to a common conduit 105, and thus to the second valve 160. In the example shown in FIG. 1 and 2, the first valve 150 is a swivel valve including a first swivel element 151 that is pivotally mounted within the fluid cartridge 100. In some examples, the first swivel element 151 is a disk (not shown) made of a rigid plastic (e.g. , polypropylene) and a lid (not shown) made of elastomer (eg Dynaflex®, Santoprene® and silicone). According to various examples, the first valve 150 includes a plurality of first well ports 155, each of which is connected to one of the first liquid wells 131 of the first set of wells 130. In the example shown in FIG. 1 and 2, a plurality of first hole ports 155 are arranged circumferentially around the first pivot member 151 such that each first hole port 155 is at the same radial distance from the center of the first pivot member 151. In other examples (not shown), the plurality the first well ports 155 may be arranged in other patterns that fluidly connect the first valve 150 to the first set 130 of wells. In some examples, each port 155 of each first well is in fluid communication with the corresponding first well 131 via a fluid channel.

According to FIG. 2, first valve 150 includes an outlet port 154 connected to second valve 160 via a common fluid passage 105 that extends from outlet port 154 of first valve 150 to inlet port 166 of second valve 160. In some examples, outlet port 154 may be located at approximately the center of the first rotary member 151. In the illustrated example, the part of the common fluid passage 105 extending from the outlet port 154 that is overlapped by the rotary member 151 (eg, extends under the first rotary member 151) is shown with a dashed line.

In the example shown in FIG. 1 and 2, the first rotary member 151 includes a selector channel 152 extending radially from the outlet port 154 of the first selector toward the circumferential edge of the rotary member 151.

In various examples, the rotary member 151 is rotatable between a plurality of angular positions such that the first valve selector passage 152 can fluidly connect any one of the first fluid wells 131 to the first valve outlet port 154 through each corresponding first well port 155. When the rotary member 151 is rotated to an angular position such that the first valve selector passage 152 is aligned with one of the first well ports 155, fluid can flow from the selected first fluid well 131 through the selector passage 152 and into the first valve outlet port 154.

In some examples, the first valve 150 may include a hard stop (not shown) to limit rotation of the rotary member 151 in a blocking position such that the first valve selector channel 152 is not aligned with any of the first well ports 155. According to some examples, the hard stop includes a protrusion that protrudes from the edge of the circumference of the rotary element 151, and a pin protruding from the stationary component (stator) (not shown) of the first valve 150, and thereby the protrusion engages with the pin when the rotary element 151 is installed in blocking position (or base position).

In various examples, it is provided that when the first rotary element 151 is set to the blocking position, the first valve 150 blocks the flow of fluid from the first set of wells 130 to the second valve 160. In some examples, the first rotary element 151 is configured to rotate from the blocking position in the first direction to any of the plurality of first angular positions to selectively permit fluid to flow from any one of the plurality of ports 155 and their associated first fluid holes 131 to the outlet port 154 of the first valve. In other examples, the first pivot member 151 is rotatable from a bidirectional blocking position to any of a plurality of first angular positions, and connects one of the first well ports 155 and their associated first fluid wells 131 to the first valve outlet port 154.

According to some examples, the first rotary element 151 can be placed in a purge position (not shown), in which the first valve 150 allows fluid to pass from the air source to separate an aliquot of liquid through the common fluid channel 105 through air bubbles.

The second valve 160 is designed and configured to selectively connect one of the second fluid wells 141 of the second set of wells 140 to the inlet 111 of the fluid circuit 110, to connect the common channel 105 and the first valve 150 to the inlet 111 of the fluid circuit 110, or to connect the common channel 105 and a first selector 150 with a bypass 121 of the bypass fluid circuit 120. In the example shown in FIG. 1 and 2, the second valve 160 is a swivel valve including a second swivel member 161 that is rotatably mounted within the liquid cartridge 100, the second swivel member 161 being rotatable between a plurality of angular positions. According to some examples, the second rotary element 161 is a disk (not shown) made of rigid plastic (eg polypropylene) and a cover (not shown) made of elastomer (eg Dynaflex®, Santoprene® and silicone). According to various examples, the second valve 160 includes an outlet port 164 connected to the inlet channel 111 of the fluid circuit 110, a bypass port 165 connected to the bypass channel 121 of the bypass circuit 120, an inlet port 166 connected to the common channel 105 and the first valve 150, and a plurality ports 167 of the second holes, each of which is associated with one of the second liquid holes 141 of the second set of 140 holes.

In the example shown in FIG. 1 and 2, a bypass port 165, a second valve inlet port 166, and a plurality of second well ports 167 are arranged circumferentially around the second rotary member 161. In other examples (not shown), a bypass port 165, a second valve inlet port 166, and a plurality of second valve ports 167 wells may be arranged in other patterns that fluidly connect second valve 160 to bypass circuit 120, first valve 150, and second set 140 of wells. In some examples, each second well port 167 is in fluid communication with a corresponding second fluid well 141 via a fluid channel.

According to FIG. 2, the outlet port 164 of the second valve is in fluid communication with the inlet port 111 extending from the second valve 160 to the inkjet device 112. 166 of the second selector and a plurality of ports 167 of the second holes are located at the same radial distance from the outlet port 164 of the second valve. In the illustrated example, the part of the inlet port 111 extending from the outlet port 164 that is overlapped by the rotary member 161 (eg, extends under the second rotary member 161) is shown with a dashed line.

In the example shown in FIG. 1 and 2, the second rotary member 161 includes a selector passage 162 extending radially from the outlet port 164 of the second valve towards the circumferential edge of the second rotary member 161.

In the example shown in FIG. 1-7, the second rotary member 161 further includes a bypass selector channel 163 located proximate the circumferential edge of the second rotary member 161. According to some examples, the bypass selector channel 163 includes a first edge 163a shown in FIG. 3 that is radially substantially aligned with the selector channel 162 of the second valve 160, and a second edge 163b that is offset from the selector channel 162 of the second valve. According to FIG. 3 and 6, when the second rotary member 161 is set to the bypass position, it is provided that the first end 163a of the bypass selector port 163 is connected to the inlet port 166 of the second valve, and the second end 163b of the bypass selector port 163 is connected to the bypass port 165. In the bypass position the second valve selector port 162 is not aligned with any of the second well ports 167 such that the second valve selector port 162 is not in fluid communication with any of the second fluid wells 141. In some embodiments, when the second rotary member 161 is in the bypass position , the second valve selector port 162 may be in fluid communication with the second fluid port 141 such that the second valve inlet port 166 is in fluid communication with the bypass port 165 while the selected second fluid port 141 is in fluid communication with the second valve outlet port 164.

According to various examples, the second rotary member 161 is rotatable between a plurality of angular positions such that the second valve 160 allows fluid to move from: (i) one of the second fluid wells 141 of the second well set 140 to the inlet 111; (ii) common passage 105 and first valve 150 to inlet passage 111; or a common channel 105 and the first valve to the bypass channel 121.

Moving the second rotary member 161 to an angled position where the second valve selector port 162 is in fluid communication with one of the second well ports 167 allows fluid to flow from the corresponding selected second fluid well 141 through the second valve selector port 162, through the second valve outlet port 164 and into inlet 111. When the second valve selector port 162 is in fluid communication with one of the second well ports 167, the first and second edges 163a, 163b of the bypass selector port 163 are offset 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 either the inlet port 166 of the second valve or the bypass port 165 of the second valve.

Moving the second rotary member 161 to an angular position where the second valve selector port 162 is in fluid communication with the second valve inlet port 166 allows fluid to flow from the common fluid port 105 and the first valve 150 through the second valve selector port 162, through the second valve outlet port 164. valve and into inlet 111. When the second valve selector port 162 is in fluid communication with the second valve inlet port 166, the first and second edges 163a, 163b of the bypass selector port 163 are offset 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 either the inlet port 166 of the second valve or the bypass port 165 of the second valve.

In some instances, the second valve 160 may include a hard stop, similar to the example discussed previously with respect to the first valve 150, to limit the rotation of the second rotary member 161 to a blocking position in which the selector channel 162 of the second valve is not aligned with any of the ports 167 of the second holes. When the second rotary member 161 is set to the blocking position, the second valve 160 blocks the flow of fluid from either the first valve 150 and/or any well of the second set of wells 140 to the outlet port 164 of the second valve, and also prevents the flow of fluid from the first valve 150 to the bypass. port 165.

In some examples, the second pivot member 161 is rotatable in a first direction from a blocking position to a communication position with the first valve, wherein the second valve selector port 162 is aligned with the second valve inlet port 166 such that the second valve 160 allows fluid to pass between the inlet port. 166 of the second valve and the exhaust port 164 of the second valve. When the second rotary member 161 is in position with the first valve, the second valve selector port 162 is aligned with the inlet port 166 such that the selector port 162 is in fluid communication with the second valve inlet port 166 and the bypass selector port 163 is not in fluid communication with either one of the ports. In some embodiments, the bypass selector channel 163 may establish fluid communication between the second well port 167 with another second well port 167 and/or with the bypass port 165.

In some examples, the second pivot member 161 is rotatable in a first direction from a blocking position to one or more second well positions such that the second valve 160 allows fluid to pass between the selected second well port 167 and the second valve outlet port 164. When the second rotary member 161 is installed in any one of the second well positions, the inlet end of the selector port 162 is in fluid communication with the selected port 167 of the second well, and the bypass selector port 163 is not in fluid communication with either port.

According to various examples of the first valve 150 and the second valve 160, automatic control and monitoring of the angular position (position) of the first rotary element 151 and the second rotary element 161 may be provided. Each rotary element may be associated with a motor or other drive means, for example, through a gear transmission, belt, pulleys, drive rollers, etc., so as to provide automated, mechanical rotation of the rotary element on request. The rotational position control and control of the rotary element can be provided by means of angular position sensors, such as encoders and/or stepper motors.

According to the example shown in FIG. 1, the liquid cartridge 100 includes a weir 191 that is in fluid communication with the outlet 170; and a pump 190 that may be in fluid communication with outlet 170. In various examples, pump 190 is configured to create a pressure difference between outlet 170 and either fluid loop 110 and/or bypass fluid loop 120 to allow fluids to flow. in two directions along any of the fluid circuits 110 and/or bypass fluid circuit 120. The pump 190 may be a powered syringe pump (not shown) that is operatively connected to the syringe. According to various examples, the actuator is configured to move the syringe plunger in a first direction to create a negative pressure differential to draw liquid through fluid loop 110 and/or bypass fluid loop 120 towards (or possibly inward) the syringe barrel. The actuator is further configured to move the plunger in a second direction opposite the first direction to create a positive differential pressure to force fluid out of the syringe into one of the fluid circuits, fluid circuit 110 and/or bypass fluid circuit 120. In other examples (not shown), the pump 190 may contain another mechanism for creating a pressure difference that can change the direction of flow of fluids.

In some examples, when the syringe pump plunger 190 changes direction, there may be a pressure lag (hysteresis) that the plunger creates. Syringe pump operation can compensate for this lag by first reversing the direction of the plunger through a partial stroke and then, after waiting a predetermined time, completing the plunger's stroke in the opposite direction. According to one example, the pump plunger 190 may move in a first direction to draw fluid into the fluid or bypass fluid loop 110, 120 and then move in a second direction to discharge fluid into the fluid or bypass fluid loop 110, 120. the fluid or bypass fluid circuit 110, 120 may be accomplished initially by reversing the movement of the plunger in the second direction for a portion of the stroke to compensate for the pressure lag generated by the syringe pump 190. After the plunger has moved for a portion of the stroke in the second direction, the movement of the plunger in the second direction may be completed, to ensure that the required volume of liquid has been discharged into the liquid or bypass liquid circuit 110, 120.

According to various examples, the fluid cartridge 100 includes a set of valves 180, which includes one or more control valves 181-183 located along the outlet channel 170 to selectively control the flow of fluid between the fluid circuit 110, the bypass circuit 120, the pump 190 and the drain hole 191 These one or more control valves 181-183 include a first control valve 181 located at the transition between the end line 115 and outlet 170, a second control valve 182 located at the transition between fluid bypass channel 121 and outlet 170, and a third control valve 183, located at the transition between the drain hole 191 and the outlet channel 170.

In some examples, the third control valve 183 is located closer to the pump 190 than to the drain 191 to help remove bubbles from the pump 190. The proximity of the third control valve 183 to the pump 190 reduces the likelihood that the bubbles discharged from the pump 190 will be are captured by the outlet port 170 to effectively debubble the liquid cartridge 100.

According to various examples, the control valves 181-183 may be pinch type valves containing small round tubes that can be compressed by external stems to seal off the respective channels. According to various examples, the material of the channels must be elastic enough to allow the pinch mode to be used. When the valve is open, only the specified channel allows the flow of fluid, thus creating a certain flow of the selected fluid in the corresponding channel.

As shown in FIG. 1, a pressure sensor 202 (pressure meter) may be connected to the outlet 170 to monitor the pressure of the fluid passing through the outlet. According to some examples, the pressure sensor 202 is configured to generate a signal indicative of a measurement of the pressure of the fluid passing through the outlet 170, wherein the operation of the pump 190 and valve set 180 may be based on the measurement of the pressure in the outlet 170.

According to FIG. 7 and 8, in various embodiments, the valve set 180 can be operated in various modes, in which certain control valves 181-183 are set to open or closed positions to selectively control the movement of fluids between the liquid circuit 110, the bypass circuit 120, the pump 190 and the drain port. 191. According to Table 1 in FIG. 8, and according to some examples, the set of valves 180 can be set to a common open mode, in which all control valves 181-183 are set to the open position, which is indicated by the symbol "O" in the table. When generally open, valve set 180 allows converging fluid flows from fluid loop 110 and bypass fluid loop 120 to exit port 170, and from outlet port 170 to drain port 191.

According to Table 1 in FIG. 8, and according to some examples, valve set 180 can be set to fluid loop mode or flow cell mode, in which the first control valve 181 is set to the open position and the second and third control valves 182, 183 are set to the closed position indicated in the table. symbol "X". In fluid loop mode, valve set 180 allows fluid to flow between fluid loop 110 and pump 190 while preventing fluid from passing between fluid bypass loop 120 and outlet 170, and between outlet 170 and drain 191. Accordingly, in fluid loop mode, fluid from of any (first or second) set of wells 130, 140 can be directed to the fluid circuit 110, buffer tank 116, outlet 170 and/or pump 190, and the fluid flow can be reversed from pump 190, outlet 170 and/ or buffer tank 116 back to the liquid circuit 110.

According to Table 1 in FIG. 8, and according to some examples, the valve set 180 may be set to a drain mode in which the third control valve 183 is set to the open position and the first and second control valves 181, 182 are set to the closed position. In drain mode, valve set 180 allows fluid to pass between pump 190 and drain 191 while preventing fluid from passing between fluid bypass loop 120 and outlet 170, and also preventing fluid from passing between fluid loop 110 and outlet 170. Accordingly, in drain mode fluid from pump 190 and/or outlet 170 may be directed to drain 191.

According to Table 1 of FIG. 8, and in some examples, valve stack 180 may be set to a bypass mode in which second control valve 182 is set to the open position and first and third control valves 181, 183 are set to the closed position. In bypass mode, valve set 180 allows fluid to pass between fluid bypass loop 120 and pump 190 while preventing fluid from passing between fluid loop 110 and outlet 170, and between outlet 170 and drain 191. Accordingly, in bypass mode, fluid from either ( first or second) set 130, 140 wells can be directed to the bypass fluid circuit 120, the outlet channel 170 and/or the pump 190, and the flow of fluid can be reversed from the pump 190 and/or the outlet channel 170 to the bypass fluid circuit 120 .

In various examples, valve set 180 is designed to minimize cross-contamination or volume error that can occur when switching between two modes of operation. According to various examples, the fluid control valves 181-183 are positioned so that in the event of a short simultaneous opening of the first and second control valves 181, 182, the fluid flow is directed to the drain hole 191, which reduces the risk of cross-contamination between two or more fluids in the jet device. 112. In various examples, fluid control valves 181-183 are actuated by a cam (not shown) located in an instrument (not shown) designed to operate with fluid cartridge 100. Interaction between fluid control valves 181-183 and the cam is arranged so that minimize the transition time between two modes of operation, and thereby reduce the possibility of cross-contamination or volume error.

Fluid Cartridge Modes

In various examples, as shown in FIG. 3-6, the fluid cartridge 100 operates in various modes to selectively direct fluid from any one of the first fluid wells 131 of the first set of wells 130 into the fluid loop 110 or bypass loop 120, or from any one of the second fluid wells 141 of the second set of wells 140 into fluid circuit 110.

According to FIG. 3, the first valve 150 and the second valve 160 can be set to the first fluid treatment mode to allow the fluid from the selected first fluid well 131 of the first set of wells 130 to flow into the fluid circuit 110, and to block the flow of fluid from the second set of wells 140. In the first liquid handling mode, the first rotary element 151 of the first valve 150 is installed so as to connect the selector channel 152 of the first valve with a selected one of the ports 155 of the first wells to ensure the flow of liquid from the corresponding first well 131 to the outlet port 154 of the first valve, and the second rotary the element 161 of the second valve 160 is positioned to connect the selector port 162 of the second valve to the inlet port 166 of the second valve to allow fluid to flow between the inlet port 166 of the second valve and the outlet port 164 of the second valve. At the same time, valve set 180 is set to fluid loop mode to allow fluid to flow from fluid loop 110 to outlet 170 and to pump 190 when valve 181 is open and valves 182 and 183 are closed. As shown in FIG. 3, an aliquot of the first liquid (shown in thick line) from the selected first well 131 is directed to the second valve 160 through the common fluid passage 105 and passed through the fluid jet device 112. After passing through the jet device 112, said aliquot of the first liquid may be temporarily held in the buffer tank 116, or transferred directly to the syringe pump 190.

According to FIG. 4, first valve 150 and second valve 160 may be set to bypass mode to allow fluid to flow from the selected first fluid well 131 of the first set of wells 130 to the bypass fluid circuit 120 and to block the flow of fluid from the second set of wells 140. In the bypass mode, the first rotary element 151 of the first valve 150 is set to a position in which the selector channel 152 of the first valve is connected to a selected one of the ports 155 of the first wells to allow the liquid from the corresponding first well 131 to move to the outlet port 154 of the first valve, and the second the rotary member 161 of the second valve 160 is positioned so that the bypass selector port 163 of the second valve is aligned with the inlet port 166 of the second valve and the bypass port 165 so that fluid can flow between the inlet port 166 of the second valve and the bypass port 165 of the second valve. At the same time, valve set 180 is set to bypass mode to allow fluid to flow from bypass fluid circuit 120 to outlet 170 and to pump 190 when valve 182 is open and valves 181 and 183 are closed. As shown in FIG. 4, an aliquot of the first liquid (shown in thickened line) from the selected first well 131 is directed through the common liquid channel 105 to the second valve 160, and into the bypass channel 121, where said aliquot of the first liquid can be temporarily retained in the buffer tank 122, and/or transferred directly to the syringe pump 190.

According to FIG. 5, the first valve 150 and the second valve 160 may be set to a second fluid treatment mode to allow fluid from the selected second fluid well 141 of the second set of wells 140 to flow into the fluid loop 110, and to block the flow of fluid from the first set of wells 130. In the second liquid handling mode, the first valve 150 is set to the blocking position, in which its selector channel 152 is not aligned with any of the first well ports 155 to block liquids from the first set of wells 130. The second valve 160 is positioned with its selector port 162 connected to a selected one of the second well ports 167 to allow fluid to flow from the corresponding second liquid well 141 to the outlet port 164 of the second valve. At the same time, valve set 180 is set to fluid loop mode to allow fluid to flow from fluid loop 110 to outlet 170 and to pump 190 when valve 181 is open and valves 182 and 183 are closed. As shown in FIG. 5, an aliquot of the second liquid (shown in thick line) from the selected second liquid well 141 is directed through the inlet 111 to the inkjet 112 for processing. After passing through the jet device 112, an aliquot of the second liquid can be temporarily retained in the buffer tank 116 and/or transferred directly to the syringe pump 190

According to FIG. 6, the liquid cartridge 100 can be set to drain mode. In the drain mode, the first valve 150 is set to the blocking position, in which the selector channel 152 of the first valve is not aligned with any of the first well ports 155 to block liquid from the first set of wells 130, and the valve set 180 is set to the drain mode, in which the valve 183 is open and valves 181 and 182 are closed to allow fluid to flow between pump 190 and drain 191 and to block fluid from flowing into the outlet from fluid circuit 110 or fluid bypass circuit 120. In drain mode, second valve 160 can be set to either position so as not to direct fluid into either fluid loop 110 or bypass fluid loop 120. As shown in FIG. 6, the used liquid contained in the syringe pump 190 or other reservoir can be discharged into the drain hole 191 for disposal.

In some examples, an aliquot of the first liquid or an aliquot of the second liquid temporarily held in the buffer tank 116 can be reintroduced into the fluidizer 112 in accordance with the reagent recycling processes discussed in US Pat. "("Liquid system for supplying reagents to the flow cell"), filed on 08/07/2014. In some examples, an aliquot of the first liquid temporarily held in buffer tank 122 can be used to mix with other liquids, such as another reagent solution, in accordance with the mixing processes discussed in US Patent Publication 2018/0185842 "REAGENT CHANNEL MIXING SYSTEM AND METHOD" ("The system of mixing reagents in the channel, and the method."

In accordance with the examples discussed in the present invention, the liquid cartridge 100 allows in the bypass liquid circuit 120 to perform operations with liquids of the second type, such as transfer, mixing or priming, and the bypass circuit 120 is completely independent of the inkjet device 112. For example, the first fluid may be stored in jet device 112 to perform a first fluid handling operation (e.g., incubation), while a second fluid may be directed to buffer tank 122 and/or syringe pump 190 via fluid bypass loop 120 to be subjected to a second operation. liquid processing (eg priming). By simultaneously executing two independent liquid processing operations, the liquid cartridge 100 can reduce the overall time of multiple liquid processes by parallelizing them.

In accordance with the examples contemplated herein, the fluid cartridge 100 allows certain fluids that may not be compatible with each other, or that may otherwise be preferred to be kept separate, to remain separated by placing a first set of fluids in a first set of wells 130, which is associated with the first valve 150, and placing the second set of fluids in the second set of wells 140, which is associated with the second valve 160. For example, the first set of fluids used for clustering and priming operations in clustering and paired-end priming (CPE )) may be contained in the first well set 130 and manipulated through the first valve 150 and bypass 163 of the second valve 160, and the second set of fluids used for sequencing-by-synthesis (SBS) operations may be contained in the second set 140 wells, and manipulated through the selector channel 161 of the second valve 160. The second valve 160 can be configured so that the bypass channel 163 does not block any of the ports 167 of the second wells, and thereby prevent any unintentional cross-contamination between the first set of liquids for CPE operations and a second set of fluids for SBS operations.

In accordance with the examples discussed in the present invention, the liquid cartridge 100 allows you to place the liquid, based on the organization of the workflow and use. For example, second set fluids for SBS operations are selected and moved more frequently during the sequencing process than first set fluids for CPE operations. Accordingly, in various examples, the second set of fluids contained in the second set of wells 140 are handled only by the second valve 160, so that while the second set of fluids are selected and transferred by the second valve 160, the first set of fluids contained in the first set of wells 130 may optionally remain inoperative and may be protected by the first valve 150. The arrangement of the first and second sets of wells 130, 140, and the first and second valves 150, 160, reduces the total distance that the valves 150, 160 must turn in sequencing process, thus increasing the overall reliability of the liquid cartridge 100.

Processing device

The liquid cartridge 100 may be removably associated with a liquid processing device. As shown in FIG. 10, the removable liquid cartridge 100 can be operatively installed in the processing apparatus 50. As discussed above, the fluid cartridge 100 includes a first valve 150 connected to a second valve 160 through a common fluid channel 105. The fluid cartridge 100 further includes a bypass circuit 120 connecting the second valve 160 to the set 180 valves. Inkjet device 112 may be operatively coupled to apparatus 50, and coupled to second cartridge valve 160 via inlet port 111. Instrument 50 may further comprise a drain port 191 (and optionally a drain reservoir) and a pump 190, the drain port and pump both being connected to a set of valves 180 of cartridge 100. Controller 200, which may be part of instrument 50, or may be a separate device or remote computer resource operatively connected to instrument 50, controls the operation of instrument 50 (e.g., processes in fluidic device 112 and operation of pump 190) , and the operation of the cartridge 100 (eg, the operation of the first and second valves 150, 160 as well as the operation of the valve set 180).

Hardware and software

The present invention in its aspects is implemented by control and computing hardware components, user generated software, data input components, and data output components. Hardware components include computing and control modules (e.g., system controller(s)), such as microprocessors and computers, configured to perform computing and/or control steps by receiving one or more input values, executing one or more algorithms, stored on a non-volatile computer-readable medium (eg, programs) that issue instructions for manipulating or otherwise influencing input values and outputting one or more output values. Such output values may be displayed or otherwise presented to the user as user-relevant information, such as information about the state of the instrument or the process being performed by the instrument, or such output quantities may be input to other processes and/or control algorithms. Input components contain elements through which data is entered for subsequent use by control and computing hardware components. Such inputs may include encoder signals, motor encoders, as well as manual input signal elements such as graphical user interfaces, keyboards, touch screens, microphones, switches, manual scanners, voice-triggered signals, and the like. Data output components may include hard drives or other storage media, graphical user interfaces, monitors, printers, indicator lights or audible alarms (eg, vibrator, siren, bell, etc.). The software contains instructions stored on a non-volatile computer-readable storage medium that, when executed by the control and computing hardware components, cause the control and computing hardware to perform one or more automatic or semi-automatic processes.

According to some examples, the instrument may include a control system comprising a computer controlled controller 200 (shown schematically in FIG. 1). Controller 200 may be a control system or computer coupled to fluid cartridge 100, or may include computer components coupled to fluid cartridge 100. Computer components may include one or more microprocessors, displays, keyboards (and/or other devices user input), memory components, printer(s), etc. The controller 200 may be configured to receive signals from a user (e.g., user commands) or from feedback devices such as pressure sensors, flow meters, and the like, and control fluid handling of the fluid cartridge 100. The controller 200 may include software algorithms that allow the user to enter fluid handling parameters into the fluid cartridge 100, schedule various fluid operations in the fluid cartridge 100, and cause the controller 200 to perform various fluid handling steps, control the execution of said operations, and display their results (on a display or on a printer) for the user.

According to various examples, the controller 200 is operatively coupled to the first valve 150, the second valve 160, the valve bank 180, and the pump 190 (links omitted in the drawings) so that the controller 200 can send instructions to the various devices of the liquid cartridge 100 to perform various steps related to operations with liquids (for example, the processes corresponding to Fig. 3-6 and 9).

Directional transfer method for liquids contained in a liquid cartridge

According to various examples, FIG. 9 illustrates a method 900 for directing fluids from any one of the first set of wells 130 and the second set of wells 140 to fluid circuit 110 or bypass fluid circuit 120.

According to FIG. 9, the method 900 comprises 910 selecting the first fluid well 131 of the first set of 130 wells operatively associated with the first valve 150 by moving the first valve 150 from the blocking position to the first fluid position when the selector channel 152 of the first valve is connected to one of the ports 155 of the first wells corresponding to the selected first fluid well 131. According to some examples, step 910 further comprises using a first actuator comprising a motor (not shown) operatively associated with the first valve 150 to move the first rotary element 151 from the blocking position to the first liquid position. According to some examples, step 910 further comprises using the controller 200 operatively associated with the first actuator to command the first valve 150 to switch from the blocking position to the first fluid position.

According to FIG. 9, the method 900 includes a step 920 that moves the first fluid from the selected first fluid well 131 through the first valve 150 into the bypass channel 121 operatively associated with the second valve 160 by placing the second valve 160 in a bypass position in which the first edge 163a of the bypass selector port 163 is aligned with inlet port 166 of the second valve, and the second end 163b of bypass selector port 163 is aligned with bypass port 165. In some examples, step 920 further comprises using a pump 190 to create a differential pressure to move fluid from the selected first fluid well 131 through the first valve 150 and into the bypass passage 121. In some examples, step 920 further comprises using a second actuator comprising a motor (not shown) operatively associated with the second valve 160 to rotate the rotary element 161 of the second valve and bring it into connection with bypass channel 121. According to some examples, step 920 further comprises using a controller 200 operatively associated with the second actuator to command the second valve 160 to switch to the bypass position.

According to FIG. 9, method 900 comprises 930 selecting a second fluid well 141 from a second set of 140 wells operatively associated with the second valve 160 by placing the second valve 160 at the second well position such that the second valve selector channel 162 is aligned with one of the ports. 167 second wells corresponding to the selected second liquid well 141. In some examples, step 930 further comprises using a second actuator to drive the second valve pivot 161 to the second well position. According to some examples, step 930 further comprises using a controller 200 operatively associated with the second actuator to command the second valve 160 to switch to the second well position. According to some examples, step 930 further comprises blocking the passage of liquid stored in the first set 131 of wells through the first valve 150, the common passage 105, and into the second valve 160 by placing the first valve in the blocking position.

According to FIG. 9, method 900 includes 940 moving the second fluid from the selected second fluid well 141 of the second set of fluid wells 140 through the second valve 160 and into the fluid circuit 110 while the first fluid transferred from the selected first fluid well 131 in step 920 is stored in the bypass 121. Step 940 may further comprise holding the selected first fluid in the buffer tank 122, and moving the selected second fluid into the jet device 112. According to some examples, step 940 further comprises using a pump 190 to create a pressure difference to move liquid from the selected second liquid well 142 through the second valve 160 and into the liquid circuit 110.

According to some examples, the method 900 comprises 950 selecting the first fluid well 131 of the first set 130 of fluid wells operatively associated with the first valve 150 by setting the first valve to the first fluid position. In some examples, step 950 includes selecting the first fluid well 131 that was selected in step 910. In some examples, step 950 includes selecting the first fluid well 131 that was not selected in step 910 and which contains a third fluid that is different from the first liquid contained in the selected first liquid well 131 at step 910.

According to some examples, method 900 comprises 960 moving fluid from a selected first fluid well 131 of a first set of fluid wells 130 through a first valve 150, a common passage 105, a second valve 160, and a fluid circuit 110 by placing the second valve 160 in the communication position with the first valve, in which the selector channel 162 of the second valve is connected to the inlet port 166 of the second valve. According to some examples, step 960 includes using a second actuator to move the second valve 160 into communication with the first valve. According to some examples, step 960 further comprises using the controller 200 operatively associated with the second valve to instruct the second valve to rotate into a position in communication with the first valve.

According to some examples, the method 900 after step 920 may include moving at least a portion of the selected first fluid from the bypass channel 121 to the outlet channel 170 and into the syringe pump 190, and then displacing said portion of the selected first fluid contained in the syringe pump 190 through the outlet channel 170 and into fluid circuit 110. In some examples, the step of moving said at least a portion of the selected first fluid from bypass channel 121 to outlet channel 170 comprises using an actuator to move the plunger of syringe pump 190 in a first direction to create a negative pressure difference. In some examples, the step of expelling a portion of the selected first fluid contained in syringe pump 190 through outlet port 170 and into fluid circuit 110 comprises using an actuator to move the plunger of syringe pump 190 in a second direction to create a positive pressure difference. According to some examples, the step of moving said at least a portion of the selected first fluid from the bypass channel 121 to the outlet channel 170 includes opening and moving the second control valve 182 to the open position, setting the first and third control valves 181, 183 to the closed position by setting the set 180 valves in bypass mode. In some examples, the step of expelling a portion of the selected first fluid from the syringe pump 190 through the outlet 170 and into the fluid circuit 110 comprises opening the first control valve 181 and setting the second and third control valves 182, 183 to the closed position by setting the valve stack 180 to flow cell mode.

According to some embodiments, in the method 900, after step 940, the selected first fluid from the bypass channel 121 can be transferred to the fluid circuit 110 by setting the second valve 160 to the bypass supply position, in which the selector channel 162 of the second valve is aligned with the bypass port 165. According to some examples, this step includes using a second actuator to move the rotary element 161 of the second valve to the position of supply from the bypass circuit. According to some examples, this step further comprises using the controller 200 operatively associated with the second actuator to command the second valve 160 to move to the bypass supply position. In some examples, this step further comprises blocking the fluid stored in the first set of wells 131 and preventing it from moving through the first valve 150, the common passage 105, and into the second valve 160 by placing the first valve in the blocked position.

In some embodiments, the method 900 after step 940 may comprise moving at least a portion of the selected second fluid from the fluid circuit 110 to the outlet 170, and to the syringe pump 190. In some examples, the step of moving at least a portion of the selected second fluid from the fluid the circuit 110 to the outlet channel 170 comprises using an actuator to move the plunger of the syringe pump 190 in a first direction to create a negative pressure difference. According to some examples, the step of moving at least a portion of the selected second fluid from the fluid circuit 110 to the outlet channel 170 includes placing the first control valve 181 in the open position and setting the second and third control valves 182, 183 in the closed position by setting the set of valves 180 to the mode flow cell.

According to some examples, the method 900 may include the process of introducing some air into the bypass channel 121 by placing the first valve 150 in the purge position and by connecting the selector channel 152 of the first valve to a source of air or other gas or liquid, and placing the second valve 160 in the bypass position. by connecting the bypass selector channel 163 to the inlet port 166 and the bypass port 165 of the second valve.

In some embodiments, steps 910, 920, 930, 940, 950, and/or 960 of method 900 may be performed in any order, and are not limited to the specific order shown in FIG. 9. Moreover, any of steps 910, 920, 930, 940, 950, and/or 960 of method 900 may be omitted.

It should be understood that all combinations of the above ideas and additional ideas, which will be discussed in more detail below (provided that these ideas do not contradict each other) are considered as part of the disclosed subject matter. In particular, all combinations of the claimed subject matter appearing at the end of this description are considered to be part of the disclosed subject matter. It should also be understood that terms that are expressly used in the present description, and which may also appear in the description of any invention to which reference is made, should correspond to the meaning most appropriate to the specific ideas disclosed in the present description.

Although the subject matter of the present invention has been described and presented in some detail with reference to certain illustrative examples, including various combinations and subcombinations of characteristics, the possibility of other examples, variations and modifications that fall within the scope of the present invention should be clear to those skilled in the art. Moreover, the descriptions of such examples, combinations and subcombinations are not intended to convey the idea that the claimed subject matter requires characteristics or combinations of characteristics other than those expressly listed in the claims. Accordingly, the scope of the present invention is intended to include all modifications and variations that fall within the scope of the appended claims.

Information disclosed in the invention includes the following items:

1. Apparatus containing: liquid circuit;

bypass liquid circuit;

a first set of liquid wells;

a second set of liquid wells;

a first valve comprising a first valve outlet port and a plurality of first valve ports operatively associated with the first set of fluid wells, wherein the first valve is configured to selectively fluidly connect the first well of the first set of fluid wells to the first valve outlet port when the valve is in the first position , and selectively fluidically connecting the second well of the first set of fluid wells to the outlet port of the first valve when the valve is set to the second position; And

a second valve comprising an outlet port of the second valve, a bypass selector channel and a plurality of ports of the second valve, the outlet port of the second valve is operatively connected to the liquid circuit, the bypass selector channel is operatively connected to the bypass liquid circuit and the outlet port of the first valve, while the second valve is configured to a selective fluid connection of the first well of the second set of fluid wells to the fluid circuit when the second valve is in the first well position, and a selective fluid connection of the bypass selector channel to the bypass fluid circuit when the second valve is in the bypass position.

2. Apparatus according to claim. 1, characterized in that it further comprises a common fluid channel connecting the outlet port of the first valve with the second valve.

3. Apparatus according to claim 1 or 2, characterized in that the second valve is rotatable between a plurality of positions.

4. Apparatus according to any one of paragraphs. 1-3, characterized in that the second valve is configured to selectively fluidly connect the outlet port of the first valve to the fluid circuit when the second valve is set to a communication position with the first valve.

5. Apparatus according to any one of paragraphs. 1-4, characterized in that the second valve is configured to selectively fluidly connect the second well of the second set of fluid wells to the fluid circuit when the second valve is set to the position of the second well.

6. Apparatus according to any one of paragraphs. 1-5, characterized in that the first valve is rotatable between multiple positions.

7. Apparatus according to any one of paragraphs. 1-6, characterized in that it additionally contains:

an outlet channel providing fluid connection of the bypass fluid circuit and the fluid circuit to the pump.

8. Apparatus according to claim. 7, characterized in that the outlet channel has a liquid connection with a drain hole.

9. Apparatus according to claim 8, characterized in that it additionally contains:

a set of valves containing one or more valves located along the outlet channel for selectively controlling the flow of liquid between the bypass liquid circuit, the liquid circuit, the pump and the drain hole.

10. Apparatus according to any one of the preceding claims, characterized in that the bypass fluid circuit comprises a buffer tank for holding a first predetermined volume of fluid.

11. Apparatus according to any one of the preceding claims, characterized in that the fluid circuit comprises a jet device and a buffer reservoir located downstream of the jet device and containing a second predetermined volume of liquid.

12. Apparatus according to claim 1, characterized in that:

the fluid circuit is in fluid communication with the flow cell;

the bypass fluid circuit includes a bypass channel;

wherein the first of the plurality of ports of the first valve is operatively connected to the first fluid well such that the first valve is configured to selectively allow fluid to flow from the first fluid well to the outlet port of the first valve; A

the outlet port of the second valve has a fluid connection with the fluid circuit, while the second valve contains:

a bypass port having a fluid connection with the bypass channel,

an inlet port in fluid communication with the outlet port of the first valve,

a second fluid well port having fluid communication with the second fluid well, and

a rotary element of the second valve, made with the possibility of rotation to a plurality of positions of the second valve,

so that the second valve selectively allows fluid to 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.

13. The apparatus according to claim 12, characterized in that the bypass port, the inlet port of the first valve and the port of the second liquid hole are located in a circular pattern, while the rotary element of the second valve contains:

a selector channel of the second valve, providing a fluid connection of the outlet port of the second valve with one of the inlet port of the second valve or the port of the second fluid well, and

a bypass selector passage providing fluid communication between the inlet port of the second valve and the bypass port when the rotary member of the second valve is in the bypass position.

14. Apparatus according to claim. 12 or 13, characterized in that the first valve contains a rotary element made with the possibility of rotation to a plurality of positions of the first valve, so that the first valve is configured to selectively control the movement of fluid from a selected one of the plurality of ports of the first valve to outlet port of the first valve; wherein

the rotary element of the first valve contains a selector channel of the first valve, providing a fluid connection of the selected one of the plurality of ports of the first valve with the outlet port of the first valve.

15. Apparatus, containing:

a fluid circuit having a fluid connection with the flow cell;

passageway;

first liquid well;

second liquid well;

a first valve comprising an outlet port and a plurality of first valve ports, wherein a first of said plurality of first valve ports is operatively coupled to the first fluid well such that the first valve is configured to selectively allow fluid to flow from the first fluid well to the first valve outlet port; And

second valve containing:

the outlet port of the second valve having a fluid connection with the fluid circuit,

a bypass port having a fluid connection with the bypass channel,

an inlet port of the second valve in fluid communication with the outlet port of the first valve,

a second fluid well port having fluid communication with the second fluid well, and

a rotary element of the second valve, made with the possibility of rotation to a plurality of positions of the second valve,

so that the second valve is configured to selectively move fluid 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.

16. The apparatus according to claim 15, characterized in that the bypass port, the inlet port of the first valve and the port of the second liquid hole are located in a circular pattern, while the rotary element of the second valve contains:

a selector channel of the second valve, providing a fluid connection of the outlet port of the second valve with one of the inlet port of the second valve or the port of the second fluid well, and

a bypass selector passage providing fluid communication between the inlet port of the second valve and the bypass port when the rotary member of the second valve is in the bypass position.

17. Apparatus according to claim. 15 or 16, characterized in that the first valve contains a rotary element of the first valve, made with the possibility of rotation to a plurality of positions of the first valve, so that the first valve is configured to selectively control the movement of fluid from a selected one of the plurality of ports of the first valve to the outlet port of the first valve; wherein

the rotary element of the first valve contains a selector channel of the first valve, providing a fluid connection of the selected one of the plurality of ports of the first valve with the outlet port of the first valve.

18. A method comprising:

selecting the first liquid stored in the first liquid well of the first set of liquid wells operatively associated with the first valve by setting the first valve from the base position to the position of the first liquid well;

transferring at least a portion of the selected first fluid from the first valve to a bypass channel operatively associated with the second valve by placing the second valve in the bypass position;

selecting a second liquid stored in the second liquid well of the second set of liquid wells operatively associated with the second valve by positioning the second valve at the position of the second liquid well;

moving at least a portion of the selected second fluid into the fluid circuit while a portion of the selected first fluid is in the bypass.

19. The method of claim 18, further comprising transferring at least a portion of the selected first fluid from the bypass channel to the fluid circuit.

20. The method of claim 18 or 19, further comprising moving at least a portion of the selected second fluid from the fluid circuit to the drain.

21. The method according to any one of paragraphs. 18-20, characterized in that it additionally contains:

selecting a second liquid stored in the second liquid well of the first set of liquid wells operatively associated with the first valve;

moving at least a portion of the selected second fluid into the fluid circuit by placing the second valve in communication with the first valve.

22. The method according to any one of paragraphs. 18-21, characterized in that it further comprises introducing an air volume into the bypass channel by setting the first valve to the cleaning position, and setting the second valve to the bypass position.

23. The method according to any one of paragraphs. 18-22, characterized in that it further comprises blocking the first liquid stored in the first set of liquid wells in order to prohibit its movement to the second valve by setting the first valve to the base position.

Claims (43)

1. A multi-valve fluid cartridge, comprising: liquid circuit (110); bypass liquid circuit (120); the first set of liquid wells (130); a second set of fluid wells (140); the first valve (150), containing the outlet port (154) of the first valve and a plurality of ports (155) of the first holes, functionally associated with the first set of liquid holes (130), while the first valve (150) is configured to selectively fluidly connect the first well of the first a set of fluid wells (130) with the outlet port (154) of the first valve when the valve is in the first position, and selective fluid connection of the second well of the first set of fluid wells (130) with the outlet port (154) of the first valve when the valve is in the second position ; And a second valve (160) containing an outlet port (164) of the second valve, a bypass selector channel (163) and a plurality of ports (167) of the second holes, functionally connected with the second set of liquid holes (140), and the outlet port (164) of the second valve is functionally connected to the fluid circuit (110), the bypass selector channel (163) is operatively connected to the bypass fluid circuit (120) and the outlet port (154) of the first valve, while the second valve (160) is configured to selectively fluidly connect the first well of the second set of fluid wells (140) with a fluid circuit (110) to allow fluid to flow from the first well of the second set of fluid holes (140) into the fluid circuit (110) when the second valve is in the position of the first hole, and selective fluid connection of the bypass selector channel (163 - with bypass liquid circuit (120) when the second valve is in the bypass position; a common channel (105) providing fluid connection of the outlet port (154) of the first valve with the second valve (160); an outlet channel (170) having a fluid connection with a drain hole (191); And a set (180) of valves containing one or more valves located along the outlet channel (170) for selectively controlling at least one of the flow between the bypass liquid circuit (120) and the pump (190), the flow between the liquid circuit (110) and pump (190) and flow between outlet (170) and drain (191). 2. The cartridge of claim 1, wherein the second valve is rotatable between multiple positions. 3. A cartridge according to claim 1 or 2, wherein the second valve is configured to selectively fluidly connect the outlet port of the first valve to the fluid circuit when the second valve is in communication with the first valve. 4. The cartridge according to any one of paragraphs. 1-3, wherein the second valve is configured to selectively fluidly connect the second well of the second set of fluid wells to the fluid circuit when the second valve is set to the second well position. 5. Cartridge according to any one of paragraphs. 1-4, wherein the first valve is rotatable between a plurality of positions. 6. A cartridge according to any one of the preceding claims, wherein the bypass fluid circuit comprises a bypass buffer tank to accommodate a first predetermined volume of fluid. 7. A cartridge according to any of the preceding claims, wherein the fluid circuit comprises an inkjet device and a liquid buffer reservoir located downstream of the inkjet device and containing a second predetermined volume of liquid. 8. A cartridge according to any one of the preceding claims, wherein: the fluid circuit is in fluid communication with the flow cell; the bypass liquid circuit contains a bypass channel; wherein the first of the plurality of first well ports is operatively coupled to the first liquid well such that the first valve is configured to selectively allow fluid to flow from the first liquid well to the outlet port of the first valve; And the outlet port of the second valve has a fluid connection with the fluid circuit, while the second valve contains: a bypass port having a fluid connection with the bypass channel, an inlet port of the second valve in fluid communication with the outlet port of the first valve, a second fluid well port having fluid communication with the second fluid well, and a rotary element of the second valve, made with the possibility of rotation to a plurality of positions of the second valve, so that the second valve selectively allows fluid to 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. 9. The cartridge according to claim 8, in which the bypass port, the inlet port of the first valve and the port of the liquid hole of the second valve are located in a circular pattern, while the rotary element of the second valve contains: a selector channel of the second valve, providing a fluid connection of the outlet port of the second valve with one of the inlet port of the second valve or the port of the second fluid well, and a bypass selector passage providing fluid communication between the inlet port of the second valve and the bypass port when the rotary member of the second valve is in the bypass position. 10. The cartridge of claim 8 or 9, wherein the first valve comprises a first valve rotatable member rotatable to a plurality of first valve positions such that the first valve is configured to selectively control fluid flow from a selected one of the plurality of ports of the first wells to outlet port of the first valve; wherein the rotary element of the first valve contains a selector channel of the first valve, providing a fluid connection of the selected one of the plurality of ports of the first holes with the outlet port of the first valve. 11. A method of using a multi-valve liquid cartridge, comprising: selecting the first liquid stored in the first liquid well of the first set of liquid wells operatively associated with the first valve by setting the first valve from the base position to the position of the first liquid well; transferring at least a portion of the selected first fluid from the first valve to a bypass channel operatively associated with the second valve by placing the second valve in the bypass position; selecting a second liquid stored in the second liquid well of the second set of liquid wells operatively associated with the second valve by positioning the second valve at the position of the second liquid well; moving at least a portion of the selected second fluid into the fluid circuit while a portion of the selected first fluid is in the bypass. 12. The method of claim. 11, further comprising moving at least a portion of the selected first fluid from the bypass channel to the fluid circuit. 13. The method of claim 11 or 12, further comprising moving at least a portion of the selected second fluid from the fluid circuit to the outlet line. 14. The method according to any one of paragraphs. 11-13, further comprising: selecting a second liquid stored in the second liquid well of the first set of liquid wells operatively associated with the first valve; moving at least a portion of the selected second fluid into the fluid circuit by placing the second valve in communication with the first valve. 15. The method according to any one of paragraphs. 11-14, further comprising introducing a volume of air into the bypass channel by setting the first valve to the purge position, and setting the second valve to the bypass position. 16. The method according to any one of paragraphs. 11-15, further comprising blocking the first liquid stored in the first set of liquid wells to prevent its movement to the second valve by setting the first valve to the base position.

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