Patent ID: 12226767

DETAILED DESCRIPTION

Although the following text discloses a detailed description of implementations of methods, apparatuses and/or articles of manufacture, it should be understood that the legal scope of the property right is defined by the words of the claims set forth at the end of this patent. Accordingly, the following detailed description is to be construed as examples only and does not describe every possible implementation, as describing every possible implementation would be impractical, if not impossible. Numerous alternative implementations could be implemented, using either current technology or technology developed after the filing date of this patent. It is envisioned that such alternative implementations would still fall within the scope of the claims.

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. Using the disclosed implementations may reduce an amount of reagent used during at least some operations, may reduce an amount of run time to perform at least some operations, and may reduce the likelihood of contamination of analytes and/or contamination (e.g., cross-talk) between reagents.

The pump manifold assemblies may include a plurality of pumps, a plurality of pump valves, fluidic lines, and a cache. When the pump manifold assembly is coupled to a flow cell comprising or having a plurality of channels, the pumps and the pump valves may be operable to individually control the flow of fluid through each channel of the plurality of channels of the flow cell. The flow cell may include a single upstream opening in communication with each of the channels and may include a plurality of 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 openings of the flow cell. The pump manifold assembly may also be adapted to flow fluid from the downstream openings of the flow cell to the upstream opening of the flow cell. Thus, the pump manifold assembly may flow fluid through the flow cell in either direction.

The sample loading manifold assemblies 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 fluid flow through the ports and between a sample cartridge carrying a sample of interest and the channels of the flow cell. In some implementations, some of the sample ports of the sample loading manifold assembly are coupled to corresponding ports of a sample cartridge interface, some of the sample ports of the sample loading manifold assembly are coupled to corresponding ports of a flow cell interface, and some of the sample ports of the sample loading manifold assembly are coupled to pumps of a 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.

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

FIG.1Aillustrates a schematic diagram of an implementation of a system100in accordance with the teachings of this disclosure. The system100can be used to perform an analysis on one or more samples of interest. The sample may include one or more DNA clusters that have been linearized to form a single stranded DNA (sstDNA). In the implementation shown, the system100is adapted to receive a flow cell cartridge assembly102and a sample cartridge104and includes, in part, a sipper manifold assembly106, a sample loading manifold assembly108, and a pump manifold assembly110. The system100also includes a drive assembly112, a controller114, an imaging system116, and a waste reservoir117. The controller114is electrically and/or communicatively coupled to the drive assembly112and to the imaging system116and is adapted to cause the drive assembly112and/or the imaging system116to perform various functions as disclosed herein.

The sample cartridge104carries one or more samples of interest (e.g., an analyte) in samples wells260and may be receivable in a sample cartridge receptacle118. The sample cartridge104may be couplable with a sample cartridge interface119including a sipper assembly262that is used to draw samples from the sample wells260. The sample wells260may be referred to as sample reservoirs. The sample cartridge104also includes prime wells264and one or more wash wells266that may contain a wash buffer and/or a cleaning solution such as bleach.

In the implementation shown, the sample loading manifold assembly108includes one or more sample valves120and the pump manifold assembly110includes one or more pumps121, one or more pump valves122, and a cache123. One or more of the valves120,122may be implemented by a rotary valve, a pinch valve, a flat valve, a solenoid valve, a check valve, a piezo valve, and/or a three-way valve. Other types of fluid control devices may prove suitable. One or more of the pumps121may be implemented by a syringe pump, a peristaltic pump, and/or a diaphragm pump. Other types of fluid transfer devices may prove suitable. The cache123may be a serpentine cache and may be adapted to receive a volume of about 4 milliliters (mL). The cache123may be adapted to temporarily store one or more reaction components during, for example, bypass manipulations of the system100ofFIG.1A. While the cache123is shown being included in the pump manifold assembly110, in another implementation, the cache123may be located in a different location. For example, the cache123may be included in the sipper manifold assembly106or in another manifold downstream of the bypass fluidic line145.

In operation, the sipper assembly262draws one or more samples from the sample wells260and the sample loading manifold assembly108and the pump manifold assembly110flow the one or more samples of interest from the sample cartridge104through a fluidic line124toward the flow cell cartridge assembly102. The flow cell cartridge assembly102may include a flow cell125having a plurality of channels126(an implementation of the flow cell125and the channels126are more clearly shown inFIG.2). In an implementation, the sample loading manifold assembly108may be adapted to individually load/address each channel126of the flow cell125with a sample of interest. The process of loading the channels126with a sample of interest may occur automatically using the system100ofFIG.1A.

In the implementation shown, the sample cartridge104and the sample loading manifold assembly108are positioned downstream of the flow cell cartridge assembly102. Thus, the sample loading manifold assembly108may load a sample of interest into the flow cell125from the rear of the flow cell125. Loading a sample of interest from the rear of the flow cell125may be referred to as “back loading.” Back loading the sample of interest into the flow cell125may reduce contamination. In the implementation shown, the sample loading manifold assembly108is coupled between the flow cell cartridge assembly102and the pump manifold assembly110.

To prime the system100with, for example, hybridization buffer and/or to remove air from the system100, the pumps121draw the hybridization buffer through the flow cell125and the sipper assembly262dispenses the hybridization buffer into the prime wells264once the system100is primed. Thereafter, the sample of interest is drawn from the sample cartridge104using sippers268of the sipper assembly262and the sample valves120, the pump valves122, and/or the pumps121selectively actuate to urge the sample of interest toward the pump manifold assembly110. The sample cartridge104may include the sample wells260that are selectively fluidically accessible via the corresponding sippers268. Thus, each sample can be selectively isolated from other samples using the corresponding sippers268and the corresponding sample valves120.

To draw the sample of interest from one of the sample wells260, a sample valve120for the corresponding sample of interest can be opened or released to fluidically connect the sample well260to an instrument fluidics system. A corresponding pump121can be actuated to draw the sample of interest from the sample well260and into a fluidic line, such as a fluidic line of the pump manifold assembly110and/or another fluidic line. In some implementations, a corresponding pump valve122can be opened, closed, and/or moved from a first position to a second position to fluidically couple the corresponding pump121to the corresponding fluidic line for the corresponding sample well260. Thus, the pump valve122can be selectively isolated from other pumps121and/or pump valves122using the corresponding pump valve122. In some implementations, a sample of interest can be temporarily stored in a line volume between a pump valve122and/or a sample valve120and a corresponding pump121.

To individually flow the sample of interest toward a corresponding channel126or channels126of the flow cell125and away from the pump manifold assembly110, the sample valves120, the pump valves122, and/or the pumps121may be selectively actuated to urge the sample of interest toward the flow cell cartridge assembly102and into the respective channels126of the flow cell125. For instance, after the sample of interest is aspirated into a line volume, the sample valve120can be closed, thereby fluidically disconnecting the sample wells260from the line volume. In some instances, the sample valve120may be moved from a first position to a second position to fluidically couple the corresponding pump121to the corresponding channel126or channels126via the sample loading manifold assembly108. The pump121can then push the sample of interest into the corresponding channel126or channels126. In some implementations, a corresponding pump valve122may be opened, closed, and/or moved from a second position to a first position to fluidically couple the corresponding pump121to the corresponding channel126or channels126. In some implementations, each channel126of the plurality of channels126receives the sample of interest. In other implementations, one or more of the channels126may selectively receive the sample of interest and others of the channels126may not receive the sample of interest. The channels126of the flow cell125that may not be receive the sample of interest may receive a wash buffer instead, for example.

The drive assembly112interfaces with the sipper manifold assembly106and the pump manifold assembly110to flow one or more reagents that interact with the sample at the flow cell125through the flow cell cartridge assembly102. In an implementation, a reversible terminator with an identifiable label is attached to the detection nucleotide to allow a single nucleotide to be incorporated by the sstDNA per cycle. In some such implementations, one or more of the nucleotides has a unique fluorescent label that emits a color when excited. The color (or absence thereof) is used to detect the corresponding nucleotide. In the implementation shown, the imaging system116is adapted to excite one or more of the identifiable labels (e.g., a fluorescent label) and thereafter obtain image data for the identifiable 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 the excitation. The image data (e.g., detection data) may be analyzed by the system100. The imaging system116may be a fluorescence spectrophotometer including an objective lens and/or a solid-state imaging device. The solid-state imaging device may include a charge coupled device (CCD) and/or a complementary metal oxide semiconductor (CMOS).

After the image data is obtained, the drive assembly112interfaces with the sipper manifold assembly106and the pump manifold assembly110to flow another reaction component (e.g., a reagent) through the flow cell125that is thereafter received by the waste reservoir117via a primary waste fluidic line127and/or otherwise exhausted by the system100. Some reaction components perform a flushing operation 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 system100, the sippers268are cleaned by dipping the sippers268in the wash wells266containing a cleaning solution such as bleach or a wash buffer. The cleaning solution is removable by dipping the sippers268in the prime wells264containing the hybridization buffer. However, other approaches of cleaning the sippers268may be suitable.

The primary waste fluidic line127is adapted to be coupled between the pump manifold assembly110and the waste reservoir117. In some implementations, the pumps121and/or the pump valves122of the pump manifold assembly110are adapted to selectively flow the reaction components from the flow cell cartridge assembly102, through the fluidic line124and the sample loading manifold assembly108to the primary waste fluidic line127.

In the implementation shown, the flow cell cartridge assembly102is receivable in a flow cell receptacle128and is couplable with a flow cell interface129. In another implementation, the flow cell receptacle128may be excluded and the flow cell cartridge assembly102may be directly coupled to the flow cell interface129.

The flow cell cartridge assembly102is coupled to a central valve130via the flow cell interface129. An auxiliary waste fluidic line132is coupled to the central valve130and to the waste reservoir117. In some implementations, the auxiliary waste fluidic line132is adapted to receive any excess fluid of a sample of interest from the flow cell cartridge assembly102, via the central valve130, and to flow the excess fluid of the sample of interest to the waste reservoir117when back loading the sample of interest into the flow cell125, as described herein. That is, the sample of interest may be loaded from the rear of the flow cell125and any excess fluid for the sample of interest may exit from the front of the flow cell125. As will be described herein, by back loading samples of interest into the flow cell125, different samples can be separately loaded to corresponding channels126and a single manifold (see, for example, the flow cell manifold173ofFIG.2) can couple the front of the flow cell125to the central valve130to direct excess fluid of each sample of interest to the auxiliary waste fluidic line132to reduce the likelihood of contamination of one sample for a first channel126with a second channel126. Once the samples of interest are loaded into the flow cell125, the single manifold can then be used for delivering common reagents from the front of the flow cell125(e.g., upstream) for each channel126and may exit the flow cell125from the rear of the flow cell125(e.g., downstream). Put another way, the sample of interest and the reagents may flow in opposite directions through the channels126of the flow cell125.

Referring to the sipper manifold assembly106, in the implementation shown, the sipper manifold assembly106includes a shared line valve134and a bypass valve136. The shared line valve134may be referred to as a reagent selector valve. The central valve130and the valves134,136of the sipper manifold assembly106may be selectively actuated to control the flow of fluid through fluidic lines138,140,142. One or more of the valves130,134,136may be implemented by a rotary valve, a pinch valve, a flat valve, a solenoid valve, a check valve, a piezo valve, etc. Other fluid control devices may prove suitable.

The sipper manifold assembly106may be coupled to a corresponding number of reagents reservoirs144via reagent sippers146. The reagent reservoirs144may contain fluid (e.g., reagent and/or another reaction component). In some implementations, the sipper manifold assembly106includes a plurality of ports. Each port of the sipper manifold assembly106may receive one of the reagent sippers146. The reagent sippers146may be referred to as fluidic lines.

The shared line valve134of the sipper manifold assembly106is coupled to the central valve130via the shared reagent fluidic line138. Different reagents may flow through the shared reagent fluidic line138at different times. In an implementation, when performing a flushing operation before changing between one reagent and another, the pump manifold assembly110may draw wash buffer through the shared reagent fluidic line138, the central valve130, and the flow cell cartridge assembly102. Thus, the shared reagent fluidic line138may be involved in the flushing operation. While one shared reagent fluidic line138is shown, any number of shared fluidic lines may be included in the system100.

The bypass valve136of the sipper manifold assembly106is coupled to the central valve130via the dedicated reagent fluidic lines140,142. The central valve130may have one or more dedicated ports that correspond to the dedicated reagent fluidic lines140,142. Each of the dedicated reagent fluidic lines140,142may be associated with a single reagent. The fluids that may flow through the dedicated reagent fluidic lines140,142may be used during sequencing operations and may include a cleave reagent, an incorporation reagent, a scan reagent, a cleave wash, and/or a wash buffer. Thus, when performing a flushing operation before changing between one reagent and another in association with the bypass valve136, the sipper manifold assembly106may draw wash buffer through the central valve130and/or the flow cell cartridge assembly102. However, because only a single reagent may flow through each of the dedicated reagent fluidic lines140,142, the dedicated reagent fluidic lines140,142themselves may not be flushed. The approach of including dedicated reagent fluidic lines140,142may be advantageous when the system100uses reagents that may have adverse reactions with other reagents. Moreover, reducing a number of fluidic lines or length of the fluidic lines that are flushed when changing between different reagents reduces reagent consumption and flush volume and may decrease cycle times of the system100. While two dedicated reagent fluidic lines140,142are shown, any number of dedicated fluidic lines may be included in the system100.

The bypass valve136is also coupled to the cache123of the pump manifold assembly110via a bypass fluidic line145. One or more reagent priming operations, hydration operations, mixing operations, and/or transfer operations may be performed using the bypass fluidic line145. The priming operations, the hydration operations, the mixing operations, and/or the transfer operations may be performed independent of the flow cell cartridge assembly102. Thus, the operations using the bypass fluidic line145may occur during, for example, incubation of one or more samples of interest within the flow cell cartridge assembly102. That is, the shared line valve134can be utilized independently of the bypass valve136such that the bypass valve136can utilize the bypass fluidic line145and/or the cache123to perform one or more operations while the shared line valve134and/or the central valve130simultaneously, substantially simultaneously, or offset synchronously perform other operations. Thus, performing multiple operations using the system100at once may reduce run time. Moreover, the bypass valve136and the bypass fluidic line145can be used to flow hybridization buffer through the pump manifold assembly110to the sample manifold assembly108to allow the hybridization buffer to follow the sample of interest through the flow cell128. Thus, the order of fluid flowing through the flow cell125may be: 1) hybridization buffer from the priming operation; 2) the sample drawn from the sample wells260via the sippers268; and 3) the hybridization buffer accessed via the bypass valve136and the bypass fluidic valve145.

Referring now to the drive assembly112, in the implementation shown, the drive assembly112includes a pump drive assembly147and a valve drive assembly148. The pump drive assembly147may be adapted to interface with the one or more pumps121to pump fluid through the flow cell125and/or to load one or more samples of interest into the flow cell cartridge assembly102. The valve drive assembly147may be adapted to interface with one or more of the valves120,122,130,134,136to control the position of the corresponding valves120,122,130,134,136. In an implementation, the shared line valve134and/or the bypass valve136are implemented by rotary valves having a first position that blocks flow to the flow cell125and a second position that allows flow from the reagent reservoir144to the flow cell125. However, either of the valves134,136may be positioned in any number of positions to flow any one or more of a first reagent, a buffer reagent, a second reagent, etc. to the flow cell cartridge assembly102. As an example, the bypass valve136may be rotated between a first position allowing fluid flow from one or more of the reagent reservoirs144, through the bypass valve136, and to the central valve130and a second position allowing fluid flow from one or more of the reagent reservoirs144, through the bypass valve136, and into the bypass fluidic line145. Other arrangements may prove suitable. For example, the bypass valve136may be positionable to allow fluid flow from the bypass fluidic line145, through the bypass valve136, and to a mixing reservoir of the reagent reservoirs144.

Referring to the controller114, in the implementation shown, the controller114includes a user interface150, a communication interface152, one or more processors154, and a memory156storing instructions executable by the one or more processors154to perform various functions including the disclosed implementations. The user interface150, the communication interface133, and the memory156are electrically and/or communicatively coupled to the one or more processors154.

In an implementation, the user interface150is adapted to receive input from a user and to provide information to the user associated with the operation of the system100and/or an analysis taking place. The user interface150may include a touch screen, a display, a key board, a speaker(s), a mouse, a track ball, and/or a voice recognition system. The touch screen and/or the display may display a graphical user interface (GUI).

In an implementation, the communication interface152is adapted to enable communication between the system100and a remote system(s) (e.g., computers) via 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, etc. Some of the communications provided to the remote system may be associated with analysis results, imaging data, etc. generated or otherwise obtained by the system100. Some of the communications provided to the system100may be associated with a fluidics analysis operation, patient records and/or a protocol(s) to be executed by the system100.

The one or more processors154and/or the system100may include one or more of a processor-based system(s) or a microprocessor-based system(s). In some implementations, the one or more processors154and/or the system100includes 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 executing various functions including the ones described herein.

The memory156can include one or more of a semiconductor memory, a magnetically readable memory, an optical memory, a hard disk drive (HDD), an optical storage drive, a solid-state storage device, a solid-state drive (SSD), a flash memory, a read-only memory (ROM), erasable programmable read-only memory (EPROM), electrically erasable programmable read-only memory (EEPROM), a random-access memory (RAM), a non-volatile RAM (NVRAM) memory, a compact disc (CD), a compact disc read-only memory (CD-ROM), a digital versatile disk (DVD), a Blu-ray disk, a redundant array of independent disks (RAID) system, a cache, and/or any other storage device or storage disk in which information is stored for any duration (e.g., permanently, temporarily, for extended periods of time, for buffering, for caching).

FIG.1Bis a cross-sectional view of an implementation of the sipper assembly262including the sippers268and the sample cartridge104including the sample wells260that can be used with the system100ofFIG.1. In the implementation shown, the sipper assembly262is an automated pipettor that includes a base270having a cavity272, a sipper array274including the sippers268and at least partially disposed within the cavity272, and a spring assembly276urging the sippers268in a direction generally indicated by arrow278and into the sample wells260. Having the spring assembly276urge the sippers268into the sample wells260allows the sippers268to be positioned adjacent a lower surface280of the sample wells260, thereby reducing dead volume within the sample well260and allowing less of the sample to be provided during a fluidics analysis operation.

Referring to the sippers268, in the implementation shown, each of the sippers268has a proximal portion282disposed within the cavity272, a distal portion284disposed within the sample wells260, and a fluidic path286extending between the portions282,284. The spring assembly276includes springs288that surround the corresponding sippers268at the proximal portion282and are seated on a corresponding spring seat290of the sipper assembly262.

Referring toFIG.10, a detailed cross-sectional view of the distal portion284of the sipper assembly262and the sample wells260of the sample cartridge104ofFIG.1Bare shown. In the implementation shown, the sippers268each has an opening292at the distal portion284and a tip293. The tip293is formed by a first surface294positioned at a first angle relative to a longitudinal axis295of the sipper268and a second surface296positioned at a second angle relative to the longitudinal axis295. As shown, the first angle is about 30° and the second angle is about 50°. However, the surfaces294,296may be disposed at different angles including the same angle.

The difference between the first and second angles off-sets a tip end297of the tip293from the longitudinal axis295and allows the opening292to be spaced from the tip end297. Because the tip end297extends past the opening292and engages the lower surface280, the opening292is less likely engage to the lower surface298of the sample well260and become occluded and/or obstructed. To further reduce an amount of dead volume present within the sample wells260, the lower surface280of the sample wells260is tapered.

FIG.2illustrates an isometric expanded view of an implementation of the flow cell cartridge assembly102that is receivable in the flow cell receptacle128of the system100ofFIG.1A. In the implementation shown, the flow cell cartridge assembly102includes a body158, a flow cell assembly160, a flow cell coupling162, an inlet gasket assembly164, and an outlet gasket assembly166. The flow cell coupling162may be referred to as a bracket. The inlet gasket assembly164and/or the outlet gasket assembly166may interface or otherwise fluidically couple with the flow cell interface129of the system100ofFIG.1A. The inlet gasket assembly164may be directly coupled to the central valve130or may be coupled to the central valve130via one or more fluidic lines (see, for example,FIG.6B).

In the implementation shown, the flow cell cartridge assembly102may also carry a radio frequency identification (RFID) tag167. The RFID tag167may be used for tracking and/or identification purposes. Other methods of tracking and/or identifying the flow cell cartridge assembly102may prove suitable.

The body158of the flow cell cartridge assembly102has perimeter walls168and a top surface170. The perimeter walls168and the top surface170define a cavity172. The cavity172includes an upper opening174and a lower opening176. The upper opening174is defined by the top surface170. The upper opening174may allow image data to be obtained of the flow cell125via the imaging system116. The lower opening176is defined by a lower edge178of the perimeter walls168. The lower opening176may allow for the sample of interest to be loaded into the channels126of the flow cell125via the outlet gasket assembly166and/or for one or more reagents to flow into the channels126of the flow cell125via the inlet gasket assembly164.

The flow cell assembly160includes the flow cell125having the plurality of channels126and a flow cell manifold173. Each channel126of the plurality of channels126has as a corresponding channel inlet180and a corresponding channel outlet182. The channel inlet180may be referred to as an inlet of the flow cell125. The channel outlet182may be referred to as outlet of the flow cell125. However, depending on the direction of the fluid flow, the channel inlets180may act as outlets to the flow cell125and the channel outlets182may act as inlets to the flow cell125. For example, when the sample of interest is loaded into the channels126from the rear of the flow cell125, the channel outlets182may act as inlets to the flow cell125.

The flow cell manifold173is adapted to be coupled to the flow cell125and may be formed by a laminate. The flow cell manifold173may provide a mechanically flexible connection with the flow cell125. The flow cell manifold173may be coupled to the flow cell125using adhesive. Other methods of coupling the flow cell125and the flow cell manifold173may prove suitable.

In the implementation shown, the flow cell manifold173includes a single inlet184, a plurality of fluidic lines186(the fluidic lines186are more clearly shown inFIG.3), and a plurality of outlets188. The inlet184may be referred to as a flow cell manifold inlet. The inlet184of the flow cell manifold173is coupled to each of the outlets188, via the fluidic lines186. The fluidic lines186may allow the flow cell assembly160to not use additional valving to control fluid flow.

The fluidic lines186may be adapted for flow splitting and may be referred to as flow splitters. In an implementation, fluid flowing through the inlet184may be substantially equally split between the channels126of the flow cell125. In some implementations, the flow cell manifold173and/or the fluidic lines186may be adapted to reduce flow resistance and/or operating pressure of the system100ofFIG.1A. The fluidic lines186may have a height of approximately 300 micrometers (μm). Other heights for the fluidic lines186may prove suitable. In another implementation, the flow cell manifold173may be excluded and the body158of the flow cell cartridge assembly102may include the fluidic lines186, the inlet184, and the plurality of outlets188. As an example, the fluidic lines186, the inlet184, and the plurality of outlets188may be molded and/or embossed into the body158of the flow cell cartridge assembly102(see, for example,FIGS.13A and13B).

The flow cell manifold173may also include inlet alignment holes190and outlet alignment holes192. The inlet alignment holes190may be positioned on either side of the inlet184and the outlet alignment holes192may be positioned adjacent the outlets188of the flow cell manifold173. The inlet alignment holes190and/or the outlet alignment holes192may be referred to as an interface of the flow cell manifold173.

The flow cell coupling162includes protrusions194. The protrusions194are receivable by the outlet alignment holes192of the flow cell manifold173to secure the flow cell manifold173relative to the flow cell125. The flow cell coupling162may include end portions196that are adapted to form a snap fit connection with the body158of the flow cell cartridge assembly102or may float within predetermined tolerances relative to the body158. The coupling between the flow cell coupling162and the body158of the flow cell assembly102may assist in retaining the flow cell125and the flow cell manifold173within the cavity172of the body158of the flow cell cartridge assembly102.

In the implementation shown, the flow cell coupling162includes a cradle197. The cradle197is a semi-circular cutout and may include tapered surfaces. The cradle197may be adapted to receive and/or secure the RFID tag167relative to the flow cell cartridge assembly102. In some implementations, the cradle197may be omitted.

The inlet gasket assembly164includes a first portion198, a second portion202, and an inlet gasket204. The inlet gasket204may be adapted to be coupled adjacent the inlet184of the flow cell manifold173and to allow fluid communication between the channels126of the flow cell125and the components of the system100ofFIG.1A. The first portion198of the inlet gasket assembly164includes protrusions206and the second portion202of the inlet gasket assembly164includes receptacles208. The protrusions206are adapted to be received by the inlet alignment holes190of the flow cell manifold173and the receptacles208of the second portion202of the inlet gasket assembly164. An interaction between the protrusions206and the receptacles208may couple the first and second portions198,202of the inlet gasket assembly164together via, for example, a snap fit connection. In another implementation, the protrusions206may be received within the receptacles208for alignment purposes. Sides210of the first portion198of the inlet gasket assembly164may be adapted to form a snap fit connection with the second portion202of the inlet gasket assembly164and/or with the body158of the flow cell cartridge assembly102.

The outlet gasket assembly166includes a plurality of gaskets212and a body214. The body214may carry the gaskets212. Each gasket212of the plurality of gaskets212is adapted to be coupled adjacent to one of the channel outlets182of the flow cell125and to allow fluid communication between the channels126of the flow cell125and the components of the system100. Sides216of the body214of the outlet gasket assembly166may be adapted to form a snap fit connection with the body158of the flow cell cartridge assembly102.

FIGS.3-5and6A and6Billustrate different implementations of the flow cell assembly160that may be used with the system100ofFIG.1A. The channels126of the flow cell assemblies160shown inFIGS.3-5and6A and6Bmay have a volume of about 18.7 microliters (μL) to about 32.4 μL. Other volumes may prove suitable.

FIG.3illustrates a plan view of the flow cell125and the flow cell manifold173of the flow cell assembly160ofFIG.2.

FIG.4illustrates a plan view of another implementation of the flow cell125and another implementation of the flow cell manifold173of the flow cell assembly160that can be used with the system100ofFIG.1A. In contrast to the implementation ofFIG.3, a width of the channels126of the flow cell assembly160ofFIG.4may be less. Spacing and/or the sizing of the fluidic lines186of the flow cell manifold173ofFIG.4may be adjusted accordingly.

FIG.5illustrates a plan view of another implementation of the flow cell125and another implementation of the flow cell manifold173of the flow cell assembly160that can be used with the system100ofFIG.1A. In contrast to other implementations disclosed, the flow cell125ofFIG.5includes two of the channels126and the flow cell manifold173includes less of the fluidic lines186. The fluidic lines186of the flow cell manifold173fluidly couple the inlet184of the flow cell manifold173and the channels126of the flow cell125. While the flow cell125ofFIG.5includes two channels126, any other number of channels126may be included including one.

FIG.6Aillustrates a plan view of another implementation of the flow cell125and another implementation of the flow cell manifold173of the flow cell assembly160that can be used with the system100ofFIG.1A. In contrast to the other implementations disclosed, the inlet184of the flow cell manifold173ofFIG.6Ais substantially in line with the outlets188of the flow cell manifold173and the fluidic lines186are arranged accordingly. Thus, a height H of the flow cell manifold173ofFIG.6Amay be less than the height of the flow cell manifolds173shown inFIGS.3,4, and5.

FIG.6Billustrates an isometric view of the flow cell125and the flow cell manifold173ofFIG.6A. In the implementation shown, a fluidic line213is coupled to the inlet184of the flow cell manifold173via the gasket204. The fluidic line213may be part of the system100ofFIG.1Aand includes a coupling215. The coupling215of the fluidic line213may be coupled to a port of the central valve130to allow fluid communication between the central valve130and the flow cell125, for example.

FIG.7illustrates an isometric view of an implementation of the sample loading manifold assembly108coupled to an implementation of the flow cell assembly160for use with the system100ofFIG.1A. In the implementation shown, the sample loading manifold assembly108includes a body217having a first face218and a second face219opposite the first face218. The first face218defines a plurality of sample ports220and a plurality of flow cell ports222. Each of the sample ports220is coupled to a corresponding port of the sample cartridge interface119via separate sample fluidic lines223. Similarly, each of the flow cell ports222is coupled to a corresponding channel126of the flow cell125via separate flow cell fluidic lines224. The flow cell fluidic lines224may be coupled to ports of the flow cell interface129. While separate fluidic lines223,224are mentioned coupling the sample ports220and the ports of the sample cartridge interface119and coupling the flow cell ports222and the channels126of the flow cell125and/or the ports of the flow cell interface129, one fluidic line may be used to fluidly couple two or more ports.

The second face219of the sample loading manifold assembly108defines pump ports226. Each pump port226is coupled to a corresponding port228of the pump manifold assembly110(the corresponding ports228of the pump manifold assembly110are more clearly shown inFIG.8) via separate pump-channel fluidic lines230.

The sample valves120of the sample loading manifold assembly108are actuatable to allow a sample of interest to be obtained from the sample cartridge104and to be loaded into one or more of the channels126of the flow cell125. To obtain the sample of interest from the sample cartridge104, one or more of the sample valves120are actuated into a first position that fluidly communicates the sample cartridge104and the pump manifold assembly110. In the first position of the sample valves120, the sample of interest may flow through the sample fluidic lines223toward and into the sample ports220, out of the pump ports226, and into the pump-channel fluidic lines230of the pump manifold assembly110.

To individually deposit the sample of interest into one or more of the channels126of the flow cell125via the outlet gasket assembly166, one or more of the sample valves120are actuatable into a second position that fluidly communicates the pump manifold assembly110and the flow cell125. In the second position of the sample valves120, the sample of interest may flow from the pump-channel fluidic lines230into the pump ports226of the sample loading manifold assembly108and out of the flow cell ports222of the sample loading manifold assembly108toward the corresponding channels126of the flow cell125via the flow cell fluidic lines224. The pump manifold assembly110may be adapted to dispense the sample of interest into the flow cell125at a relatively slow rate to allow a substantially uniform transfer. When the sample of interest is being loaded into the channels126of the flow cell125, the central valve130may be positioned to vent the flow cell125to the auxiliary waste fluidic line132. After the sample of interest is dispensed to the flow cell125, an incubation process may be performed for seeding. In some implementations, 100 microliters (μL) of the sample of interest is deposited within the channels126of the flow cell125at a time, incubated, and seeded. Other volumes may prove suitable. The process of incrementally depositing a smaller amount of the sample of interest within the channels126, incubating, and seeding may be repeated a threshold number of times.

Prior to obtaining the sample of interest from the sample cartridge104, in some implementations, the pump manifold assembly110may be primed with buffer. The buffer may be obtained from the bypass fluidic line145. Priming the pump manifold assembly110with the buffer may provide the pump manifold assembly110with the stroke to dispense the sample of interest into the flow cell125, for example.

FIG.8is a schematic illustration of an implementation of a portion of the pump manifold assembly110for use with the system100ofFIG.1A. In the implementation shown, the pump manifold assembly110includes a body232carrying the pump valves122, a cache valve234, and the pumps121. The pumps121may be syringe pumps and may be adapted to receive a volume of approximately 500 microliters (μL). Other volumes may prove suitable.

The pump valves122, the cache valve234, and/or the pumps121are operable to individually control fluid flow to each channel126of the plurality of channels126of the flow cell125. In the implementation shown, two pump drive assemblies147are provided. The pump drive assemblies147may be adapted to individually actuate one or more of the pumps121to perform one or more of the operations disclosed. In an implementation, one of the pump drive assemblies147may operate two of the pumps121and the other of the pump drive assemblies147may operate six of the pumps121. Other arrangements may prove suitable.

The pump valves122, the cache valve234, and/or the pumps121may be operable to flow one or more reagents through the bypass fluidic line145and/or to the primary waste fluidic line127. The body232of the pump manifold assembly110may also carry a plurality of sensors236,237. The sensors236,237may include pressure sensors or flow rate sensors. Other types of sensors may prove suitable. In another implementation, one or more of the sensors236,237and/or the cache valve234may be excluded. In some such implementations, the bypass fluidic line145may also be excluded. Other arrangements may prove suitable.

The pump manifold assembly110includes the cache123, the pump-channel fluidic lines230, a plurality of pump fluidic lines238, a shared fluidic line240, a cache fluidic line242, and the primary waste fluidic line127. The cache fluidic line242is coupled to and between the cache123and the cache valve234. The pump-channel fluidic line230and the pump fluidic line238may be collectively referred to as a pump-channel fluidic line. In the implementation shown, each pump valve122is coupled to a corresponding pump-channel fluidic line230, a corresponding pump fluidic line238, and the shared fluidic line240. Each pump121is coupled to a corresponding pump fluidic line238. The pumps121are operable to individually control fluid flow to the pump-channel fluidic line230and to one of the channels126of the flow cell125.

The cache valve234is coupled to the cache fluidic line242, the primary waste fluidic line127, and the shared fluidic line240. The sensors236,237may be adapted to determine one or more of a pressure value or a flow rate value of one or more of: at least one of the pump-channel fluidic lines230or the shared fluidic line240. Five sensors236are coupled to the pump-channel fluidic lines230. The sensors236may be differently positioned. Additional or less sensors including zero sensors may prove suitable.

To draw fluid from or to urge fluid toward the flow cell125using one or more of the pumps121, one or more of the pump valves122may be actuated into a first position that fluidly communicates the pump-channel fluidic lines230and the pump fluidic lines238and one or more of the pumps121may be actuated to move the fluid.

To move reaction components toward the waste reservoir117using one or more of the pumps121, one or more of the pump valves122may be actuated to a second position that fluidly communicates the pump fluidic lines238and the shared fluidic line240, the cache valve234may be actuated to a first position that fluidly communicates the shared fluidic line240and the primary waste fluidic line127, and one or more of the pumps121may be actuated to move the fluid.

To perform a mixing operation using one or more reaction components received through the bypass fluidic line145, the pump valves122may be actuated to a second position that fluidly communicates the pump fluidic lines238and the shared fluidic line240, the cache valve234may be actuated to a second position that fluidly couples the cache fluidic line242and the shared fluidic line240, and one or more of the pumps121may be actuated to move the fluid. In some implementations, a larger volume of the reaction component(s) may be transferred through the bypass fluidic line145to prime the shared fluidic line240using all of the pumps121. Then, to increase precision on a subsequent fluid transfer, two of the pumps121may be used while the remaining pumps121are idle, for example. A different number of pumps121including using one pump121may be used instead.

FIG.9illustrates a schematic illustration of another implementation of a system300in accordance with the teachings of this disclosure. In the implementation shown, the system300includes the flow cell interface128and the pump manifold assembly110. The flow cell interface128is adapted to be coupled to the flow cell125having the plurality of channels126. The pump manifold assembly110carries the pump valves122and the pumps121. While the system300includes two pump valves122and two pumps121, providing the system300with a different number of valves122and/or pumps121may prove suitable.

In the implementation shown, the pump manifold assembly110includes the pump-channel fluidic lines230, the pump fluidic lines238, and the shared fluidic line240. The pump valves122and the pumps121may be operable to individually control fluid flow through each channel126of the plurality of channels126of the flow cell125via the corresponding pump-channel fluidic lines230. Each pump valve122may be coupled to a corresponding pump-channel fluidic line238, a corresponding pump fluidic line230, and the shared fluidic line240. Each pump121may be coupled to a corresponding pump fluidic line238. Other fluidic line arrangements may prove suitable.

FIG.10illustrates a schematic illustration of another implementation of a system400in accordance with the teachings of this disclosure. In the implementation shown, the system400includes one or more of the valves130,134, and/or136, the flow cell interface128, the pump manifold assembly110, and the bypass fluidic line145. The valves130,134and/or136are adapted to be coupled to the corresponding reagent reservoirs144. The flow cell interface128is adapted to be coupled to the flow cell125having the plurality of channels126. The pump manifold assembly110includes the pumps121, the pump valves122, and the cache123. Each pump121may be operable to individually control fluid flow for each channel126of the plurality of channels126of the flow cell125. The bypass fluidic line145is operatively coupled between the one or more valves130,134,136and the cache123. Other fluidic line arrangements may prove suitable.

FIG.11illustrates a schematic illustration of another implementation of a system500in accordance with the teachings of this disclosure. In the implementation shown, the system500includes the flow cell interface128, the sample cartridge interface119, and the sample loading manifold assembly108. The flow cell interface119is adapted to be coupled to the flow cell125having the plurality of channels126. The sample cartridge interface119is adapted to be coupled to the sample cartridge104and the sample cartridge interface119is positioned downstream of the flow cell interface128. The sample loading manifold assembly108is positioned between the flow cell interface128and the sample cartridge interface129.

The sample loading manifold assembly108includes the body217carrying the plurality of sample valves120and defining the sample ports220and the flow cell ports222. Each sample port220is coupled to a corresponding port502of the sample cartridge interface119via one of the sample fluidic lines223. Each flow cell port222is coupled to a corresponding port504of the flow cell interface119. The ports504of the flow cell interface119are associated with a corresponding one of the channels126of the flow cell125via the flow cell fluidic lines224.

FIG.12illustrates a schematic illustration of another implementation of a system600in accordance with the teachings of this disclosure. In the implementation shown, the system600includes one or more of the valves130,134, and/or136, the flow cell interface128, the sample cartridge interface119, and the pump manifold assembly110. One or more of the valves130,134, and/or136may be adapted to be coupled to corresponding reagent reservoirs144. The flow cell interface128is adapted to be coupled to the flow cell125having the plurality of channels126. The sample cartridge interface128includes the plurality of ports502and is adapted to be coupled to the sample cartridge104carrying a sample of interest. The sample cartridge interface119is positioned downstream of the flow cell interface128.

In the implementation shown, the pump manifold assembly110includes the pumps121and the pump valves122. Each pump121and the corresponding pump valve122are operable to individually control the flow between each port502of the plurality ports502of the sample cartridge interface119and each channel126of the plurality of channels126of the flow cell125with the sample of interest.

FIG.13Aillustrates a plan view of another implementation of the flow cell125and another implementation of the flow cell manifold173of the flow cell cartridge assembly102that can be used with the system100ofFIG.1A. In contrast to the other implementations disclosed, the body158of the flow cell cartridge assembly102defines the fluidic lines186, the inlet184, and the plurality of outlets188. In the implementation shown, the fluidic lines186are also coupled to the channel outlets182of the channels126of the flow cell125to allow fluidic communication with, for example, the fluidic line124and/or the sample loading manifold assembly108.

FIG.13Billustrates a cross-sectional view of the flow cell cartridge assembly102ofFIG.13A. In the implementation shown, the body158of the flow cell cartridge assembly102defines receptacles250. Inner gaskets252and outer gaskets254are disposed within the receptacles250. The inner gaskets254may be adapted to matingly engage the flow cell125to allow fluid communication between the fluidic lines186of the body158of the flow cell cartridge assembly102and the channels126of the flow cell. The outer gaskets254may be adapted to matingly engage with the flow cell interface129of the system100to allow fluid communication between the system100and the flow cell cartridge assembly102.

FIGS.14-17illustrates flowcharts for methods of performing a pumping operation and/or a sample of interest loading operation using the system100ofFIG.1Aor any of the other systems300,400,500, and/or600disclosed herein. In the flow charts ofFIGS.14and16, the blocks surrounded by solid lines may be included in an implementation of a process1200and1400while the blocks surrounded in dashed lines may be optional in the implementation of the process. However, regardless of the way the border of the blocks is presented inFIGS.14-17, the order of execution of the blocks may be changed, and/or some of the blocks described may be changed, eliminated, combined and/or subdivided into multiple blocks.

The process1200ofFIG.14begins with the flow cell125having the plurality of channels126being coupled to the flow cell interface129(block1202). At block1204, one or more of the plurality of pump valves122and one or more of the plurality of pumps121of the pump manifold assembly110are operated to load each channel126of the plurality of channels126of the flow cell125with a sample of interest.

One or more of the plurality of pump valves122and one or more of the plurality of pumps121of the pump manifold assembly110are operated to individually control fluid flow through each channel126of the plurality of channels126via a corresponding pump-channel fluidic line230(block1206). Operating one or more of the plurality of pumps121may include flowing the sample of interest into each channel126in a first direction. Operating one or more of the plurality of pumps121may also include flowing reagent through the channels126of the flow cell125in a second direction opposite the first direction. The pump manifold assembly110may include the plurality of pump-channel fluidic lines230, the plurality of pump fluidic lines238, and the shared fluidic line240. Each pump valve122may be coupled to a corresponding pump-channel fluidic line230, a corresponding pump fluidic line238, and the shared fluidic line240. Each pump121may be coupled to a corresponding pump fluidic line238.

One of more of the plurality of pumps121of the pump manifold assembly110are operated to control fluid flow between the bypass fluidic line145and the cache123of the pump manifold assembly110(block1208). In some implementations, the bypass fluidic line145couples the cache123and the bypass valve136.

At block1210, one or more of the pump valves122, one or more of the pumps121, or the cache valve234of the pump manifold assembly110are operated to control fluid flow between at least one of the shared fluidic line240and the primary waste fluidic line127or between the bypass fluidic line145and the primary waste fluidic line127. One or more of the pumps121of the pump manifold assembly110are operated to flow the sample of interest out of the channels126of the flow channel125and into the auxiliary waste fluidic line132(block1212).

The process1300ofFIG.15begins with the flow cell125having the plurality of channels126being coupled to the flow cell interface129(block1302). At block1304, one or more of the plurality of pump valves122and one or more of the plurality of pumps121of the pump manifold assembly110are operated to individually control fluid flow through each channel126of the plurality of channels126via the corresponding pump-channel fluidic lines230. The pump manifold assembly110may include the plurality of pump-channel fluidic lines230, the plurality of pump fluidic lines238, and the shared fluidic line240. Each pump valve122may be coupled to a corresponding pump-channel fluidic line230, a corresponding pump fluidic line238, and the shared fluidic line240. Each pump121may be coupled to a corresponding pump fluidic line238.

The process1400ofFIG.16begins with the flow cell125having the plurality of channels126being coupled to the flow cell interface129(block1402). At block1404, the sample cartridge104is coupled to the sample cartridge interface119. The sample cartridge interface119may be positioned downstream of the flow cell interface129. The sample cartridge104may carry a sample of interest. One or more of the sample valves120of the sample loading manifold assembly108are operated to individually load each channel126of the plurality of channels126of the flow cell125with a sample of interest (block1406).

In some implementations, operating one or more sample valves120includes moving a sample of interest from the sample cartridge104to a corresponding sample port220of the sample loading manifold assembly108, out of an associated pump port226of the sample loading manifold assembly108, and into a corresponding pump-channel fluidic line230of the pump manifold assembly110. Operating one or more sample valves120may also include moving a sample of interest from a corresponding pump-channel fluidic line230, through the associated pump port226, and through the flow cell port222of the sample loading manifold assembly108. Each flow cell port222may be coupled to a corresponding port502of the flow cell interface119and associated with one of the channels126of the plurality of channels126of the flow cell125.

Each sample valve120of the sample loading manifold assembly108may be operable to fluidly communicate one of the ports502of the sample cartridge interface119and one or more of the pumps121and to fluidly communicate a pump121and a corresponding channel126of the plurality of channels126of the flow cell125. In some implementations, operating one or more sample valves120includes flowing the sample of interest into each channel126of the flow cell125in a first direction. The process1400may also include controlling a flow of reagent through the channels126of the flow cell125in a second direction opposite the first direction.

At block1408, one or more of the plurality of pumps121are operated to individually control fluid flow for each channel126of the plurality of channels126of the flow cell125. Reagent may be flowed through the shared reagent fluidic line138to the channels126of the flow cell125and subsequently another reagent may be flowed through the dedicated reagent fluidic line140and/or142to the channels126of the flow cell125(block1410). At block1412, the sample of interest is flowed out of the channels126of the flow cell125and into the auxiliary waste fluidic line132.

The process1500ofFIG.17begins with the flow cell125having the plurality of channels126being coupled to the flow cell interface129(block1502). At block1504, the sample cartridge104is coupled to the sample cartridge interface119. The sample cartridge interface119may be positioned downstream of the flow cell interface129. The sample cartridge104may carry one or more samples of interest. One or more of the sample valves120of the sample loading manifold assembly108are operated to individually load each channel126of the plurality of channels126of the flow cell125with a corresponding sample of interest or the same sample of interest (block1506).

A method comprises coupling a flow cell having a plurality of channels to a flow cell interface, the flow cell interface fluidically 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 fluidically connect a first channel of the plurality of channels with a first pump of a plurality of pumps. The first pump fluidically connected to the first channel via a first pump-channel fluidic line. The method comprises pumping a first volume of a first reagent through the first channel using the first pump via the first pump-channel fluidic line and moving the first pump valve of the plurality of pump valves to a second position to fluidically connect the pump and the first pump-channel fluidic line with a shared fluidic line in fluid communication with a waste reservoir. The method comprises pumping the first volume of the first reagent into the waste reservoir through the shared fluidic line and moving a second pump valve of a plurality of pump valves to a first position to fluidically connect a second channel of the plurality of channels with a second pump of the plurality of pumps. The second pump fluidically connected to the second channel via a second pump-channel fluidic line. The method comprises pumping a second volume of the first reagent into the second channel using the second pump via the second pump-channel fluidic line and moving the second pump valve of the plurality of pump valves to a second position to fluidically connect the second pump and the second pump-channel fluidic line with the shared fluidic line in fluid communication with the waste reservoir. The method comprises pumping the second volume of the first reagent into the waste reservoir through the shared fluidic line.

The method of any one or more of the preceding implementations and/or any one or more of the implementations disclosed below, further comprising moving a bypass valve to a first position to fluidically couple a bypass fluidic line and a cache of the pump manifold assembly, and pumping a third volume of the first reagent or another reagent through the bypass fluidic line and into the cache.

The method of any one or more of the preceding implementations and/or any one or more of the implementations disclosed below, further comprising actuating one or more of the plurality of pump valves, one or more of the plurality of pumps, or a cache valve of the pump manifold assembly and pumping reagent between at least one of the shared fluidic line and a primary waste fluidic line in fluidic communication with the waste reservoir or the bypass fluidic line and the primary waste fluidic line.

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 plurality of pump valves and one or more of the plurality of pumps of the pump manifold assembly to load one or more of the plurality of channels of the flow cell with a sample of interest.

The method of any one or more of the preceding implementations and/or any one or more of the implementations disclosed below, operating the 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 comprises operating one or more of the plurality of pumps of the pump manifold assembly to control a flow of reagent through the channels of the flow cell in a second direction opposite the first direction.

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 plurality of pumps of the pump manifold assembly to flow the sample of interest out of the one or more channels of the flow cell and into an auxiliary waste fluidic line, the auxiliary waste fluidic line being upstream of the flow cell interface.

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 and comprising a plurality of pump-channel fluidic lines, a plurality of pump fluidic lines, and a shared fluidic line. The pump valves and the pumps are operable to individually control fluid flow through each channel of the plurality of channels of the flow cell via the corresponding pump-channel fluidic lines. Each pump valve being coupled to a corresponding pump-channel fluidic line, a corresponding pump fluidic line, and the shared fluidic line and being movable between a first position fluidically coupling a corresponding channel of the plurality of channels, a corresponding pump-channel fluidic line, and a corresponding pump fluidic line and a second position fluidically coupling a corresponding pump fluidic line, the shared fluidic line, and a waste reservoir. Each pump coupled to a corresponding pump fluidic line.

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

The apparatus of any one or more of the preceding implementations and/or any one or more of the implementations disclosed below, the pump manifold assembly further comprises a cache valve and a cache fluidic line. The cache valve being coupled to the cache fluidic line and the shared fluidic line.

The apparatus of any one or more of the preceding implementations and/or any one or more of the implementations disclosed below, the pump manifold assembly further comprises a primary waste fluidic line coupled to the waste reservoir, the cache valve coupled to the primary waste fluidic line.

The apparatus of any one or more of the preceding implementations and/or any one or more of the implementations disclosed below, the pump manifold assembly further comprises a plurality of sensors adapted to determine one or more of a pressure value or a flow rate value of one or more of: at least one of the pump-channel fluidic lines or the shared fluidic line.

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 pair of pump drive assemblies that are operable to drive the plurality of pumps.

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 cartridge interface adapted to be coupled to a sample cartridge, the sample cartridge interface positioned downstream of the flow cell interface.

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 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 coupled to a corresponding port of the sample cartridge interface via a sample fluidic line. Each flow cell port 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 fluidic line. Each pump port coupled to a corresponding pump-channel fluidic line of the plurality of pump-channel fluidic lines.

The apparatus of any one or more of the preceding implementations and/or any one or more of the implementations disclosed below, the sample valves of the sample loading manifold assembly and pumps of the pump manifold assembly are operable to individually load each channel of the plurality of channels of the flow cell with a sample of interest.

The apparatus of any one or more of the preceding implementations and/or any one or more of the implementations disclosed below, each sample valve is operable to fluidly communicate a port of the sample cartridge and a corresponding pump of the plurality of pumps of the pump manifold assembly and to fluidly communicate a pump of the plurality of pumps of the pump manifold assembly and a corresponding channel of the plurality of channels of the flow cell.

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 fluidic line coupled to the central valve and adapted to be coupled to the waste reservoir, the auxiliary waste fluidic line being positioned upstream of the flow cell interface.

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 fluidic lines, and a shared reagent fluidic line. The shared reagent fluidic line coupling the shared line valve and the central valve and adapted to flow one or more reagents to the flow cell via the central valve. Each dedicated reagent fluidic line coupling the bypass valve and the central valve and adapted to flow a reagent to the flow cell via the central valve.

An apparatus comprises 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 comprises 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 for each channel of the plurality of channels of the flow cell and a bypass fluidic line operatively coupled between the one or more valves and the cache.

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 sample valve and a corresponding pump of the pump manifold assembly is 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.

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 flow cell assembly including the flow cell having the plurality of channels and a flow cell manifold. The flow cell manifold includes an inlet, a plurality of fluidic lines, and a plurality of outlets. Each outlet of the flow cell manifold is coupled to a corresponding channel of the flow cell.

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

The method of any one or more of the preceding implementations and/or any one or more of the implementations disclosed below, 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, out of an associated pump port of the sample loading manifold assembly, and into a pump-channel fluidic line of a pump manifold assembly, and moving the first sample of interest from the pump-channel fluidic 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.

The method of any one or more of the preceding implementations and/or any one or more of the implementations disclosed below, moving the first sample valve of the one or more sample valves to the first position includes fluidically coupling a port of a sample cartridge interface and a corresponding pump and moving the first sample valve of the one or more sample valves to the second position includes fluidically coupling the corresponding pump and the first channel of the plurality of channels of the flow cell.

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 for each channel of the plurality of channels of the flow cell.

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 the first sample of interest out of the first channel of the flow cell and into an auxiliary waste fluidic line, the auxiliary waste fluidic line being upstream of the flow cell and fluidically coupled to the central valve and the waste reservoir.

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 fluidic line to the plurality of channels of the flow cell and subsequently flowing another reagent through a dedicated reagent fluidic line to the plurality of channels of the flow cell.

An apparatus comprising a flow cell interface adapted to be coupled to a flow cell having a plurality of channels and a central valve and an auxiliary waste fluidic line coupled to the central valve and adapted to be coupled to a waste reservoir. The central valve coupled to the flow cell interface and movable between a first position fluidically connecting an inlet of the plurality of channels to the auxiliary waste fluidic line and a second position fluidically connecting a 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 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 and comprises 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 fluidic 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 fluidic line. Each of the sample valves are movable between a first position fluidically connecting a corresponding sample port and a corresponding outlet of the plurality of channels and a second position fluidically coupling the corresponding outlet of the plurality of channels and the waste reservoir.

The apparatus of any one or more of the preceding implementations and/or any one or more of the implementations disclosed below, the sample valves are operable to individually load each channel of the plurality of channels of the flow cell.

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 and 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 fluidic line.

The apparatus of any one or more of the preceding implementations and/or any one or more of the implementations disclosed below, each sample valve is operable to fluidly communicate a port of the sample cartridge and a corresponding pump of the plurality of pumps and to fluidly communicate a pump of the plurality of pumps and a corresponding channel of the plurality of channels of the flow cell.

The apparatus of any one or more of the preceding implementations and/or any one or more of the implementations disclosed below, the pumps are operable to individually control fluid flow for each channel of the plurality of channels of the flow cell.

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 comprising the pumps and a cache. Further comprising a bypass valve and a bypass fluidic line coupling the bypass valve and the cache.

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 fluidic lines, and a shared reagent fluidic line. The shared reagent fluidic line coupling the shared line valve and the central valve and adapted to flow one or more reagents to the flow cell. E ach dedicated reagent fluidic line coupling the bypass fluidic line and the central valve and adapted to flow toward the flow cell.

The apparatus of any one or more of the preceding implementations and/or any one or more of the implementations disclosed below, the pump manifold assembly carries a plurality of pump valves and a cache valve and includes a plurality of pump-channel fluidic lines, a plurality of pump fluidic lines, a shared fluidic line, a cache fluidic line, and a primary waste fluidic line. The cache fluidic line being coupled to and between the cache and the cache valve. Each pump valve being coupled to a corresponding pump-channel fluidic line, a corresponding pump fluidic line, and the shared fluidic line. The cache valve being coupled to the cache fluidic line, the primary waste fluidic line, and the shared fluidic line.

The apparatus of any one or more of the preceding implementations and/or any one or more of the implementations disclosed below, the pump valves and the pumps are operable to individually control fluid flow for each channel of the plurality of channels of the flow cell and the pump valves, the cache valve, and the pumps are operable to control fluid flow between the bypass fluidic line and the shared fluidic line.

The apparatus of any one or more of the preceding implementations and/or any one or more of the implementations disclosed below, the pump valves, the cache valve, and the pumps are operable to control fluid flow between the shared fluidic line and the primary waste fluidic line.

An apparatus comprises 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 comprises 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 positioned downstream of the flow cell interface. The apparatus comprises a pump adapted to load a channel of the flow cell with the sample of interest via the flow cell interface associated with an outlet of the flow cell and a corresponding port of the sample cartridge interface.

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 a corresponding pump valve are operable to individually control the flow of the 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.

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 sample valve is operable to individually load each channel of the plurality of channels of the flow cell with the sample of interest.

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 flow cell assembly including the flow cell having a plurality of channels and a flow cell manifold. The flow cell manifold includes an inlet, a plurality of fluidic lines, and a plurality of outlets. Each outlet of the flow cell manifold is coupled to a corresponding channel of the flow cell.

The foregoing description is provided to enable a person skilled in the art to practice the various configurations described herein. While the subject technology has been particularly described with reference to the various figures and configurations, it should be understood that these are for illustration purposes only and should not be taken as limiting the scope of the subject technology.

As used herein, an element or step recited in the singular and proceeded with the word “a” or “an” should be understood as not excluding plural of said elements or steps, unless such exclusion is explicitly stated. Furthermore, references to “one implementation” are not intended to be interpreted as excluding the existence of additional implementations that also incorporate the recited features. Moreover, unless explicitly stated to the contrary, implementations “comprising,” “including,” or “having” an element or a plurality of elements having a particular property may include additional elements whether or not they have that property. Moreover, the terms “comprising,” including,” having,” or the like are interchangeably used herein.

The terms “substantially,” “approximately,” and “about” used throughout this Specification are used to describe and account for small fluctuations, such as due to variations in processing. For example, they can refer to less than or equal to ±5%, such as less than or equal to ±2%, such as less than or equal to ±1%, such as less than or equal to ±0.5%, such as less than or equal to ±0.2%, such as less than or equal to ±0.1%, such as less than or equal to ±0.05%.

There may be many other ways to implement the subject technology. Various functions and elements described herein may be partitioned differently from those 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 generic principles defined herein may be applied to other implementations. Thus, many changes and modifications may be made to the subject technology, by one having ordinary skill in the art, without departing from the scope of the subject technology. For instance, different numbers of a given module or unit may be employed, a different type or types of a given module or unit may be employed, a given module or unit may be added, or a given module or unit may be omitted.

Underlined and/or italicized headings and subheadings are used for convenience only, do not limit the subject technology, and are not referred to in connection with the interpretation of 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 later come to be known to those of ordinary skill in the art are expressly incorporated herein by reference and intended to be encompassed by the subject technology. Moreover, nothing disclosed herein is intended to be dedicated to the public regardless of whether such disclosure is explicitly recited in the above description.

It should be appreciated that all combinations of the foregoing concepts and additional concepts discussed in greater detail below (provided such concepts are not mutually inconsistent) are contemplated as being part of the subject matter disclosed herein. In particular, all combinations of claimed subject matter appearing at the end of this disclosure are contemplated as being part of the subject matter disclosed herein.