Flow Cell Assembly and Associated Reagent Selector Valve

Abstract

A flow cell assembly and associated reagent selector valve are provided. According to one embodiment, an apparatus includes a system including a reagent cartridge receptacle. The apparatus includes a flow cell assembly. The apparatus includes a reagent cartridge receptacle receptacle. The reagent cartridge includes a plurality of reagent reservoirs. The apparatus includes a manifold assembly. The manifold assembly includes a reagent selector valve fluidly coupled to the reagent reservoirs and adapted to selectively flow reagents from corresponding reagent reservoirs to the flow cell assembly. At least one surface of the manifold assembly associated with the reagent selector valve is coupled to a portion of the flow cell assembly.

Description

Technical Field

[0001] The present invention relates to a flow cell assembly and a related reagent selector valve. (Cross - reference to related applications) This application claims priority to U.S. Provisional Patent Application No. 62 / 955,176, filed on December 30, 2019, the content of which is hereby incorporated by reference in its entirety for all purposes.

Background Art

[0002] Sequencing platforms may include valves and pumps. The valves and pumps can be used to perform various fluid operations.

Summary of the Invention

Means for Solving the Problems

[0003] According to a first embodiment, the apparatus comprises or includes a system comprising a reagent cartridge receptacle. The apparatus comprises or includes a flow cell assembly. The apparatus comprises or includes a reagent cartridge receivable within the reagent cartridge receptacle. The reagent cartridge comprises or includes a plurality of reagent reservoirs. The apparatus comprises or includes a manifold assembly. The manifold assembly comprises or includes a reagent selector valve fluidly coupled to the reagent reservoirs and adapted to selectively flow a reagent from a corresponding reagent reservoir to the flow cell assembly. At least one surface of the surface of the manifold assembly associated with the reagent selector valve is coupled to a portion of the flow cell assembly.

[0004] According to a second embodiment, the device comprises or includes a flow cell assembly. The device comprises or includes a system comprising or including a manifold assembly, and a flow cell receptacle adapted to hold the flow cell assembly. The manifold assembly comprises or includes a reagent selector valve disposed directly adjacent to the flow cell assembly. The reagent selector valve comprises or includes a surface configured to directly couple to a portion of the flow cell assembly and is adapted to selectively flow reagents to the flow cell assembly. The reagent selector valve comprises at least one of a ceramic rotor or a ceramic stator. The reagent selector valve comprises or includes a valve drive assembly operably coupled to the reagent selector valve. The valve drive assembly comprises or includes a brushless motor.

[0005] According to a third embodiment, an apparatus comprises or includes a system comprising or including a reagent cartridge receptacle. The apparatus comprises or includes a flow cell assembly. The apparatus comprises or includes a reagent cartridge receptacle. The reagent cartridge comprises or includes a plurality of reagent reservoirs. The apparatus comprises or includes a manifold assembly coupled directly adjacent to the flow cell assembly. The manifold assembly comprises or includes a reagent selector valve, fluidly coupled to the reagent reservoirs and adapted to selectively flow reagents from corresponding reagent reservoirs to the flow cell assembly.

[0006] According to a fourth embodiment, an apparatus includes or comprises a flow cell assembly. The apparatus includes or comprises a system including or comprising a manifold assembly, and a flow cell receptacle adapted to hold the flow cell assembly. The manifold assembly is disposed directly adjacent to the flow cell assembly, and the manifold assembly includes or comprises a reagent selector valve adapted to selectively flow reagents to the flow cell assembly.

[0007] According to a fifth embodiment, an apparatus comprises or includes a system comprising or including a manifold assembly disposed directly adjacent to the flow cell assembly, and a reagent selector valve adapted to selectively allow the flow of reagents.

[0008] Furthermore, in the first, second, third, fourth and / or fifth embodiments above, the apparatus and / or method may further comprise or include any one or more of the following: According to one embodiment, a surface of the reagent selector valve is mechanically coupled directly to the flow cell assembly.

[0009] According to another embodiment, the reagent selector valve comprises or includes at least one of a ceramic rotor or a ceramic stator. According to another embodiment, the manifold assembly further comprises or includes a valve drive assembly operably coupled to the reagent selector valve.

[0010] According to another embodiment, the valve drive assembly comprises or includes a brushless motor. According to another embodiment, the manifold assembly is adapted to be directly coupled to the flow cell assembly.

[0011] According to another embodiment, a system comprises or includes a manifold assembly. According to another embodiment, the system comprises or includes a flow cell receptacle adapted to hold a flow cell assembly.

[0012] According to another embodiment, the reagent selector valve of the manifold assembly is disposed within the flow cell receptacle. According to another embodiment, a surface of the reagent selector valve is adapted to be mechanically coupled directly to the flow cell assembly.

[0013] According to another embodiment, the manifold assembly is disposed within the flow cell receptacle. According to another embodiment, the reagent selector valve comprises or includes a bypass port.

[0014] According to another embodiment, the system further comprises or includes a bypass fluid line and a cache, the bypass fluid line fluidly coupling the bypass port and the cache. According to another embodiment, the manifold assembly comprises or includes a flow cell valve coupled between the reagent selector valve and a flow cell assembly, the flow cell assembly comprising or including a flow cell having a plurality of channels, the flow cell valve adapted to selectively flow reagents into corresponding channels.

[0015] According to another embodiment, the flow cell valve comprises or includes a plurality of outlet ports adapted to be coupled to corresponding channels of the flow cell. According to another embodiment, the flow cell valve and the reagent selector valve have opposing surfaces, further comprising or including a valve actuation assembly adapted to interface with the flow cell valve and the reagent selector valve at the opposing surfaces and control the position of the corresponding valve.

[0016] According to another embodiment, the flow cell valve comprises or includes a flow cell valve body having a flow cell valve stator and a flow cell valve rotor. The flow cell valve body has a common fluid line and a plurality of flow cell valve fluid lines. The common fluid line is coupled to the reagent selector valve. The flow cell valve rotor interfaces with the flow cell valve stator to fluidly couple the common fluid line to one or more of the flow cell valve fluid lines.

[0017] According to another embodiment, the flow cell valve rotor comprises or includes a radial groove adapted to fluidly couple a common fluid line to one or more of the flow cell valve fluid lines.

[0018] According to another embodiment, the flow cell valve rotor comprises or includes an arcuate groove coupled to a distal end of the radial groove, the arcuate groove adapted to allow a common fluid line to be fluidly coupled to two or more of the flow cell valve fluid lines.

[0019] According to another embodiment, a reagent selector valve comprises or includes a reagent valve body having both a reagent valve stator and a reagent valve rotor. The reagent valve body has a common fluid line and a plurality of reagent fluid lines. The reagent fluid lines are adapted to be fluidly coupled to corresponding reagent reservoirs. The reagent valve rotor interfaces with the reagent valve stator to fluidly couple the common fluid line and the corresponding reagent fluid lines.

[0020] According to another embodiment, the reagent valve rotor comprises or includes radial grooves adapted to fluidly couple a common fluid line and a corresponding reagent fluid line. According to another embodiment, the reagent valve body comprises or includes a flow cell interface, and the flow cell assembly is coupled to the flow cell interface.

[0021] According to another embodiment, the device further comprises or includes a valve drive assembly that interfaces with and is adjacently coupled to an end of the reagent selector valve. According to another embodiment, the flow cell assembly comprises or includes a body coupled to the reagent selector valve.

[0022] According to another embodiment, the device further comprises or includes a vibration isolation assembly. According to another embodiment, the vibration isolation assembly comprises or includes a housing rotatably coupled to the reagent selector valve and the valve drive assembly.

[0023] According to another embodiment, the manifold assembly is disposed within the flow cell receptacle. According to another embodiment, the manifold assembly is adapted to be directly coupled to the flow cell assembly.

[0024] According to another embodiment, the manifold assembly comprises or includes a flow cell valve coupled between the reagent selector valve and a flow cell assembly, the flow cell assembly comprising or including a flow cell having a plurality of channels, the flow cell valve adapted to selectively flow reagents into corresponding channels.

[0025] According to another embodiment, the device further comprises or includes a vibration isolation assembly. According to another embodiment, the vibration isolation assembly comprises or includes magnets and is adapted to magnetically levitate the manifold assembly.

[0026] According to another embodiment, the vibration assembly comprises or includes a shock absorber. 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]

[0027] [Figure 1A] 1 shows a schematic diagram of one embodiment of a system according to the teachings of the present disclosure. [Figure 1B]FIG. 1B is a schematic diagram of another embodiment of the system of FIG. 1A. [Figure 1C] FIG. 1B is a schematic diagram of another embodiment of the system of FIG. 1A. [Diagram 2] FIG. 1B is a schematic diagram of one embodiment of the flow cell valve and reagent selector valve of FIG. 1A. [Diagram 3] FIG. 1B is a schematic diagram of one embodiment of the reagent selector valve of FIG. 1A. [Figure 4A] FIG. 1B is a schematic diagram of one embodiment of the reagent selector valve, valve actuation assembly, and flow cell assembly of FIG. 1A. [Figure 4B] FIG. 4B is a cross-sectional view of the reagent selector valve, valve actuation assembly, and flow cell assembly of FIG. 4A. [Diagram 5] FIG. 1B is a schematic diagram of another embodiment of the flow cell assembly of FIG. 1A showing different configurations / positions of the reagent selector valve. [Figure 6] 13 is a schematic diagram of another embodiment of the valve drive assembly, reagent selector valve, and flow cell assembly. [Figure 7] 1 illustrates an isometric view of one embodiment of a vibration isolation assembly including a housing and a shock absorber. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0028] Although the following text discloses detailed descriptions of embodiments 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 exemplary only and does not describe all possible embodiments, as describing every possible embodiment would be impractical, if not impossible. Numerous alternative embodiments may be implemented using either current technology or technology developed after the filing date of this patent. It is contemplated that such alternative embodiments would still fall within the scope of the claims.

[0029] FIG. 1A shows a schematic diagram of one embodiment of a system 100 according to the teachings of the present disclosure. System 100 can 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 single stranded DNA (sstDNA). In the illustrated embodiment, system 100 includes a reagent cartridge receptacle 102 that is adapted to receive a reagent cartridge 104. System 100 holds a flow cell assembly 106. System 100 includes a flow cell receptacle 107.

[0030] The system also includes an imaging system 132, a controller 133, a drive assembly 134, and a waste reservoir 136. The drive assembly 134 includes a pump drive assembly 138 and a valve drive assembly 140. The valve drive assembly 140 may include a brushless direct current (DC) motor, a stepper motor, and / or a strain wave gear servo drive. However, other methods of implementing the valve drive assembly 140 may be suitable. For example, a piezoelectric motor could be used.

[0031] The valve actuation assembly 140 may be adapted to perform a threshold number of relatively high torque events (HTEs). The relatively high torque events may be associated with approximately 160 ounces per inch. However, other torque values ​​may be associated with the high torque events. The threshold number of high torque events may be approximately 1000. However, a different number of high torque events may be achieved based on design characteristics, materials used, and / or other operating parameters.

[0032] Controller 133 is electrically and / or communicatively coupled to drive assembly 134 and imaging system 132, and is adapted to cause drive assembly 134 and / or imaging system 132 to perform various functions as disclosed herein. Waste reservoir 136 may be selectively receivable within a waste reservoir receptacle 142 of system 100.

[0033] The reagent cartridge 104 may hold one or more samples of interest. A drive assembly 115 interfaces with the reagent cartridge 104 to flow one or more reagents (e.g., A, T, G, C nucleotides) that interact with the sample through the reagent cartridge 104 and / or flow cell assembly 106.

[0034] In one illustrated embodiment, a reversible terminator is attached to the reagent to allow for the incorporation of a single nucleotide by the sstDNA per cycle. In some such embodiments, 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 embodiment, the imaging system 132 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, while 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 132 may be a fluorescence spectrophotometer including an objective lens and / or a solid-state imager. The solid-state imager may include a charge coupled device (CCD) and / or a complementary metal oxide semiconductor (CMOS).

[0035] After the image data is acquired, the drive assembly 134 interface connects to the reagent cartridge 104, flows another reaction component (e.g., reagent) through the reagent cartridge 104, and then it is received by the waste reservoir 142 and / or discharged by the reagent cartridge 104 in other ways. The reaction component performs a flushing operation that chemically cleaves the fluorescent label and reversible terminator from the sstDNA. The flushing operation may also be performed using air. When this is finished, the sstDNA is ready for the next cycle.

[0036] The reagent cartridge 104 includes a plurality of reagent reservoirs 108. The system 100 includes a manifold assembly 110. The manifold assembly 110 can be disposed within and / or adjacent to the flow cell assembly 107. Alternatively, the manifold assembly 110 can be part of the flow cell assembly 106 and / or the reagent cartridge 104.

[0037] In the illustrated embodiment, at least a portion of the manifold assembly 110 is coupled directly adjacent to the flow cell assembly 106. A portion of the manifold assembly 110, such as a mini-valve assembly, may be directly coupled to the flow cell assembly 106 or may be spaced from the flow cell assembly 106, for example, via an intermediate component. Advantageously, disposing a portion of the manifold assembly 110 directly adjacent to the flow cell assembly 106 can reduce reagent consumption, for example, reduce dead volume in the fluid line, reduce carryover, reduce switching time, and / or reduce results between times.

[0038] The manifold assembly 110 includes a reagent selector valve 112. The reagent selector valve 112 is adapted to be fluidly coupled to the reagent reservoirs 108. The reagent selector valve 112 is also adapted to selectively flow a reagent from a corresponding reagent reservoir 108 to the flow cell assembly 106. In some embodiments, the reagent selector valve 112 may have a small footprint. For example, the reagent selector valve 112 may have a footprint of approximately 45 millimeters (mm) by 45 mm. Other dimensions of the reagent selector valve 112 may be suitable. For example, the footprint of the reagent selector valve 112 may be less than 45 mm by 45 mm.

[0039] The reagent selector valve 112 may include a bypass port 114. The system includes a bypass fluid line 116 and a cache 118. The bypass fluid line 116 fluidly couples the bypass port 114 and the cache 118. The cache 118 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 the cache 118 is shown as part of the system 100, in an alternative embodiment, the cache 118 may be located in a different location. For example, the cache 118 may be located within the manifold assembly 110 and / or the reagent cartridge 104. Other locations for the channel 118 may also be suitable.

[0040] The manifold assembly 110 also includes a flow cell valve 120. The flow cell valve 120 may be coupled between the reagent selector valve 112 and the flow cell assembly 106. The flow cell valve 120 may be coupled directly to the reagent selector valve 112. In some embodiments, such as when only a single flow cell or a single channel is utilized, the flow cell valve 120 may be omitted, with the reagent selector valve 112 being fluidly coupled directly to the flow cell and / or channel.

[0041] The flow cell assembly 106 includes a flow cell 121 that includes at least one channel 122, a flow cell inlet 124, and a flow cell outlet 126. In the illustrated embodiment, where the flow cell includes multiple channels 122, the flow cell valves 120 are adapted to selectively flow reagents into corresponding channels 122.

[0042] The flow cell valve 120 includes a number of outlet ports 128. The outlet ports 128 are adapted to be coupled to corresponding channels 122 of the flow cell 106. A fluid line 130 is shown fluidly coupling the outlet ports 128 and the channels 122. The fluid line 130 may be part of a fluid coupling. The fluid coupling may be flexible. The fluid coupling may be a laminate.

[0043] The flow cell valve 120 and the reagent selector valve 112 can have opposing surfaces 144, 146. In some embodiments, the valve drive assembly 140 is adapted to interface with the flow cell valve 120 and the reagent selector valve 112 at the opposing surfaces 144, 146 to control the position of the corresponding valves 120, 112, respectively. However, the valve drive assembly 140 may interface with the valves 120, 112 in different ways.

[0044] Referring now to drive assembly 134, in the embodiment shown, drive assembly 134 includes a pump drive assembly 138 and a valve drive assembly 140. Pump drive assembly 138 is adapted to interface with one or more pumps 148 to pump fluid through reagent cartridge 104. Pump 148 may be implemented by a syringe pump, a peristaltic pump, a diaphragm pump, or the like. Pump 148 may be disposed between flow cell assembly 106 and waste reservoir 142, although in other embodiments pump 148 may be disposed upstream of flow cell assembly 106 or may be omitted entirely.

[0045] In the embodiment shown, the system 100 includes a sample loading manifold assembly 192 and a sample cartridge receptacle 194 adapted to receive a sample cartridge 196. The sample loading manifold assembly 192 includes one or more sample valves 198. The sample valves 198 may be referred to as sample fill valves.

[0046] The sample loading manifold assembly 192 and pump 148 are adapted to flow one or more samples of interest from the sample cartridge 195 towards the flow cell assembly 106. In one embodiment, the sample loading manifold assembly 192 may be adapted to individually load / direct a sample of interest into each channel 122 of the flow cell 121. The process of loading the channels 122 with a sample of interest may be performed automatically using the system 100 of FIG. 1A.

[0047] Turning to the controller 133, in the illustrated embodiment, the controller 133 includes a user interface 152, a communication interface 154, one or more processors 156, and a memory 158 that stores instructions executable by the one or more processors 156 to perform various functions including the disclosed embodiments. The user interface 152, the communication interface 154, and the memory 158 are electrically and / or communicatively coupled to the one or more processors 156.

[0048] In one embodiment, the user interface 152 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 analyses performed. The user interface 152 may include a touch screen, a display, a keyboard, a speaker, a mouse, a trackball, and / or a voice recognition system. The touch screen and / or the display may display a graphical user interface (GUI).

[0049] In one embodiment, the communication interface 154 is adapted to enable communication between the system 100 and a remote system (e.g., a computer) over a network. The network 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 associated with 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 associated with fluid analysis operations, patient records, and / or protocols performed by the system 100.

[0050] The one or more processors 156 and / or system 100 may include one or more of a processor-based system or a microprocessor-based system. In some embodiments, the one or more processors 156 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.

[0051] The memory 158 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® disk, 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).

[0052] Figure IB shows a schematic diagram of another embodiment of the system 100 of Figure IA. In the illustrated embodiment, the system 100 includes a reagent cartridge receptacle 102. A flow cell assembly 106 is included. A reagent cartridge 104 is receivable within the reagent cartridge receptacle 102. The reagent cartridge 108 includes a plurality of reagent reservoirs 108.

[0053] Included is a manifold assembly 110 that includes a reagent selector valve 112 that is fluidly coupled to the reagent reservoirs 108 and adapted to selectively flow reagents from corresponding reagent reservoirs 108 to the flow cell assembly 106. At least one surface 199 of the manifold assembly 110 associated with the reagent selector valve 112 is coupled to a portion 200 of the flow cell assembly 106.

[0054] FIG. 1C shows a schematic diagram of another embodiment of the system 100 of FIG. 1A. The illustrated embodiment includes a flow cell assembly. The system 100 includes a manifold assembly 110 and a flow cell receptacle 107 adapted to hold the flow cell assembly 106. The manifold assembly includes a reagent selector valve 112 disposed directly adjacent to the flow cell assembly 106. The reagent selector valve 112 includes a surface 119 configured to directly couple to a portion 200 of the flow cell assembly 106 and is adapted to selectively flow a reagent to the flow cell assembly 106. The reagent selector valve 112 includes at least one of a ceramic rotor or a ceramic stator (see, e.g., FIG. 3). A valve drive assembly 140 is included. The valve drive assembly 140 is operably coupled to the reagent selector valve 112. The valve drive assembly 140 includes a brushless motor.

[0055] 2 is a schematic diagram of one embodiment of the flow cell valve 120 and the reagent selector valve 112 of FIG. 1A. The combination of the flow cell valve 120 and the reagent selector valve 112 may be referred to as a dual rotary valve. The flow cell valve 120 and / or the reagent selector valve 112 may be adapted to perform a threshold number of life cycles. The life cycles may be associated with fluidly coupling the flow cell valve 120 and / or the reagent selector valve 112 with the flow cell assembly 106 and / or the reagent cartridge 104. The threshold number of life cycles may include more than about 2000 attachment events. The number of life cycles may include about 4 million port-to-port movements. Other thresholds for different life cycles may be achieved based on, for example, design requirements and / or materials used.

[0056] Flow cell valve 120 and reagent selector valve 112 may be controlled (e.g., actuated) electronically and / or manually. As a result of controlling flow cell valve 120 and reagent selector valve 112 in this manner, not only may user error be reduced, but system 100 may be relatively (or more) user friendly.

[0057] The flow cell valve 120 and the reagent selector valve 112 are coupled at an interface 159. In the illustrated embodiment, the flow cell valve 120 includes a flow cell valve body 160 having a flow cell valve stator 162. The flow cell stator 162 may include a ceramic and / or a polymer hybrid. Other materials for the flow cell valve 120 may also be suitable. The flow cell stator 162 may be sized to fit within a small area, such as 25 millimeters (mm) by 25 mm. However, other sizes of the flow cell stator 162 may also be suitable.

[0058] The flow cell valve 120 also includes a flow cell valve rotor 164. The flow cell valve rotor 164 may include a ceramic and / or polymer hybrid. The flow cell valve body 160 has a common fluid line 166 and a plurality of flow cell valve fluid lines 168. The flow cell fluid line 168 is adapted to be coupled to the flow cell assembly 106. In some embodiments, the common fluid line 166 is about 65 millimeters, and in other embodiments, the common fluid line 166 is about 259 mm. Thus, the common fluid line 166 may be about 65 mm to about 259 mm. However, the common fluid line 166 may be any other length. The flow cell fluid lines 168 may be used to individually direct the channels 122. The common fluid line 166 is coupled to the reagent selector valve 112.

[0059] The flow cell valve rotor 162 is adapted to interface with the flow cell valve stator 162 to fluidly couple the common fluid line 166 to one or more of the flow cell valve fluid lines 168. For example, the flow cell valve stator 162 can be rotated by the valve actuation assembly 140 to fluidly couple the common fluid line 166 to one of the flow cell valve fluid lines 168. Although four flow cell valve fluid lines 168 are shown, any number of flow cell valve fluid lines could instead be included.

[0060] The flow cell valve rotor 164 includes radial grooves 169 adapted to fluidly couple (e.g., direct / point) the common fluid line 166 and one or more of the flow cell valve fluid lines 168. In one embodiment, the flow cell valve rotor 164 can be rotated from about 0° to about 90°. However, the flow cell valve rotor 164 can be rotated a greater or lesser amount depending on the location of the corresponding ports 171 of the flow cell valve fluid lines 168 that open into the flow cell stator 162.

[0061] The radial groove 169 may include chamfered sides. The chamfered sides may be adapted to reduce carryover. The flow cell valve rotor 164 also includes an arcuate groove 170. The arcuate groove 170 is coupled to a distal end 172 of the radial groove 169 and is adapted to allow the common fluid line 166 to be fluidly coupled to two or more of the flow cell valve fluid lines 168. For example, the flow cell valve rotor 164 may be indexed such that the arcuate groove 170 covers two or more ports 171 of the flow cell valve fluid lines 168, thereby allowing fluid communication of more than two of the flow cell valve fluid lines 168.

[0062] 3 is a schematic diagram of one embodiment of the reagent selector valve 112 of FIG. 1A. The reagent selector valve 112 includes a reagent selector valve body 175 having a reagent valve stator 176. The reagent selector valve 112 also includes a reagent valve rotor 178. The reagent valve stator 176 and / or the reagent valve rotor 178 may include a ceramic and / or a polymer hybrid. Other materials for the reagent selector valve 112 may also be suitable. The reagent selector valve body 175 includes a common fluid line 180, a plurality of reagent fluid lines 182, and a flow cell fluid line 108. The reagent fluid line 182 is adapted to be fluidly coupled to a corresponding reagent reservoir 108. The common fluid line 180 is fluidly coupled to the reagent fluid line 182 and the flow cell fluid line 168.

[0063] The reagent valve rotor 178 interfaces with the reagent valve stator 176 to fluidly couple a common fluid line 180 and a corresponding reagent fluid line 182. Specifically, in the illustrated embodiment, the reagent valve rotor 178 includes radial grooves 169 adapted to fluidly couple the common fluid line 180 and the corresponding reagent fluid line 182. The common fluid line 180 may be fluidly coupled to the flow cell fluid line 168 and / or the bypass port 114.

[0064] Reagent fluid line 182 has an outlet port 184 at the location of reagent valve stator 176. Reagent fluid line 182 also includes a number of inlet ports 185. Inlet ports 185 are defined by sides 186 of reagent selector valve body 175. Although inlet port 185 is defined by three of sides 186, inlet port 185 may be defined in a different manner. For example, inlet port 185 may be defined by two of sides 186. Reagent valve rotor 178 is not illustrated as including arcuate grooves like arcuate grooves 170 of flow cell valve rotor 164, but alternatively, reagent valve rotor 178 may include arcuate grooves.

[0065] 4A is a schematic diagram of one embodiment of the reagent selector valve 112, valve actuation assembly 140, and flow cell assembly 106 of FIG. 1A. In the illustrated embodiment, the reagent selector valve body 175 has a flow cell interface 188. The flow cell interface 188 may be a side 186 of the reagent selector valve body 175 where the inlet port 185 is not defined, but may be defined to allow the flow cell fluid line 168 to be in fluid communication with the flow cell assembly 106. The flow cell assembly 106 is coupled to the flow cell interface 188. In this manner, the body 201 of the flow cell assembly 106 is coupled to the reagent selector valve 112. In other words, one surface of the reagent selector valve 112 is directly mechanically coupled to the flow cell assembly 106. Alternatively, the body 201 of the flow cell assembly 106 may be coupled to the flow cell valve 120. In some embodiments, an intermediate component, such as a flexible manifold or other fluid transport component, may be implemented between the flow cell interface 188 of the reagent selector valve body 175 and the flow cell assembly 106, and / or between the flow cell valve 120 and the flow cell assembly 106. Other arrangements may also be suitable.

[0066] The valve drive assembly 140 is adapted to interface with and is coupled adjacent to the end 189 of the reagent selector valve 112. For example, the valve drive assembly 140 may be adapted to rotate the reagent valve rotor 178.

[0067] Although the flow cell valve 120 is not shown in FIG. 4A, in other embodiments, the flow cell valve 120 may be included. For example, the flow cell valve 120 may be included when the flow cell 121 includes a plurality of channels 122 and / or when the flow cell assembly 106 does not include a manifold that couples the plurality of channels 122 and the reagent selector valve 112.

[0068] In the illustrated embodiment, a gearbox 190 is also included. The gearbox 190 and / or the valve drive assembly 140 may be adapted to apply a relatively high torque value to the reagent selector valve 112 and / or the flow cell valve 120. This relatively high torque value may be about 140 ounces per inch. Other torque values can also be achieved using the gearbox 190 and / or the valve drive assembly 140. The gearbox 190 may induce the rotation of the reagent valve rotor 178. The gearbox 190 may be a multi-stage planetary gearbox or a spur gearbox. Other types of gearboxes may also be suitable. The gearbox 190 is coupled between the valve drive assembly 140 and the reagent selector valve 112. The gearbox 190 may be adapted to reduce the likelihood that vibrations generated by the valve drive assembly 140, the reagent reservoir valve 112, and / or the flow cell valve 120 affect the flow cell assembly 106. The gearbox 190 may include a wave gear type drive unit. The gearbox 190 may include a harmonic gear. Other types of gears may also be suitable. The gearbox 190 may be adapted to provide speed reduction by gears and a large torque.

[0069] 4B is a cross-sectional view of the reagent selector valve 112, the valve drive assembly 140, and the flow cell assembly 106 of FIG. 4A. A gearbox 190 is also included. In the illustrated embodiment, the longitudinal axis 202 of the valve drive assembly 140 is offset relative to the longitudinal axis 204 of the reagent selector valve 112. Thus, the longitudinal axis 202 of the valve drive assembly 140 and the longitudinal axis 204 of the reagent selector valve 112 are asymmetric. In other embodiments, the gearbox 190 and the reagent selector valve 112 may be collinear with the longitudinal axis 202 of the valve drive assembly 140.

[0070] In the illustrated embodiment, the gearbox 190 may be a multi-stage planetary gearbox or a spur gearbox. The gearbox 190 may be adapted to allow the axis 202 and axis 204 to be offset relative to one another. The offset axis 202 and axis 204 may allow the flow cell cartridge assembly 106 to be coupled to the flow cell interface 188 without the valve drive assembly 140 interfering with the coupling. In particular, when a larger valve drive assembly 140 is used, offsetting the axis 202 and axis 204 may allow the flow cell cartridge assembly 106 to be coupled to the flow cell interface 188. The flow cell interface 188 may be considered to be at the highest position of the reagent selector valve 112 based on the orientation shown in FIG. 4. However, the flow cell interface 188 may be located elsewhere on the reagent selector valve 112 or on any of the other disclosed components.

[0071] 5 is a schematic diagram of another embodiment of the flow cell assembly 106 of FIG. 1A illustrating different configurations / positions of the reagent selector valve 112. For example, the reagent selector valve 112 can be positioned above the flow cell assembly 106, below the flow cell assembly 106, or directly coupled to or in-line with the flow cell assembly 106. Alternative positions of the reagent selector valve 112 are shown in dashed lines. Other relative positions between the flow cell assembly 106 and the reagent selector valve 112 may also be suitable.

[0072] 6 is a schematic diagram of another embodiment of the valve drive assembly 140, the reagent selector valve 112, and the flow cell assembly 106. The illustrated embodiment also includes a vibration isolation assembly 206 and a gearbox 190. The vibration isolation assembly 206 can be adapted to isolate vibrational displacements from the flow cell assembly 106, such as may be generated when the reagent selector valve 112 is actuated.

[0073] The vibration isolation assembly 206 may include a housing 207 to which the valve drive assembly 140, the gear box 190, and the reagent selector valve 112 are rotatably coupled. The vibration isolation assembly 206 may include one or more magnets 208 that may magnetically isolate and / or magnetically levitate the valve drive assembly 140, the gear box 190, and the reagent selector valve 112 to prevent vibrations generated by the valve drive assembly 140 and / or the reagent selector valve 112 from affecting the flow cell cartridge assembly 106. The vibration isolation assembly 206 may be implemented in different manners. For example, the vibration isolation assembly 206 may be a shock absorber 210. The shock absorber 210 may include a spring, a gel isolator, a gasket, and the like.

[0074] The valve drive assembly 140 may include a stepper motor. Alternatively, the valve drive assembly 140 may include a brushless DC motor. A brushless DC motor may have less vibration during operation. A brushless DC motor may also meet a threshold torque value.

[0075] 7 illustrates an isometric view of one embodiment of a vibration isolation assembly 206 including a housing 207 and a shock absorber 210. The shock absorber 210 includes a number of gel isolators 211. Other types of shock absorbers may additionally or alternatively be included.

[0076] In the embodiment shown, the housing 207 includes a base 212 and a support 214. The support 214 is coupled to the base 212 via a shock absorber 210. The support 214 includes a first support portion 216 and a second support portion 218. The first support portion 216 holds the valve drive assembly 140. The second support portion 218 defines a through hole 220 and is disposed between the valve drive assembly 140 and the reagent selector valve 112. The gear box 190 extends through the through hole 220 of the second support portion 218.

[0077] The gel isolator 211 can be disposed between the base 212 and the support 214. Specifically, the gel isolator 211 can be disposed between the base 212 and the first support portion 216.

[0078] A gel isolator 211 may also be disposed between the second support portion 218 and the valve drive assembly 140. Alternatively, a rigid coupling or another type of coupling may be provided between the valve drive assembly 140 and the second support portion 218. In such an embodiment, four gel isolators 211 may be provided between the first support portion 216 and the base 212, but no gel isolators 211 may be provided between the second support portion 218 and the valve drive assembly 140. Other arrangements may also be suitable. Regardless of the number and / or arrangement of the gel isolators 211 or, more generally, the shock absorbers 210, the gel isolators 211 may be adapted to reduce the likelihood that operating the valve drive assembly 140 and / or the reagent selector valve 112 will affect the flow cell assembly 106.

[0079] An apparatus comprising: a system including a reagent cartridge receptacle; a flow cell assembly; a reagent cartridge receivable within the reagent cartridge receptacle and including a plurality of reagent reservoirs; and a manifold assembly including a reagent selector valve, the reagent selector valve being fluidly coupled to the reagent reservoirs and adapted to selectively flow reagents from corresponding reagent reservoirs to the flow cell assembly, wherein at least one surface of the manifold assembly associated with the reagent selector valve is coupled to a portion of the flow cell assembly.

[0080] An apparatus according to any one or more of the preceding embodiments and / or any one or more of the embodiments disclosed below, wherein a surface of the reagent selector valve is directly mechanically coupled to the flow cell assembly.

[0081] The apparatus of any one or more of the preceding embodiments and / or any one or more of the embodiments disclosed below, wherein the reagent selector valve comprises at least one of a ceramic rotor or a ceramic stator.

[0082] The apparatus according to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below, wherein the manifold assembly further comprises a valve drive assembly operably coupled to the reagent selector valve.

[0083] The apparatus according to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below, wherein the valve drive assembly comprises a brushless motor. The apparatus according to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below, wherein the manifold assembly comprises a flow cell valve coupled between the reagent selector valve and the flow cell assembly, the flow cell assembly comprises a flow cell having a plurality of channels, and the flow cell valve is adapted to selectively flow a reagent to the corresponding channel.

[0084] The apparatus according to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below, wherein the flow cell valve comprises a plurality of outlet ports adapted to be coupled to the corresponding channels of the flow cell.

[0085] The apparatus according to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below, wherein the flow cell valve and the reagent selector valve have surfaces facing in opposite directions, and the apparatus further comprises a valve drive assembly adapted to interface with the flow cell valve and the reagent selector valve at the surfaces facing in opposite directions and control the positions of the corresponding valves.

[0086] The apparatus of any one or more of the preceding embodiments and / or any one or more of the embodiments disclosed below, wherein the flow cell valve comprises a flow cell valve body having a flow cell valve stator and a flow cell valve rotor, the flow cell valve body having a common fluid line coupled to the reagent selector valve and a plurality of flow cell valve fluid lines, and the flow cell valve rotor interfaces with the flow cell valve stator to fluidly couple the common fluid line and one or more of the flow cell valve fluid lines.

[0087] An apparatus as in any one or more of the preceding embodiments and / or any one or more of the embodiments disclosed below, wherein the flow cell valve rotor comprises a radial groove adapted to fluidly couple the common fluid line and one or more of the flow cell valve fluid lines.

[0088] An apparatus as in any one or more of the preceding embodiments and / or any one or more of the embodiments disclosed below, wherein the flow cell valve rotor comprises an arcuate groove coupled to a distal end of the radial groove, the arcuate groove adapted to enable a common fluid line to be fluidly coupled to two or more of the flow cell valve fluid lines.

[0089] The apparatus of any one or more of the preceding embodiments and / or any one or more of the embodiments disclosed below, wherein the reagent valve body comprises a flow cell interface and the flow cell assembly is coupled to the flow cell interface.

[0090] The apparatus of any one or more of the preceding embodiments and / or any one or more of the embodiments disclosed below, further comprising a valve actuation assembly interfaced with and adjacently coupled to an end of the reagent selector valve.

[0091] The apparatus of any one or more of the preceding embodiments and / or any one or more of the embodiments disclosed below, further comprising a vibration isolation assembly. The apparatus of any one or more of the preceding embodiments and / or any one or more of the embodiments disclosed below, wherein the vibration isolation assembly comprises a housing rotatably coupled to the reagent selector valve and the valve drive assembly.

[0092] An apparatus comprising: a system including a flow cell assembly and a flow cell receptacle adapted to hold the flow cell assembly; and a manifold assembly, wherein the manifold assembly comprises: a reagent selector valve disposed directly adjacent to the flow cell assembly, the reagent selector valve having a surface configured to directly couple to a portion of the flow cell assembly and adapted to selectively flow reagent to the flow cell assembly, the reagent selector valve comprising at least one of a ceramic rotor or a ceramic stator; and a valve drive assembly operably coupled to the reagent selector valve, the valve drive assembly comprising a brushless motor.

[0093] The apparatus of any one or more of the preceding embodiments and / or any one or more of the embodiments disclosed below, wherein the reagent selector valve of the manifold assembly is disposed within the flow cell receptacle.

[0094] An apparatus according to any one or more of the preceding embodiments and / or any one or more of the embodiments disclosed below, wherein a surface of the reagent selector valve is adapted to be directly mechanically coupled to the flow cell assembly.

[0095] The manifold assembly further comprises a flow cell valve coupled between the reagent selector valve and the flow cell assembly, the flow cell assembly comprises a flow cell having a plurality of channels, and the flow cell valve is adapted to selectively flow a sample into the corresponding channel, the apparatus according to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed hereinafter.

[0096] The apparatus according to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed hereinafter, further comprising a vibration isolation assembly. The apparatus according to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed hereinafter, wherein the vibration isolation assembly comprises a magnet and is adapted to magnetically levitate the manifold assembly.

[0097] The apparatus according to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed hereinafter, wherein the vibration assembly comprises a shock absorber. The foregoing description is provided to enable a person skilled in the art to practice the various configurations described herein. Although the subject technology has been particularly 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.

[0098] 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. Furthermore, references to "one embodiment" are not intended to be interpreted as excluding the existence of additional embodiments that also incorporate the recited features. Furthermore, unless expressly stated to the contrary, embodiments 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.

[0099] As used throughout this specification, the terms "substantially," "approximately," and "about" are used to account for 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.

[0100] 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 embodiments may be readily apparent to those skilled in the art, and the general principles defined herein may be applied to other embodiments. 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 given modules or units may be used, different or multiple types of given modules or units may be used, given modules or units may be added, or given modules or units may be omitted.

[0101] 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 embodiments described throughout this disclosure that are known or that later become known to those skilled 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.

[0102] 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. A system including a reagent cartridge receptacle; a flow cell assembly comprising a flow cell, the flow cell comprising a channel having a flow cell inlet and a flow cell outlet; a reagent cartridge receivable within the reagent cartridge receptacle and including a plurality of reagent reservoirs; a manifold assembly including a reagent selector valve including a reagent selector valve body; An apparatus comprising: the reagent selector valve is fluidly coupled to the reagent reservoir and adapted to selectively flow reagents from corresponding reagent reservoirs to the flow cell assembly; An apparatus, wherein a surface of the reagent selector valve body of the reagent selector valve of the manifold assembly is directly and mechanically coupled to a portion of the flow cell assembly so that the reagent selector valve of the manifold assembly supplies a reagent contained in a selected one of the multiple reagent reservoirs to the flow cell.

2. The apparatus of claim 1 , wherein the reagent selector valve comprises at least one of a ceramic rotor or a ceramic stator.

3. 3. The apparatus of claim 1 or claim 2, wherein the manifold assembly further comprises a valve drive assembly operatively coupled to the reagent selector valve for driving the reagent selector valve.

4. The apparatus of claim 3 , wherein the valve drive assembly comprises a brushless motor.

5. 5. The apparatus of claim 3 or claim 4, wherein the manifold assembly comprises a flow cell valve mechanically coupled between the reagent selector valve and the flow cell assembly, the flow cell valve adapted to selectively flow reagents into the channels of the flow cell.

6. The apparatus of claim 5, wherein the flow cell has a plurality of channels, and the flow cell valve has a plurality of outlet ports adapted to be fluidly coupled to the channels of the flow cell, each outlet port adapted to be fluidly coupled to a corresponding channel of the flow cell.

7. An apparatus as described in claim 5 or claim 6, wherein the valve actuation assembly is operably coupled to the flow cell valve and the reagent selector valve, thereby adapted to control the position of the flow cell valve and the reagent selector valve.

8. 8. The apparatus of claim 5, wherein the flow cell valve comprises a flow cell valve body having a flow cell valve stator and a flow cell valve rotor, the flow cell valve body having a common fluid line coupled to the reagent selector valve and a plurality of flow cell valve fluid lines, the flow cell valve rotor being rotated relative to the flow cell valve stator to fluidly couple the common fluid line and one or more of the flow cell valve fluid lines.

9. The apparatus of claim 8 , wherein the flow cell valve rotor comprises a radial groove adapted to fluidly couple the common fluid line and the one or more of the flow cell valve fluid lines.

10. 10. The apparatus of claim 9, wherein the flow cell valve rotor comprises an arcuate groove coupled to a distal end of the radial groove, the arcuate groove adapted to allow the common fluid line to be fluidly coupled to two or more of the flow cell valve fluid lines.

11. The apparatus of claim 1, wherein the reagent selector valve body includes a flow cell interface, and the flow cell assembly is coupled to the flow cell interface.

12. 11. The apparatus of claim 3, wherein the valve drive assembly is adapted to be adjacent to the reagent selector valve and to be mechanically coupled thereto via a gearbox.

13. The apparatus of claim 12, further comprising a vibration isolation assembly adapted to isolate vibrational displacements from the flow cell assembly.

14. 14. The apparatus of claim 13, wherein the vibration isolation assembly comprises a housing coupled to the reagent selector valve and the valve drive assembly.

15. A flow cell assembly comprising a flow cell, the flow cell comprising a channel having a flow cell inlet and a flow cell outlet; and a flow cell receptacle adapted to hold the flow cell assembly; and a manifold assembly; 11. An apparatus comprising: a reagent selector valve disposed adjacent to the flow cell assembly, the reagent selector valve comprising a surface adapted to selectively flow a reagent to the flow cell assembly and at least one of a ceramic rotor or a ceramic stator; a valve drive assembly operatively coupled to the reagent selector valve to drive the reagent selector valve, the valve drive assembly comprising a brushless motor; Equipped with The surface of the reagent selector valve is directly and mechanically coupled to a portion of the flow cell assembly such that the reagent selector valve delivers the reagent to the flow cell.

16. The apparatus of claim 15 , wherein the reagent selector valve of the manifold assembly is disposed within the flow cell receptacle.

17. 17. The apparatus of claim 15 or claim 16, wherein the manifold assembly further comprises a flow cell valve mechanically coupled between the reagent selector valve and the flow cell assembly, the flow cell valve adapted to selectively flow the reagent into the channel of the flow cell.

18. An apparatus described in any one of claims 15 to 17, further comprising a vibration isolation assembly configured to isolate vibrational displacement from the flow cell assembly.

19. 20. The apparatus of claim 18, wherein the vibration isolation assembly comprises a magnet and is adapted to magnetically levitate the manifold assembly relative to the valve drive assembly.

20. The apparatus of claim 18 , wherein the vibration isolation assembly includes a shock absorber.

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