System and associated sample loading manifold assembly

Abstract

The device includes one or more valves adapted to be coupled to corresponding reagent reservoirs and a flow cell interface adapted to be coupled to a flow cell. The device includes a sample cartridge interface having one or more ports and adapted to be coupled to a sample cartridge carrying a sample of interest. The sample cartridge interface is positioned downstream from the flow cell interface. The device includes a pump adapted to load the sample of interest into a channel of the flow cell via the flow cell interface associated with an outlet of the flow cell and a corresponding port of the sample cartridge interface.

Description

[Technical field]

[0001] (Related Applications) This application claims the benefit of and priority to U.S. Provisional Patent Application No. 62 / 902,364, filed September 18, 2019, the contents of which are incorporated herein by reference in their entirety for all purposes. [Background technology]

[0002] The sequencing platform may include valves and pumps that may be used to perform various fluidic operations. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] US Patent Application Publication No. 2003 / 0162304 [Patent Document 2] US Patent Application Publication No. 2011 / 0072914 [Patent Document 3] US Patent Application Publication No. 2015 / 0045234 [Patent Document 4] US Patent Application Publication No. 2015 / 0093815 [Patent Document 5] US Patent Application Publication No. 2018 / 0188279 [Patent Document 6] U.S. Patent No. 6,190,751 Summary of the Invention

[0004] According to a first implementation, the method comprises or includes coupling a flow cell comprising or having a plurality of channels to a flow cell interface. The flow cell interface is fluidly coupled to a pump manifold assembly. The method comprises or includes operating one or more of a plurality of pump valves and one or more of a plurality of pumps of the pump manifold assembly to individually control fluid flow through each of the plurality of channels via a corresponding pump channel fluid line. The pump manifold assembly comprises or includes a plurality of pump channel fluid lines, a plurality of pump fluid lines, and a shared fluid line. Each pump valve is coupled to a corresponding pump channel fluid line, a corresponding pump fluid line, and a shared fluid line. Each pump is coupled to a corresponding pump fluid line.

[0005] According to a second implementation, the device comprises or includes a flow cell interface adapted to be coupled to a flow cell comprising or having a plurality of channels. The device comprises or includes a pump manifold assembly carrying a plurality of pump valves and a plurality of pumps, and comprising or having a plurality of pump channel fluid lines, a plurality of pump fluid lines, and a shared fluid line. The pump valves and pumps are operable to individually control the flow of fluid through each of the plurality of channels of the flow cell via a corresponding pump channel fluid line. Each pump valve is coupled to a corresponding pump channel fluid line, a corresponding pump fluid line, and a shared fluid line. Each pump is coupled to a corresponding pump fluid line.

[0006] According to a third implementation, the device comprises or includes one or more valves adapted to be coupled to corresponding reagent reservoirs. The device comprises or includes a flow cell interface adapted to be coupled to a flow cell comprising or having a plurality of channels. The device comprises or includes a pump manifold assembly comprising or having a plurality of pumps, a plurality of pump valves, and a cache. Each pump is operable to individually control fluid flow in each of the plurality of channels of the flow cell. The device comprises or includes a bypass fluid line operably coupled between the one or more valves and the cache.

[0007] According to a fourth implementation, the method comprises or includes coupling a flow cell with or having a plurality of channels to a flow cell interface. The method comprises or includes coupling a sample cartridge to a sample cartridge interface positioned downstream of the flow cell interface. The sample cartridge carries a sample of interest. The method comprises or includes operating one or more sample valves of a sample loading manifold assembly to individually load the sample of interest into each of the plurality of channels of the flow cell in a first direction via a corresponding outlet of the flow cell. The method comprises or includes flowing reagents through the plurality of channels in a second direction opposite the first direction via a corresponding inlet of the flow cell.

[0008] According to a fifth implementation, the device comprises or includes a flow cell interface adapted to be coupled to a flow cell comprising or having a plurality of channels. The device comprises or includes a sample cartridge interface adapted to be coupled to a sample cartridge. The sample cartridge interface is positioned downstream of the flow cell interface. The device comprises or includes a sample loading manifold assembly positioned between the flow cell interface and the sample cartridge interface and comprising or including a body carrying a plurality of sample valves and defining a plurality of sample ports and a plurality of flow cell ports. Each sample port is coupled to a corresponding port of the sample cartridge interface via a sample fluid line. Each flow cell port is coupled to a corresponding port of the flow cell interface and associated with one of the channels of the plurality of channels of the flow cell via a flow cell fluid line.

[0009] According to a sixth implementation, the device comprises or includes one or more valves adapted to be coupled to corresponding reagent reservoirs. The system comprises or includes a flow cell interface adapted to be coupled to a flow cell comprising or having a plurality of channels. The device comprises or includes a sample cartridge interface comprising or having a plurality of ports and adapted to be coupled to a sample cartridge carrying a sample of interest. The sample cartridge interface is positioned downstream of the flow cell interface. The device comprises or includes a pump manifold assembly comprising or having a plurality of pumps and a plurality of pump valves. Each pump and corresponding pump valve is operable to individually control the flow of the sample of interest between each port of the plurality of ports of the sample cartridge interface and a corresponding channel of the plurality of channels of the flow cell.

[0010] According to a seventh implementation, the method comprises or includes coupling a flow cell with or having a plurality of channels to a flow cell interface. The flow cell interface is fluidly coupled to a pump manifold assembly. The method comprises or includes moving a first pump valve of a plurality of pump valves of the pump manifold assembly to a first position to fluidly connect a first channel of the plurality of channels with a first pump of the plurality of pumps. The first pump is fluidly connected to the first channel via a first pump channel fluid line. The method comprises or includes pumping a first volume of a first reagent through the first channel using the first pump via the first pump channel fluid line, and moving the first pump valve of the plurality of pump valves to a second position to fluidly connect the pump and the first pump channel fluid line with a shared fluid line that fluidly communicates with a waste reservoir. The method comprises or includes pumping a first volume of a first reagent through a shared fluid line into a waste reservoir and moving a second pump valve of the plurality of pump valves to a first position to fluidly connect a second channel of the plurality of channels with a second pump of the plurality of pumps. The second pump is fluidly connected to the second channel through a second pump channel fluid line. The method comprises or includes pumping a second volume of a first reagent into the second channel using the second pump through the second pump channel fluid line and moving a second pump valve of the plurality of pump valves to a second position to fluidly connect the second pump and the second pump channel fluid line with a shared fluid line that is in fluid communication with the waste reservoir. The method comprises or includes pumping a second volume of a first reagent through the shared fluid line into a waste reservoir.

[0011] According to an eighth implementation, the device comprises or includes a flow cell interface adapted to be coupled to a flow cell comprising or having a plurality of channels, and a pump manifold assembly carrying a plurality of pump valves and a plurality of pumps and comprising or including a plurality of pump channel fluid lines, a plurality of pump fluid lines, and a shared fluid line. The pump valves and pumps are operable to individually control fluid flow through each channel of the plurality of channels of the flow cell via a corresponding pump channel fluid line. Each pump valve is coupled to a corresponding pump channel fluid line, a corresponding pump fluid line, and a shared fluid line, and is movable between a first position fluidically coupling a corresponding channel of the plurality of channels, a corresponding pump channel fluid line, and a corresponding pump fluid line, and a second position fluidically coupling a corresponding pump fluid line, a shared fluid line, and a waste reservoir. Each pump is coupled to a corresponding pump fluid line.

[0012] According to an eighth implementation, the device comprises or includes one or more valves adapted to be coupled to corresponding reagent reservoirs, a flow cell interface adapted to be coupled to a flow cell comprising or having a plurality of channels, and a pump manifold assembly comprising or having a plurality of pumps, a plurality of pump valves, and a cache. Each pump may be operable to individually control fluid flow in each of the plurality of channels of the flow cell. The device comprises or includes a bypass fluid line operably coupled between the one or more valves and the cache.

[0013] According to a ninth implementation, the method comprises or includes coupling a flow cell with or having a first channel and a second channel to a flow cell interface, and moving a first sample valve of one or more sample valves of a sample loading manifold assembly to a first position to fluidly couple a first sample reservoir of a sample cartridge to an outlet of a first channel of the flow cell. The method comprises or includes pumping a first sample of interest from the first sample reservoir through the outlet of the first channel into the first channel of the flow cell. An inlet of the first channel is fluidly connected to a waste reservoir through a central valve when the central valve is in the first position. The method comprises or includes moving a first sample valve of one or more sample valves of the sample loading manifold assembly to a second position to fluidly disconnect a first sample reservoir of the sample cartridge and fluidly connect an outlet of the first channel with a waste reservoir, and moving a central valve to a second position to fluidly couple a reagent reservoir with the first channel and the second channel of the flow cell. The method comprises or includes pumping a first volume of reagent through the first channel and into the waste reservoir.

[0014] According to a tenth implementation, the device comprises or includes a flow cell interface adapted to be coupled to a flow cell comprising or having a plurality of channels, a central valve, and an auxiliary waste fluid line coupled to the central valve and adapted to be coupled to a waste reservoir. The central valve is coupled to the flow cell interface and is movable between a first position fluidly connecting the inlets of the plurality of channels to the auxiliary waste fluid line and a second position fluidly connecting the reagent reservoir and the plurality of channels. The device comprises or includes a sample cartridge interface adapted to be coupled to a sample cartridge. The sample cartridge interface is positioned downstream of the flow cell interface, and the sample loading manifold assembly is positioned between the flow cell interface and the sample cartridge interface and comprises or includes a body carrying a plurality of sample valves and defining a plurality of sample ports and a plurality of flow cell ports. Each sample port is coupled to a corresponding port of the sample cartridge interface via a sample fluid line. Each flow cell port is coupled to a corresponding port of the flow cell interface and associated with one of the plurality of channels of the flow cell via a flow cell fluid line. Each of the sample valves is movable between a first position fluidly connecting a corresponding sample port with a corresponding outlet of the plurality of channels and a second position fluidly connecting a corresponding outlet of the plurality of channels with a waste reservoir.

[0015] According to an eleventh embodiment, the device comprises or includes one or more valves adapted to be coupled to corresponding reagent reservoirs and a flow cell interface adapted to be coupled to a flow cell. The device comprises or includes a sample cartridge interface having one or more ports and adapted to be coupled to a sample cartridge carrying a sample of interest. The sample cartridge interface is positioned downstream of the flow cell interface. The device comprises or includes a pump adapted to load the sample of interest into a channel of the flow cell via the flow cell interface associated with an outlet of the flow cell and a corresponding port of the sample cartridge interface.

[0016] Further, according to the first, second, third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, and eleventh implementation forms described above, the apparatus and / or method may further comprise or include any one or more of the following:

[0017] According to one implementation, the method further comprises or includes moving the bypass valve to a first position to fluidly couple the bypass fluid line to a cache of the pump manifold assembly, and pumping a third volume of the first reagent or another reagent through the bypass fluid line and into the cache.

[0018] According to another implementation, the method further comprises or includes actuating one or more of a plurality of pump valves, one or more of a plurality of pumps, or a cache valve of the pump manifold assembly, and pumping reagents at least one of between the shared fluid line and a main waste fluid line fluidly connected to the waste reservoir, or between the bypass fluid line and the main waste fluid line.

[0019] According to another implementation, the method further comprises or includes operating one or more of the plurality of pump valves and one or more of the plurality of pumps of the pump manifold assembly to load the sample of interest into one or more of the plurality of channels of the flow cell.

[0020] According to another implementation, operating one or more of the plurality of pumps to load a target sample into one or more of the plurality of channels of the flow cell comprises or includes flowing the target sample in a first direction, and further comprises or includes operating one or more of the plurality of pumps of a pump manifold assembly to control a flow of reagents through the channels of the flow cell in a second direction opposite to the first direction.

[0021] According to another implementation, the method further comprises or includes operating one or more of a plurality of pumps of a pump manifold assembly to flow the sample of interest from one or more channels of the flow cell to an auxiliary waste fluid line, the auxiliary waste fluid line being upstream of the flow cell interface.

[0022] According to another implementation, the pump manifold assembly further comprises or includes a cache and further comprises or includes a bypass valve and a bypass fluid line coupling the bypass valve and the cache.

[0023] According to another implementation, the pump manifold assembly further comprises or includes a cache valve and a cache fluid line. The cache valve is coupled to the cache fluid line and the shared fluid line.

[0024] According to another implementation, the pump manifold assembly further comprises or includes a main waste fluid line coupled to the waste reservoir. The cache valve is coupled to the main waste fluid line.

[0025] According to another implementation, the pump manifold assembly further comprises or includes a plurality of sensors adapted to determine one or more of a pressure value or a flow value of at least one of the pump channel fluid lines or one or more of the shared fluid lines.

[0026] According to another implementation, the system further comprises or includes a pair of pump drive assemblies operable to drive the multiple pumps.

[0027] According to another implementation, the flow cell further comprises or includes a sample cartridge interface adapted to be coupled to a sample cartridge, the sample cartridge interface being positioned downstream of the flow cell interface.

[0028] According to another implementation, the apparatus further comprises or includes a sample loading manifold assembly positioned between the flow cell interface and the sample cartridge interface and comprising or including a body carrying a plurality of sample valves and defining a plurality of sample ports, a plurality of flow cell ports, and a plurality of pump ports. Each sample port is coupled to a corresponding port of the sample cartridge interface via a sample fluid line. Each flow cell port is coupled to a corresponding port of the flow cell interface and associated with one of the channels of the plurality of channels of the flow cell via a flow cell fluid line. Each pump port is coupled to a corresponding pump channel fluid line of the plurality of pump channel fluid lines.

[0029] According to another implementation, the sample valves of the sample loading manifold assembly and the pumps of the pump manifold assembly are operable to individually load a sample of interest into each channel of the multiple channels of the flow cell.

[0030] According to another implementation, each sample valve is operable to fluidly connect a port of the sample cartridge to a corresponding pump of the multiple pumps of the pump manifold assembly, and to fluidly connect a pump of the multiple pumps of the pump manifold assembly to a corresponding channel of the multiple channels of the flow cell.

[0031] According to another implementation, the flow cell interface further comprises or includes a central valve and an auxiliary waste fluid line coupled to the central valve and adapted to be coupled to a waste reservoir, the auxiliary waste fluid line being positioned upstream of the flow cell interface.

[0032] According to another implementation, the system further comprises or includes a shared line valve, a bypass valve, a plurality of dedicated reagent fluid lines, and a shared reagent fluid line. The shared reagent fluid line couples the shared line valve and the central valve and is adapted to flow one or more reagents to the flow cell via the central valve. Each dedicated reagent fluid line couples the bypass valve and the central valve and is adapted to flow a reagent to the flow cell via the central valve.

[0033] According to another implementation, the system further comprises or includes a sample loading manifold assembly including or having a plurality of sample valves, each sample valve and corresponding pump of the pump manifold assembly operable to individually load each channel of the plurality of channels of the flow cell, the sample loading manifold assembly being positioned downstream of the flow cell.

[0034] According to another implementation, the system further comprises or includes a flow cell assembly comprising or including a flow cell comprising or having a plurality of channels and a flow cell manifold comprising or including an inlet, a plurality of fluid lines, and a plurality of outlets, each outlet of the flow cell manifold being coupled to a corresponding channel of the flow cell.

[0035] According to another implementation, pumping the first sample of interest from the first sample reservoir into the first channel of the flow cell comprises or includes moving the first sample of interest from the sample cartridge to a corresponding sample port of the sample loading manifold assembly and out of an associated pump port of the sample loading manifold assembly into a pump channel fluid line of the pump manifold assembly, and moving the first sample of interest from the pump channel fluid line through the associated pump port and through a corresponding flow cell port of the sample loading manifold assembly, each flow cell port being coupled to a corresponding port of the flow cell interface and associated with one of the channels of the plurality of channels of the flow cell.

[0036] According to another implementation, moving a first sample valve of the one or more sample valves to a first position comprises or includes fluidly coupling a port of the sample cartridge interface with a corresponding pump, and moving a first sample valve of the one or more sample valves to a second position comprises or includes fluidly coupling a corresponding pump with a first channel of a plurality of channels of the flow cell.

[0037] According to another implementation, the method further comprises or includes operating one or more of a plurality of pumps to individually control fluid flow in each of a plurality of channels of the flow cell.

[0038] According to another implementation, the method further comprises or includes flowing the first sample of interest from the first channel of the flow cell to an auxiliary waste fluid line, the auxiliary waste fluid line being upstream of the flow cell and fluidly coupled to the central valve and the waste reservoir.

[0039] According to another implementation, the method further comprises or includes flowing a reagent through a shared reagent fluid line into the multiple channels of the flow cell, followed by flowing a separate reagent through a dedicated reagent fluid line into the multiple channels of the flow cell.

[0040] According to another implementation, the sample valve is operable to individually load each channel of multiple channels of the flow cell.

[0041] According to another implementation, the sample loading manifold assembly further comprises or includes a plurality of pumps, the body of the sample loading manifold assembly further defining a plurality of pump ports, each pump port being coupled to one of the pumps of the plurality of pumps via a pump channel fluid line.

[0042] According to another implementation, each sample valve is operable to fluidly connect a port of the sample cartridge to a corresponding pump of the plurality of pumps, and to fluidly connect a pump of the plurality of pumps to a corresponding channel of the plurality of channels of the flow cell.

[0043] According to another implementation, the pump is operable to individually control fluid flow in each of a plurality of channels of the flow cell.

[0044] According to another implementation, the system further comprises or includes a pump manifold assembly comprising a pump and a cache, and further comprises or includes a bypass valve and a bypass fluid line coupling the bypass valve and the cache.

[0045] According to another implementation, the system further comprises or includes a shared line valve, a plurality of dedicated reagent fluid lines, and a shared reagent fluid line, the shared reagent fluid line coupling the shared line valve and the central valve and adapted to flow one or more reagents to the flow cell, and each dedicated reagent fluid line coupling the bypass fluid line and the central valve and adapted to flow toward the flow cell.

[0046] According to another implementation, the pump manifold assembly carries a plurality of pump valves and a cache valve and comprises or includes a plurality of pump channel fluid lines, a plurality of pump fluid lines, a shared fluid line, a cache fluid line, and a main waste fluid line. The cache fluid lines are coupled to the cache and the cache valves and are coupled between the cache and the cache valves. Each pump valve is coupled to a corresponding pump channel fluid line, a corresponding pump fluid line, and the shared fluid line. The cache valves are coupled to the cache fluid lines, the main waste fluid line, and the shared fluid line.

[0047] According to another implementation, the pump valve and the pump are operable to individually control fluid flow in each of the multiple channels of the flow cell, and the pump valve, cache valve, and pump are operable to control fluid flow between a bypass fluid line and a shared fluid line.

[0048] According to another implementation, the pump valve, the cache valve, and the pump are operable to control the flow of fluid between the shared fluid line and the main waste fluid line.

[0049] According to another implementation, the system further comprises or includes a pump manifold assembly comprising or having a plurality of pumps including or including a pump and a plurality of pump valves, each pump and corresponding pump valve operable to individually control the flow of a sample of interest between each of the one or more ports of the sample cartridge interface and a corresponding channel of the flow cell.

[0050] According to another implementation, the system further comprises or includes a sample loading manifold assembly comprising or having a plurality of sample valves, each operable to individually load a sample of interest into each of a plurality of channels of the flow cell.

[0051] According to another implementation, the method further comprises or includes a flow cell assembly comprising or including a flow cell comprising or having a plurality of channels and a flow cell manifold comprising or including an inlet, a plurality of fluid lines, and a plurality of outlets, each outlet of the flow cell manifold being coupled to a corresponding channel of the flow cell.

[0052] It is understood that all combinations of the foregoing concepts and additional concepts, described in more detail below (provided such concepts are not mutually inconsistent), are considered to be part of the subject matter disclosed herein and / or may be combined to achieve particular benefits of particular embodiments. In particular, all combinations of claimed subject matter appearing at the end of this disclosure are considered to be part of the subject matter disclosed herein. [Brief description of the drawings]

[0053] [Figure 1A] 1 shows a schematic diagram of one implementation of a system according to the teachings of the present disclosure.

[0054] [Figure 1B] 2 is a cross-sectional view of one implementation of a sipper assembly including a sipper and a sample cartridge including a sample well that can be used with the system of FIG. 1.

[0055] [Figure 1C] FIG. 1C is a detailed cross-sectional view of a distal portion of the sipper assembly and a sample well of the sample cartridge of FIG. 1B.

[0056] [Diagram 2] 1B shows an isometric close-up view of one implementation of a flow cell cartridge assembly that can be received in the flow cell receptacle of the system of FIG. 1A.

[0057] [Diagram 3] 3 shows a plan view of the flow cell and flow cell manifold of the flow cell assembly of FIG. 2.

[0058] [Figure 4] 1B shows a plan view of another implementation of a flow cell and another implementation of a flow cell manifold of a flow cell assembly that can be used with the system of FIG. 1A.

[0059] [Diagram 5] 1B shows a plan view of another implementation of a flow cell and another implementation of a flow cell manifold of a flow cell assembly that can be used with the system of FIG. 1A.

[0060] [Figure 6A] 1B shows a plan view of another implementation of a flow cell and another implementation of a flow cell manifold of a flow cell assembly that can be used with the system of FIG. 1A.

[0061] [Figure 6B] 6B shows an isometric view of the flow cell and flow cell manifold and fluid lines of FIG. 6A that can be used with the system of FIG. 1A.

[0062] [Figure 7] 1B shows an isometric view of an implementation of a sample loading manifold assembly coupled to an implementation of a flow cell assembly that can be used with the system of FIG. 1A.

[0063] [Figure 8] FIG. 1B is a schematic diagram of one implementation of a portion of a pump manifold assembly that can be used with the system of FIG. 1A.

[0064] [Figure 9] 1 shows a schematic diagram of another implementation of a system according to the teachings of the present disclosure, including a flow cell interface and a pump manifold assembly.

[0065] [Figure 10]1 shows a schematic diagram of another implementation of a system according to the teachings of the present disclosure, including one or more valves, a flow cell interface, and a pump manifold assembly.

[0066] [Figure 11] 1 shows a schematic diagram of another implementation of a system according to the teachings of the present disclosure, including a flow cell interface, a sample loading manifold assembly, and a sample cartridge interface.

[0067] [Figure 12] 1 shows a schematic diagram of another implementation of a system according to the teachings of the present disclosure, including one or more valves, a flow cell interface, a sample cartridge interface, and a pump manifold assembly.

[0068] [Figure 13A] 1B shows a plan view of another implementation of a flow cell and another implementation of a flow cell manifold of a flow cell cartridge assembly that can be used with the system of FIG. 1A.

[0069] [Figure 13B] FIG. 13B shows a cross-sectional view of the flow cell cartridge assembly of FIG. 13A.

[0070] [Figure 14] 1B shows a flowchart of a method for performing a pumping operation using the system of FIG. 1A or any of the other systems disclosed herein.

[0071] [Figure 15] 1B shows a flowchart of another method of performing a pumping operation using the system of FIG. 1A or any of the other systems disclosed herein.

[0072] [Figure 16]1B shows a flowchart of a method for performing a subject sample loading operation using the system of FIG. 1A or any of the other systems disclosed herein.

[0073] [Figure 17] 1B shows a flowchart of another method of performing a subject sample loading operation using the system of FIG. 1A or any of the other systems disclosed herein. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0074] Although the following text discloses a detailed description of implementations of methods, apparatus, and / or products, it should be understood that the legal scope of ownership is defined by the claims at the end of this patent. Therefore, the following "Description of the Preferred Embodiments" should be construed as examples only and does not describe all possible implementations, as describing all possible implementations would be impractical, if not impossible. Numerous alternative implementations may be implemented using either current technology or technology developed after the filing date of this patent. It is contemplated that such alternative implementations would still fall within the scope of the claims.

[0075] The implementations disclosed herein relate to pump manifold assemblies and sample loading manifold assemblies for use with sequencing and / or array platforms or other systems. Use of the disclosed implementations may reduce the amount of reagents used during at least some operations, may reduce the amount of execution time to perform at least some operations, and may reduce the likelihood of contamination of specimens and / or contamination between reagents (e.g., crosstalk).

[0076] The pump manifold assembly may include multiple pumps, multiple pump valves, fluid lines, and a cache. When the pump manifold assembly is coupled to a flow cell that includes or has multiple channels, the pumps and pump valves may be operable to individually control the flow of fluid through each of the multiple channels of the flow cell. The flow cell may include a single upstream opening in communication with each of the channels and may include multiple downstream openings in communication with each of the channels. The pump manifold assembly may be adapted to flow fluid from the upstream opening of the flow cell to the downstream opening of the flow cell. The pump manifold assembly may also be adapted to flow fluid from the downstream opening of the flow cell to the upstream opening of the flow cell. Thus, the pump manifold assembly can flow fluid through the flow cell in either direction.

[0077] The sample loading manifold assembly may include a plurality of sample valves and a plurality of ports. The sample valves of the sample loading manifold assembly may be adapted to control the flow of fluid through the ports and between a sample cartridge carrying a sample of interest and a channel of the flow cell. In some implementations, some of the sample ports of the sample loading manifold assembly are coupled to corresponding ports of the sample cartridge interface, some of the sample ports of the sample loading manifold assembly are coupled to corresponding ports of the flow cell interface, and some of the sample ports of the sample loading manifold assembly are coupled to pumps of the pump manifold assembly. The sample cartridge may be coupled to the sample cartridge interface, and the flow cell may be coupled to the flow cell interface.

[0078] The sample valves of the sample loading manifold assembly and the pumps of the pump manifold assembly can be operable to individually load each channel of the flow cell with a sample of interest. The sample loading assembly can be positioned downstream of the flow cell. Thus, the sample of interest can be loaded into the channels of the flow cell from the rear of the flow cell.

[0079] FIG. 1A shows a schematic diagram of one implementation of a system 100 according to the teachings of the present disclosure. The system 100 can be used to perform an analysis on one or more samples of interest. The sample can include one or more DNA clusters that have been linearized to form single stranded DNA (sstDNA). In the illustrated implementation, the system 100 is adapted to receive a flow cell cartridge assembly 102 and a sample cartridge 104, and includes, in part, a shipper manifold assembly 106, a sample loading manifold assembly 108, and a pump manifold assembly 110. The system 100 also includes a drive assembly 112, a controller 114, an imaging system 116, and a waste reservoir 117. The controller 114 is electrically and / or communicatively coupled to the drive assembly 112 and the imaging system 116, and is adapted to cause the drive assembly 112 and / or the imaging system 116 to perform various functions as disclosed herein.

[0080] The sample cartridge 104 carries one or more samples of interest (e.g., analytes) in sample wells 260 and may be receivable in a sample cartridge receptacle 118. The sample cartridge 104 may be matable with a sample cartridge interface 119 that includes a sipper assembly 262 used to draw sample from the sample wells 260. The sample wells 260 may be referred to as sample reservoirs. The sample cartridge 104 also includes a prime well 264 and one or more wash wells 266 that may contain a wash solution, such as a wash buffer and / or bleach.

[0081] In the illustrated implementation, the sample loading manifold assembly 108 includes one or more sample valves 120, and the pump manifold assembly 110 includes one or more pumps 121, one or more pump valves 122, and a cache 123. One or more of the valves 120, 122 may be implemented by rotary valves, pinch valves, flat valves, solenoid valves, check valves, piezoelectric valves, and / or three-way valves. Other types of fluid control devices may prove suitable. One or more of the pumps 121 may be implemented by syringe pumps, peristaltic pumps, and / or diaphragm pumps. Other types of fluid transfer devices may prove suitable. The cache 123 may be a serpentine cache and may be adapted to receive a volume of about 4 milliliters (mL). The cache 123 may be adapted to temporarily store one or more reaction components, for example, during a bypass operation of the system 100 of FIG. 1A. Although cache 123 is shown as being included in pump manifold assembly 110, in other implementations cache 123 may be located in a different location. For example, cache 123 may be included in shipper manifold assembly 106 or in another manifold downstream of bypass fluid line 145.

[0082] During operation, the sipper assembly 162 draws one or more samples from the sample wells 260 and the sample loading manifold assembly 108, and the pump manifold assembly 110 flows one or more samples of interest from the sample cartridge 104 through the fluid lines 124 toward the flow cell cartridge assembly 102. The flow cell cartridge assembly 102 may include a flow cell 125 having multiple channels 126 (an implementation of the flow cell 125 and channels 126 is shown more clearly in FIG. 2). In one implementation, the sample loading manifold assembly 108 may be adapted to individually load / address a sample of interest into each channel 126 of the flow cell 125. The process of loading the channels 126 with a sample of interest may be performed automatically using the system 100 of FIG. 1A.

[0083] In the illustrated implementation, the sample cartridge 104 and the sample loading manifold assembly 108 are positioned downstream of the flow cell cartridge assembly 102. Thus, the sample loading manifold assembly 108 can load a sample of interest into the flow cell 125 from the rear of the flow cell 125. Loading a sample of interest from the rear of the flow cell 125 can be referred to as "rear loading." Rear loading the sample of interest into the flow cell 125 can reduce contamination. In the illustrated implementation, the sample loading manifold assembly 108 is coupled between the flow cell cartridge assembly 102 and the pump manifold assembly 110.

[0084] For example, to prime the system 100 with hybridization buffer and / or to remove air from the system 100, the pump 121 draws hybridization buffer through the flow cell 125, and the sipper assembly 262 delivers hybridization buffer into the prime well 264 once the system 100 is primed. The sample of interest is then drawn from the sample cartridge 104 using a sipper 268 of the sipper assembly 162 and a sample valve 120, and the pump valve 122 and / or the pump 121 are selectively actuated to urge the sample of interest towards the pump manifold assembly 110. The sample cartridge 104 may include sample wells 260 that are selectively fluidly accessible via a corresponding sipper 268. Thus, each sample may be selectively separated from other samples using a corresponding sipper 268 and a corresponding sample valve 120.

[0085] To draw a sample of interest from one of the sample wells 260, the sample valve 120 of the corresponding sample of interest can be opened or released to fluidly connect the sample well 260 to the instrument fluid system. The corresponding pump 121 can be actuated to draw the sample of interest from the sample well 260 into a fluid line, such as a fluid line of the pump manifold assembly 110 and / or another fluid line. In some implementations, the corresponding pump valve 122 can be opened, closed, and / or moved from a first position to a second position to fluidly couple the corresponding pump 121 to the corresponding fluid line of the corresponding sample well 260. Thus, the pump valve 122 can be selectively isolated from the other pump 121 and / or pump valve 122 using the corresponding pump valve 122. In some implementations, the sample of interest can be temporarily stored in a line volume between the pump valve 122 and / or sample valve 120 and the corresponding pump 121.

[0086] The sample valve 120, the pump valve 122, and / or the pump 121 may be selectively actuated to urge the sample of interest into each channel 126 of the flow cell 125 toward the flow cell cartridge assembly 102 to individually flow the sample of interest toward the corresponding channel or channels 126 of the flow cell 125 and away from the pump manifold assembly 110. For example, the sample valve 120 may be closed after the sample of interest is aspirated into the line volume, thereby fluidically disconnecting the sample well 260 from the line volume. In some cases, the sample valve 120 may be moved from a first position to a second position to fluidly couple the corresponding pump 121 to the corresponding channel or channels 126 via the sample loading manifold assembly 108. The pump 121 may then push the sample of interest into the corresponding channel or channels 126. In some implementations, a corresponding pump valve 122 may be opened, closed, and / or moved from a second position to a first position to fluidly couple a corresponding pump 121 to a corresponding channel 126 or to multiple channels 126. In some implementations, each channel 126 of multiple channels 126 receives a sample of interest. In other implementations, one or more of the channels 126 may selectively receive a sample of interest, while other channels of the channels 126 may not receive a sample of interest. A channel 126 of a flow cell 125 that may not receive a sample of interest may instead receive a wash buffer, for example.

[0087] The drive assembly 112 interfaces with the shipper manifold assembly 106 and the pump manifold assembly 110 to flow one or more reagents through the flow cell cartridge assembly 102 that interact with the sample in the flow cell 125. In one implementation, a reversible terminator having a distinguishable label is attached to the detection nucleotide to allow for incorporation of a single nucleotide by the sstDNA per cycle. In some such implementations, one or more of the nucleotides have a unique fluorescent label that emits a color when excited. The color (or lack thereof) is used to detect the corresponding nucleotide. In the illustrated implementation, the imaging system 116 is adapted to excite one or more of the distinguishable labels (e.g., fluorescent labels) and then acquire image data of the distinguishable labels. The labels may be excited by incident light and / or a laser, and the image data may include one or more colors emitted by the respective labels in response to excitation. The image data (e.g., detection data) may be analyzed by the system 100. The imaging system 116 may be a fluorescence spectrophotometer including an objective lens and / or a solid-state imager. Solid-state imaging devices may include charge coupled devices (CCDs) and / or complementary metal oxide semiconductors (CMOSs).

[0088] After image data is acquired, the drive assembly 112 interfaces with the sipper manifold assembly 106 and the pump manifold assembly 110 to flow another reaction component (e.g., a reagent) through the flow cell 125, which is then received by the waste reservoir 117 via the main waste fluid line 127 and / or otherwise discharged by the system 100. Some reaction components undergo a flushing action that chemically cleaves the fluorescent label and the reversible terminator from the sstDNA. The sstDNA is then ready for another cycle. In some implementations, between runs of the system 100, the sipper 268 is washed by immersing the sipper 268 in a wash well 266 containing a wash solution, such as bleach, or a wash buffer. The wash solution can be removed by immersing the sipper 268 in a prime well 264 containing a hybridization buffer. However, other approaches to washing the sipper 268 may be suitable.

[0089] A main waste fluid line 127 is adapted to be coupled between the pump manifold assembly 110 and the waste reservoir 117. In some implementations, the pump 121 and / or pump valve 122 of the pump manifold assembly 110 are adapted to selectively flow reaction components from the flow cell cartridge assembly 102 through the fluid line 124 and the sample loading manifold assembly 108 to the main waste fluid line 127.

[0090] In the illustrated implementation, the flow cell cartridge assembly 102 is receivable in a flow cell receptacle 128 and matable with a flow cell interface 129. In another implementation, the flow cell receptacle 128 can be omitted and the flow cell cartridge assembly 102 can be directly mated to the flow cell interface 129.

[0091] The flow cell cartridge assembly 102 is coupled to a central valve 130 via a flow cell interface 129. An auxiliary waste fluid line 132 is coupled to the central valve 130 and to a waste reservoir 117. In some implementations, the auxiliary waste fluid line 132 is adapted to receive any excess fluid of the sample of interest from the flow cell cartridge assembly 102 via the central valve 130 and to flow the excess fluid of the sample of interest to the waste reservoir 117 when the sample of interest is rear-loaded into the flow cell 125, as described herein. That is, the sample of interest may be loaded from the rear of the flow cell 125, and any excess fluid of the sample of interest may exit from the front of the flow cell 125. As described herein, by rear-loading the sample of interest into the flow cell 125, different samples can be loaded separately into corresponding channels 126, and a single manifold (see, e.g., flow cell manifold 173 in FIG. 2) can couple the front of the flow cell 125 to a central valve 130 to direct excess fluid of each sample of interest into an auxiliary waste fluid line 132 to reduce the possibility of contamination of one sample in a first channel 126 with a second channel 126. Once the sample of interest is loaded into the flow cell 125, a single manifold can then be used to deliver a common reagent from the front (e.g., upstream) of the flow cell 125 for each channel 126 and exit the flow cell 125 from the rear (e.g., downstream) of the flow cell 125. In other words, the sample of interest and the reagent can flow in opposite directions through the channels 126 of the flow cell 125.

[0092] With reference to the sipper manifold assembly 106, in the illustrated implementation, the sipper manifold assembly 106 includes a shared line valve 134 and a bypass valve 136. The shared line valve 134 may be referred to as a reagent selector valve. The central valve 130 and the valves 134, 136 of the sipper manifold assembly 106 may be selectively actuated to control the flow of fluid through the fluid lines 138, 140, 142. One or more of the valves 130, 134, 136 may be implemented by rotary valves, pinch valves, flat valves, solenoid valves, check valves, piezoelectric valves, etc. Other fluid control devices may prove suitable.

[0093] The shipper manifold assembly 106 may be coupled to a corresponding number of reagent reservoirs 144 via reagent sippers 146. The reagent reservoirs 144 may contain fluids (e.g., reagents and / or other reaction components). In some implementations, the shipper manifold assembly 106 includes multiple ports. Each port of the shipper manifold assembly 106 may receive one of the reagent sippers 146. The reagent sippers 146 may be referred to as fluid lines.

[0094] The shared line valve 134 of the sipper manifold assembly 106 is coupled to the central valve 130 via a shared reagent fluid line 138. Different reagents can flow through the shared reagent fluid line 138 at different times. In one implementation, when performing a flushing operation before changing between one reagent and another, the pump manifold assembly 110 can draw a wash buffer through the shared reagent fluid line 138, the central valve 130, and the flow cell cartridge assembly 102. Thus, the shared reagent fluid line 138 can be involved in the flushing operation. Although one shared reagent fluid line 138 is shown, any number of shared fluid lines can be included in the system 100.

[0095] The bypass valve 136 of the sipper manifold assembly 106 is coupled to the central valve 130 via dedicated reagent fluid lines 140, 142. The central valve 130 may have one or more dedicated ports corresponding to the dedicated reagent fluid lines 140, 142. Each of the dedicated reagent fluid lines 140, 142 may be associated with a single reagent. The fluids that may flow through the dedicated reagent fluid lines 140, 142 may be used during sequencing operations and may include cleavage reagents, incorporation reagents, scanning reagents, cleavage washes, and / or wash buffers. Thus, when performing a flushing operation prior to changing between one reagent and another in association with the bypass valve 136, the sipper manifold assembly 106 may draw wash buffers through the central valve 130 and / or the flow cell cartridge assembly 102. However, because only a single reagent may flow through each of the dedicated reagent fluid lines 140, 142, the dedicated reagent fluid lines 140, 142 themselves may not be flushed. The approach of including dedicated reagent fluid lines 140, 142 can be advantageous when the system 100 uses reagents that may have adverse reactions with other reagents. Additionally, by reducing the number of fluid lines or the length of the fluid lines that are flushed when changing between different reagents, reagent consumption and flush volumes can be reduced, decreasing cycle times for the system 100. Although two dedicated reagent fluid lines 140, 142 are shown, any number of dedicated fluid lines can be included in the system 100.

[0096] The bypass valve 136 is also coupled to the cache 123 of the pump manifold assembly 110 via a bypass fluid line 145. One or more reagent priming, hydration, mixing, and / or transfer operations may be performed using the bypass fluid line 145. The priming, hydration, mixing, and / or transfer operations may be performed independent of the flow cell cartridge assembly 102. Thus, operations using the bypass fluid line 145 may occur, for example, during incubation of one or more samples of interest in the flow cell cartridge assembly 102. That is, the shared line valve 134 may be utilized independent of the bypass valve 136, such that the bypass valve 136 may utilize the bypass fluid line 145 and / or the cache 123 to perform one or more operations while the shared line valve 134 and / or the central valve 130 are performing other operations simultaneously, substantially simultaneously, or offset synchronously. Thus, execution time may be reduced by performing multiple operations at once using the system 100. Additionally, bypass valve 136 and bypass fluid line 145 can be used to flow hybridization buffer through pump manifold assembly 110 to sample manifold assembly 108, allowing the hybridization buffer to follow the sample of interest through flow cell 128. Thus, the order of fluids flowing through flow cell 125 can be: 1) hybridization buffer from the priming operation, 2) sample drawn from sample well 260 via shipper 268, and 3) hybridization buffer accessed via bypass valve 136 and bypass fluid valve 145.

[0097] Referring now to the drive assembly 112, in the illustrated implementation, the drive assembly 112 includes a pump drive assembly 147 and a valve drive assembly 148. The pump drive assembly 147 may be adapted to interface with one or more pumps 121 to pump fluid through the flow cell 125 and / or to load one or more samples of interest into the flow cell cartridge assembly 102. The valve drive assembly 147 may be adapted to interface with one or more of the valves 120, 122, 130, 134, 136 to control the position of the corresponding valves 120, 122, 130, 134, 136. In one implementation, the shared line valve 134 and / or the bypass valve 136 are implemented by rotary valves having a first position that blocks flow to the flow cell 125 and a second position that allows flow from the reagent reservoir 144 to the flow cell 125. However, either of the valves 134, 136 may be positioned in any number of positions to flow any one or more of the first reagent, buffer reagent, second reagent, etc. to the flow cell cartridge assembly 102. As an example, the bypass valve 136 may be rotated between a first position that allows fluid flow from one or more of the reagent reservoirs 144 through the bypass valve 136 to the central valve 130, and a second position that allows fluid flow from one or more of the reagent reservoirs 144 through the bypass valve 136 into the bypass fluid line 145. Other configurations may prove suitable. For example, the bypass valve 136 may be positionable to allow fluid flow from the bypass fluid line 145 through the bypass valve 136 to a mixing reservoir of the reagent reservoir 144.

[0098] Turning to the controller 114, in the illustrated implementation, the controller 114 includes a user interface 150, a communication interface 152, one or more processors 154, and a memory 156 that stores instructions executable by the one or more processors 154 to perform various functions including the disclosed implementations. The user interface 150, the communication interface 133, and the memory 156 are electrically and / or communicatively coupled to the one or more processors 154.

[0099] In one implementation, the user interface 150 is adapted to receive input from a user and provide information to the user associated with the operation of the system 100 and / or the analysis performed. The user interface 150 may include a touch screen, a display, a keyboard, a speaker(s), a mouse, a trackball, and / or a voice recognition system. The touch screen and / or the display may display a graphical user interface (GUI).

[0100] In one implementation, the communication interface 152 is adapted to enable communication between the system 100 and a remote system(s) (e.g., a computer) over a network(s). The network(s) may include the Internet, an intranet, a local-area network (LAN), a wide-area network (WAN), a coaxial cable network, a wireless network, a wired network, a satellite network, a digital subscriber line (DSL) network, a cellular network, a Bluetooth connection, a near field communication (NFC) connection, and the like. Some of the communications provided to the remote system may be related to analysis results, imaging data, and the like, generated or otherwise obtained by the system 100. Some of the communications provided to the system 100 may be related to fluid analysis operations, patient records, and / or protocol(s) executed by the system 100.

[0101] The one or more processors 154 and / or system 100 may include one or more of a processor-based system(s) or a microprocessor-based system(s). In some implementations, the one or more processors 154 and / or system 100 include one or more of a programmable processor, a programmable controller, a microprocessor, a microcontroller, a graphics processing unit (GPU), a digital signal processor (DSP), a reduced-instruction set computer (RISC), an application specific integrated circuit (ASIC), a field programmable gate array (FPGA), a field programmable logic device (FPLD), a logic circuit, and / or another logic-based device that performs various functions, including those described herein.

[0102] The memory 156 may be any of a variety of memory types, including semiconductor memory, magnetically readable memory, optical memory, hard disk drive (HDD), optical storage drive, solid-state storage device, solid-state drive (SSD), flash memory, read-only memory (ROM), erasable programmable read-only memory (EPROM), electrically erasable programmable read-only memory (EEPROM), random-access memory (RAM), non-volatile RAM (NVRAM) memory, compact disc (CD), compact disc read-only memory (CD-ROM), digital versatile disk (DVD), Blu-ray disc, redundant array of independent disks, and the like. The storage device or disks may include one or more of: a storage device, a RAID (repeater, partition, or independent disks), a cache, and / or any other storage device or disk on which information is stored for any duration (e.g., permanently, temporarily, long term, for buffering, for caching).

[0103] 1B is a cross-sectional view of one implementation of a sipper assembly 262 including a sipper 268 and a sample cartridge 104 including a sample well 260 that can be used with the system 100 of FIG. 1. In the illustrated implementation, the sipper assembly 262 is an automated pipettor that includes a base 270 having a cavity 272, a sipper array 274 including a sipper 268 and disposed at least partially within the cavity 272, and a spring assembly 276 that biases the sipper 268 in a direction generally indicated by arrow 278 and into the sample well 260. Having the spring assembly 276 biases the sipper 268 into the sample well 260 to position the sipper 268 adjacent a lower surface 280 of the sample well 260, thereby reducing dead volume within the sample well 260 and providing less sample during a fluid analysis operation.

[0104] With reference to the shippers 268, in the illustrated implementation, each shipper 268 has a proximal portion 282 disposed within the cavity 272, a distal portion 284 disposed within the sample well 260, and a fluid pathway 286 extending between portions 282 and 284. The spring assembly 276 includes a spring 288 that surrounds the corresponding shipper 268 at the proximal portion 282 and seats on a corresponding spring seat 290 of the shipper assembly 262.

[0105] 1C, a detailed cross-sectional view of the distal portion 284 of the sipper assembly 262 of FIG. 1B and the sample well 260 of the sample cartridge 104 is shown. In the illustrated implementation, the sipper 268 each has an opening 292 and a tip 293 at the distal portion 284. The tip 293 is formed by a first surface 294 positioned at a first angle relative to a longitudinal axis 295 of the sipper 268 and a second surface 296 positioned at a second angle relative to the longitudinal axis 295. As shown, the first angle is approximately 30° and the second angle is approximately 50°. However, the surfaces 294, 296 may be disposed at different angles, including the same angle.

[0106] The difference between the first and second angles allows tip end 297 of tip 293 to be offset from longitudinal axis 295 to space opening 292 away from tip end 297. Because tip end 297 extends beyond opening 292 and engages lower surface 280, opening 292 is less likely to engage lower surface 298 of sample well 260 and become blocked and / or obstructed. To further reduce the amount of dead volume present in sample well 260, lower surface 280 of sample well 260 is tapered.

[0107] 2 shows an isometric close-up view of one implementation of a flow cell cartridge assembly 102 that can be received in the flow cell receptacle 128 of the system 100 of FIG. 1A. In the illustrated implementation, the flow cell cartridge assembly 102 includes a body 158, a flow cell assembly 160, a flow cell coupling 162, an inlet gasket assembly 164, and an outlet gasket assembly 166. The flow cell coupling 162 may be referred to as a bracket. The inlet gasket assembly 164 and / or the outlet gasket assembly 166 may interface with or otherwise fluidly couple to the flow cell interface 129 of the system 100 of FIG. 1A. The inlet gasket assembly 164 may be directly coupled to the central valve 130 or may be coupled to the central valve 130 via one or more fluid lines (see, e.g., FIG. 6B).

[0108] In the illustrated implementation, the flow cell cartridge assembly 102 may also carry a radio frequency identification (RFID) tag 167. The RFID tag 167 may be used for tracking and / or identification purposes. Other methods of tracking and / or identifying the flow cell cartridge assembly 102 may prove suitable.

[0109] The body 158 of the flow cell cartridge assembly 102 has a peripheral wall 168 and a top surface 170. The peripheral wall 168 and the top surface 170 define a cavity 172. The cavity 172 includes an upper opening 174 and a lower opening 176. The upper opening 174 is defined by the top surface 170. The upper opening 174 may allow image data of the flow cell 125 to be acquired via the imaging system 116. The lower opening 176 is defined by a lower edge 178 of the peripheral wall 168. The lower opening 176 may allow a sample of interest to be loaded into the channel 126 of the flow cell 125 via the outlet gasket assembly 166 and / or one or more reagents to be flowed into the channel 126 of the flow cell 125 via the inlet gasket assembly 164.

[0110] The flow cell assembly 160 includes a flow cell 125 having a plurality of channels 126 and a flow cell manifold 173. Each channel 126 of the plurality of channels 126 has a corresponding channel inlet 180 and a corresponding channel outlet 182. The channel inlet 180 may be referred to as an inlet of the flow cell 125. The channel outlet 182 may be referred to as an outlet of the flow cell 125. However, depending on the direction of fluid flow, the channel inlet 180 may function as an outlet of the flow cell 125 and the channel outlet 182 may function as an inlet of the flow cell 125. For example, when a sample of interest is loaded into the channel 126 from the rear of the flow cell 125, the channel outlet 182 may function as an inlet of the flow cell 125.

[0111] The flow cell manifold 173 is adapted to be coupled to the flow cell 125 and may be formed by a laminate. The flow cell manifold 173 may provide a mechanically flexible connection with the flow cell 125. The flow cell manifold 173 may be coupled to the flow cell 125 using an adhesive. Other methods of coupling the flow cell 125 and the flow cell manifold 173 may prove suitable.

[0112] In the illustrated implementation, the flow cell manifold 173 includes a single inlet 184, multiple fluid lines 186 (fluid lines 186 are shown more clearly in FIG. 3), and multiple outlets 188. The inlet 184 may be referred to as a flow cell manifold inlet. The inlet 184 of the flow cell manifold 173 is coupled to each of the outlets 188 via the fluid lines 186. The fluid lines 186 may enable the flow cell assembly 160 to control the flow of fluid without the use of additional valving.

[0113] The fluid lines 186 may be adapted for flow division and may be referred to as flow splitters. In one implementation, the fluid flowing through the inlet 184 may be divided substantially equally between the channels 126 of the flow cell 125. In some implementations, the flow cell manifold 173 and / or the fluid lines 186 may be adapted to reduce the flow resistance and / or operating pressure of the system 100 of FIG. 1A. The fluid lines 186 may have a height of about 300 micrometers (μm). Other heights of the fluid lines 186 may prove suitable. In another implementation, the flow cell manifold 173 may be omitted and the body 158 of the flow cell cartridge assembly 102 may include the fluid lines 186, the inlet 184, and the multiple outlets 188. As an example, the fluid lines 186, the inlet 184, and the multiple outlets 188 may be molded and / or embossed into the body 158 of the flow cell cartridge assembly 102 (see, for example, FIGS. 13A and 13B).

[0114] The flow cell manifold 173 may also include inlet alignment holes 190 and outlet alignment holes 192. The inlet alignment holes 190 may be positioned on either side of the inlet 184, and the outlet alignment holes 192 may be positioned adjacent to the outlet 188 of the flow cell manifold 173. The inlet alignment holes 190 and / or the outlet alignment holes 192 may be referred to as interfaces of the flow cell manifold 173.

[0115] The flow cell coupling 162 includes a protrusion 194 that is receivable by the outlet alignment hole 192 of the flow cell manifold 173 to secure the flow cell manifold 173 relative to the flow cell 125. The flow cell coupling 162 may include an end portion 196 adapted to form a snap-fit ​​connection with the body 158 of the flow cell cartridge assembly 102, or may float within a predetermined tolerance relative to the body 158. The bond between the flow cell coupling 162 and the body 158 of the flow cell assembly 102 may help retain the flow cell 125 and the flow cell manifold 173 within the cavity 172 of the body 158 of the flow cell cartridge assembly 102.

[0116] In the illustrated implementation, the flow cell coupling 162 includes a cradle 197. The cradle 197 is a semicircular cutout and may include a tapered surface. The cradle 197 may be adapted to receive and / or secure the RFID tag 167 to the flow cell cartridge assembly 102. In some implementations, the cradle 197 may be omitted.

[0117] The inlet gasket assembly 164 includes a first portion 198, a second portion 202, and an inlet gasket 204. The inlet gasket 204 may be adapted to be coupled adjacent to the inlet 184 of the flow cell manifold 173 and to enable fluid communication between the channel 126 of the flow cell 125 and the components of the system 100 of FIG. 1A. The first portion 198 of the inlet gasket assembly 164 includes a protrusion 206 and the second portion 202 of the inlet gasket assembly 164 includes a receptacle 208. The protrusion 206 is adapted to be received by the inlet alignment hole 190 of the flow cell manifold 173 and the receptacle 208 of the second portion 202 of the inlet gasket assembly 164. Interaction between the protrusion 206 and the receptacle 208 may couple the first and second portions 198, 202 of the inlet gasket assembly 164 together, for example, via a snap-fit ​​connection. In another implementation, the protrusion 206 may be received in a receptacle 208 for alignment purposes. A side 210 of the first portion 198 of the inlet gasket assembly 164 may be adapted to form a snap-fit ​​connection with the second portion 202 of the inlet gasket assembly 164 and / or the body 158 of the flow cell cartridge assembly 102.

[0118] The outlet gasket assembly 166 includes a plurality of gaskets 212 and a body 214. The body 214 may carry the gaskets 212. Each gasket 212 of the plurality of gaskets 212 is adapted to be coupled adjacent to one of the channel outlets 182 of the flow cell 125 and to enable fluid communication between the channel 126 of the flow cell 125 and a component of the system 100. A side 216 of the body 214 of the outlet gasket assembly 166 may be adapted to form a snap-fit ​​connection with the body 158 of the flow cell cartridge assembly 102.

[0119] Figures 3-5 and 6A-6B show different implementations of a flow cell assembly 160 that can be used with the system 100 of Figure 1A. The channel 126 of the flow cell assembly 160 shown in Figures 3-5 and 6A-6B can have a volume of about 18.7 microliters (μL) to about 32.4 μL. Other volumes may prove suitable.

[0120] FIG. 3 shows a top view of the flow cell 125 and flow cell manifold 173 of the flow cell assembly 160 of FIG.

[0121] Figure 4 shows a plan view of another implementation of a flow cell 125 of a flow cell assembly 160 and another implementation of a flow cell manifold 173 that can be used with the system 100 of Figure 1A. In contrast to the implementation of Figure 3, the width of the channel 126 of the flow cell assembly 160 of Figure 4 may be smaller. The spacing and / or size of the fluid lines 186 of the flow cell manifold 173 of Figure 4 may be adjusted accordingly.

[0122] 5 shows a plan view of another implementation of a flow cell 125 and a flow cell manifold 173 of a flow cell assembly 160 that can be used with the system 100 of FIG. 1A. In contrast to the other disclosed implementations, the flow cell 125 of FIG. 5 includes two of the channels 126 and the flow cell manifold 173 includes fewer of the fluid lines 186. The fluid lines 186 of the flow cell manifold 173 fluidly couple the inlets 184 of the flow cell manifold 173 and the channels 126 of the flow cell 125. The flow cell 125 of FIG. 5 includes two channels 126, but any other number of channels 126, including one, may be included.

[0123] Figure 6A shows a plan view of another implementation of the flow cell 125 and flow cell manifold 173 of the flow cell assembly 160 that can be used with the system 100 of Figure 1A. In contrast to the other disclosed implementations, the inlet 184 of the flow cell manifold 173 of Figure 6A is substantially aligned with the outlet 188 of the flow cell manifold 173, and the fluid lines 186 are arranged accordingly. Thus, the height H of the flow cell manifold 173 of Figure 6A may be less than the height of the flow cell manifold 173 shown in Figures 3, 4, and 5.

[0124] Figure 6B shows an isometric view of the flow cell 125 and flow cell manifold 173 of Figure 6A. In the illustrated implementation, a fluid line 213 is coupled to the inlet 184 of the flow cell manifold 173 via a gasket 204. The fluid line 213 may be part of the system 100 of Figure 1A and includes a coupling 215. The coupling 215 of the fluid line 213 may be coupled to a port of the central valve 130, for example, to enable fluid communication between the central valve 130 and the flow cell 125.

[0125] 7 shows an isometric view of an implementation of a sample loading manifold assembly 108 coupled to an implementation of a flow cell assembly 160 for use with the system 100 of FIG. 1A. In the illustrated implementation, the sample loading manifold assembly 108 includes a body 217 having a first side 218 and a second side 219 opposite the first side 218. The first side 218 defines a number of sample ports 220 and a number of flow cell ports 222. Each of the sample ports 220 is coupled to a corresponding port of the sample cartridge interface 119 via a separate sample fluid line 223. Similarly, each of the flow cell ports 222 is coupled to a corresponding channel 126 of the flow cell 125 via a separate flow cell fluid line 224. The flow cell fluid lines 224 can be coupled to a port of the flow cell interface 129. Although separate fluid lines 223, 224 are mentioned as connecting the same sample port 220 to a port of the sample cartridge interface 119, and connecting the flow cell port 222 to the channel 126 of the flow cell 125 and / or a port of the flow cell interface 129, one fluid line can be used to fluidly connect two or more ports.

[0126] The second face 219 of the sample loading manifold assembly 108 defines pump ports 226. Each pump port 226 is coupled to a corresponding port 228 of the pump manifold assembly 110 via a separate pump channel fluid line 230 (the corresponding ports 228 of the pump manifold assembly 110 are shown more clearly in FIG. 8 ).

[0127] The sample valves 120 of the sample loading manifold assembly 108 are actuable to allow a sample of interest to be obtained from the sample cartridge 104 and loaded into one or more of the channels 126 of the flow cell 125. To obtain a sample of interest from the sample cartridge 104, one or more of the sample valves 120 are actuated to a first position that fluidly connects the sample cartridge 104 with the pump manifold assembly 110. In the first position of the sample valves 120, the sample of interest can flow through the sample fluid line 223 to and into the sample port 220 and out the pump port 226 into the pump channel fluid line 230 of the pump manifold assembly 110.

[0128] One or more of the sample valves 120 are actuable to a second position that fluidly communicates the pump manifold assembly 110 with the flow cell 125 to individually place the sample of interest into one or more of the channels 126 of the flow cell 125 through the outlet gasket assembly 166. In the second position of the sample valve 120, the sample of interest can flow from the pump channel fluid line 230 into the pump port 226 of the sample loading manifold assembly 108 and out of the flow cell port 222 of the sample loading manifold assembly 108 via the flow cell fluid line 224 toward the corresponding channel 126 of the flow cell 125. The pump manifold assembly 110 can be adapted to deliver the sample of interest into the flow cell 125 at a relatively slow rate to enable substantially uniform transfer. When the sample of interest is loaded into the channel 126 of the flow cell 125, the central valve 130 can be positioned to vent the flow cell 125 to the auxiliary waste fluid line 132. After the sample of interest is delivered to the flow cell 125, an incubation process may be performed for seeding. In some implementations, 100 microliters (μL) of the sample of interest is placed, incubated, and seeded into the channel 126 of the flow cell 125 at one time. Other volumes may prove suitable. The process of placing, incubating, and seeding incrementally smaller amounts of the sample of interest into the channel 126 may be repeated a threshold number of times.

[0129] Prior to obtaining a sample of interest from the sample cartridge 104, in some implementations, the pump manifold assembly 110 may be primed with a buffer solution. The buffer solution may be obtained from the bypass fluid line 145. Priming the pump manifold assembly 110 with a buffer solution may, for example, provide the pump manifold assembly 110 with a stroke to deliver the sample of interest into the flow cell 125.

[0130] Figure 8 is a schematic diagram of one implementation of a portion of a pump manifold assembly 110 for use with the system 100 of Figure 1A. In the illustrated implementation, the pump manifold assembly 110 includes a body 232 carrying a pump valve 122, a cache valve 234, and a pump 121. The pump 121 may be a syringe pump and may be adapted to receive a volume of approximately 500 microliters (μL). Other volumes may prove suitable.

[0131] The pump valve 122, the cache valve 234, and / or the pump 121 are operable to individually control the flow of fluid to each channel 126 of the multiple channels 126 of the flow cell 125. In the illustrated implementation, two pump drive assemblies 147 are provided. The pump drive assemblies 147 may be adapted to individually actuate one or more of the pumps 121 to perform one or more of the disclosed operations. In one implementation, one of the pump drive assemblies 147 may operate two of the pumps 121 and the other of the pump drive assemblies 147 may operate six of the pumps 121. Other configurations may prove suitable.

[0132] The pump valve 122, the cache valve 234, and / or the pump 121 may be operable to flow one or more reagents through the bypass fluid line 145 and / or the main waste fluid line 127. The body 232 of the pump manifold assembly 110 may also carry a number of sensors 236, 237. The sensors 236, 237 may include pressure sensors or flow sensors. Other types of sensors may prove suitable. In another implementation, one or more of the sensors 236, 237 and / or the cache valve 234 may be omitted. In some such implementations, the bypass fluid line 145 may also be omitted. Other configurations may prove suitable.

[0133] The pump manifold assembly 110 includes a cache 123, a pump channel fluid line 230, a plurality of pump fluid lines 238, a shared fluid line 240, a cache fluid line 242, and a main waste fluid line 127. The cache fluid line 242 is coupled to and between the cache 123 and the cache valve 234. The pump channel fluid lines 230 and the pump fluid lines 238 may be collectively referred to as pump channel fluid lines. In the illustrated implementation, each pump valve 122 is coupled to a corresponding pump channel fluid line 230, a corresponding pump fluid line 238, and the shared fluid line 240. Each pump 121 is coupled to a corresponding pump fluid line 238. The pumps 121 are operable to individually control the flow of fluid to the pump channel fluid lines 230 and one of the channels 126 of the flow cell 125.

[0134] The cache valve 234 is coupled to the cache fluid line 242, the main waste fluid line 127, and the shared fluid line 240. The sensors 236, 237 may be adapted to determine one or more of a pressure or flow value of at least one of the pump channel fluid lines 230 or one or more of the shared fluid lines 240. Five sensors 236 are coupled to the pump channel fluid line 230. The sensors 236 may be positioned differently. Additional sensors or fewer sensors, including zero sensors, may prove suitable.

[0135] To use one or more of the pumps 121 to draw fluid from or force fluid towards the flow cell 125, one or more of the pump valves 122 can be actuated to a first position that fluidly connects the pump channel fluid line 230 and the pump fluid line 238, and one or more of the pumps 121 can be actuated to move fluid.

[0136] To move reaction components toward the waste reservoir 117 using one or more of the pumps 121, one or more of the pump valves 122 can be actuated to a second position that fluidly connects the pump fluid line 238 with the shared fluid line 240, the cache valve 234 can be actuated to a first position that fluidly connects the shared fluid line 240 with the main waste fluid line 127, and one or more of the pumps 121 can be actuated to move fluid.

[0137] To perform a mixing operation using one or more reaction components received through the bypass fluid line 145, the pump valve 122 may be actuated to a second position fluidly connecting the pump fluid line 238 with the shared fluid line 240, the cache valve 234 may be actuated to a second position fluidly connecting the cache fluid line 242 with the shared fluid line 240, and one or more of the pumps 121 may be actuated to move fluid. In some implementations, all of the pumps 121 may be used to transfer a larger volume of the reaction component(s) through the bypass fluid line 145 to prime the shared fluid line 240. Then, for example, two of the pumps 121 may be used while the remaining pumps 121 are idled to increase the accuracy of subsequent fluid transfers. A different number of pumps 121 may be used instead, including using one pump 121.

[0138] 9 shows a schematic diagram of another implementation of a system 300 according to the teachings of the present disclosure. In the illustrated implementation, the system 300 includes a flow cell interface 128 and a pump manifold assembly 110. The flow cell interface 128 is adapted to be coupled to a flow cell 125 having a plurality of channels 126. The pump manifold assembly 110 carries a pump valve 122 and a pump 121. Although the system 300 includes two pump valves 122 and two pumps 121, it may prove suitable to provide the system 300 with a different number of valves 122 and / or pumps 121.

[0139] In the illustrated implementation, the pump manifold assembly 110 includes pump channel fluid lines 230, pump fluid lines 238, and a shared fluid line 240. The pump valves 122 and pumps 121 may be operable to individually control the flow of fluid through each channel 126 of the multiple channels 126 of the flow cell 125 via a corresponding pump channel fluid line 230. Each pump valve 122 may be coupled to a corresponding pump channel fluid line 238, a corresponding pump fluid line 230, and the shared fluid line 240. Each pump 121 may be coupled to a corresponding pump fluid line 238. Other fluid line configurations may prove suitable.

[0140] 10 shows a schematic diagram of another implementation of a system 400 according to the teachings of the present disclosure. In the illustrated implementation, the system 400 includes one or more of the valves 130, 134, and / or 136, a flow cell interface 128, a pump manifold assembly 110, and a bypass fluid line 145. The valves 130, 134, and / or 136 are adapted to be coupled to corresponding reagent reservoirs 144. The flow cell interface 128 is adapted to be coupled to a flow cell 125 having a plurality of channels 126. The pump manifold assembly 110 includes a pump 121, a pump valve 122, and a cache 123. Each pump 121 may be operable to individually control the fluid flow of each channel 126 of the plurality of channels 126 of the flow cell 125. The bypass fluid line 145 is operably coupled between one or more of the valves 130, 134, 136 and the cache 123. Other fluid line configurations may prove suitable.

[0141] 11 shows a schematic diagram of another implementation of a system 500 according to the teachings of the present disclosure. In the illustrated implementation, the system 500 includes a flow cell interface 128, a sample cartridge interface 119, and a sample loading manifold assembly 108. The flow cell interface 119 is adapted to be coupled to a flow cell 125 having a plurality of channels 126. The sample cartridge interface 119 is adapted to be coupled to a sample cartridge 104, the sample cartridge interface 119 being positioned downstream of the flow cell interface 128. The sample loading manifold assembly 108 is positioned between the flow cell interface 128 and the sample cartridge interface 129.

[0142] The sample loading manifold assembly 108 includes a body 217 that carries a plurality of sample valves 120 and defines a sample port 220 and a flow cell port 222. Each sample port 220 is coupled to a corresponding port 502 of the sample cartridge interface 119 via one of the sample fluid lines 223. Each flow cell port 222 is coupled to a corresponding port 504 of the flow cell interface 119. The ports 504 of the flow cell interface 119 are associated with a corresponding one of the channels 126 of the flow cell 125 via a flow cell fluid line 224.

[0143] 12 shows a schematic diagram of another implementation of a system 600 according to the teachings of the present disclosure. In the illustrated implementation, the system 600 includes one or more of the valves 130, 134, and / or 136, a flow cell interface 128, a sample cartridge interface 119, and a pump manifold assembly 110. One or more of the valves 130, 134, and / or 136 may be adapted to be coupled to a corresponding reagent reservoir 144. The flow cell interface 128 is adapted to be coupled to a flow cell 125 having a plurality of channels 126. The sample cartridge interface 128 includes a plurality of ports 502 and is adapted to be coupled to a sample cartridge 104 carrying a sample of interest. The sample cartridge interface 119 is positioned downstream of the flow cell interface 128.

[0144] In the illustrated implementation, the pump manifold assembly 110 includes a pump 121 and a pump valve 122. Each pump 121 and corresponding pump valve 122 is operable to individually control flow of a sample of interest between a respective port 502 of a plurality of ports 502 of the sample cartridge interface 119 and a respective channel 126 of a plurality of channels 126 of the flow cell 125.

[0145] 13A shows a plan view of another implementation of a flow cell 125 of a flow cell cartridge assembly 102 and another implementation of a flow cell manifold 173 that can be used with the system 100 of FIG. 1A. In contrast to the other disclosed implementations, the body 158 of the flow cell cartridge assembly 102 defines a fluid line 186, an inlet 184, and a number of outlets 188. In the illustrated implementation, the fluid line 186 is also coupled to a channel outlet 182 of the channel 126 of the flow cell 125 to enable fluid communication with, for example, the fluid line 124 and / or the sample loading manifold assembly 108.

[0146] 13B shows a cross-sectional view of the flow cell cartridge assembly 102 of FIG. 13A. In the illustrated implementation, the body 158 of the flow cell cartridge assembly 102 defines a receptacle 250. An inner gasket 252 and an outer gasket 254 are disposed within the receptacle 250. The inner gasket 254 may be adapted to matingly engage with the flow cell 125 to enable fluid communication between the fluid line 186 of the body 158 of the flow cell cartridge assembly 102 and the channel 126 of the flow cell. The outer gasket 254 may be adapted to matingly engage with the flow cell interface 129 of the system 100 to enable fluid communication between the system 100 and the flow cell cartridge assembly 102.

[0147] 14-17 show flow charts of methods for performing pumping and / or loading operations of a sample of interest using the system 100 of FIG. 1A or any of the other systems 300, 400, 500, and / or 600 disclosed herein. In the flow charts of FIGS. 14 and 16, blocks surrounded by solid lines may be included in implementations of the processes 1200 and 1400, and blocks surrounded by dashed lines may be optional in implementations of the processes. However, regardless of how the block boundaries are presented in FIGS. 14-17, the order of execution of the blocks may be changed and / or some of the described blocks may be modified, omitted, combined, and / or subdivided into multiple blocks.

[0148] 14 begins with a flow cell 125 having a plurality of channels 126 being coupled to a flow cell interface 129 (block 1202). In block 1204, one or more of a plurality of pump valves 122 and one or more of a plurality of pumps 121 of the pump manifold assembly 110 are operated to load each channel 126 of the plurality of channels 126 of the flow cell 125 with a sample of interest.

[0149] One or more of the plurality of pump valves 122 and one or more of the plurality of pumps 121 of the pump manifold assembly 110 are operated to individually control the flow of fluid through each channel 126 of the plurality of channels 126 via a corresponding pump channel fluid line 230 (block 1206). Operating one or more of the plurality of pumps 121 may include flowing a sample of interest in a first direction within each channel 126. Operating one or more of the plurality of pumps 121 may also include flowing a reagent through the channel 126 of the flow cell 125 in a second direction opposite the first direction. The pump manifold assembly 110 may include a plurality of pump channel fluid lines 230, a plurality of pump fluid lines 238, and a shared fluid line 240. Each pump valve 122 may be coupled to a corresponding pump channel fluid line 230, a corresponding pump fluid line 238, and a shared fluid line 240. Each pump 121 may be coupled to a corresponding pump fluid line 238.

[0150] One or more of the pumps 121 of the pump manifold assembly 110 are operated to control fluid flow between the bypass fluid line 145 and the cache 123 of the pump manifold assembly 110 (block 1208). In some implementations, the bypass fluid line 145 couples the cache 123 and the bypass valve 136.

[0151] In block 1210, one or more of the pump valves 122, one or more of the pumps 121, or the cache valve 234 of the pump manifold assembly 110 are operated to control fluid flow between at least one of the shared fluid line 240 and the main waste fluid line 127, or between the bypass fluid line 145 and the main waste fluid line 127. One or more of the pumps 121 of the pump manifold assembly 110 are operated to flow the sample of interest from the channel 126 of the flow channel 125 into the auxiliary waste fluid line 132 (block 1212).

[0152] 15 begins with a flow cell 125 having a plurality of channels 126 being coupled to a flow cell interface 129 (block 1302). In block 1304, one or more of a plurality of pump valves 122 and one or more of a plurality of pumps 121 of a pump manifold assembly 110 are operated to individually control the flow of fluid through each channel 126 of the plurality of channels 126 via a corresponding pump channel fluid line 230. The pump manifold assembly 110 may include a plurality of pump channel fluid lines 230, a plurality of pump fluid lines 238, and a shared fluid line 240. Each pump valve 122 may be coupled to a corresponding pump channel fluid line 230, a corresponding pump fluid line 238, and a shared fluid line 240. Each pump 121 may be coupled to a corresponding pump fluid line 238.

[0153] The process 1400 of FIG. 16 begins with a flow cell 125 having a plurality of channels 126 being coupled to a flow cell interface 129 (block 1402). In block 1404, a sample cartridge 104 is coupled to the sample cartridge interface 119. The sample cartridge interface 119 may be positioned downstream of the flow cell interface 129. The sample cartridge 104 may carry a sample of interest. One or more of the sample valves 120 of the sample loading manifold assembly 108 are operated to individually load the sample of interest into each channel 126 of the plurality of channels 126 of the flow cell 125 (block 1406).

[0154] In some implementations, operating one or more sample valves 120 includes moving the sample of interest from the sample cartridge 104 to a corresponding sample port 220 of the sample loading manifold assembly 108 and out an associated pump port 226 of the sample loading manifold assembly 108 to a corresponding pump channel fluid line 230 of the pump manifold assembly 110. Operating one or more sample valves 120 may also include moving the sample of interest from the corresponding pump channel fluid line 230 through the associated pump port 226 and through a flow cell port 222 of the sample loading manifold assembly 108. Each flow cell port 222 may be coupled to a corresponding port 502 of the flow cell interface 119 and associated with one of the channels 126 of the multiple channels 126 of the flow cell 125.

[0155] Each sample valve 120 of the sample loading manifold assembly 108 may be operable to fluidly communicate one of the ports 502 of the sample cartridge interface 119 with one or more of the pumps 121, and to fluidly communicate the pump 121 with a corresponding channel 126 of the plurality of channels 126 of the flow cell 125. In some implementations, operating the one or more sample valves 120 includes flowing a sample of interest in a first direction into each channel 126 of the flow cell 125. The process 1400 may also include controlling a flow of reagent through the channel 126 of the flow cell 125 in a second direction opposite the first direction.

[0156] In block 1408, one or more of the plurality of pumps 121 are operated to individually control fluid flow in each of the plurality of channels 126 of the flow cell 125. A reagent may be flowed into the channel 126 of the flow cell 125 through a shared reagent fluid line 138, and subsequently another reagent may be flowed into the channel 126 of the flow cell 125 through a dedicated reagent fluid line 140 and / or 142 (block 1410). In block 1412, the sample of interest is flowed from the channel 126 of the flow cell 125 to the auxiliary waste fluid line 132.

[0157] The process 1500 of FIG. 17 begins with a flow cell 125 having a plurality of channels 126 being coupled to a flow cell interface 129 (block 1502). In block 1504, a sample cartridge 104 is coupled to the sample cartridge interface 119. The sample cartridge interface 119 may be positioned downstream of the flow cell interface 129. The sample cartridge 104 may carry one or more samples of interest. One or more of the sample valves 120 of the sample loading manifold assembly 108 are operated to individually load a corresponding sample of interest or the same sample of interest into each channel 126 of the plurality of channels 126 of the flow cell 125 (block 1506).

[0158] The method includes coupling a flow cell having a plurality of channels to a flow cell interface, the flow cell interface being fluidly coupled to a pump manifold assembly, and moving a first pump valve of a plurality of pump valves of the pump manifold assembly to a first position to fluidly connect a first channel of the plurality of channels with a first pump of the plurality of pumps. The first pump is fluidly connected to the first channel via a first pump channel fluid line. The method includes pumping a first volume of a first reagent through the first channel using the first pump via the first pump channel fluid line, and moving the first pump valve of the plurality of pump valves to a second position to fluidly connect the pump and the first pump channel fluid line with a shared fluid line that fluidly communicates with a waste reservoir. The method includes pumping the first volume of the first reagent through the shared fluid line into the waste reservoir, and moving a second pump valve of the plurality of pump valves to the first position to fluidly connect a second channel of the plurality of channels with a second pump of the plurality of pumps. A second pump is fluidly connected to the second channel via a second pump channel fluid line. The method includes pumping a second volume of the first reagent into the second channel using the second pump via the second pump channel fluid line and moving a second pump valve of the plurality of pump valves to a second position to fluidly connect the second pump and the second pump channel fluid line with a shared fluid line that is in fluid communication with a waste reservoir. The method includes pumping the second volume of the first reagent through the shared fluid line into the waste reservoir.

[0159] The method of any one or more of the implementations described above and / or any one or more of the implementations disclosed below, further comprising moving a bypass valve to a first position to fluidly couple the bypass fluid line with a cache of the pump manifold assembly, and pumping a third volume of the first reagent or another reagent through the bypass fluid line and into the cache.

[0160] A method as in any one or more of the implementations described above and / or any one or more of the implementations disclosed below, further comprising actuating one or more of a plurality of pump valves, one or more of a plurality of pumps, or a cache valve of a pump manifold assembly, and pumping reagents at least one of between the shared fluid line and a main waste fluid line fluidly connected to the waste reservoir, or between the bypass fluid line and the main waste fluid line.

[0161] The method of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, further comprising operating one or more of the pump valves and one or more of the pumps of the pump manifold assembly to load a sample of interest into one or more of the channels of the flow cell.

[0162] The method of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein operating one or more of the plurality of pumps to load one or more of the channels of the plurality of channels of the flow cell with the sample of interest includes flowing the sample of interest in a first direction, the method further including operating one or more of the plurality of pumps of a pump manifold assembly to control a flow of reagent through the channels of the flow cell in a second direction opposite the first direction.

[0163] The method of any one or more of the aforementioned implementations and / or any one or more of the implementations disclosed below, further comprising operating one or more of a plurality of pumps of a pump manifold assembly to flow a sample of interest from one or more channels of the flow cell to an auxiliary waste fluid line, the auxiliary waste fluid line being upstream of the flow cell interface.

[0164] An apparatus comprising: a flow cell interface adapted to be coupled to a flow cell having a plurality of channels; and a pump manifold assembly carrying a plurality of pump valves and a plurality of pumps, the pump manifold assembly comprising a plurality of pump channel fluid lines, a plurality of pump fluid lines, and a shared fluid line. The pump valves and pumps are operable to individually control fluid flow through each of the plurality of channels of the flow cell via a corresponding pump channel fluid line. Each pump valve is coupled to a corresponding pump channel fluid line, a corresponding pump fluid line, and a shared fluid line, and is movable between a first position fluidly coupling a corresponding channel of the plurality of channels, a corresponding pump channel fluid line, and a corresponding pump fluid line, and a second position fluidly coupling a corresponding pump fluid line, a shared fluid line, and a waste reservoir. Each pump is coupled to a corresponding pump fluid line.

[0165] The apparatus of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the pump manifold assembly further comprises a cache. The apparatus further comprises a bypass valve and a bypass fluid line coupling the bypass valve and the cache.

[0166] The apparatus of any one or more of the implementations previously described and / or any one or more of the implementations disclosed below, wherein the pump manifold assembly further comprises a cache valve and a cache fluid line, The cache valve is coupled to the cache fluid line and the shared fluid line.

[0167] The apparatus of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the pump manifold assembly further comprises a main waste fluid line coupled to the waste reservoir, and the cache valve is coupled to the main waste fluid line.

[0168] The apparatus of any one or more of the implementations described above and / or any one or more of the implementations disclosed below, wherein the pump manifold assembly further comprises a plurality of sensors adapted to determine one or more pressure or flow values ​​of at least one of the pump channel fluid lines or one or more of the shared fluid lines.

[0169] The apparatus of any one or more of the aforementioned implementations and / or any one or more of the implementations disclosed below, further comprising a pair of pump drive assemblies operable to drive the multiple pumps.

[0170] The device of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, further comprising a sample cartridge interface adapted to be coupled to a sample cartridge, the sample cartridge interface being positioned downstream of the flow cell interface.

[0171] The apparatus of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, further comprising a sample loading manifold assembly positioned between the flow cell interface and the sample cartridge interface, the sample loading manifold assembly comprising or including a body carrying a plurality of sample valves and defining a plurality of sample ports, a plurality of flow cell ports, and a plurality of pump ports. Each sample port is coupled to a corresponding port of the sample cartridge interface via a sample fluid line. Each flow cell port is coupled to a corresponding port of the flow cell interface and associated with one of the channels of the plurality of channels of the flow cell via a flow cell fluid line. Each pump port is coupled to a corresponding pump channel fluid line of the plurality of pump channel fluid lines.

[0172] An apparatus as described in any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the sample valves of the sample loading manifold assembly and the pumps of the pump manifold assembly are operable to individually load a sample of interest into each channel of the multiple channels of the flow cell.

[0173] An apparatus as described in any one or more of the aforementioned implementations and / or any one or more of the implementations disclosed below, wherein each sample valve is operable to fluidly connect a port of the sample cartridge to a corresponding pump of the multiple pumps of the pump manifold assembly, and to fluidly connect a pump of the multiple pumps of the pump manifold assembly to a corresponding channel of the multiple channels of the flow cell.

[0174] The apparatus of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, further comprising a central valve and an auxiliary waste fluid line coupled to the central valve and adapted to be coupled to a waste reservoir, the auxiliary waste fluid line being positioned upstream of the flow cell interface.

[0175] The apparatus of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, further comprising a shared line valve, a bypass valve, a plurality of dedicated reagent fluid lines, and a shared reagent fluid line. The shared reagent fluid line couples the shared line valve and the central valve and is adapted to flow one or more reagents to the flow cell through the central valve. Each dedicated reagent fluid line couples the bypass valve and the central valve and is adapted to flow a reagent to the flow cell through the central valve.

[0176] The apparatus includes one or more valves adapted to be coupled to corresponding reagent reservoirs and a flow cell interface adapted to be coupled to a flow cell having a plurality of channels. The apparatus includes a pump manifold assembly having a plurality of pumps, a plurality of pump valves, and a cache. Each pump is operable to individually control fluid flow in each of the plurality of channels of the flow cell, and a bypass fluid line is operably coupled between the one or more valves and the cache.

[0177] The apparatus of any one or more of the preceding and / or any one or more of the implementations disclosed below, further comprising a sample loading manifold assembly having a plurality of sample valves, each sample valve and corresponding pump of the pump manifold assembly operable to individually load each channel of the plurality of channels of the flow cell. The sample loading manifold assembly is positioned downstream of the flow cell.

[0178] The apparatus of any one or more of the preceding and / or any one or more of the implementations disclosed below, further comprising a flow cell assembly including a flow cell having a plurality of channels and a flow cell manifold, the flow cell manifold including an inlet, a plurality of fluid lines, and a plurality of outlets, each outlet of the flow cell manifold being coupled to a corresponding channel of the flow cell.

[0179] The method includes coupling a flow cell having a first channel and a second channel to the flow cell interface, and moving a first sample valve of one or more sample valves of a sample loading manifold assembly to a first position to fluidly couple a first sample reservoir of the sample cartridge to an outlet of the first channel of the flow cell. The method includes pumping a first sample of interest from the first sample reservoir through the outlet of the first channel into the first channel of the flow cell. An inlet of the first channel is fluidly connected to a waste reservoir via a central valve when the central valve is in the first position. The method includes moving a first sample valve of one or more sample valves of the sample loading manifold assembly to a second position to fluidly disconnect the first sample reservoir of the sample cartridge and fluidly connect an outlet of the first channel with the waste reservoir, and moving the central valve to the second position to fluidly couple a reagent reservoir to the first channel and the second channel of the flow cell. The method includes pumping a first volume of a reagent through a first channel and into a waste reservoir.

[0180] The method of any one or more of the implementations described above and / or any one or more of the implementations disclosed below, wherein pumping the first sample of interest from the first sample reservoir into the first channel of the flow cell includes moving the first sample of interest from the sample cartridge to a corresponding sample port of the sample loading manifold assembly and out of an associated pump port of the sample loading manifold assembly into a pump channel fluid line of the pump manifold assembly, and moving the first sample of interest from the pump channel fluid line through the associated pump port and through the corresponding flow cell port of the sample loading manifold assembly, wherein each flow cell port is coupled to a corresponding port of the flow cell interface and associated with one of the channels of the plurality of channels of the flow cell.

[0181] The method of any one or more of the implementations described above and / or any one or more of the implementations disclosed below, wherein moving a first sample valve of the one or more sample valves to a first position includes fluidly coupling a port of the sample cartridge interface with a corresponding pump, and moving a first sample valve of the one or more sample valves to a second position includes fluidly coupling a corresponding pump with a first channel of the plurality of channels of the flow cell.

[0182] The method of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, further comprising operating one or more of a plurality of pumps to individually control fluid flow in each of a plurality of channels of the flow cell.

[0183] The method of any one or more of the aforementioned implementations and / or any one or more of the implementations disclosed below, further comprising flowing the first sample of interest from the first channel of the flow cell into an auxiliary waste fluid line, the auxiliary waste fluid line being upstream of the flow cell and fluidly coupled to the central valve and the waste reservoir.

[0184] The method of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, further comprising flowing a reagent through a shared reagent fluid line into the multiple channels of the flow cell, and subsequently flowing another reagent through a dedicated reagent fluid line into the multiple channels of the flow cell.

[0185] An apparatus comprising: a flow cell interface adapted to be coupled to a flow cell having a plurality of channels; a central valve; and an auxiliary waste fluid line coupled to the central valve and adapted to be coupled to a waste reservoir. The central valve is coupled to the flow cell interface and is movable between a first position fluidly connecting the inlets of the plurality of channels to the auxiliary waste fluid line and a second position fluidly connecting the reagent reservoir and the plurality of channels. The apparatus comprises a sample cartridge interface adapted to be coupled to a sample cartridge. The sample cartridge interface is positioned downstream of the flow cell interface. The apparatus comprises a sample loading manifold assembly positioned between the flow cell interface and the sample cartridge interface, the manifold assembly comprising a body carrying a plurality of sample valves and defining a plurality of sample ports and a plurality of flow cell ports. Each sample port is coupled to a corresponding port of the sample cartridge interface via a sample fluid line. Each flow cell port is coupled to a corresponding port of the flow cell interface and associated with one of the plurality of channels of the flow cell via a flow cell fluid line. Each of the sample valves is movable between a first position fluidly connecting a corresponding sample port with a corresponding outlet of the plurality of channels and a second position fluidly connecting a corresponding outlet of the plurality of channels with a waste reservoir.

[0186] An apparatus as described in any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the sample valve is operable to individually load each channel of the multiple channels of the flow cell.

[0187] The apparatus of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, further comprising a plurality of pumps, wherein the body of the sample loading manifold assembly further defines a plurality of pump ports, each pump port being coupled to one of the pumps of the plurality of pumps via a pump channel fluid line.

[0188] An apparatus as described in any one or more of the aforementioned implementations and / or any one or more of the implementations disclosed below, wherein each sample valve is operable to fluidly connect a port of the sample cartridge to a corresponding pump of the plurality of pumps, and to fluidly connect a pump of the plurality of pumps to a corresponding channel of the plurality of channels of the flow cell.

[0189] An apparatus as described in any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the pump is operable to individually control fluid flow in each of the multiple channels of the flow cell.

[0190] The apparatus of any one or more of the implementations previously described and / or any one or more of the implementations disclosed below, further comprising a pump manifold assembly comprising a pump and a cache, and further comprising a bypass valve and a bypass fluid line coupling the bypass valve and the cache.

[0191] The apparatus of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, further comprising a shared line valve, a plurality of dedicated reagent fluid lines, and a shared reagent fluid line, the shared reagent fluid line coupling the shared line valve and the central valve and adapted to flow one or more reagents to the flow cell, and each dedicated reagent fluid line coupling the bypass fluid line and the central valve and adapted to flow toward the flow cell.

[0192] The apparatus of any one or more of the implementations described above and / or any one or more of the implementations disclosed below, wherein the pump manifold assembly carries a plurality of pump valves and a cache valve and includes a plurality of pump channel fluid lines, a plurality of pump fluid lines, a shared fluid line, a cache fluid line, and a main waste fluid line. The cache fluid lines are coupled to the cache and the cache valves and are coupled between the cache and the cache valves. Each pump valve is coupled to a corresponding pump channel fluid line, a corresponding pump fluid line, and a shared fluid line. The cache valves are coupled to the cache fluid lines, the main waste fluid line, and the shared fluid line.

[0193] An apparatus as described in any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the pump valves and pumps are operable to individually control fluid flow in each of the multiple channels of the flow cell, and the pump valves, cache valves, and pumps are operable to control fluid flow between the bypass fluid line and the shared fluid line.

[0194] An apparatus as described in any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the pump valve, the cache valve, and the pump are operable to control fluid flow between the shared fluid line and the main waste fluid line.

[0195] The apparatus includes one or more valves adapted to be coupled to corresponding reagent reservoirs and a flow cell interface adapted to be coupled to a flow cell. The apparatus includes a sample cartridge interface having one or more ports and adapted to be coupled to a sample cartridge carrying a sample of interest. The sample cartridge interface is positioned downstream of the flow cell interface. The apparatus includes a pump adapted to load the sample of interest into a channel of the flow cell via the flow cell interface associated with an outlet of the flow cell and a corresponding port of the sample cartridge interface.

[0196] The apparatus of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, further comprising a pump manifold assembly having a plurality of pumps including the pump and a plurality of pump valves, each pump and corresponding pump valve operable to individually control flow of a sample of interest between each port of the one or more ports of the sample cartridge interface and a corresponding channel of the flow cell.

[0197] The apparatus of any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, further comprising a sample loading manifold assembly having a plurality of sample valves, each operable to individually load a sample of interest into each of the plurality of channels of the flow cell.

[0198] The apparatus of any one or more of the preceding and / or any one or more of the implementations disclosed below, further comprising a flow cell assembly including a flow cell having a plurality of channels and a flow cell manifold, the flow cell manifold including an inlet, a plurality of fluid lines, and a plurality of outlets, each outlet of the flow cell manifold being coupled to a corresponding channel of the flow cell.

[0199] The foregoing description is provided to enable one skilled in the art to practice the various configurations described herein. While the subject technology has been specifically described with reference to various figures and configurations, it should be understood that these are for illustrative purposes only and should not be construed as limiting the scope of the subject technology.

[0200] As used herein, elements or steps described in the singular and followed by the word "a" or "an" should be understood as not excluding a plurality of those elements or steps, unless such exclusion is expressly stated. Moreover, references to "one implementation" are not intended to be interpreted as excluding the existence of additional implementations that also incorporate the recited features. Furthermore, unless expressly stated to the contrary, implementations that "comprising," "including," or "having" an element or elements having a particular characteristic may include additional elements whether or not they have that characteristic. Moreover, the terms "comprising," "including," "having," and the like are used interchangeably herein.

[0201] As used throughout this specification, the terms "substantially," "approximately," and "about" are used to describe and take into account small variations due to processing variations and the like. For example, they can refer to ±5% or less, such as ±2% or less, such as ±1% or less, such as ±0.5% or less, such as ±0.2% or less, such as ±0.1% or less, such as ±0.05% or less).

[0202] There may be many other ways to implement the subject technology. The various functions and elements described herein may be divided differently than shown without departing from the scope of the subject technology. Various modifications to these implementations may be readily apparent to those skilled in the art, and the general principles defined herein may be applied to other implementations. Thus, many changes and modifications may be made to the subject technology by those skilled in the art without departing from the scope of the subject technology. For example, a different number of a given module or unit may be used, different or multiple types of a given module or unit may be used, a given module or unit may be added, or a given module or unit may be omitted.

[0203] Underlined and / or italicized headings and subheadings are used for convenience only, are not limiting of the subject technology, and are not referred to in connection with interpreting the description of the subject technology. All structural and functional equivalents to the elements of the various implementations described throughout this disclosure that are known or that later become known to those of ordinary skill in the art are expressly incorporated herein by reference and are intended to be encompassed by the subject technology. Furthermore, nothing disclosed herein is intended to be publicly exclusive, regardless of whether such disclosure is expressly set forth in the description above.

[0204] It is to be understood that all combinations of the foregoing concepts and additional concepts, described in more detail below (provided such concepts are not mutually inconsistent), are considered to be part of the subject matter disclosed herein. In particular, all combinations of claimed subject matter appearing at the end of this disclosure are considered to be part of the subject matter disclosed herein.

Claims

1. 1. A method comprising: coupling a flow cell having a first channel and a second channel to the flow cell interface; moving a first sample valve of the one or more sample valves of the sample loading manifold assembly to a first position to fluidly connect a first sample reservoir of the sample cartridge with the pump manifold assembly; pumping a first sample of interest from the first sample reservoir into the pump manifold assembly; moving the first sample valve to a second position to fluidly connect the pump manifold assembly with the flow cell; pumping a first sample of interest from the pump manifold assembly through an outlet of the first channel and into the first channel of the flow cell; a pumping means for fluidly connecting an inlet of the first channel to a waste reservoir through the central valve when the central valve is in a first position; moving the first sample valve of the one or more sample valves of the sample loading manifold assembly to a second position to fluidly disconnect the first sample reservoir of the sample cartridge and fluidly connect the outlet of the first channel with the waste reservoir; moving the central valve to a second position to fluidly couple a reagent reservoir to the first channel and the second channel of the flow cell; pumping a first volume of reagent through the inlet of the first channel and into the waste reservoir; A method comprising:

2. 2. The method of claim 1, wherein pumping the first sample of interest from the first sample reservoir into the first channel of the flow cell comprises moving the first sample of interest from the sample cartridge to a corresponding sample port of the sample loading manifold assembly and out of an associated pump port of the sample loading manifold assembly into a pump channel fluid line of a pump manifold assembly; and moving the first sample of interest from the pump channel fluid line through the associated pump port and through a corresponding flow cell port of the sample loading manifold assembly, wherein each flow cell port is coupled to a corresponding port of the flow cell interface and associated with one of the channels of the plurality of channels of the flow cell.

3. 3. The method of claim 1 or 2, wherein moving the first sample valve of the one or more sample valves to the first position comprises fluidly coupling a port of a sample cartridge interface with a corresponding pump, and moving the first sample valve of the one or more sample valves to the second position comprises fluidly coupling the corresponding pump with the first channel of the plurality of channels of the flow cell.

4. The method of any one of claims 1 to 3, further comprising operating one or more of a plurality of pumps to individually control fluid flow in each of the plurality of channels of the flow cell.

5. 5. The method of claim 1, further comprising flowing the first sample of interest from the first channel of the flow cell into an auxiliary waste fluid line, the auxiliary waste fluid line being upstream of the flow cell and fluidly coupled to the central valve and the waste reservoir.

6. 6. The method of claim 1, further comprising flowing a reagent through a shared reagent fluid line into the multiple channels of the flow cell, and subsequently flowing another reagent through a dedicated reagent fluid line into the multiple channels of the flow cell.

7. 1. An apparatus comprising: a flow cell interface adapted to be coupled to a flow cell having a plurality of channels; a central valve and an auxiliary waste fluid line coupled to the central valve and adapted to be coupled to a waste reservoir, the central valve being coupled to the flow cell interface and movable between a first position fluidly connecting the inlets of the plurality of channels to the auxiliary waste fluid line and a second position fluidly connecting a reagent reservoir and the inlets of the plurality of channels; a sample cartridge interface adapted to be coupled to a sample cartridge, the sample cartridge interface being positioned downstream of the flow cell interface; a sample loading manifold assembly positioned between the flow cell interface and the sample cartridge interface, a body carrying a plurality of sample valves and defining a plurality of sample ports and a plurality of flow cell ports, each sample port coupled to a corresponding port of the sample cartridge interface via a sample fluid line, each flow cell port coupled to a corresponding port of the flow cell interface and associated with one of the plurality of channels of the flow cell via a flow cell fluid line, each of the sample valves being movable between a first position for fluidly connecting a port of the sample cartridge to a corresponding pump of a plurality of pumps and a second position for fluidly connecting a pump of the plurality of pumps to a corresponding outlet of the plurality of channels of the flow cell and fluidly connecting the corresponding outlet of the plurality of channels to the waste reservoir; a sample loading manifold assembly comprising: Equipped with The apparatus further comprises a plurality of pumps, the body of the sample loading manifold assembly further defining a plurality of pump ports, each pump port being coupled to one of the pumps of the plurality of pumps via a pump channel fluid line.

8. The apparatus of claim 7 , wherein the sample valve is operable to individually load each channel of the plurality of channels of the flow cell.

9. The apparatus of claim 7 , wherein the pump is operable to individually control fluid flow in each of the plurality of channels of the flow cell.

10. 10. The apparatus of any one of claims 7 to 9, further comprising a pump manifold assembly comprising the pump and cache, and further comprising a bypass valve and a bypass fluid line coupling the bypass valve and the cache.

11. 11. The apparatus of claim 10, further comprising a shared line valve, a plurality of dedicated reagent fluid lines, and a shared reagent fluid line, the shared reagent fluid line connecting the shared line valve and the central valve and adapted to flow one or more reagents to the flow cell, and each dedicated reagent fluid line connecting the bypass fluid line and the central valve and adapted to flow toward the flow cell.

12. 12. The apparatus of claim 10 or 11, wherein the pump manifold assembly carries a plurality of pump valves and a cache valve and includes a plurality of pump channel fluid lines, a plurality of pump fluid lines, a shared fluid line, a cache fluid line, and a main waste fluid line, the cache fluid lines coupled to and between the cache and the cache valves, each pump valve coupled to a corresponding pump channel fluid line, a corresponding pump fluid line, and the shared fluid line, and the cache valves coupled to the cache fluid lines, the main waste fluid line, and the shared fluid line.

13. 13. The apparatus of claim 12, wherein the pump valve and the pump are operable to individually control fluid flow in each of the plurality of channels of the flow cell, and the pump valve, the cache valve, and the pump are operable to control fluid flow between the bypass fluid line and the shared fluid line.

14. 14. The apparatus of claim 13, wherein the pump valve, the cache valve, and the pump are operable to control fluid flow between the shared fluid line and the main waste fluid line.

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