WO2025244815A1 - Flow cell assemblies and related systems and methods - Google Patents
Flow cell assemblies and related systems and methodsInfo
- Publication number
- WO2025244815A1 WO2025244815A1 PCT/US2025/027429 US2025027429W WO2025244815A1 WO 2025244815 A1 WO2025244815 A1 WO 2025244815A1 US 2025027429 W US2025027429 W US 2025027429W WO 2025244815 A1 WO2025244815 A1 WO 2025244815A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- flow cell
- assembly
- cartridge assembly
- reagent
- controller
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502715—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/06—Fluid handling related problems
- B01L2200/0689—Sealing
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/14—Process control and prevention of errors
- B01L2200/143—Quality control, feedback systems
- B01L2200/147—Employing temperature sensors
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/16—Reagents, handling or storing thereof
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0809—Geometry, shape and general structure rectangular shaped
- B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
- B01L2300/0877—Flow chambers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/18—Means for temperature control
- B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
- B01L2300/1827—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using resistive heater
Definitions
- Sequencing platforms may use flow cell assemblies when performing different processes.
- an apparatus comprising: a system, comprising: a receptacle; a cartridge assembly receivable within the receptacle, the cartridge assembly comprising: a well; and an outlet port fluidly coupled to the well.
- the apparatus comprising a flow cell assembly, comprising: a body carrying a flow cell inlet gasket; a flow cell supported by the body and comprising a channel; and a sensor assembly comprising a heater and a thermal sensor.
- the outlet port is fluidly coupled to the flow cell inlet gasket.
- a leak test is to be performed on the cartridge assembly and the flow cell assembly using the thermal sensor.
- an apparatus comprising: a cartridge assembly, comprising: a well; and an outlet port fluidly coupled to the well.
- the apparatus comprising a flow cell assembly, comprising: a body carrying a flow cell inlet gasket and an outlet gasket; a flow cell supported by the body and comprising a channel; and a sensor assembly comprising a heater and a thermal sensor.
- the outlet port is fluidly coupled to the flow cell inlet gasket.
- a leak test is to be performed on the cartridge assembly and the flow cell assembly using the thermal sensor.
- an apparatus comprising: a cartridge assembly, comprising: a well; and an outlet port fluidly coupled to the well.
- the apparatus comprising a flow cell assembly, comprising: a body carrying a flow cell inlet gasket and an outlet gasket; a flow cell supported by the body and comprising a channel; and a sensor assembly comprising a heater and a thermal sensor.
- the outlet port is fluidly coupled to the flow cell inlet gasket. A leak test is to be performed on the cartridge assembly and the flow cell assembly using the thermal sensor.
- an apparatus comprising: a cartridge assembly; a first flow cell assembly including a first flow cell and a first sensor assembly comprising a heater and a thermal sensor; and a second flow cell assembly including a second flow cell different than the first flow cell.
- the second flow cell assembly comprises a second sensor assembly comprising a heater and a thermal sensor.
- the first flow cell assembly and the second flow cell assembly are interchangeably mechanically and fluidly couplable with the cartridge assembly.
- a leak test is to be performed on the cartridge assembly and the first flow cell assembly when coupled using the thermal sensor of the first sensor assembly.
- a leak test is to be performed on the cartridge assembly and the second flow cell assembly when coupled using the thermal sensor of the second sensor assembly.
- an apparatus comprising: a system, comprising: a receptacle; a liquid reservoir receivable within the receptacle and having: a body comprising a storage chamber, and a fluidic port fluidly coupled to the storage chamber.
- the apparatus comprising a cartridge assembly, comprising: a fluidic interface couplable to the fluidic port; a well; a channel fluidly coupled between the fluidic interface and the well; and an outlet port fluidly coupled to the well.
- the apparatus comprising a flow cell assembly, comprising: a body carrying a flow cell inlet gasket and an outlet gasket; a flow cell supported by the body and comprising a channel; and a sensor assembly comprising a heater and a thermal sensor.
- the outlet port is fluidly coupled to the flow cell inlet gasket. A leak test is to be performed on the cartridge assembly and the flow cell assembly using the thermal sensor.
- a method comprising: heating a flow cell to a threshold temperature using a heater of a flow cell assembly, the flow cell assembly coupled to a cartridge assembly and positioned in a receptacle of a system; flowing reagent from the cartridge assembly into the flow cell using a pump of the cartridge assembly; accessing, using a controller, a measured temperature value from a thermal sensor of the flow cell assembly; and determining, using the controller, a presence of a leak in at least one of the cartridge assembly or the flow cell assembly based on the measured temperature value.
- an apparatus comprising: a system, comprising: a receptacle.
- the apparatus comprising a cartridge assembly receivable within the receptacle, the cartridge assembly comprising: a well comprising reagent; and an outlet port fluidly coupled to the well; and a flow cell assembly, comprising: a body carrying a flow cell inlet gasket; a flow cell supported by the body and comprising a channel; and a sensor assembly comprising a thermal sensor.
- the outlet port is fluidly coupled to the flow cell inlet gasket.
- the reagent is preheated prior to entering the channel of the flow cell using a heater of at least one of the system or the cartridge assembly.
- a leak test is to be performed on the cartridge assembly and the flow cell assembly using the thermal sensor.
- a method comprising: preheating reagent to a threshold temperature using a heater; flowing the pre-heated reagent from a cartridge assembly into a flow cell using a pump of the cartridge assembly, the flow cell assembly coupled to the cartridge assembly and positioned in a receptacle of a system; accessing, using a controller, a measured temperature value from a thermal sensor of the flow cell assembly; and determining, using the controller, a presence of a leak in at least one of the cartridge assembly or the flow cell assembly based on the measured temperature value.
- an apparatus comprising: a system, comprising: a receptacle.
- the apparatus comprises a cartridge assembly receivable within the receptacle, the cartridge assembly comprising: a well; and an outlet port fluidly coupled to the well.
- the apparatus comprising a flow cell assembly, comprising: a body; a flow cell supported by the body and comprising a channel; and a sensor assembly comprising a heater and a thermal sensor, wherein the outlet port is fluidly coupled to the flow cell, wherein a leak test is to be performed on the cartridge assembly and the flow cell assembly using the thermal sensor.
- an apparatus comprising: a cartridge assembly, comprising: a well; and an outlet port fluidly coupled to the well; a flow cell assembly, comprising: a body; a flow cell supported by the body and comprising a channel; and a sensor assembly comprising a heater and a thermal sensor.
- the outlet port is fluidly coupled to the flow cell.
- a leak test is to be performed on the cartridge assembly and the flow cell assembly using the thermal sensor.
- a method comprising: heating a flow cell to a threshold temperature using a heater of a flow cell assembly, the flow cell assembly coupled to a cartridge assembly and positioned in a receptacle of a system; flowing reagent into the flow cell; accessing, using a controller, a measured temperature value from a thermal sensor of the flow cell assembly; and determining, using the controller, a presence of a leak in at least one of the cartridge assembly or the flow cell assembly based on the measured temperature value.
- a method comprising: preheating reagent to a threshold temperature using a heater; flowing the pre-heated reagent into a flow cell, the flow cell assembly coupled to a cartridge assembly and positioned in a receptacle of a system; accessing, using a controller, a measured temperature value from a thermal sensor of the flow cell assembly; and determining, using the controller, a presence of a leak in at least one of the cartridge assembly or the flow cell assembly based on the measured temperature value.
- an apparatus and/or method may further comprise or include any one or more of the following:
- the system comprises a controller and wherein the leak test comprises by 1) priming the cartridge assembly and the flow cell assembly, 2) accessing a measured temperature value from the thermal sensor using the controller, 3) determining a difference between the measured temperature value and a reference temperature value using the controller, and 4) identifying at least one of the cartridge assembly or the flow cell assembly having a leak if the difference is greater than a threshold using the controller.
- the reference temperature is between about 40°C and about 60°C.
- the reference temperature is about 55°C.
- the leak test comprises the flow cell being heated to a threshold temperature using the heater after the flow cell is primed, reagent being flowed from the cartridge assembly into the flow cell inlet gasket and the flow cell using a pump, and a temperature value of the flow cell being measured using the thermal sensor.
- the cartridge assembly comprises a pump and wherein the leak test comprises 1 ) a valve being actuated to a closed position, 2) a vacuum being generated in at least one of the cartridge assembly or the flow cell assembly using the pump, 3) the flow cell being heated to a threshold temperature using the heater, 4) the valve being actuated to an open position, 5) reagent being flowed from the cartridge assembly into the flow cell inlet gasket of the flow cell assembly and the channel of the flow cell using the pump, and 6) a plurality of temperature values of the flow cell being measured using the thermal sensor.
- the system comprises a controller and wherein the leak test comprises accessing measured temperature values from the thermal sensor using the controller, determining a difference between the measured temperature values using the controller, and identifying at least one of the cartridge assembly or the flow cell assembly having a leak if the difference between the measured temperature values is greater than a threshold using the controller.
- the threshold is between about 2 degrees Celsius and about 15 degrees Celsius.
- the threshold comprises about 3 degrees Celsius.
- the cartridge assembly does not include a pressure sensor.
- the flow cell assembly does not include a pressure sensor.
- the system comprises a controller and wherein the controller is to generate an alert if the controller identifies at least one of the cartridge assembly or the flow cell assembly as having a leak.
- the flow cell assembly carries an outlet gasket and wherein the cartridge assembly comprises a pump coupled to at least one of the outlet gasket of the flow cell assembly or between the well and the flow cell assembly.
- the pump comprises a syringe pump.
- the cartridge assembly comprises a valve coupled between the outlet port of the cartridge assembly and the well and wherein the system comprises a valve drive assembly to interface with the valve.
- the body of the flow cell assembly carries a flow cell outlet gasket and an outlet gasket and comprising a fluidic aperture and wherein the flow cell comprises a flow cell inlet and a flow cell outlet, the flow cell inlet fluidly coupled to the flow cell inlet gasket and the flow cell outlet fluidly coupled to the flow cell outlet gasket.
- the flow cell assembly comprises a first laminate coupled to the body of the flow cell assembly and forming a first fluidic channel between the flow cell outlet gasket and the fluidic aperture and a second laminate coupled to the body of the flow cell assembly and forming a second fluidic channel between the fluidic aperture and the outlet gasket.
- the body comprises a first groove and a second groove, the first laminate covering the first groove to form the first fluidic channel and the second laminate covering the second groove to form the second fluidic channel.
- the flow cell assembly is coupled to the cartridge assembly by a coupling.
- the coupling comprises a snap fit connection.
- the sensor assembly comprises a die.
- the die comprises the thermal sensor.
- the die comprises a complementary metal-oxide semiconductor.
- the sensor assembly comprises a printed circuit board and wherein the heater is positioned between die and the printed circuit board.
- a liquid reservoir receivable within the receptacle and having a body comprising a storage chamber, and a fluidic port fluidly coupled to the storage chamber wherein the cartridge assembly comprises: a fluidic interface couplable to the fluidic port; and a channel fluidly coupled between the fluidic interface and the well.
- the system comprises a pneumatic interface and the body of the liquid reservoir comprises a pneumatic port fluidly couplable to the storage chamber.
- the system comprises a dry instrument.
- the cartridge assembly comprises a valve coupled between the outlet port of the cartridge assembly and the well.
- the cartridge assembly comprises a pump coupled to at least one of the outlet gasket of the flow cell assembly or between the well and the flow cell assembly.
- the flow cell assembly comprises a second flow cell supported by the body.
- the flow cell and the second flow cell are fluidly coupled in series.
- the flow cell outlet of the flow cell is fluidly coupled to the flow cell outlet gasket via the second flow cell.
- a third flow cell assembly comprising a third flow cell and a fourth flow cell, the third flow cell assembly couplable to the cartridge assembly in place of the flow cell assembly and in place of the second flow cell assembly.
- determining the presence of the leak comprises determining, using the controller, a difference between the measured temperature value and a reference temperature value and identifying, using the controller, at least one of the cartridge assembly or the flow cell assembly having the leak if the difference is greater than a threshold.
- determining the presence of the leak comprises actuating a valve of the cartridge assembly to a closed position, generating a vacuum in at least one of the cartridge assembly or the flow cell assembly using the pump, heating the flow cell to a threshold temperature using a heater of the flow cell assembly, actuating the valve to an open position, flowing the reagent from the cartridge assembly to the flow cell using the pump, and determining a plurality of temperature values of the flow cell using the thermal sensor.
- determining, using the controller, the presence of the leak comprises accessing measured temperature values from the thermal sensor, determining, using the controller, a difference between the measured temperature values, and identifying, using the controller, at least one of the cartridge assembly or the flow cell assembly having the leak if the difference between the measured temperature values is greater than a threshold.
- flowing the reagent under positive pressure comprises pressurizing a storage chamber of a liquid reservoir comprising the reagent and flowing the reagent from the storage chamber to the cartridge assembly.
- the system comprises the heater.
- the cartridge assembly comprises the heater.
- the leak test comprises not heating the flow cell.
- the system comprises a controller and wherein the leak test comprises 1 ) flowing the preheated reagent into the flow cell using a pump, 2) accessing a measured temperature value from the thermal sensor using the controller, 3) determining a difference between the measured temperature value and a reference temperature value using the controller, and 4) identifying at least one of the cartridge assembly or the flow cell assembly having a leak if the difference is greater than a threshold using the controller.
- the leak test comprises the flow cell being heated to a threshold temperature using the heater after the flow cell is primed, reagent being flowed from the cartridge assembly into the flow cell using a pump, and a temperature value of the flow cell being measured using the thermal sensor.
- the cartridge assembly comprises a pump and wherein the leak test comprises 1 ) a valve being actuated to a closed position, 2) a vacuum being generated in at least one of the cartridge assembly or the flow cell assembly using the pump, 3) the flow cell being heated to a threshold temperature using the heater, 4) the valve being actuated to an open position, 5) reagent being flowed from the cartridge assembly into the flow cell assembly and the channel of the flow cell using the pump, and 6) a plurality of temperature values of the flow cell being measured using the thermal sensor.
- the threshold is about 3 degrees Celsius.
- the method includes flowing reagent under positive pressure into the cartridge assembly comprising dry reagent to rehydrate the dry reagent.
- the cartridge assembly comprising a well and an outlet port fluidly coupled to the well.
- Flowing reagent from the cartridge assembly into the flow cell comprises flowing the rehydrated reagent into a flow cell inlet gasket of the flow cell assembly using a pump, the flow cell assembly comprising a body carrying the flow cell inlet gasket and a flow cell supported by the body, the flow cell inlet gasket fluidly coupled to the outlet port and the flow cell.
- flowing the reagent under positive pressure comprises pressurizing a storage chamber of a liquid reservoir comprising the reagent and flowing the reagent from the storage chamber to the cartridge assembly.
- flowing reagent into the flow cell comprises flowing reagent from the cartridge assembly.
- flowing reagent into the flow cell comprises flowing reagent from a well of the cartridge assembly.
- flowing reagent into the flow cell comprises flowing reagent into the flow cell using a pump of the cartridge assembly.
- flowing reagent into the flow cell comprises flowing reagent into the flow cell under positive pressure.
- flowing the preheated reagent into the flow cell comprises flowing the preheated reagent from a well of the cartridge assembly.
- flowing the preheated reagent into the flow cell comprises flowing the preheated reagent into the flow cell comprises using a pump of the cartridge assembly.
- flowing the preheated reagent into the flow cell comprises flowing the preheated reagent into the flow cell under positive pressure.
- the system does not include a pressure sensor.
- the leak test comprises the flow cell being heated to a threshold temperature using the heater after the flow cell is primed, reagent being flowed from the cartridge assembly into the flow cell inlet gasket and the flow cell, and a temperature value of the flow cell being measured using the thermal sensor.
- the reagent is to be flowed from the cartridge assembly into the flow cell inlet gasket and the flow cell under positive pressure.
- the cartridge assembly comprises a pump, and wherein the reagent is to be flowed from the cartridge assembly into the flow cell inlet gasket and the flow cell using the pump of the cartridge assembly.
- FIG. 1 illustrates a schematic diagram of an implementation of a system in accordance with the teachings of this disclosure.
- FIG. 2 is an isometric view of an example implementation of a cartridge assembly and a flow cell assembly that can be used to implement the cartridge assembly and the flow cell assembly of FIG. 1 .
- FIG. 3 is an isometric partially expanded view of the flow cell assembly of FIG. 2.
- FIG. 4 is an isometric view of the first flow cell and the second flow cell of the flow cell assembly of FIG. 2.
- FIG. 5 is an expanded isometric view of an example implementation of another flow cell assembly having a body that can be used to implement the flow cell assembly of FIG. 1 .
- FIG. 6 is an isometric view of the flow cell of the flow cell assembly of FIG. 5.
- FIG. 7 is an expanded isometric view of an example implementation of a flow cell assembly having a body that can be used to implement the flow cell assembly of FIG. 1 .
- FIG. 8 is an isometric view of the flow cell of the flow cell assembly of FIG. 7.
- FIG. 9 illustrates a flow chart for a method of determining the presence of a leak using the system of FIG. 1 , the cartridge assembly of FIGS. 1 - 2, the flow cell assemblies and sensor assemblies of FIGS. 1 - 8 or any of the other implementations disclosed herein.
- FIG. 10 is a graph showing results using the disclosed implementations including an x- axis relating to time, a first y-axis relating to pressure and a second y-axis relating to temperature.
- FIG. 1 1 is a graph showing results using the disclosed implementations including an x- axis relating to time and a y-axis relating to temperature.
- FIG. 12 illustrates a schematic diagram of an example of a system that may be used to perform an analysis on one or more samples of interest.
- FIG. 13 shows an example of a fluidic arrangement that may be incorporated into a variation of the system of FIG. 12.
- FIG. 1 illustrates a schematic diagram of an implementation of a system 100 in accordance with the teachings of this disclosure.
- the system 100 be referred to as a dry instrument.
- the phrase dry instrument means that liquid such as reagent may not flow through the instrument itself.
- the system 100 may be a dry instrument if liquid flows from a consumable to waste, for example.
- the 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 are linearized to form a single stranded DNA (sstDNA).
- the system 100 receives a liquid reservoir 102, a cartridge assembly 104, and a flow cell assembly 106 and includes, in part, a pneumatic interface 108, a receptacle 110, a regulator 112, a gas source 114, a drive assembly 115, an actuator 116, a controller 117, an imaging system 1 18, and a waste reservoir 1 19.
- the liquid reservoir 102 and/or the cartridge assembly 104 may be referred to as a consumable, a reagent reservoir, or a reagent assembly.
- the waste reservoir 1 19 may alternatively be carried by the liquid reservoir 102 as an example.
- the system 100 may alternatively omit the pneumatic interface 108, the regulator 112, the gas source 114, and/or the actuator 117.
- the liquid reservoir 102 may be omitted in such implementations, for example, where the cartridge assembly 104 includes liquid reagent.
- the controller 1 17 is electrically and/or communicatively coupled to the regulator 112, the drive assembly 1 15, the actuator 116, and the imaging system 1 18 and causes the regulator 112, the drive assembly 1 15, the actuator 116, and/or the imaging system 1 18 to perform various functions as disclosed herein.
- the cartridge assembly 104 is received within the receptacle 110 in the implementation shown and the cartridge assembly 104 includes a well 120 and an outlet port 122 fluidly coupled to the well 120.
- the flow cell assembly 106 includes a body 124, a flow cell 126, and a sensor assembly 128.
- the body 124 of the flow cell assembly 106 carries a flow cell inlet gasket 130 and the outlet port 122 is fluidly coupled to the flow cell inlet gasket 130.
- the flow cell 126 is supported by the body 124 of the flow cell assembly 106 and the flow cell 126 includes a channel 132.
- the sensor assembly 128 is shown including a heater 134 and a thermal sensor 136.
- the thermal sensor 136 may be referred to as a temperature sensor.
- the heater 134 may be a resistive heater, a microheater, and/or a flexible heater.
- the thermal sensor 136 may be implemented by a semi-conductor based sensor. The thermal sensor 136 may alternatively be implemented in different ways, however. A leak test is performed on the cartridge assembly 104 and the flow cell assembly 106 using the thermal sensor 136 in operation.
- the leak test may include priming the cartridge assembly 104 and the flow cell assembly 106 and accessing a measured temperature value from the thermal sensor 136 using the controller 117.
- the controller 1 17 may determine a difference between the measured temperature value and a reference temperature value and at least one of the cartridge assembly 104 or the flow cell assembly 106 having a leak if the difference is greater than a threshold using the controller 1 17, for example. If air flows through the flow cell 126 because of the presence of a leak that allows air to be drawn into the consumable, the temperature of the flow cell 126 may not drop as much as compared to if no leak were present.
- the leak test that compares the measured temperature to a reference temperature value may be used for identifying larger leaks in the cartridge assembly 104 and/or the flow cell assembly 106.
- the reference temperature may be between about 40°C and about 60°C in some examples.
- the reference temperature may be about 55°C in some examples.
- the leak test may also include the heater 134 heating the flow cell 126 to a threshold temperature after the flow cell 126 is primed and a pump 138 flowing reagent 139 from the well 120 and/or the cartridge assembly 104 into the flow cell inlet gasket 130 of the flow cell assembly 106.
- the pump 138 of the cartridge assembly 104 may alternatively not be used.
- the reagent 139 may be flowed into the flow cell assembly 106 under positive pressure and/or using an alternative pump such as a pump of the system 100.
- the reagent 139 used for the leak tests may be buffer reagent.
- the reagent 139 may flow through a valve 140 and directly to the flow cell assembly 106 in some implementations.
- the reagent 139 may not flow through the well 120 in such implementations.
- the reagent 139 may alternatively flow from the well 120 or another source.
- the thermal sensor 136 may obtain a temperature value of the flow cell 126 before, while, and/or after the reagent 139 flows into the channel 132 of the flow cell 126.
- the leak test may additionally or alternatively include the valve 140 being actuated to a closed position and the pump 138 generating a vacuum in at least one of the cartridge assembly 104 or the flow cell assembly 106.
- the vacuum may be held for a threshold amount of time. The vacuum may be held for about 10 minutes, for example. If the cartridge assembly 104 and/or the flow cell 126 have a leak, the vacuum may draw air into the cartridge assembly 103 and/or the flow cell 126. If air is drawn into the cartridge assembly 103 and/or the flow cell 126, subsequent temperature values at the flow cell 126 determined by the thermal sensor 136 may be affected. For example, attempting to flow reagent 139 through the flow cell 126 when air is present may not significantly decrease the temperature of the flow cell 126, for example.
- the leak test may include the heater 134 heating the flow cell 126 to a threshold temperature and the valve 140 being actuated to an open position.
- Reagent 139 may be flowed from the well 120, from the cartridge assembly 104, and/or another source into the flow cell inlet gasket 130 of the flow cell assembly 106 and the channel 132 of the flow cell 126 using the pump 138 and the thermal sensor 136 may measure a plurality of temperature values of the flow cell 126. If air flows through the flow cell 126 in addition to the reagent 139 because of the presence of a leak, the temperature of the flow cell 126 may not drop as much as compared to if no leak were present.
- the controller 1 17 may access the measured temperature values from the thermal sensor 136 and determine a difference between the measured temperature values.
- the controller 117 may identify at least one of the cartridge assembly 104 or the flow cell assembly 106 having a leak if the difference between the measured temperature values is greater than a threshold.
- the threshold may be between about 2 degrees Celsius and about 15 degrees Celsius in some examples.
- the threshold may be between about 3 degrees Celsius.
- the threshold may be between about 1 degrees Celsius and about 5 degrees Celsius in some examples.
- the disclosed leak tests are performed using the thermal sensor 136.
- the thermal sensor 136 may be positioned adjacent the flow cell inlet gasket 130. The positioning of the thermal senor 136 may allow the temperature change and/or drop of the flow cell 126 to be accurately measured when reagent 139 is flowed into the flow cell 126, for example. No pressure sensors may be used when performing the leak tests.
- the cartridge assembly 104 does not include a pressure sensor in the implementation shown.
- the flow cell assembly 106 does not include a pressure sensor in the implementation shown.
- the leak tests may additionally or alternatively include preheating the reagent 139 prior to the reagent 139 flowing into the flow cell 126.
- the system 100 and/or the cartridge assembly 104 may include a heater in such implementations.
- the heater may be a resistive heater, a flexible heater, a Peltier heater, an infrared (IR) heater, etc.
- the leak tests may include a heater preheating the reagent 139, the pump 138 flowing preheated reagent into the flow cell 126, and the controller 117 accessing a measured temperature value from the thermal sensor 136.
- the controller 1 17 may determine a difference between the measured temperature value and a reference temperature value and identify at least one of the cartridge assembly 104 or the flow cell assembly 106 having a leak if the difference is greater than a threshold. Air may be present in the cartridge assembly 104 and/or the flow cell assembly 106 if the preheated reagent 139 does not increase the temperature of the flow cell 126 a threshold amount.
- the controller 1 17 may be generate an alert if the controller 117 identifies at least one of the cartridge assembly 104 or the flow cell assembly 106 has a leak.
- the alert may be an audio alert, a visual alert, a tactile alert (e.g., vibration), a mobile application notification, for example.
- the cartridge assembly includes the pump 138 and the flow cell assembly 106 carries an outlet gasket 142 in the implementation shown.
- the pump 138 is coupled to the outlet gasket 142 of the flow cell assembly 106.
- the pump 138 may alternatively be positioned between the well 120 and the flow cell assembly 106 or in another location.
- the pump 138 may be a syringe pump 144.
- the pump 138 may alternatively be part of the system 100.
- the pump 138 may alternatively be omitted.
- the pump 138 may be implemented by the syringe pump 144, a peristaltic pump, a diaphragm pump, etc.
- the well 120 may contain reagent 139 and the syringe pump 144 is used to flow the reagent 139 from the well 120 to the flow cell 126.
- the regent 139 may be rehydrated reagent and/or liquid reagent.
- the reagent 139 may be lyophilized reagent(s) before rehydrating, for example, and may be referred to as dry reagent or dried reagent.
- the cartridge assembly 104 is shown including the valve(s) 140 coupled between the outlet port 122 of the cartridge assembly 104 and the well 120.
- the system 100 has a valve drive assembly 146 that interfaces with the valve 140.
- the valve drive assembly 146 may interface with the valve 140 to actuate the valve 140 to control the flow of the liquid 203 from the liquid reservoir 102 to the well 120 and/or the flow cell 126, for example.
- the liquid 203 may be reagent, buffer reagent, etc.
- the valve 140 may be implemented by a three-way valve, a valve manifold, a rotary valve, a selector valve, a pinch valve, a flat valve, a solenoid valve, a check valve, a piezo valve, etc.
- the flow cell assembly 106 includes the body 124 carrying the flow cell inlet gasket 130, a flow cell outlet gasket 150, and an outlet gasket 142.
- the body 124 also includes a fluidic aperture 152 in the implementation shown.
- the flow cell assembly 106 is shown including a first laminate 154, a second laminate 156, and the flow cell 126 is supported by the body 124.
- a “flow cell” can include a device having a lid extending over a reaction structure to form a flow channel therebetween that is in communication with a plurality of reaction sites of the reaction structure, and can include a detection device that detects designated reactions that occur at or proximate to the reaction sites.
- the flow cell inlet gasket 130 may be referred to as a flow cell assembly inlet gasket and the outlet gasket 142 may be referred to as a flow cell assembly outlet gasket.
- the flow cell inlet gasket 130 may thus be both the inlet gasket for the flow cell assembly 106 and the inlet gasket for the flow cell 126.
- the flow cell 126 may support the sample of interest.
- the cartridge assembly 104 may include a flow cell receptacle that receives the flow cell 126.
- the first laminate 154 is coupled to the body 124 and forms a first fluidic channel 158 between the flow cell outlet gasket 150 and the fluidic aperture 152 and the second laminate 156 is coupled to the body 124 and forms a second fluidic channel 160 between the fluidic aperture 152 and the outlet gasket 142.
- the first laminate 154 and/or the second laminate 156 can be coupled to the body 124 by laser welding.
- the body 124 of the flow cell assembly 106 includes a first groove 161 and a second groove 162. The first laminate covers the first groove 161 to form the first fluidic channel and the second laminate covers the second groove 162 to form the second fluidic channel.
- the flow cell 126 is supported by the body 124 and includes the channel 132 having a flow cell inlet 164 and a flow cell outlet 166.
- the flow cell inlet 164 is fluidly coupled to the flow cell inlet gasket 130 and the flow cell outlet 166 is fluidly coupled to the flow cell outlet gasket 150.
- the outlet port 122 of the cartridge assembly 104 is fluidly coupled to the flow cell inlet gasket 130 once the flow cell assembly 106 is coupled to the cartridge assembly 104, for example.
- the flow cell assembly 106 is coupled to the cartridge assembly 104 by a coupling 168 in the implementation shown.
- the coupling 168 may be a snap-fit connection 170.
- the coupling 168 may be implemented in a different way, however.
- the cartridge assembly 104 also includes a pair of locating posts 171 and the body 124 of the flow cell assembly 106 has a pair of locating holes 172 that register with the corresponding locating posts 171 .
- One of the locating holes 172 may be circular and the other of the locating holes 172 may be oblong as an example.
- the sensor assembly 128 includes a die 173.
- the die 173 is shown including the thermal sensor 136.
- the die 173 may also include an additional thermal sensor(s) 174 as shown.
- the thermal sensor 174 may be used to control a temperature of the flow cell 126, for example.
- the thermal sensor 174 may be controlled by a proportional-integral-derivative (PID) controller.
- PID proportional-integral-derivative
- the die 173 may be implemented by a complementary metal-oxide semiconductor (CMOS) 175 in some examples.
- CMOS complementary metal-oxide semiconductor
- the die 173 may be implemented in other ways, however.
- the die 173 may include a solid-state imaging device, a charge coupled device (CCD), and/or an infrared (IR) senor.
- the sensor assembly 128 includes a printed circuit board (PCB) 176 and the heater 134 is positioned between die 173 and the PCB 176.
- the die 173 and/or the heater 134 may be coupled to the PCB 176.
- the liquid reservoir 102 is receivable within the receptacle 110 and has the body 148 including a storage chamber 177, a pneumatic port 178 fluidly couplable to the storage chamber 177, and a fluidic port 179 fluidly coupled to the storage chamber 177.
- the cartridge assembly 104 has a fluidic interface 180 couplable to the fluidic port 179, the well 120, and a channel 181 fluidly coupled between the fluidic interface 180 and the well 120.
- the cartridge assembly 104 also includes the outlet port 122 fluidly coupled to the well 120, an inlet port 182, and an outlet port 183 fluidly coupled to the waste reservoir 119.
- the outlet port 1838 may alternatively be fluidly coupled to the liquid reservoir 102 when the waste reservoir 119 is omitted and/or included with the liquid reservoir 102.
- the liquid reservoir 102 is receivable within the receptacle 110 and includes the body 124, a cover 184, and a lid assembly 185.
- the body 124 has a top surface 186 and the storage chamber 177 has an opening 187 at the top surface 186.
- the body 124 also has a sipper chamber 188 having an opening 190 at the top surface 186 and a fluidic sinus 192 fluidly coupling the storage chamber 177 and the sipper chamber 188.
- the cover 184 covers the opening 187 of the storage chamber 177 and the lid assembly
- the lid assembly 185 is coupled to the top surface 186.
- the lid assembly 185 may be laser welded to the top surface 186 of the liquid reservoir 102.
- the lid assembly 185 may be coupled to the top surface
- the cover 184 may be implemented by plastic, foil, rubber, a seal, and/or a plug.
- the lid assembly 185 has a first portion 194 covering the opening 187 of the storage chamber 1 T1 and a second portion 196 covering the opening 190 of the sipper chamber 188.
- the top surface 186 of the body 124 and the second portion 196 define a plenum 198.
- the first portion 194 of the lid assembly 185 has the pneumatic port 178, a cantilever 200, and a compliant barrier 202.
- the cantilever 200 and the compliant barrier 202 may be formed using a two-shot molding process in some implementations.
- the compliant barrier 202 may comprise or be formed of a thermoplastic elastomer (TPE) as an example.
- TPE thermoplastic elastomer
- the compliant barrier 202 may have a thickness of about 0.9 millimeters (mm).
- the compliant barrier 202 may be made of another material and/or have a different thickness, however.
- the pneumatic port 178 is fluidly coupled to the plenum 198.
- the cantilever 200 may be referred to as a piercer.
- the cantilever 200 has a distal end and the compliant barrier 202 covers the cantilever 200 and defines a portion of the plenum 198.
- the fluidic port 179 is fluidly coupled to the opening 190 of the sipper chamber 188.
- the actuator 117 is movable to engage the compliant barrier 202 in operation and move the distal end of the cantilever 200 to pierce the cover 184 and allow the storage chamber 177 to be fluidly coupled to the plenum 198.
- the system 100 can thus indirectly actuate the cantilever 200 without the system 100 compromising and/or accessing an interior of the liquid reservoir 102.
- the engagement between the actuator 1 17 and the compliant barrier 202 does not vent the plenum 198 to atmosphere as a result.
- Liquid 203 is contained within the storage chamber 177 and dried reagent 139 is contained within the well 120.
- the liquid 203 may be a rehydrating liquid and/or a wash buffer.
- the wash buffer may be referred to as buffer reagent.
- the liquid 203 may be a different type of liquid, however.
- the dried reagent 139 may be lyophilized reagent as an example.
- the liquid reservoir 102 may include any number of storage chambers 177 including one storage chamber as shown and the cartridge assembly 104 may include any number wells 120 including one well as shown.
- the number of storage chambers 177 that the liquid reservoir 102 has may correspond to the number of wells 120 that the cartridge assembly 104 has in some examples.
- the liquid reservoir 102 and/or the cartridge assembly 104 includes a thermoplastic.
- the liquid reservoir 102 and/or the cartridge assembly 104 may additionally or alternatively include polypropylene and/or cyclic olefin copolymer (COC) with an over molded Santoprene thermoplastic elastomer (TPE) or another thermoplastic elastomer.
- COC polypropylene and/or cyclic olefin copolymer
- TPE over molded Santoprene thermoplastic elastomer
- Other materials may prove suitable for the liquid reservoir 102 and/or the cartridge assembly 104.
- the cover 184 that covers the opening 187 may include foil and the compliant barrier 202 may include an elastomer and/or a conformable foil.
- the foil may be a foil with a lacquer backing for bonding to the thermoplastic of the body 124 in some implementations.
- the lacquer is a coating applied to the cover 184 that promotes the bonding to the body 124 when heat staked, for example.
- the cover 184 and/or the compliant barrier 202 may additionally or alternatively include plastic.
- the body 148 of the liquid reservoir 102 includes a port 204 that defines the opening 187 in the implementation shown.
- the cover 184 is coupled to the port 204.
- the cover 184 may alternatively be coupled within the port 204 to seal the port 204, for example.
- the port 204 may alternatively be omitted.
- the cover 184 is pierced by the cantilever 200 in operation prior to the storage chamber 177 being pressurized by the gas source 114, for example.
- the cantilever 200 piercing the cover 184 may allow the pneumatic interface 108 to pressurize the storage chamber 177.
- the actuator 117 may engage and move the compliant barrier 202 and in turn move the cantilever 200 to pierce the cover 184.
- the cover 184 may be pierced in different ways, however.
- the lid assembly 185 in the implementation shown includes a body 205 having the cantilever 200 and the compliant barrier 202 is coupled to the body 205 and covers the cantilever 200.
- the body 205 has an aperture 206 and the compliant barrier 202 covers the aperture 206.
- the aperture 206 may alternatively be referred to as an opening or a window.
- the actuator 117 can move the cantilever 200 by moving the compliant barrier 202 relative to and/or through the aperture 206.
- the aperture 206 being larger may reduce an amount of force used to actuate the cantilever 200.
- the cantilever 200 may be adapted to pierce the cover 184 and allow the cover 184 to be pneumatically coupled to the plenum 198.
- the body 205 has a living hinge 207 coupled to the cantilever 200.
- the living hinge 207 allows the cantilever 200 to move relative to the remainder of the body 205 and for the cantilever 200 to pierce the cover 184.
- the cantilever 200 may be movably coupled to the body 205 in different ways, however.
- the cartridge assembly 104 includes a cover 208 shown covering the well 120.
- the cover 208 may include and/or form a vent 210 that allows air flow out of the well 120.
- the vent 210 is sized to substantially retain the dried reagent 139 within the well 120.
- the use of the dried reagent 139 in the disclosed implementations may simplify storage requirements, reduce shipping costs, and increase the speed of workflows by, for example, avoiding thaw time before the reagent may be used.
- the well 120 includes a port 212 and the liquid 203 can flow into the well 120 via the port 212 in practice to rehydrate the dried reagent 139.
- the vent 210 may vent gas from the well 120 as the liquid 203 flows into the well 120 and the cover 208 prevents or inhibits the dried reagent 139 and/or the liquid 203 from escaping from the well 120. Put another way, the vent 210 retains the dried reagent 139 and/or the liquid 203 within the wells 120 and prevents or inhibits the dried reagent 139 and/or the liquid 203 from migrating out of the wells 120.
- the vent 210 and the cover 208 prevents or inhibits cross-contamination between reagents when the liquid reservoir 102 includes more than one well 120.
- the liquid 203 and the dried reagent 139 can be flowed into and out of the well 120 to mix the liquid 203 from the liquid reservoir 102 and the dried reagent 139.
- the system 100 and/or the liquid reservoir 102 may include a mixing chamber that is used to mix the liquid 203 and the dried reagent 139 in some implementations.
- the gas source 114 may be used to pressurize the liquid reservoir 102 to flow the liquid 203 into the well 120 and/or the pump 138 may draw the liquid 203 from the liquid reservoir 102 and flow the liquid 203 into the well 120 to rehydrate the dried reagent 139.
- the pump 138 may be used to draw the rehydrated reagent from the well 120 and flow the rehydrated reagents to the flow cell 126 in some implementations.
- the gas source 114 may be provided by the system 100 and/or the gas source 1 14 may be carried by the liquid reservoir 102.
- the gas source 1 14 may alternatively be omitted.
- the liquid reservoir 102 and/or the system 100 includes a valve 216 that may be selectively actuatable to control the flow of fluid (gas) to the liquid reservoir 102.
- the valve 216 may be implemented by a valve manifold, a rotary valve, a selector valve, a pinch valve, a flat valve, a solenoid valve, a check valve, a piezo valve, etc.
- the regulator 112 can be positioned between the gas source 114 and the valve 216 and regulates a pressure of the gas provided to the valve 216.
- the regulator 112 may be a valve that controls the flow of the gas from the gas source 114.
- the gas source 114 and/or the pump 138 may flow the liquid 203 to rehydrate dried reagents 139 and to flow one or more liquid reagents (e.g., A, T, G, C nucleotides) through the liquid reservoir 102 that interact with the sample.
- the gas source 1 14 may flow the liquid 203 to rehydrate the dry reagents 139 on the cartridge assembly 104 and the pump 138 on the cartridge assembly 104 may flow the rehydrated reagent (e.g., A, T, G, C nucleotides) to the flow cell 126 that interact with the sample as an example.
- the reagent with a reversible terminator in an implementation allows a single nucleotide to be incorporated by the sstDNA per cycle.
- One or more of the nucleotides has a unique fluorescent label in such implementations that emits a color when excited. The color (or absence thereof) is used to detect the corresponding nucleotide.
- the imaging system 118 excites one or more of the identifiable labels (e.g., a fluorescent label) in the implementation shown and the sensor assembly 128 of the flow cell assembly 106 and/or the imaging system 118 obtains 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 system 100 may include a light source and the flow cell assembly 106 may include an image sensor in some examples.
- the image data (e.g., detection data) may be analyzed by the system 100.
- the imaging system 1 18 may 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).
- CCD charge coupled device
- CMOS complementary metal oxide semiconductor
- the drive assembly 115 interfaces with the liquid reservoir 102 to flow another reaction component (e.g., a reagent) through the flow cell 126 that is thereafter received by the waste reservoir 119 and/or otherwise exhausted by the cartridge assembly 104.
- the reaction component performs a flushing operation that chemically cleaves the fluorescent label and the reversible terminator from the sstDNA.
- the sstDNA is then ready for another cycle.
- the drive assembly 115 includes a pump drive assembly 218 and the valve drive assembly 146.
- the pump drive assembly 218 interfaces with the pump 138 to pump fluid through the liquid reservoir 102 and/or the flow cell 126 and the valve drive assembly 146 interfaces with the valves 140 and/or 216 to control the position of the valves 140 and/or 216.
- the controller 117 includes a user interface 222, a communication interface 224, one or more processors 226, and a memory 228 storing instructions executable by the one or more processors 226 to perform various functions including the disclosed implementations.
- the user interface 222, the communication interface 224, and the memory 228 are electrically and/or communicatively coupled to the one or more processors 226.
- the user interface 222 receives input from a user and provides information to the user associated with the operation of the system 100 and/or an analysis taking place.
- the user interface 222 may include a touch screen, a display, a keyboard, 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).
- GUI graphical user interface
- the communication interface 224 enables communication between the system 100 and a remote system(s) (e.g., computers) via a network(s).
- the network(s) may include an intranet, a local-area network (LAN), a wide-area network (WAN), the intranet, 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 system 100.
- Some of the communications provided to the system 100 may be associated with a fluidics analysis operation, patient records, and/or a protocol(s) to be executed by the system 100.
- the one or more processors 226 and/or the system 100 may include one or more of a processor-based system(s) or a microprocessor-based system(s).
- the one or more processors 226 and/or the system 100 includes a reduced-instruction set computer(s) (RISC), an application specific integrated circuit(s) (ASICs), a field programable gate array(s) (FPGAs), a field programable logic device(s) (FPLD(s)), a logic circuit(s) , and/or another logic-based device executing various functions including the ones described herein.
- RISC reduced-instruction set computer
- ASICs application specific integrated circuit
- FPGAs field programable gate array
- FPLD(s) field programable logic device
- a logic circuit(s) and/or another logic-based device executing various functions including the ones described herein.
- the memory 228 can include one or more of a hard disk drive, a flash memory, a readonly memory (ROM), erasable programable read-only memory (EPROM), electrically erasable programable read-only memory (EEPROM), a random-access memory (RAM), non-volatile RAM (NVRAM) memory, a compact disk (CD), a digital versatile disk (DVD), 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).
- ROM readonly memory
- EPROM erasable programable read-only memory
- EEPROM electrically erasable programable read-only memory
- RAM random-access memory
- NVRAM non-volatile RAM
- CD compact disk
- DVD digital versatile disk
- 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. 2 is an isometric view of an example implementation of a cartridge assembly 300 and a flow cell assembly 302 that can be used to implement the cartridge assembly 104 and the flow cell assembly 106 of FIG. 1 .
- the cartridge assembly 300 includes the fluidic interface 180 and a plurality of the wells 120.
- the flow cell assembly 302 is coupled to the cartridge assembly 300 by the snap-fit connection 170.
- the flow cell assembly 302 also includes a second flow cell 304 supported or otherwise carried by the body 124.
- the first flow cell 126 and the second flow cell 304 may be substantially identical structures in some implementations.
- the first flow cell 126 and the second flow cell 304 may be different structures in other implementations.
- the first flow cell 126 and the second flow cell 304 are shown being in an end-to-end vertical configuration relative to the cartridge assembly 300.
- the first flow cell 126 and the second flow cell 304 may be considered to be in an end-to-end horizontal configuration relative to the cartridge assembly 300 if the first flow cell 126 and the second flow cell 304 are oriented about 90° to the position shown.
- the second flow cell 304 has a channel 132 including a flow cell inlet 164 and a flow cell outlet 166.
- the flow cell 126 may be referred to as a third flow cell and the second flow cell 304 may be referred to as a fourth flow cell.
- the flow cell 126 and the second flow cell 304 are fluidly coupled in series in the implementation shown.
- the flow cell outlet 166 of the flow cell 126 is fluidly coupled to the flow cell outlet gasket 150 via the second flow cell 304, for example.
- the flow cell 126 and the second flow cell 304 may be coupled in different ways, however.
- the flow cell 126 and the second flow cell 304 may be coupled in parallel and/or oriented differently as examples.
- FIG. 3 is an isometric partially expanded view of the flow cell assembly 302 of FIG. 2.
- the flow cell assembly 302 shows the first laminate 154 and the second laminate 156 that are used to form the first fluidic channel 158 and the second fluidic channel 160.
- the body 124 of the flow cell assembly 106 and the flow cell 126 are coupled by a coupling 306.
- the coupling 306 includes a first snap-fit cantilever 308 and a second snap-fit cantilever 310.
- the first snap-fit cantilever 308 is positioned on a first side 312 of the flow cell 126 and the second snap-fit cantilever 310 is positioned on a second side 314 of the flow cell 126.
- the first snap-fit cantilever 308 biases the flow cell 126 in the x-direction and the second snap-fit cantilever 310 biases the flow cell 126 in the y-direction in the implementation shown.
- the coupling 306 also includes a pair of hold downs 316 having a lip 318 that is arranged to be positioned overtop of the flow cell 126. Both of the hold downs 316 are positioned on a side 320 of the flow cell 126. The hold downs 316 may be in a different position.
- the coupling 306 has a x-datum projection 322 and a y-datum projection 324 in the implementation shown against which the flow cell 126 engages.
- the coupling 306 also includes has a second x-datum projection 326.
- the first snap-fit cantilever 308 biases the flow cell 126 into engagement with the x-datum projections 322, 326 and the second snap-fit cantilever 310 biases the flow cell 126 into engagement with the y- datum projection 324.
- the second flow cell 304 and the body 124 of the flow cell assembly 106 are coupled by a coupling 328 that is similar or the same as the coupling 306.
- the body 124 has locating posts 329 in the implementation shown and the second laminate 156 has locating holes 330 that receive the corresponding locating posts 329.
- the locating holes 330 receiving the locating posts 329 aligns the second laminate 156 relative to the body 124 to form the second fluidic channel 160.
- FIG. 4 is an isometric view of the first flow cell 126 and the second flow cell 304 of the flow cell assembly 302 of FIG. 2.
- Each of the flow cells 126 includes a corresponding sensor assembly 128 having a plurality of thermal sensors 136, 174.
- the flow cells 126 have multiple thermal sensors 136, 174 displaced along the length of the fluidic path in the implementation shown.
- Each sensor assembly 128 is shown including six thermal sensors 136, 174.
- One of the thermal sensors 136, 174 may be used when heating the flow cell assembly 302 to the threshold temperature and one of the thermal sensors 136, 174 may be used when performing the leak tests disclosed, in some examples.
- the thermal sensors 136, 174 may be used as desired to implement the teachings of this disclosure, however.
- FIG. 5 is an expanded isometric view of an example implementation of another flow cell assembly 400 having a body 401 that can be used to implement the flow cell assembly 106 of FIG. 1 .
- the flow cell assembly 400 may be referred to as a second flow cell assembly 400.
- the flow cell assembly 400 is similar to the flow cell assembly 302 in that both the flow cell assembly 302 and the flow cell assembly 400 mechanically and fluidly couple with the cartridge assembly 300 and/or the system 100 interchangably.
- the flow cell assembly 302 and the flow cell assembly 400 have cantilevers 402 of the snap-fit connection 170 in the same or substantially the same location to allow the flow cell assembly 302 and the flow cell assembly 400 to mechanically couple with the cartridge assembly 300 in the same or similar way.
- the flow cell assembly 302 and the flow cell assembly 400 may also have the flow cell inlet gasket 130 and the outlet gasket 142 in the same or substantially the same location to allow the flow cell assembly 302 and the flow cell assembly 400 to fluidly couple with the cartridge assembly 300 in the same or in a similar way.
- the flow cell assembly 400 includes a flow cell 404 but does not include an additional flow cell in the implementation shown.
- the flow cell 404 may be referred to as a second flow cell.
- the flow cell 404 may be different from the flow cell 126 shown in FIG. 2.
- the flow cell 404 may have different flow cell channel volumes from the flow cell channel volumes of the flow cell 126 shown in FIG. 2, for example.
- the flow cell outlet gasket 150 is shown positioned closer to the flow cell inlet gasket 130 to allow the flow cell inlet 164 and the flow cell outlet 166 of the flow cell 404 to fluidly couple with the gaskets 142, 150.
- the flow cell outlet gasket 150 may be positioned closer to the flow cell inlet gasket 130 in the flow cell assembly 400 as compared to the relative position of the flow cell outlet gasket 150 and the flow cell inlet gasket 130 in the flow cell assembly 302 of FIG. 2.
- the flow cell assembly 400 includes the first laminate 154 and the second laminate 156 similar to the laminates 154, 156 used with the flow cell assembly 302 of FIG. 2.
- the flow cell assembly 400 does not include an additional flow cell so the laminates 154, 156 used with the flow cell assembly 400 have a different configuration from the laminates 154, 156 used with the flow cell assembly 302 of FIG. 2.
- the first laminate 154 is to be coupled to the body 401 and forms the first fluidic channel 158 between the flow cell outlet gasket 150 and the fluidic aperture 152
- the second laminate 156 is to be coupled to the body 401 and forms the second fluidic channel 160 between the fluidic aperture 152 and the outlet gasket 142.
- the body 124 also defines a window 406 to allow visual access of the flow cell 126.
- FIG. 6 is an isometric view of the flow cell 404 of the flow cell assembly 400 of FIG. 5.
- the flow cell 404 includes a sensor assembly 128 having a plurality of thermal sensors 136, 174.
- the sensor assembly 128 is shown including four thermal sensors 136, 174.
- One of the thermal sensors 136, 174 may be used when heating the flow cell assembly 302 to the threshold temperature and one of the thermal sensors 136, 174 may be used when performing the leak tests disclosed, in some examples.
- the thermal sensors 136, 174 may be used as desired to implement the teachings of this disclosure, however.
- FIG. 7 is an expanded isometric view of an example implementation of a flow cell assembly 500 having a body 501 that can be used to implement the flow cell assembly 106 of FIG.
- the flow cell assembly 500 is similar to the flow cell assembly 106 and the flow cell assembly 400 in that each of the flow cell assembly 106, the flow cell assembly 400, and the flow cell assembly 500 mechanically and fluidly couple with the cartridge assembly 300 and/or the system 100 interchangeably.
- the flow cell assembly 106, the flow cell assembly 400, and the flow cell assembly 500 have the cantilevers 402 of the snap-fit connection 170 in the same or substantially the same location to allow the flow cell assembly 106, the flow cell assembly 400, and the flow cell assembly 500 to mechanically couple with the cartridge assembly 300 in the same or similar way.
- the flow cell assembly 106, the flow cell assembly 400, and the flow cell assembly 500 may also have the flow cell inlet gasket 130 and the outlet gasket 142 in the same or substantially the same location to allow the flow cell assembly 106, the flow cell assembly 400, and the flow cell assembly 500 to fluidly couple with the cartridge assembly 300 in the same or similar way.
- the system 100 and/or the cartridge assembly 300 may remain the same or substantially the same while allowing the flexibility of using different flow cell assemblies.
- the flow cell assembly 500 includes a flow cell 502 but does not include an additional flow cell in the implementation shown.
- the flow cell 502 may be the same or different from the flow cell 404 shown in FIG. 5 and/or the flow cell 126 shown in FIG. 2, for example.
- the flow cell 502 may have different flow cell channel volumes from the flow cell channel volumes of the flow cell 126 shown in FIG. 2, for example
- the flow cell assembly 500 includes the first laminate 154 and the second laminate 156 similar to the laminates 154, 156 used with the flow cell assembly 400 of FIG. 5.
- the gaskets 130, 150 of FIG. 6 are further spaced apart because of the size of the flow cell 502 as compared to the spacing of the gaskets 130, 150 of FIG. 5.
- the first laminate 154 of the flow cell assembly 500 is thus longer to accommodate the position of the gaskets 130, 142 , and/or 150 of the flow cell assembly 500 as compared to the length of the first laminate 154 in the flow cell assembly 400.
- FIG. 8 is an isometric view of the flow cell 502 of the flow cell assembly 500 of FIG. 7.
- the flow cell 502 includes a sensor assembly 128 having a plurality of thermal sensors 136, 174.
- the sensor assembly 128 is shown including six thermal sensors 136, 174.
- One of the thermal sensors 136, 174 may be used when heating the flow cell assembly 302 to the threshold temperature and one of the thermal sensors 136, 174 may be used when performing the leak tests disclosed, in some examples.
- the thermal sensors 136, 174 may be used as desired to implement the teachings of this disclosure, however.
- FIG. 9 illustrates a flow chart for a method of determining the presence of a leak using the system 100 of FIG. 1 , the cartridge assembly 104 and/or 300 of FIGS. 1 - 2, the flow cell assemblies 106, 302, 400, 500 and sensor assemblies 128 of FIGS. 1 - 8, or any of the other implementations disclosed herein.
- 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 process 1200 of FIG. 9 starts with the cartridge assembly 104 and the flow cell assembly 106 being primed with reagent 139 (Block 904).
- the flow cell 126 is heated to a threshold temperature using the heater 134 of a flow cell assembly 106 (Block 906).
- the flow cell assembly 106 is coupled to the cartridge assembly 104 and may be positioned in the receptacle 1 10 of the system 100.
- the reagent 139 may be buffer reagent that is drawn into the flow cell assembly 106 using the pump 138 to prime the flow cell assembly 106.
- the reagent 139 may be pulled directly from the storage chamber 177 through the valve 140 and into the flow cell assembly 106.
- the reagent 138 may alternatively be flowed to one of the empty wells 120 using positive pressure and the reagent 138 may then be pulled from that empty well 120 across the flow cell 126 using the pump 144.
- the reagent 138 may alternatively flow across the flow cell 126 under positive pressure.
- Reagent 139 is flowed into the flow cell 126 (Block 908).
- the reagent flowing into the flow cell 126 may include the reagent 138 flowing from the cartridge assembly 104.
- the reagent 139 flowing into the flow cell 126 may include the reagent 138 flowing from a well 120 of the cartridge assembly 104.
- the reagent 139 flowing from the cartridge assembly 104 into the flow cell 126 may include the reagent 139 flowing into the flow cell inlet gasket 130 of the flow cell assembly 106 using the pump 138 of the cartridge assembly 104.
- the flow cell assembly 106 includes the body 124 carrying the flow cell inlet gasket 130 and the flow cell 126 supported by the body 124.
- the flow cell inlet gasket 130 is fluidly coupled to the outlet port 122 and the flow cell 126.
- a measured temperature value from a thermal sensor 136 of the flow cell assembly 106 is accessed, using a controller 1 17, (Block 910) and a presence of a leak in at least one of the cartridge assembly 104 or the flow cell assembly 106 is determined, using the controller 117, based on the measured temperature value (Block 910).
- the presence of the leak may be determined by determining a difference between the measured temperature value and a reference temperature value using the controller 1 17 and identifying at least one of the cartridge assembly 104 or the flow cell assembly 106 having the leak if the difference is greater than a threshold using the controller 117.
- the presence of the leak may be determined by actuating the valve 140 of the cartridge assembly 104 to a closed position and a vacuum being generated in at least one of the cartridge assembly 104 or the flow cell assembly 106 using the pump 138.
- the flow cell 126 may be heated to a threshold temperature using the heater 134 of the flow cell assembly 106 and the valve 140 may be actuated to an open position.
- the reagent 139 may be flowed from the well 120, from the cartridge assembly 104, and/or from another source (e.g., the system 100) to the flow cell 126 and a plurality of temperature values of the flow cell 126 may be determined using the thermal sensor 136.
- the reagent 139 may be flowed using the pump 139.
- the presence of the leak may be determined using the controller 117 by accessing measured temperature values from the thermal sensor 136 and determining a difference between the measured temperature values using the controller 117. At least one of the cartridge assembly 104 or the flow cell assembly is identified having the leak if the difference between the measured temperature values is greater than a threshold. An alert is generated if the controller 117 determines the presence of the leak in at least one of the cartridge assembly 104 or the flow cell assembly 106 (Block 914).
- FIG. 10 is a graph 10000 showing results of the disclosed implementations including an x-axis 11002 relating to time and a y-axis 1 1004 relating to temperature.
- a first line 10007 shows the temperature of the flow cell dropping below a threshold level 10008 when reagent flows through the flow cell. The first line 10007 dropping below the threshold level 10008 indicates that the fluid flowing through the flow cell does not include a significant amount of air and, thus, no leak or substantially no leak is present.
- a second line 10010 shows the temperature of the flow cell not dropping below the threshold level 10008 when reagent flows through the flow cell. The second line 10010 not dropping below the threshold level 10008 indicates that the fluid flowing through the flow cell includes air and, thus, a leak is present.
- FIG. 1 1 is a graph 10050 showing results of the disclosed implementations including an x-axis 10052 relating to time, a first y-axis 10054 relating to pressure and a second y-axis 10056 relating to temperature.
- First lines 10058, 10060 show a segment 16061 where a vacuum is generated and second segments 10062 where the pressure and temperature drop a similar amount when reagent flows through the flow cell.
- the second segments 10062 having similar temperature and/or pressure drops indicates that the fluid flowing through the flow cell does not include a significant amount of air and, thus, no leak or substantially no leak is present in the cartridge assembly and/or the flow cell assembly.
- Second lines 10064, 10066 include the segment 16061 where a vacuum is generated and second segments 10062 where the pressure and temperature drop different amount when reagent flows through the flow cell, specifically when reagent is initially flowed through the flow cell after the vacuum is released.
- the second segments 10062 having different temperature and/or pressure drops indicates that the fluid flowing through the flow cell includes air and, thus, a leak or a minor leak is present.
- Examples described herein may be used in various biological or chemical processes and systems for academic analysis, commercial analysis, or other analysis. More specifically, examples described herein may be used in various processes and systems where it is desired to detect an event, property, quality, or characteristic that is indicative of a designated reaction. Bioassay systems such as those described herein may be configured to perform a plurality of designated reactions that may be detected individually or collectively. For example, bioassay systems may be used to sequence a dense array of nucleic acid features through iterative cycles of enzymatic manipulation and image acquisition. In some examples, nucleic acids can be attached to a surface and amplified. Examples of such amplification are described in U.S.
- Components that are used in the bioassay systems may include one or more microfluidic channels that deliver reagents or other reaction components to a reaction site.
- the reaction sites may be randomly distributed across a substantially planar surface; or may be patterned across a substantially planar surface.
- Each of the reaction sites may be imaged to detect light from the reaction site.
- the signals indicating photons emitted from the reaction sites and detected by image sensors may provide illumination values. These illumination values may be combined into an image indicating photons as detected from the reaction sites. These images may be further analyzed to identify compositions, reactions, conditions, etc., at each reaction site.
- system (1100) illustrates a schematic diagram of an example of a system (1100) that may be used to perform an analysis on one or more samples of interest.
- the sample may include one or more clusters of nucleotides (e.g., DNA) that have been linearized to form a single stranded DNA (sstDNA).
- system (1 100) is configured to receive a flow cell cartridge assembly (1 102) including a flow cell assembly (1103) and a sample cartridge (1104).
- System (1100) includes a flow cell receptacle (1 122) that receives flow cell cartridge assembly (1 102), a vacuum chuck (1 124) that supports flow cell assembly (1103), and a flow cell interface (1126) that is used to establish a fluidic coupling between system (1 100) and flow cell assembly (1103).
- Flow cell interface (1126) may include one or more manifolds.
- System (1100) further includes a sipper manifold assembly (1106), a sample loading manifold assembly (1108), and a pump manifold assembly (1110).
- System (1100) also includes a drive assembly (1112), a controller (1114), an imaging system (1116), and a waste reservoir (1118). Controller (1114) is electrically and/or communicatively coupled to drive assembly (11 12) and to imaging system (1116); and is configured to cause drive assembly (1112) and/or the imaging system (1116) to perform various functions as disclosed herein.
- flow cell assembly (1103) includes a flow cell (1128) having a channel (1130) and defining a plurality of first openings (1132), which are fluidically coupled to the channel (1 130) and arranged on a first side (1134) of the channel (1 130).
- Flow cell (1128) further includes a plurality of second openings (1136) fluidically coupled to the channel (1130) and arranged on a second side (1 138) of the channel (1130). Fluid may thus flow through flow cell (1128) via channel. While the flow cell (1 128) is shown including one channel (1130), flow cell (1128) may include two or more channels (1130).
- Flow cell assembly (1103) also includes a flow cell manifold assembly (1140) coupled to flow cell (1128) and having a first manifold fluidic line (1142) and a second manifold fluidic line (1144).
- Flow cell manifold assembly (1140) may be in the form of a laminate including a plurality of layers as discussed in more detail below.
- first manifold fluidic line (1142) has a first fluidic line opening (1 146) and is fluidically coupled to each of the first openings (1 132) of flow cell (1 128); and second manifold fluidic line (1 144) has a second fluidic line opening (1148) and is fluidically coupled to each of the second openings (1 136).
- flow cell assembly (1 103) includes gaskets (1 150) coupled to flow cell manifold assembly (1 140) and fluidically coupled to fluidic line openings (1 146, 148).
- flow cell manifold assembly (1 140) may include additional fluidic lines (1152) that couple first fluidic line openings (1146) to a single manifold port (1 154).
- a single gasket (1 150) may be coupled to flow cell manifold assembly (1140) that surrounds the manifold port (1154) and is in fluidic communication with a plurality of channels (1130).
- flow cell interface (1126) engages with corresponding gaskets (1150) to establish a fluidic coupling between system (1 100) and flow cell (1128).
- the engagement between flow cell interface (1 126) and gaskets (1 150) reduces or eliminates fluid leakage between flow cell interface (1 126) and flow cell (1128).
- first manifold fluidic line (1142) has a portion (1 156) that is substantially parallel to a longitudinal axis (1 158) of channel (1130); and second manifold fluidic line (1144) has a portion (1 160) that is substantially parallel to longitudinal axis (1 158) of channel (1130). Additionally, first manifold fluidic line (1 142) is shown being at least partially adjacent a first end (1162) of flow cell (1128) and spaced from a second end (1 164) of flow cell (1128); and second manifold fluidic line (1144) is shown being at least partially adjacent second end (1164) of flow cell (1128) and spaced from first end (1162). Other arrangements of manifold fluidic lines (1 142, 144) may prove suitable, however.
- system (1100) includes a sample cartridge receptacle (1166) that receives sample cartridge (1104) that carries one or more samples of interest (e.g., an analyte).
- System (1 100) also includes a sample cartridge interface (1 168) that establishes a fluidic connection with sample cartridge (1104).
- Sample loading manifold assembly (1108) includes one or more sample valves (1170).
- Pump manifold assembly (1110) includes one or more pumps (1172), one or more pump valves (1174), and a cache (1 176). Valves (1170, 1174) and pumps (1 172) may take any suitable form.
- Cache (1176) may include a serpentine cache and may temporarily store one or more reaction components during, for example, bypass manipulations of the system (1 100). While cache (1176) is shown being included in pump manifold assembly (11 10), cache (1176) may alternatively be located elsewhere (e.g., in sipper manifold assembly (1106) or in another manifold downstream of a bypass fluidic line (1178), etc.).
- Sample loading manifold assembly (1108) and pump manifold assembly (1110) flow one or more samples of interest from sample cartridge (1104) through a fluidic line (1180) toward flow cell cartridge assembly (1102).
- sample loading manifold assembly (1108) may individually load or address each channel (1130) of flow cell (1128) with a respective sample of interest. The process of loading channel (1 130) with a sample of interest may occur automatically using system (1 100).
- sample cartridge (1104) and sample loading manifold assembly (1108) are positioned downstream of flow cell cartridge assembly (1102).
- sample loading manifold assembly (1108) is coupled between flow cell cartridge assembly (1 102) and pump manifold assembly (1110).
- sample valves (1170), pump valves (1174), and/or pumps (1172) may be selectively actuated to urge the sample of interest toward pump manifold assembly (11 10).
- Sample cartridge (1104) may include a plurality of sample reservoirs that are selectively fluidically accessible via the corresponding sample valves (1 170).
- sample valves (1170), pump valves (1174), and/or pumps (1172) may be selectively actuated to urge the sample of interest toward flow cell cartridge assembly (1102) and into respective channels (1 130) of flow cell (1 128).
- Drive assembly (11 12) interfaces with sipper manifold assembly (1 106) and pump manifold assembly (11 10) to flow one or more reagents that interact with the sample within flow cell (1128).
- a reversible terminator is attached to the reagent to allow a single nucleotide to be incorporated onto a growing DNA strand.
- 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.
- imaging system (11 16) excites one or more of the identifiable labels (e.g., a fluorescent label) and thereafter obtains 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 system (1100). Examples of features and functionalities that may be incorporated into imaging system (1 116) will be described in greater detail below.
- drive assembly (1112) interfaces with sipper manifold assembly (1106) and pump manifold assembly (1110) to flow another reaction component (e.g., a reagent) through flow cell (1128) that is thereafter received by waste reservoir (1 118) via a primary waste fluidic line (1182) and/or otherwise exhausted by system (1100).
- reaction components may perform a flushing operation that chemically cleaves the fluorescent label and the reversible terminator from the sstDNA. The sstDNA may then be ready for another cycle.
- the primary waste fluidic line (1 182) is coupled between pump manifold assembly (1110) and waste reservoir (1118).
- pumps (1172) and/or pump valves (1174) of pump manifold assembly (1 110) selectively flow the reaction components from flow cell cartridge assembly (1102), through fluidic line (1 180) and sample loading manifold assembly (1108) to primary waste fluidic line (1182).
- Flow cell cartridge assembly (1 102) is coupled to a central valve (1 184) via flow cell interface (1 126).
- Central valve (1 184) is coupled with flow cell interface (1126) via a fluidic line (1 185).
- An auxiliary waste fluidic line (1186) is coupled to central valve (1 184) and to waste reservoir (11 18).
- auxiliary waste fluidic line (1186) receives excess fluid of a sample of interest from flow cell cartridge assembly (1102), via central valve (1 184), and flows the excess fluid of the sample of interest to waste reservoir (11 18) when back loading the sample of interest into flow cell (1128), as described herein.
- Sipper manifold assembly (1 106) includes a shared line valve (1 188) and a bypass valve (1190).
- Shared line valve (1188) may be referred to as a reagent selector valve.
- Central valve (1184) and the valves (1188, 190) of sipper manifold assembly (1106) may be selectively actuated to control the flow of fluid through fluidic lines (1192, 1194, 1196).
- Sipper manifold assembly (1106) may be coupled to a corresponding number of reagent reservoirs (1198) via reagent sippers (1200).
- Reagent reservoirs (1198) may contain fluid (e.g., reagent and/or another reaction component).
- sipper manifold assembly (1106) includes a plurality of ports.
- Each port of sipper manifold assembly (1106) may receive one of the reagent sippers (1200).
- Reagent sippers (1200) may be referred to as fluidic lines.
- Some forms of reagent sippers (1200) may include an array of sipper tubes extending downwardly along the z-dimension from ports in the body of sipper manifold assembly (1106).
- Reagent reservoirs (1 198) may be provided in a cartridge, and the tubes of reagent sippers (1200) may be configured to be inserted into corresponding reagent reservoirs (1198) in the reagent cartridge so that liquid reagent may be drawn from each reagent reservoir (1198) into the sipper manifold assembly (1106).
- Shared line valve (1188) of sipper manifold assembly (1106) is coupled to central valve (1184) via shared reagent fluidic line (1196). Different reagents may flow through shared reagent fluidic line (1196) at different times. In some versions, when performing a flushing operation before changing between one reagent and another, pump manifold assembly (11 10) may draw wash buffer through shared reagent fluidic line (1196), central valve (1184), and flow cell cartridge assembly (1102).
- Bypass valve (1 190) of sipper manifold assembly (1 106) is coupled to central valve (1184) via dedicated reagent fluidic lines (1194, 1196).
- Each of the dedicated reagent fluidic lines (1 194, 196) may be associated with a single reagent.
- the fluids that may flow through dedicated reagent fluidic lines (1194, 1196) may 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.
- bypass valve (1 190) is also coupled to cache (1 176) of pump manifold assembly (11 10) via bypass fluidic line (1178).
- One or more reagent priming operations, hydration operations, mixing operations, and/or transfer operations may be performed using bypass fluidic line (1 178).
- the priming operations, the hydration operations, the mixing operations, and/or the transfer operations may be performed independent of flow cell cartridge assembly (1102).
- the operations using bypass fluidic line (1 178) may occur during, for example, incubation of one or more samples of interest within flow cell cartridge assembly (1 102).
- shared line valve (1188) may be utilized independently of bypass valve (1 190) such that bypass valve (1190) may utilize bypass fluidic line (1 178) and/or cache (1176) to perform one or more operations while shared line valve (1 188) and/or central valve (1184) simultaneously, substantially simultaneously, or offset synchronously perform other operations.
- Drive assembly (11 12) includes a pump drive assembly (1202) and a valve drive assembly (1204).
- Pump drive assembly (1202) may be adapted to interface with one or more pumps (1172) to pump fluid through flow cell (1128) and/or to load one or more samples of interest into flow cell (1128).
- Valve drive assembly (1204) may be adapted to interface with one or more of the valves (1170, 1174, 1184, 1188, 1190) to control the position of the corresponding valves (1170, 1174, 1184, 1188, 1190).
- FIG. 13 shows an example of a fluidic arrangement (2220) that may be incorporated into a variation of the system (1100) of FIG. 12.
- Fluidic arrangement (2220) of this example includes a pump manifold assembly (2222), which may operate similar to pump manifold assembly (1110) described above; a sample loading manifold assembly (2228), which may operate similar to sample loading manifold assembly (1108) described above; a flow cell interface (2240), which may operate similar to flow cell interface (1 126) described above; a sipper manifold assembly (2250), which may operate similar to sipper manifold assembly (1106) described above; and a waste reservoir (2270), which may operate similar to waste reservoir (1118) described above.
- a pump manifold assembly (2222), which may operate similar to pump manifold assembly (1110) described above
- a sample loading manifold assembly (2228) which may operate similar to sample loading manifold assembly (1108) described above
- a flow cell interface (2240) which may operate similar to flow cell interface (1 126) described above
- Pump manifold assembly (2222) is coupled with a port assembly (2258) of sipper manifold assembly (2250) via a fluidic line (2224), which may be similar to fluidic line (1178); and with sample loading manifold assembly (2228) via a fluidic line (2226).
- Sample loading manifold assembly (2228) is coupled with flow cell interface (2240) via fluidic line (2230), which may be similar to fluidic line (1180); and with port assembly (2258) via fluidic lines (2232, 234).
- Flow cell interface (2240) is coupled with sipper manifold assembly (2250) via fluidic line (2242), which may be similar to fluidic line (1185).
- Sipper manifold assembly (2250) includes a manifold body (2252) and a common output port (2256), which provides fluid communication via fluidic line (1185).
- a valve assembly (2254) controls fluid flow through common output port (2256) and may operate similar to central valve (1184).
- Port assembly (2258) of sipper manifold assembly (2250) is coupled with waste reservoir (2270) via fluidic line (2272), which may be similar to fluidic line (1 186).
- a plurality of reagent sippers (2260) extend from manifold body (2252) and are flu idically coupled with valve assembly (2254) via respective fluid channels (2262) in manifold body (2252).
- Reagent sippers (2260) may operate similar to reagent sippers (2200).
- Valve assembly (2254) is operable to selectively couple fluid channels (2262) with flow cell interface (2240) via common output port (2256) and fluidic line (2230), to thereby selectively provide various reagents to flow cell interface (2240).
- a flow cell e.g., like flow cell (1128) that is coupled with flow cell interface (2240) may selectively receive those different reagents based on control of valve assembly (2254).
- Port assembly (2258) may provide a fluidic interface between pump manifold assembly (2222) and sipper manifold assembly (2250), thereby allowing sipper manifold assembly (2250) to receive pressurized fluid from pump manifold assembly (2222).
- Port assembly (2258) may also provide a fluidic interface between sample loading manifold assembly (2228) and sipper manifold assembly (2250), thereby allowing sipper manifold assembly (2250) to receive sample fluid from sample loading manifold assembly (2228).
- port assembly (2258) may provide a fluidic interface between waste reservoir (2270) and sipper manifold assembly (2250), thereby allowing sipper manifold assembly (2250) to communicate waste fluid to waste reservoir (2270). Communication of fluids via port assembly (2258) may be regulated, at least in part, by valve assembly (2254).
- Example 1 An apparatus comprising: a system, comprising: a receptacle; a cartridge assembly receivable within the receptacle, the cartridge assembly comprising: a well; and an outlet port fluidly coupled to the well; and a flow cell assembly, comprising: a body; a flow cell supported by the body and comprising a channel; and a sensor assembly comprising a heater and a thermal sensor, wherein the outlet port is fluidly coupled to the flow cell, wherein a leak test is to be performed on the cartridge assembly and the flow cell assembly using the thermal sensor.
- Example 2 The apparatus of Example 1 , wherein the system comprises a controller and wherein the leak test comprisesi ) priming the cartridge assembly and the flow cell assembly, 2) accessing a measured temperature value from the thermal sensor using the controller, 3) determining a difference between the measured temperature value and a reference temperature value using the controller, and 4) identifying at least one of the cartridge assembly or the flow cell assembly having a leak if the difference is greater than a threshold using the controller.
- Example 3 The apparatus of Example 2, wherein the reference temperature is between about 40°C and about 60°C.
- Example 4 The apparatus of any one of Examples 2 - 3, wherein the reference temperature is about 55°C.
- Example 5 The apparatus of any one of the preceding Examples, wherein the leak test comprises the flow cell being heated to a threshold temperature using the heater after the flow cell is primed, reagent being flowed from the cartridge assembly into the flow cell using a pump, and a temperature value of the flow cell being measured using the thermal sensor.
- Example 6 The apparatus of any one of the preceding Examples, wherein the cartridge assembly comprises a pump and wherein the leak test comprises 1 ) a valve being actuated to a closed position, 2) a vacuum being generated in at least one of the cartridge assembly or the flow cell assembly using the pump, 3) the flow cell being heated to a threshold temperature using the heater, 4) the valve being actuated to an open position, 5) reagent being flowed from the cartridge assembly into the flow cell assembly and the channel of the flow cell using the pump, and 6) a plurality of temperature values of the flow cell being measured using the thermal sensor.
- the leak test comprises 1 ) a valve being actuated to a closed position, 2) a vacuum being generated in at least one of the cartridge assembly or the flow cell assembly using the pump, 3) the flow cell being heated to a threshold temperature using the heater, 4) the valve being actuated to an open position, 5) reagent being flowed from the cartridge assembly into the flow cell assembly and the channel of the flow cell using the pump, and 6)
- Example 7 The apparatus of any of the preceding Examples, wherein the system comprises a controller and wherein the leak test comprises accessing measured temperature values from the thermal sensor using the controller, determining a difference between the measured temperature values using the controller, and identifying at least one of the cartridge assembly or the flow cell assembly having a leak if the difference between the measured temperature values is greater than a threshold using the controller.
- Example 8 The apparatus of Example 7, wherein the threshold is between about 2 degrees Celsius and about 15 degrees Celsius.
- Example 9 The apparatus of any one of Examples 7 - 8, wherein the threshold is about 3 degrees Celsius.
- Example 10 The apparatus of anyone of the preceding Examples, wherein the cartridge assembly does not include a pressure sensor.
- Example 1 1 The apparatus of any one of the preceding Examples, wherein the flow cell assembly does not include a pressure sensor.
- Example 12 The apparatus of any one of the preceding Examples, wherein the system comprises a controller and wherein the controller is to generate an alert if the controller identifies at least one of the cartridge assembly or the flow cell assembly as having a leak.
- Example 13 The apparatus of any one of the preceding Examples, wherein the flow cell assembly carries an outlet gasket and wherein the cartridge assembly comprises a pump coupled to at least one of the outlet gasket of the flow cell assembly or between the well and the flow cell assembly.
- Example 14 The apparatus of Example 13, wherein the pump comprises a syringe pump.
- Example 15 The apparatus of any one of the preceding Examples, further comprising dried reagent contained within the well and wherein a pump is used to flow rehydrated dried reagent from the well to the flow cell.
- Example 16 The apparatus of any one of the preceding Examples, wherein the cartridge assembly comprises a valve coupled between the outlet port of the cartridge assembly and the well and wherein the system comprises a valve drive assembly to interface with the valve.
- Example 17 The apparatus of any one of any one of the preceding Examples, wherein the body of the flow cell assembly carries a flow cell outlet gasket and an outlet gasket and comprising a fluidic aperture and wherein the flow cell comprises a flow cell inlet and a flow cell outlet, the flow cell inlet fluidly coupled to the flow cell inlet gasket and the flow cell outlet fluidly coupled to the flow cell outlet gasket.
- Example 18 The apparatus of Example 17, wherein the flow cell assembly comprises a first laminate coupled to the body of the flow cell assembly and forming a first fluidic channel between the flow cell outlet gasket and the fluidic aperture and a second laminate coupled to the body of the flow cell assembly and forming a second fluidic channel between the fluidic aperture and the outlet gasket.
- Example 19 The apparatus of Example 18, wherein the body comprises a first groove and a second groove, the first laminate covering the first groove to form the first fluidic channel and the second laminate covering the second groove to form the second fluidic channel.
- Example 20 The apparatus of any one of the preceding Examples, wherein the flow cell assembly is coupled to the cartridge assembly by a coupling.
- Example 21 The apparatus of Example 20, wherein the coupling comprises a snap fit connection.
- Example 22 The apparatus of any one of the preceding Examples, wherein the sensor assembly comprises a die.
- Example 23 The apparatus of Example 22, wherein the die comprises the thermal sensor.
- Example 24 The apparatus of any one of Examples 22 - 23, wherein the die comprises a complementary metal-oxide semiconductor.
- Example 25 The apparatus of any one of Examples 22 - 24, wherein the sensor assembly comprises a printed circuit board and wherein the heater is positioned between the die and the printed circuit board.
- Example 26 The apparatus of any one of the preceding Examples, further comprising a liquid reservoir receivable within the receptacle and having a body comprising a storage chamber, and a fluidic port fluidly coupled to the storage chamber, wherein the cartridge assembly comprises: a fluidic interface couplable to the fluidic port; and a channel fluidly coupled between the fluidic interface and the well.
- Example 27 The apparatus of Example 26, wherein the system comprises a pneumatic interface and the body of the liquid reservoir comprises a pneumatic port fluidly couplable to the storage chamber.
- Example 28 The apparatus of any one of the preceding Examples, wherein the system comprises a dry instrument.
- Example 29 An apparatus, comprising: a cartridge assembly, comprising: a well; and an outlet port fluidly coupled to the well; a flow cell assembly, comprising: a body; a flow cell supported by the body and comprising a channel; and a sensor assembly comprising a heater and a thermal sensor, wherein the outlet port is fluidly coupled to the flow cell, wherein a leak test is to be performed on the cartridge assembly and the flow cell assembly using the thermal sensor.
- Example 30 The apparatus of Example 29, wherein the cartridge assembly comprises a valve coupled between the outlet port of the cartridge assembly and the well.
- Example 31 The apparatus of any one of Examples 29 - 30, wherein the cartridge assembly comprises a pump coupled to at least one of the outlet gasket of the flow cell assembly or between the well and the flow cell assembly.
- Example 32 The apparatus of any one of Examples 29 - 31 , wherein the flow cell assembly comprises a second flow cell supported by the body.
- Example 33 The apparatus of Example 32, wherein the flow cell and the second flow cell are fluidly coupled in series.
- Example 34 The apparatus of any one of Examples 32 - 33, wherein the flow cell outlet of the flow cell is fluidly coupled to the flow cell outlet gasket via the second flow cell.
- Example 35 The apparatus of any one of Examples 29 - 34, further comprising a second flow cell assembly comprising a second flow cell different than the flow cell, the second flow cell assembly couplable to the cartridge assembly in place of the flow cell assembly.
- Example 36 The apparatus of Example 35, further comprising a third flow cell assembly comprising a third flow cell and a fourth flow cell, the third flow cell assembly couplable to the cartridge assembly in place of the flow cell assembly and in place of the second flow cell assembly.
- Example 37 An apparatus, comprising: a cartridge assembly; and a first flow cell assembly including a first flow cell and a first sensor assembly comprising a heater and a thermal sensor; and a second flow cell assembly including a second flow cell different than the first flow cell, the second flow cell assembly comprises a second sensor assembly comprising a heater and a thermal sensor, wherein the first flow cell assembly and the second flow cell assembly are interchangeably mechanically and fluidly couplable with the cartridge assembly, wherein a leak test is to be performed on the cartridge assembly and the first flow cell assembly when coupled using the thermal sensor of the first sensor assembly, and wherein a leak test is to be performed on the cartridge assembly and the second flow cell assembly when coupled using the thermal sensor of the second sensor assembly.
- Example 38 An apparatus comprising: a system, comprising: a receptacle; a liquid reservoir receivable within the receptacle and having: a body comprising a storage chamber, and a fluidic port fluidly coupled to the storage chamber; a cartridge assembly, comprising: a fluidic interface couplable to the fluidic port; a well; a channel fluidly coupled between the fluidic interface and the well; and an outlet port fluidly coupled to the well; and a flow cell assembly, comprising: a body carrying a flow cell inlet gasket and an outlet gasket; a flow cell supported by the body and comprising a channel; and a sensor assembly comprising a heater and a thermal sensor, wherein the outlet port is fluidly coupled to the flow cell inlet gasket, wherein a leak test is to be performed on the cartridge assembly and the flow cell assembly using the thermal sensor.
- a system comprising: a receptacle; a liquid reservoir receivable within the receptacle and having: a body
- Example 39 A method, comprising: heating a flow cell to a threshold temperature using a heater of a flow cell assembly, the flow cell assembly coupled to a cartridge assembly and positioned in a receptacle of a system; flowing reagent into the flow cell; accessing, using a controller, a measured temperature value from a thermal sensor of the flow cell assembly; and determining, using the controller, a presence of a leak in at least one of the cartridge assembly or the flow cell assembly based on the measured temperature value.
- Example 40 The method of Example 39, further comprising priming the cartridge assembly and the flow cell assembly with reagent prior to heating the flow cell to the threshold temperature.
- Example 41 The method of any one of Examples 39 - 40, wherein determining the presence of the leak comprises determining, using the controller, a difference between the measured temperature value and a reference temperature value and identifying, using the controller, at least one of the cartridge assembly or the flow cell assembly having the leak if the difference is greater than a threshold.
- Example 42 The method of any one of Examples 39 - 41 , wherein determining the presence of the leak comprises actuating a valve of the cartridge assembly to a closed position, generating a vacuum in at least one of the cartridge assembly or the flow cell assembly using the pump, heating the flow cell to a threshold temperature using a heater of the flow cell assembly, actuating the valve to an open position, flowing the reagent from the cartridge assembly to the flow cell using the pump, and determining a plurality of temperature values of the flow cell using the thermal sensor.
- Example 43 The method any one of Examples 39 - 42, wherein determining, using the controller, the presence of the leak comprises accessing measured temperature values from the thermal sensor, determining, using the controller, a difference between the measured temperature values, and identifying, using the controller, at least one of the cartridge assembly or the flow cell assembly having the leak if the difference between the measured temperature values is greater than a threshold.
- Example 44 The method of any one of Examples 39 - 43, further comprising generating an alert if the controller determines the presence of the leak in at least one of the cartridge assembly or the flow cell assembly.
- Example 45 The method of any one of Examples 39 - 44, further comprising flowing reagent under positive pressure into the cartridge assembly comprising dry reagent to rehydrate the dry reagent, the cartridge assembly comprising a well and an outlet port fluidly coupled to the well, wherein flowing reagent from the cartridge assembly into the flow cell comprises flowing the rehydrated reagent into a flow cell inlet gasket of the flow cell assembly using a pump, the flow cell assembly comprising a body carrying the flow cell inlet gasket and a flow cell supported by the body, the flow cell inlet gasket fluidly coupled to the outlet port and the flow cell.
- Example 46 The method of Example 45, wherein flowing the reagent under positive pressure comprises pressurizing a storage chamber of a liquid reservoir comprising the reagent and flowing the reagent from the storage chamber to the cartridge assembly.
- Example 47 The method of any one of Examples 38 - 46, wherein flowing reagent into the flow cell comprises flowing reagent from the cartridge assembly.
- Example 48 The method of any one of Examples 38 - 47, wherein flowing reagent into the flow cell comprises flowing reagent from a well of the cartridge assembly.
- Example 49 The method of any one of Examples 38 - 48, wherein flowing reagent into the flow cell comprises flowing reagent into the flow cell using a pump of the cartridge assembly.
- Example 50 The method of any one of Examples 38 - 48, wherein flowing reagent into the flow cell comprises flowing reagent into the flow cell under positive pressure.
- Example 51 An apparatus comprising: a system, comprising: a receptacle; a cartridge assembly receivable within the receptacle, the cartridge assembly comprising: a well comprising reagent; and an outlet port fluidly coupled to the well; and a flow cell assembly, comprising: a body carrying a flow cell inlet gasket; a flow cell supported by the body and comprising a channel; and a sensor assembly comprising a thermal sensor, wherein the outlet port is fluidly coupled to the flow cell inlet gasket, wherein the reagent is preheated prior to entering the channel of the flow cell using a heater of at least one of the system or the cartridge assembly, wherein a leak test is to be performed on the cartridge assembly and the flow cell assembly using the thermal sensor.
- Example 52 The apparatus of Example 51 , wherein the system comprises the heater.
- Example 53 The apparatus of Example 51 , wherein the cartridge assembly comprises the heater.
- Example 54 The apparatus of any one of Examples 51 - 53, wherein the leak test comprises not heating the flow cell.
- Example 55 The apparatus of any one of Examples 51 - 54, wherein the system comprises a controller and wherein the leak test comprises 1 ) flowing the preheated reagent into the flow cell using a pump, 2) accessing a measured temperature value from the thermal sensor using the controller, 3) determining a difference between the measured temperature value and a reference temperature value using the controller, and 4) identifying at least one of the cartridge assembly or the flow cell assembly having a leak if the difference is greater than a threshold using the controller.
- Example 56 A method, comprising: preheating reagent to a threshold temperature using a heater; flowing the pre-heated reagent into a flow cell, the flow cell assembly coupled to a cartridge assembly and positioned in a receptacle of a system; accessing, using a controller, a measured temperature value from a thermal sensor of the flow cell assembly; and determining, using the controller, a presence of a leak in at least one of the cartridge assembly or the flow cell assembly based on the measured temperature value.
- Example 57 The method of Example 56, wherein flowing the preheated reagent into the flow cell comprises flowing the preheated reagent from a well of the cartridge assembly.
- Example 58 The method of Example 57, wherein flowing the preheated reagent into the flow cell comprises flowing the preheated reagent into the flow cell comprises using a pump of the cartridge assembly.
- Example 59 The method of any one of Examples 56 - 57, wherein flowing the preheated reagent into the flow cell comprises flowing the preheated reagent into the flow cell under positive pressure.
- Example 60 The apparatus of any one of Examples 1 - 28, and 38, wherein the system does not include a pressure sensor.
- Example 61 The apparatus of any one of Examples 1 - 28, wherein the leak test comprises the flow cell being heated to a threshold temperature using the heater after the flow cell is primed, reagent being flowed from the cartridge assembly into the flow cell inlet gasket and the flow cell, and a temperature value of the flow cell being measured using the thermal sensor.
- Example 62 The apparatus of Example 60, wherein the reagent is to be flowed from the cartridge assembly into the flow cell inlet gasket and the flow cell under positive pressure.
- Example 63 The apparatus of Example 60, wherein the cartridge assembly comprises a pump, and wherein the reagent is to be flowed from the cartridge assembly into the flow cell inlet gasket and the flow cell using the pump of the cartridge assembly.
- cartridges and reservoirs are described herein with regard to reagent cartridges and reagent reservoirs, these cartridges or reservoirs may also be used to house other liquids, including without limitation buffers, samples, and washes, either separate from or in combination with reagents or other liquids.
- a cartridge may have a first chamber housing a reagent, a second chamber housing a buffer, and a third chamber housing a wash.
- cartridges and reservoirs described herein may include one or more additional chambers that may be used, for example, as waste chambers on the cartridge that may or may not include corresponding sipper chambers.
- connection is broadly defined herein to encompass a variety of divergent arrangements and assembly techniques. These arrangements and techniques include, but are not limited to (1 ) the direct joining of one component and another component with no intervening components therebetween (/.e., the components are in direct physical contact); and (2) the joining of one component and another component with one or more components therebetween, provided that the one component being “connected to” or “contacting” or “coupled to” the other component is somehow in operative communication (e.g., electrically, fluidly, physically, optically, etc.) with the other component (notwithstanding the presence of one or more additional components therebetween).
- operative communication e.g., electrically, fluidly, physically, optically, etc.
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Abstract
Flow cell assemblies and related systems and methods are disclosed. In accordance with an implementation, an apparatus includes: a system, including: a receptacle; a cartridge assembly receivable within the receptacle. The cartridge assembly includes a well; and an outlet port fluidly coupled to the well. The apparatus includes a flow cell assembly, including: a body; a flow cell supported by the body and including a channel; and a sensor assembly comprising a heater and a thermal sensor. The outlet port is fluidly coupled to the flow cell. A leak test is to be performed on the cartridge assembly and the flow cell assembly using the thermal sensor.
Description
FLOW CELL ASSEMBLIES AND RELATED SYSTEMS AND METHODS
RELATED APPLICATION SECTION
[0001] This application claims the benefit of and priority to U.S. Provisional Patent Application Number 63/650,127, filed May 21 , 2024, the content of which is incorporated by reference herein in its entirety and for all purposes.
BACKGROUND
[0002] Sequencing platforms may use flow cell assemblies when performing different processes.
SUMMARY
[0003] Advantages over the prior art and benefits as described later in this disclosure can be achieved through the provision of flow cell assemblies and related systems and methods. Various implementations of the apparatus and methods are described below, and the apparatus and methods, including and excluding the additional implementations enumerated below, in any combination (provided these combinations are not inconsistent), may overcome these shortcomings and achieve the benefits described herein.
[0004] In accordance with a first implementation, an apparatus comprising: a system, comprising: a receptacle; a cartridge assembly receivable within the receptacle, the cartridge assembly comprising: a well; and an outlet port fluidly coupled to the well. The apparatus comprising a flow cell assembly, comprising: a body carrying a flow cell inlet gasket; a flow cell supported by the body and comprising a channel; and a sensor assembly comprising a heater and a thermal sensor. The outlet port is fluidly coupled to the flow cell inlet gasket. A leak test is to be performed on the cartridge assembly and the flow cell assembly using the thermal sensor.
[0005] In accordance with a second implementation, an apparatus, comprising: a cartridge assembly, comprising: a well; and an outlet port fluidly coupled to the well. The apparatus comprising a flow cell assembly, comprising: a body carrying a flow cell inlet gasket and an outlet gasket; a flow cell supported by the body and comprising a channel; and a sensor assembly comprising a heater and a thermal sensor. The outlet port is fluidly coupled to the flow cell inlet gasket. A leak test is to be performed on the cartridge assembly and the flow cell assembly using the thermal sensor.
[0006] In accordance with a third implementation, an apparatus, comprising: a cartridge assembly, comprising: a well; and an outlet port fluidly coupled to the well. The apparatus comprising a flow cell assembly, comprising: a body carrying a flow cell inlet gasket and an outlet gasket; a flow cell supported by the body and comprising a channel; and a sensor assembly comprising a heater and a thermal sensor. The outlet port is fluidly coupled to the flow cell inlet gasket. A leak test is to be performed on the cartridge assembly and the flow cell assembly using the thermal sensor.
[0007] In accordance with a fourth implementation, an apparatus, comprising: a cartridge assembly; a first flow cell assembly including a first flow cell and a first sensor assembly comprising a heater and a thermal sensor; and a second flow cell assembly including a second flow cell different than the first flow cell. The second flow cell assembly comprises a second sensor assembly comprising a heater and a thermal sensor. The first flow cell assembly and the second flow cell assembly are interchangeably mechanically and fluidly couplable with the cartridge assembly. A leak test is to be performed on the cartridge assembly and the first flow cell assembly when coupled using the thermal sensor of the first sensor assembly. A leak test is to be performed on the cartridge assembly and the second flow cell assembly when coupled using the thermal sensor of the second sensor assembly.
[0008] In accordance with a fifth implementation, an apparatus comprising: a system, comprising: a receptacle; a liquid reservoir receivable within the receptacle and having: a body comprising a storage chamber, and a fluidic port fluidly coupled to the storage chamber. The apparatus comprising a cartridge assembly, comprising: a fluidic interface couplable to the fluidic port; a well; a channel fluidly coupled between the fluidic interface and the well; and an outlet port fluidly coupled to the well. The apparatus comprising a flow cell assembly, comprising: a body carrying a flow cell inlet gasket and an outlet gasket; a flow cell supported by the body and comprising a channel; and a sensor assembly comprising a heater and a thermal sensor. The outlet port is fluidly coupled to the flow cell inlet gasket. A leak test is to be performed on the cartridge assembly and the flow cell assembly using the thermal sensor.
[0009] In accordance with a sixth implementation, a method, comprising: heating a flow cell to a threshold temperature using a heater of a flow cell assembly, the flow cell assembly coupled to a cartridge assembly and positioned in a receptacle of a system; flowing reagent from the cartridge assembly into the flow cell using a pump of the cartridge assembly; accessing, using a controller, a measured temperature value from a thermal sensor of the flow cell assembly; and
determining, using the controller, a presence of a leak in at least one of the cartridge assembly or the flow cell assembly based on the measured temperature value.
[0010] In accordance with a seventh implementation, an apparatus comprising: a system, comprising: a receptacle. The apparatus comprising a cartridge assembly receivable within the receptacle, the cartridge assembly comprising: a well comprising reagent; and an outlet port fluidly coupled to the well; and a flow cell assembly, comprising: a body carrying a flow cell inlet gasket; a flow cell supported by the body and comprising a channel; and a sensor assembly comprising a thermal sensor. The outlet port is fluidly coupled to the flow cell inlet gasket. The reagent is preheated prior to entering the channel of the flow cell using a heater of at least one of the system or the cartridge assembly. A leak test is to be performed on the cartridge assembly and the flow cell assembly using the thermal sensor.
[0011] In accordance with a eighth implementation, a method, comprising: preheating reagent to a threshold temperature using a heater; flowing the pre-heated reagent from a cartridge assembly into a flow cell using a pump of the cartridge assembly, the flow cell assembly coupled to the cartridge assembly and positioned in a receptacle of a system; accessing, using a controller, a measured temperature value from a thermal sensor of the flow cell assembly; and determining, using the controller, a presence of a leak in at least one of the cartridge assembly or the flow cell assembly based on the measured temperature value.
[0012] In accordance with a nineth implementation, an apparatus comprising: a system, comprising: a receptacle. The apparatus comprises a cartridge assembly receivable within the receptacle, the cartridge assembly comprising: a well; and an outlet port fluidly coupled to the well. The apparatus comprising a flow cell assembly, comprising: a body; a flow cell supported by the body and comprising a channel; and a sensor assembly comprising a heater and a thermal sensor, wherein the outlet port is fluidly coupled to the flow cell, wherein a leak test is to be performed on the cartridge assembly and the flow cell assembly using the thermal sensor.
[0013] In accordance with a tenth implementation, an apparatus, comprising: a cartridge assembly, comprising: a well; and an outlet port fluidly coupled to the well; a flow cell assembly, comprising: a body; a flow cell supported by the body and comprising a channel; and a sensor assembly comprising a heater and a thermal sensor. The outlet port is fluidly coupled to the flow cell. A leak test is to be performed on the cartridge assembly and the flow cell assembly using the thermal sensor.
[0014] In accordance with an eleventh implementation, a method, comprising: heating a flow cell to a threshold temperature using a heater of a flow cell assembly, the flow cell assembly coupled to a cartridge assembly and positioned in a receptacle of a system; flowing reagent into the flow cell; accessing, using a controller, a measured temperature value from a thermal sensor of the flow cell assembly; and determining, using the controller, a presence of a leak in at least one of the cartridge assembly or the flow cell assembly based on the measured temperature value.
[0015] In accordance with an twelfth implementation, a method, comprising: preheating reagent to a threshold temperature using a heater; flowing the pre-heated reagent into a flow cell, the flow cell assembly coupled to a cartridge assembly and positioned in a receptacle of a system; accessing, using a controller, a measured temperature value from a thermal sensor of the flow cell assembly; and determining, using the controller, a presence of a leak in at least one of the cartridge assembly or the flow cell assembly based on the measured temperature value.
[0016] In further accordance with the foregoing first, second, third, fourth, fifth, sixth, seventh, eighth, nineth, tenth, eleventh, and/or twelfth implementations, an apparatus and/or method may further comprise or include any one or more of the following:
[0017] In an implementation, the system comprises a controller and wherein the leak test comprises by 1) priming the cartridge assembly and the flow cell assembly, 2) accessing a measured temperature value from the thermal sensor using the controller, 3) determining a difference between the measured temperature value and a reference temperature value using the controller, and 4) identifying at least one of the cartridge assembly or the flow cell assembly having a leak if the difference is greater than a threshold using the controller.
[0018] In another implementation, the reference temperature is between about 40°C and about 60°C.
[0019] In another implementation, the reference temperature is about 55°C.
[0020] In another implementation, the leak test comprises the flow cell being heated to a threshold temperature using the heater after the flow cell is primed, reagent being flowed from the cartridge assembly into the flow cell inlet gasket and the flow cell using a pump, and a temperature value of the flow cell being measured using the thermal sensor.
[0021] In another implementation, the cartridge assembly comprises a pump and wherein the leak test comprises 1 ) a valve being actuated to a closed position, 2) a vacuum being generated in at least one of the cartridge assembly or the flow cell assembly using the pump, 3) the flow
cell being heated to a threshold temperature using the heater, 4) the valve being actuated to an open position, 5) reagent being flowed from the cartridge assembly into the flow cell inlet gasket of the flow cell assembly and the channel of the flow cell using the pump, and 6) a plurality of temperature values of the flow cell being measured using the thermal sensor.
[0022] In another implementation, the system comprises a controller and wherein the leak test comprises accessing measured temperature values from the thermal sensor using the controller, determining a difference between the measured temperature values using the controller, and identifying at least one of the cartridge assembly or the flow cell assembly having a leak if the difference between the measured temperature values is greater than a threshold using the controller.
[0023] In another implementation, the threshold is between about 2 degrees Celsius and about 15 degrees Celsius.
[0024] In another implementation, the threshold comprises about 3 degrees Celsius.
[0025] In another implementation, the cartridge assembly does not include a pressure sensor.
[0026] In another implementation, the flow cell assembly does not include a pressure sensor.
[0027] In another implementation, the system comprises a controller and wherein the controller is to generate an alert if the controller identifies at least one of the cartridge assembly or the flow cell assembly as having a leak.
[0028] In another implementation, the flow cell assembly carries an outlet gasket and wherein the cartridge assembly comprises a pump coupled to at least one of the outlet gasket of the flow cell assembly or between the well and the flow cell assembly.
[0029] In another implementation, the pump comprises a syringe pump.
[0030] In another implementation, further comprising dried reagent contained within the well and wherein a pump is used to flow rehydrated dried reagent from the well to the flow cell.
[0031] In another implementation, the cartridge assembly comprises a valve coupled between the outlet port of the cartridge assembly and the well and wherein the system comprises a valve drive assembly to interface with the valve.
[0032] In another implementation, the body of the flow cell assembly carries a flow cell outlet gasket and an outlet gasket and comprising a fluidic aperture and wherein the flow cell comprises a flow cell inlet and a flow cell outlet, the flow cell inlet fluidly coupled to the flow cell inlet gasket and the flow cell outlet fluidly coupled to the flow cell outlet gasket.
[0033] In another implementation, the flow cell assembly comprises a first laminate coupled to the body of the flow cell assembly and forming a first fluidic channel between the flow cell outlet gasket and the fluidic aperture and a second laminate coupled to the body of the flow cell assembly and forming a second fluidic channel between the fluidic aperture and the outlet gasket.
[0034] In another implementation, the body comprises a first groove and a second groove, the first laminate covering the first groove to form the first fluidic channel and the second laminate covering the second groove to form the second fluidic channel.
[0035] In another implementation, the flow cell assembly is coupled to the cartridge assembly by a coupling.
[0036] In another implementation, the coupling comprises a snap fit connection.
[0037] In another implementation, the sensor assembly comprises a die.
[0038] In another implementation, the die comprises the thermal sensor.
[0039] In another implementation, the die comprises a complementary metal-oxide semiconductor.
[0040] In another implementation, the sensor assembly comprises a printed circuit board and wherein the heater is positioned between die and the printed circuit board.
[0041] In another implementation, further comprising a liquid reservoir receivable within the receptacle and having a body comprising a storage chamber, and a fluidic port fluidly coupled to the storage chamber, wherein the cartridge assembly comprises: a fluidic interface couplable to the fluidic port; and a channel fluidly coupled between the fluidic interface and the well.
[0042] In another implementation, the system comprises a pneumatic interface and the body of the liquid reservoir comprises a pneumatic port fluidly couplable to the storage chamber.
[0043] In another implementation, the system comprises a dry instrument.
[0044] In another implementation, the cartridge assembly comprises a valve coupled between the outlet port of the cartridge assembly and the well.
[0045] In another implementation, the cartridge assembly comprises a pump coupled to at least one of the outlet gasket of the flow cell assembly or between the well and the flow cell assembly.
[0046] In another implementation, the flow cell assembly comprises a second flow cell supported by the body.
[0047] In another implementation, the flow cell and the second flow cell are fluidly coupled in series.
[0048] In another implementation, the flow cell outlet of the flow cell is fluidly coupled to the flow cell outlet gasket via the second flow cell.
[0049] In another implementation, further comprising a second flow cell assembly comprising a second flow cell different than the flow cell, the second flow cell assembly couplable to the cartridge assembly in place of the flow cell assembly.
[0050] In another implementation, further comprising a third flow cell assembly comprising a third flow cell and a fourth flow cell, the third flow cell assembly couplable to the cartridge assembly in place of the flow cell assembly and in place of the second flow cell assembly.
[0051] In another implementation, further comprising priming the cartridge assembly and the flow cell assembly with reagent prior to heating the flow cell to the threshold temperature.
[0052] In another implementation, determining the presence of the leak comprises determining, using the controller, a difference between the measured temperature value and a reference temperature value and identifying, using the controller, at least one of the cartridge assembly or the flow cell assembly having the leak if the difference is greater than a threshold.
[0053] In another implementation, determining the presence of the leak comprises actuating a valve of the cartridge assembly to a closed position, generating a vacuum in at least one of the cartridge assembly or the flow cell assembly using the pump, heating the flow cell to a threshold temperature using a heater of the flow cell assembly, actuating the valve to an open position, flowing the reagent from the cartridge assembly to the flow cell using the pump, and determining a plurality of temperature values of the flow cell using the thermal sensor.
[0054] In another implementation, determining, using the controller, the presence of the leak comprises accessing measured temperature values from the thermal sensor, determining, using the controller, a difference between the measured temperature values, and identifying, using the controller, at least one of the cartridge assembly or the flow cell assembly having the leak if the difference between the measured temperature values is greater than a threshold.
[0055] In another implementation, further comprising generating an alert if the controller determines the presence of the leak in at least one of the cartridge assembly or the flow cell assembly.
[0056] In another implementation, further comprising flowing reagent under positive pressure into the cartridge assembly, the cartridge assembly comprising the well and an outlet port fluidly coupled to the well, wherein flowing reagent from the cartridge assembly into the flow cell comprises flowing the rehydrated reagent into a flow cell inlet gasket of the flow cell assembly using a pump, the flow cell assembly comprising a body carrying the flow cell inlet gasket and a flow cell supported by the body, the flow cell inlet gasket fluidly coupled to the outlet port and the flow cell.
[0057] In another implementation, flowing the reagent under positive pressure comprises pressurizing a storage chamber of a liquid reservoir comprising the reagent and flowing the reagent from the storage chamber to the cartridge assembly.
[0058] In another implementation, the system comprises the heater.
[0059] In another implementation, the cartridge assembly comprises the heater.
[0060] In another implementation, the leak test comprises not heating the flow cell.
[0061] In another implementation, the system comprises a controller and wherein the leak test comprises 1 ) flowing the preheated reagent into the flow cell using a pump, 2) accessing a measured temperature value from the thermal sensor using the controller, 3) determining a difference between the measured temperature value and a reference temperature value using the controller, and 4) identifying at least one of the cartridge assembly or the flow cell assembly having a leak if the difference is greater than a threshold using the controller.
[0062] In another implementation, the leak test comprises the flow cell being heated to a threshold temperature using the heater after the flow cell is primed, reagent being flowed from the cartridge assembly into the flow cell using a pump, and a temperature value of the flow cell being measured using the thermal sensor.
[0063] In another implementation, the cartridge assembly comprises a pump and wherein the leak test comprises 1 ) a valve being actuated to a closed position, 2) a vacuum being generated in at least one of the cartridge assembly or the flow cell assembly using the pump, 3) the flow cell being heated to a threshold temperature using the heater, 4) the valve being actuated to an open position, 5) reagent being flowed from the cartridge assembly into the flow cell assembly
and the channel of the flow cell using the pump, and 6) a plurality of temperature values of the flow cell being measured using the thermal sensor.
[0064] In another implementation, the threshold is about 3 degrees Celsius.
[0065] In another implementation, the method includes flowing reagent under positive pressure into the cartridge assembly comprising dry reagent to rehydrate the dry reagent. The cartridge assembly comprising a well and an outlet port fluidly coupled to the well. Flowing reagent from the cartridge assembly into the flow cell comprises flowing the rehydrated reagent into a flow cell inlet gasket of the flow cell assembly using a pump, the flow cell assembly comprising a body carrying the flow cell inlet gasket and a flow cell supported by the body, the flow cell inlet gasket fluidly coupled to the outlet port and the flow cell.
[0066] In another implementation, flowing the reagent under positive pressure comprises pressurizing a storage chamber of a liquid reservoir comprising the reagent and flowing the reagent from the storage chamber to the cartridge assembly.
[0067] In another implementation, flowing reagent into the flow cell comprises flowing reagent from the cartridge assembly.
[0068] In another implementation, flowing reagent into the flow cell comprises flowing reagent from a well of the cartridge assembly.
[0069] In another implementation, flowing reagent into the flow cell comprises flowing reagent into the flow cell using a pump of the cartridge assembly.
[0070] In another implementation, flowing reagent into the flow cell comprises flowing reagent into the flow cell under positive pressure.
[0071] In another implementation, flowing the preheated reagent into the flow cell comprises flowing the preheated reagent from a well of the cartridge assembly.
[0072] In another implementation, flowing the preheated reagent into the flow cell comprises flowing the preheated reagent into the flow cell comprises using a pump of the cartridge assembly.
[0073] In another implementation, flowing the preheated reagent into the flow cell comprises flowing the preheated reagent into the flow cell under positive pressure.
[0074] In another implementation, the system does not include a pressure sensor.
[0075] In another implementation, the leak test comprises the flow cell being heated to a threshold temperature using the heater after the flow cell is primed, reagent being flowed from the cartridge assembly into the flow cell inlet gasket and the flow cell, and a temperature value of the flow cell being measured using the thermal sensor.
[0076] In another implementation, the reagent is to be flowed from the cartridge assembly into the flow cell inlet gasket and the flow cell under positive pressure.
[0077] In another implementation, the cartridge assembly comprises a pump, and wherein the reagent is to be flowed from the cartridge assembly into the flow cell inlet gasket and the flow cell using the pump of the cartridge assembly.
[0078] 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 and/or may be combined to achieve the particular benefits of a particular aspect. 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.
BRIEF DESCRIPTION OF THE DRAWINGS
[0079] FIG. 1 illustrates a schematic diagram of an implementation of a system in accordance with the teachings of this disclosure.
[0080] FIG. 2 is an isometric view of an example implementation of a cartridge assembly and a flow cell assembly that can be used to implement the cartridge assembly and the flow cell assembly of FIG. 1 .
[0081] FIG. 3 is an isometric partially expanded view of the flow cell assembly of FIG. 2.
[0082] FIG. 4 is an isometric view of the first flow cell and the second flow cell of the flow cell assembly of FIG. 2.
[0083] FIG. 5 is an expanded isometric view of an example implementation of another flow cell assembly having a body that can be used to implement the flow cell assembly of FIG. 1 .
[0084] FIG. 6 is an isometric view of the flow cell of the flow cell assembly of FIG. 5.
[0085] FIG. 7 is an expanded isometric view of an example implementation of a flow cell assembly having a body that can be used to implement the flow cell assembly of FIG. 1 .
[0086] FIG. 8 is an isometric view of the flow cell of the flow cell assembly of FIG. 7.
[0087] FIG. 9 illustrates a flow chart for a method of determining the presence of a leak using the system of FIG. 1 , the cartridge assembly of FIGS. 1 - 2, the flow cell assemblies and sensor assemblies of FIGS. 1 - 8 or any of the other implementations disclosed herein.
[0088] FIG. 10 is a graph showing results using the disclosed implementations including an x- axis relating to time, a first y-axis relating to pressure and a second y-axis relating to temperature.
[0089] FIG. 1 1 is a graph showing results using the disclosed implementations including an x- axis relating to time and a y-axis relating to temperature.
[0090] FIG. 12 illustrates a schematic diagram of an example of a system that may be used to perform an analysis on one or more samples of interest.
[0091] FIG. 13 shows an example of a fluidic arrangement that may be incorporated into a variation of the system of FIG. 12.
DETAILED DESCRIPTION
[0092] 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.
[0093] FIG. 1 illustrates a schematic diagram of an implementation of a system 100 in accordance with the teachings of this disclosure. The system 100 be referred to as a dry instrument. The phrase dry instrument means that liquid such as reagent may not flow through the instrument itself. The system 100 may be a dry instrument if liquid flows from a consumable to waste, for example.
[0094] The 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 are linearized to form a single stranded
DNA (sstDNA). In the implementation shown, the system 100 receives a liquid reservoir 102, a cartridge assembly 104, and a flow cell assembly 106 and includes, in part, a pneumatic interface 108, a receptacle 110, a regulator 112, a gas source 114, a drive assembly 115, an actuator 116, a controller 117, an imaging system 1 18, and a waste reservoir 1 19. The liquid reservoir 102 and/or the cartridge assembly 104 may be referred to as a consumable, a reagent reservoir, or a reagent assembly. The waste reservoir 1 19 may alternatively be carried by the liquid reservoir 102 as an example. The system 100 may alternatively omit the pneumatic interface 108, the regulator 112, the gas source 114, and/or the actuator 117. The liquid reservoir 102 may be omitted in such implementations, for example, where the cartridge assembly 104 includes liquid reagent. The controller 1 17 is electrically and/or communicatively coupled to the regulator 112, the drive assembly 1 15, the actuator 116, and the imaging system 1 18 and causes the regulator 112, the drive assembly 1 15, the actuator 116, and/or the imaging system 1 18 to perform various functions as disclosed herein.
[0095] The cartridge assembly 104 is received within the receptacle 110 in the implementation shown and the cartridge assembly 104 includes a well 120 and an outlet port 122 fluidly coupled to the well 120. The flow cell assembly 106 includes a body 124, a flow cell 126, and a sensor assembly 128. The body 124 of the flow cell assembly 106 carries a flow cell inlet gasket 130 and the outlet port 122 is fluidly coupled to the flow cell inlet gasket 130. The flow cell 126 is supported by the body 124 of the flow cell assembly 106 and the flow cell 126 includes a channel 132. The sensor assembly 128 is shown including a heater 134 and a thermal sensor 136. The thermal sensor 136 may be referred to as a temperature sensor. The heater 134 may be a resistive heater, a microheater, and/or a flexible heater. The thermal sensor 136 may be implemented by a semi-conductor based sensor. The thermal sensor 136 may alternatively be implemented in different ways, however. A leak test is performed on the cartridge assembly 104 and the flow cell assembly 106 using the thermal sensor 136 in operation.
[0096] The leak test may include priming the cartridge assembly 104 and the flow cell assembly 106 and accessing a measured temperature value from the thermal sensor 136 using the controller 117. The controller 1 17 may determine a difference between the measured temperature value and a reference temperature value and at least one of the cartridge assembly 104 or the flow cell assembly 106 having a leak if the difference is greater than a threshold using the controller 1 17, for example. If air flows through the flow cell 126 because of the presence of a leak that allows air to be drawn into the consumable, the temperature of the flow cell 126 may not drop as much as compared to if no leak were present. The leak test that
compares the measured temperature to a reference temperature value may be used for identifying larger leaks in the cartridge assembly 104 and/or the flow cell assembly 106. The reference temperature may be between about 40°C and about 60°C in some examples. The reference temperature may be about 55°C in some examples.
[0097] The leak test may also include the heater 134 heating the flow cell 126 to a threshold temperature after the flow cell 126 is primed and a pump 138 flowing reagent 139 from the well 120 and/or the cartridge assembly 104 into the flow cell inlet gasket 130 of the flow cell assembly 106. The pump 138 of the cartridge assembly 104 may alternatively not be used. The reagent 139 may be flowed into the flow cell assembly 106 under positive pressure and/or using an alternative pump such as a pump of the system 100. The reagent 139 used for the leak tests may be buffer reagent. The reagent 139 may flow through a valve 140 and directly to the flow cell assembly 106 in some implementations. The reagent 139 may not flow through the well 120 in such implementations. The reagent 139 may alternatively flow from the well 120 or another source. The thermal sensor 136 may obtain a temperature value of the flow cell 126 before, while, and/or after the reagent 139 flows into the channel 132 of the flow cell 126.
[0098] The leak test may additionally or alternatively include the valve 140 being actuated to a closed position and the pump 138 generating a vacuum in at least one of the cartridge assembly 104 or the flow cell assembly 106. The vacuum may be held for a threshold amount of time. The vacuum may be held for about 10 minutes, for example. If the cartridge assembly 104 and/or the flow cell 126 have a leak, the vacuum may draw air into the cartridge assembly 103 and/or the flow cell 126. If air is drawn into the cartridge assembly 103 and/or the flow cell 126, subsequent temperature values at the flow cell 126 determined by the thermal sensor 136 may be affected. For example, attempting to flow reagent 139 through the flow cell 126 when air is present may not significantly decrease the temperature of the flow cell 126, for example.
[0099] The leak test may include the heater 134 heating the flow cell 126 to a threshold temperature and the valve 140 being actuated to an open position. Reagent 139 may be flowed from the well 120, from the cartridge assembly 104, and/or another source into the flow cell inlet gasket 130 of the flow cell assembly 106 and the channel 132 of the flow cell 126 using the pump 138 and the thermal sensor 136 may measure a plurality of temperature values of the flow cell 126. If air flows through the flow cell 126 in addition to the reagent 139 because of the presence of a leak, the temperature of the flow cell 126 may not drop as much as compared to if no leak were present.
[0100] The controller 1 17 may access the measured temperature values from the thermal sensor 136 and determine a difference between the measured temperature values. The controller 117 may identify at least one of the cartridge assembly 104 or the flow cell assembly 106 having a leak if the difference between the measured temperature values is greater than a threshold. The threshold may be between about 2 degrees Celsius and about 15 degrees Celsius in some examples. The threshold may be between about 3 degrees Celsius. The threshold may be between about 1 degrees Celsius and about 5 degrees Celsius in some examples.
[0101] The disclosed leak tests are performed using the thermal sensor 136. The thermal sensor 136 may be positioned adjacent the flow cell inlet gasket 130. The positioning of the thermal senor 136 may allow the temperature change and/or drop of the flow cell 126 to be accurately measured when reagent 139 is flowed into the flow cell 126, for example. No pressure sensors may be used when performing the leak tests. The cartridge assembly 104 does not include a pressure sensor in the implementation shown. The flow cell assembly 106 does not include a pressure sensor in the implementation shown.
[0102] The leak tests may additionally or alternatively include preheating the reagent 139 prior to the reagent 139 flowing into the flow cell 126. The system 100 and/or the cartridge assembly 104 may include a heater in such implementations. The heater may be a resistive heater, a flexible heater, a Peltier heater, an infrared (IR) heater, etc.
[0103] The leak tests may include a heater preheating the reagent 139, the pump 138 flowing preheated reagent into the flow cell 126, and the controller 117 accessing a measured temperature value from the thermal sensor 136. The controller 1 17 may determine a difference between the measured temperature value and a reference temperature value and identify at least one of the cartridge assembly 104 or the flow cell assembly 106 having a leak if the difference is greater than a threshold. Air may be present in the cartridge assembly 104 and/or the flow cell assembly 106 if the preheated reagent 139 does not increase the temperature of the flow cell 126 a threshold amount. For example, if the flow cell 126 is at about 25°C and the reagent 139 is preheated to between about 65°C and 70°C, the temperature of the flow cell 126 will increase when exposed to the heated reagent 139 if no leak or substantially no leak is present. If the flow cell 126 is at about 25"C and the reagent 139 is preheated to between about 65°C - 70°C, the temperature of the flow cell 126 will not increase or will not substantially increase when exposed to the heated reagent 139 if a leak is present.
[0104] The controller 1 17 may be generate an alert if the controller 117 identifies at least one of the cartridge assembly 104 or the flow cell assembly 106 has a leak. The alert may be an audio alert, a visual alert, a tactile alert (e.g., vibration), a mobile application notification, for example.
[0105] The cartridge assembly includes the pump 138 and the flow cell assembly 106 carries an outlet gasket 142 in the implementation shown. The pump 138 is coupled to the outlet gasket 142 of the flow cell assembly 106. The pump 138 may alternatively be positioned between the well 120 and the flow cell assembly 106 or in another location. The pump 138 may be a syringe pump 144. The pump 138 may alternatively be part of the system 100. The pump 138 may alternatively be omitted. The pump 138 may be implemented by the syringe pump 144, a peristaltic pump, a diaphragm pump, etc. While the pump 138 may be positioned downstream of the flow cell 126 as shown, the pump 138 may be positioned upstream of the flow cell 126 or omitted entirely. The well 120 may contain reagent 139 and the syringe pump 144 is used to flow the reagent 139 from the well 120 to the flow cell 126. The regent 139 may be rehydrated reagent and/or liquid reagent. The reagent 139 may be lyophilized reagent(s) before rehydrating, for example, and may be referred to as dry reagent or dried reagent.
[0106] The cartridge assembly 104 is shown including the valve(s) 140 coupled between the outlet port 122 of the cartridge assembly 104 and the well 120. The system 100 has a valve drive assembly 146 that interfaces with the valve 140. For example, the valve drive assembly 146 may interface with the valve 140 to actuate the valve 140 to control the flow of the liquid 203 from the liquid reservoir 102 to the well 120 and/or the flow cell 126, for example. The liquid 203 may be reagent, buffer reagent, etc. The valve 140 may be implemented by a three-way valve, a valve manifold, a rotary valve, a selector valve, a pinch valve, a flat valve, a solenoid valve, a check valve, a piezo valve, etc.
[0107] The flow cell assembly 106 includes the body 124 carrying the flow cell inlet gasket 130, a flow cell outlet gasket 150, and an outlet gasket 142. The body 124 also includes a fluidic aperture 152 in the implementation shown. The flow cell assembly 106 is shown including a first laminate 154, a second laminate 156, and the flow cell 126 is supported by the body 124. As used herein, a “flow cell” can include a device having a lid extending over a reaction structure to form a flow channel therebetween that is in communication with a plurality of reaction sites of the reaction structure, and can include a detection device that detects designated reactions that occur at or proximate to the reaction sites. The flow cell inlet gasket 130 may be referred to as a flow cell assembly inlet gasket and the outlet gasket 142 may be referred to as a flow cell
assembly outlet gasket. The flow cell inlet gasket 130 may thus be both the inlet gasket for the flow cell assembly 106 and the inlet gasket for the flow cell 126.
[0108] The flow cell 126 may support the sample of interest. The cartridge assembly 104 may include a flow cell receptacle that receives the flow cell 126. The first laminate 154 is coupled to the body 124 and forms a first fluidic channel 158 between the flow cell outlet gasket 150 and the fluidic aperture 152 and the second laminate 156 is coupled to the body 124 and forms a second fluidic channel 160 between the fluidic aperture 152 and the outlet gasket 142. The first laminate 154 and/or the second laminate 156 can be coupled to the body 124 by laser welding. The body 124 of the flow cell assembly 106 includes a first groove 161 and a second groove 162. The first laminate covers the first groove 161 to form the first fluidic channel and the second laminate covers the second groove 162 to form the second fluidic channel.
[0109] The flow cell 126 is supported by the body 124 and includes the channel 132 having a flow cell inlet 164 and a flow cell outlet 166. The flow cell inlet 164 is fluidly coupled to the flow cell inlet gasket 130 and the flow cell outlet 166 is fluidly coupled to the flow cell outlet gasket 150. The outlet port 122 of the cartridge assembly 104 is fluidly coupled to the flow cell inlet gasket 130 once the flow cell assembly 106 is coupled to the cartridge assembly 104, for example.
[0110] The flow cell assembly 106 is coupled to the cartridge assembly 104 by a coupling 168 in the implementation shown. The coupling 168 may be a snap-fit connection 170. The coupling 168 may be implemented in a different way, however. The cartridge assembly 104 also includes a pair of locating posts 171 and the body 124 of the flow cell assembly 106 has a pair of locating holes 172 that register with the corresponding locating posts 171 . One of the locating holes 172 may be circular and the other of the locating holes 172 may be oblong as an example.
[0111] The sensor assembly 128 includes a die 173. The die 173 is shown including the thermal sensor 136. The die 173 may also include an additional thermal sensor(s) 174 as shown. The thermal sensor 174 may be used to control a temperature of the flow cell 126, for example. The thermal sensor 174 may be controlled by a proportional-integral-derivative (PID) controller.
[0112] The die 173 may be implemented by a complementary metal-oxide semiconductor (CMOS) 175 in some examples. The die 173 may be implemented in other ways, however. For example, the die 173 may include a solid-state imaging device, a charge coupled device (CCD), and/or an infrared (IR) senor. The sensor assembly 128 includes a printed circuit board (PCB)
176 and the heater 134 is positioned between die 173 and the PCB 176. The die 173 and/or the heater 134 may be coupled to the PCB 176.
[0113] The liquid reservoir 102 is receivable within the receptacle 110 and has the body 148 including a storage chamber 177, a pneumatic port 178 fluidly couplable to the storage chamber 177, and a fluidic port 179 fluidly coupled to the storage chamber 177. The cartridge assembly 104 has a fluidic interface 180 couplable to the fluidic port 179, the well 120, and a channel 181 fluidly coupled between the fluidic interface 180 and the well 120. The cartridge assembly 104 also includes the outlet port 122 fluidly coupled to the well 120, an inlet port 182, and an outlet port 183 fluidly coupled to the waste reservoir 119. The outlet port 1838 may alternatively be fluidly coupled to the liquid reservoir 102 when the waste reservoir 119 is omitted and/or included with the liquid reservoir 102.
[0114] The liquid reservoir 102 is receivable within the receptacle 110 and includes the body 124, a cover 184, and a lid assembly 185. The body 124 has a top surface 186 and the storage chamber 177 has an opening 187 at the top surface 186. The body 124 also has a sipper chamber 188 having an opening 190 at the top surface 186 and a fluidic sinus 192 fluidly coupling the storage chamber 177 and the sipper chamber 188.
[0115] The cover 184 covers the opening 187 of the storage chamber 177 and the lid assembly
185 is coupled to the top surface 186. The lid assembly 185 may be laser welded to the top surface 186 of the liquid reservoir 102. The lid assembly 185 may be coupled to the top surface
186 in different ways, however, including adhesive or using another coupling for example. The cover 184 may be implemented by plastic, foil, rubber, a seal, and/or a plug.
[0116] The lid assembly 185 has a first portion 194 covering the opening 187 of the storage chamber 1 T1 and a second portion 196 covering the opening 190 of the sipper chamber 188. The top surface 186 of the body 124 and the second portion 196 define a plenum 198.
[0117] The first portion 194 of the lid assembly 185 has the pneumatic port 178, a cantilever 200, and a compliant barrier 202. The cantilever 200 and the compliant barrier 202 may be formed using a two-shot molding process in some implementations. The compliant barrier 202 may comprise or be formed of a thermoplastic elastomer (TPE) as an example. The compliant barrier 202 may have a thickness of about 0.9 millimeters (mm). The compliant barrier 202 may be made of another material and/or have a different thickness, however.
[0118] The pneumatic port 178 is fluidly coupled to the plenum 198. The cantilever 200 may be referred to as a piercer. The cantilever 200 has a distal end and the compliant barrier 202
covers the cantilever 200 and defines a portion of the plenum 198. The fluidic port 179 is fluidly coupled to the opening 190 of the sipper chamber 188.
[0119] The actuator 117 is movable to engage the compliant barrier 202 in operation and move the distal end of the cantilever 200 to pierce the cover 184 and allow the storage chamber 177 to be fluidly coupled to the plenum 198. The system 100 can thus indirectly actuate the cantilever 200 without the system 100 compromising and/or accessing an interior of the liquid reservoir 102. The engagement between the actuator 1 17 and the compliant barrier 202 does not vent the plenum 198 to atmosphere as a result.
[0120] Liquid 203 is contained within the storage chamber 177 and dried reagent 139 is contained within the well 120. The liquid 203 may be a rehydrating liquid and/or a wash buffer. The wash buffer may be referred to as buffer reagent. The liquid 203 may be a different type of liquid, however. The dried reagent 139 may be lyophilized reagent as an example. The liquid reservoir 102 may include any number of storage chambers 177 including one storage chamber as shown and the cartridge assembly 104 may include any number wells 120 including one well as shown. The number of storage chambers 177 that the liquid reservoir 102 has may correspond to the number of wells 120 that the cartridge assembly 104 has in some examples.
[0121] The liquid reservoir 102 and/or the cartridge assembly 104 includes a thermoplastic. The liquid reservoir 102 and/or the cartridge assembly 104 may additionally or alternatively include polypropylene and/or cyclic olefin copolymer (COC) with an over molded Santoprene thermoplastic elastomer (TPE) or another thermoplastic elastomer. Other materials may prove suitable for the liquid reservoir 102 and/or the cartridge assembly 104.
[0122] The cover 184 that covers the opening 187 may include foil and the compliant barrier 202 may include an elastomer and/or a conformable foil. The foil may be a foil with a lacquer backing for bonding to the thermoplastic of the body 124 in some implementations. The lacquer is a coating applied to the cover 184 that promotes the bonding to the body 124 when heat staked, for example. The cover 184 and/or the compliant barrier 202 may additionally or alternatively include plastic. The body 148 of the liquid reservoir 102 includes a port 204 that defines the opening 187 in the implementation shown. The cover 184 is coupled to the port 204. The cover 184 may alternatively be coupled within the port 204 to seal the port 204, for example. The port 204 may alternatively be omitted.
[0123] The cover 184 is pierced by the cantilever 200 in operation prior to the storage chamber 177 being pressurized by the gas source 114, for example. The cantilever 200 piercing the
cover 184 may allow the pneumatic interface 108 to pressurize the storage chamber 177. The actuator 117 may engage and move the compliant barrier 202 and in turn move the cantilever 200 to pierce the cover 184. The cover 184 may be pierced in different ways, however.
[0124] The lid assembly 185 in the implementation shown includes a body 205 having the cantilever 200 and the compliant barrier 202 is coupled to the body 205 and covers the cantilever 200. The body 205 has an aperture 206 and the compliant barrier 202 covers the aperture 206. The aperture 206 may alternatively be referred to as an opening or a window. The actuator 117 can move the cantilever 200 by moving the compliant barrier 202 relative to and/or through the aperture 206. The aperture 206 being larger may reduce an amount of force used to actuate the cantilever 200. The cantilever 200 may be adapted to pierce the cover 184 and allow the cover 184 to be pneumatically coupled to the plenum 198. The body 205 has a living hinge 207 coupled to the cantilever 200. The living hinge 207 allows the cantilever 200 to move relative to the remainder of the body 205 and for the cantilever 200 to pierce the cover 184. The cantilever 200 may be movably coupled to the body 205 in different ways, however.
[0125] The cartridge assembly 104 includes a cover 208 shown covering the well 120. The cover 208 may include and/or form a vent 210 that allows air flow out of the well 120. The vent 210 is sized to substantially retain the dried reagent 139 within the well 120. The use of the dried reagent 139 in the disclosed implementations may simplify storage requirements, reduce shipping costs, and increase the speed of workflows by, for example, avoiding thaw time before the reagent may be used.
[0126] The well 120 includes a port 212 and the liquid 203 can flow into the well 120 via the port 212 in practice to rehydrate the dried reagent 139. The vent 210 may vent gas from the well 120 as the liquid 203 flows into the well 120 and the cover 208 prevents or inhibits the dried reagent 139 and/or the liquid 203 from escaping from the well 120. Put another way, the vent 210 retains the dried reagent 139 and/or the liquid 203 within the wells 120 and prevents or inhibits the dried reagent 139 and/or the liquid 203 from migrating out of the wells 120. The vent 210 and the cover 208 prevents or inhibits cross-contamination between reagents when the liquid reservoir 102 includes more than one well 120. The liquid 203 and the dried reagent 139 can be flowed into and out of the well 120 to mix the liquid 203 from the liquid reservoir 102 and the dried reagent 139. The system 100 and/or the liquid reservoir 102 may include a mixing chamber that is used to mix the liquid 203 and the dried reagent 139 in some implementations.
[0127] The gas source 114 may be used to pressurize the liquid reservoir 102 to flow the liquid 203 into the well 120 and/or the pump 138 may draw the liquid 203 from the liquid reservoir 102
and flow the liquid 203 into the well 120 to rehydrate the dried reagent 139. The pump 138 may be used to draw the rehydrated reagent from the well 120 and flow the rehydrated reagents to the flow cell 126 in some implementations. The gas source 114 may be provided by the system 100 and/or the gas source 1 14 may be carried by the liquid reservoir 102. The gas source 1 14 may alternatively be omitted.
[0128] The liquid reservoir 102 and/or the system 100 includes a valve 216 that may be selectively actuatable to control the flow of fluid (gas) to the liquid reservoir 102. The valve 216 may be implemented by a valve manifold, a rotary valve, a selector valve, a pinch valve, a flat valve, a solenoid valve, a check valve, a piezo valve, etc. The regulator 112 can be positioned between the gas source 114 and the valve 216 and regulates a pressure of the gas provided to the valve 216. The regulator 112 may be a valve that controls the flow of the gas from the gas source 114.
[0129] The gas source 114 and/or the pump 138 may flow the liquid 203 to rehydrate dried reagents 139 and to flow one or more liquid reagents (e.g., A, T, G, C nucleotides) through the liquid reservoir 102 that interact with the sample. The gas source 1 14 may flow the liquid 203 to rehydrate the dry reagents 139 on the cartridge assembly 104 and the pump 138 on the cartridge assembly 104 may flow the rehydrated reagent (e.g., A, T, G, C nucleotides) to the flow cell 126 that interact with the sample as an example. The reagent with a reversible terminator in an implementation allows a single nucleotide to be incorporated by the sstDNA per cycle. One or more of the nucleotides has a unique fluorescent label in such implementations that emits a color when excited. The color (or absence thereof) is used to detect the corresponding nucleotide. The imaging system 118 excites one or more of the identifiable labels (e.g., a fluorescent label) in the implementation shown and the sensor assembly 128 of the flow cell assembly 106 and/or the imaging system 118 obtains 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 system 100 may include a light source and the flow cell assembly 106 may include an image sensor in some examples. The image data (e.g., detection data) may be analyzed by the system 100. The imaging system 1 18 may 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).
[0130] After the image data is obtained, the drive assembly 115 interfaces with the liquid reservoir 102 to flow another reaction component (e.g., a reagent) through the flow cell 126 that
is thereafter received by the waste reservoir 119 and/or otherwise exhausted by the cartridge assembly 104. The reaction component performs a flushing operation that chemically cleaves the fluorescent label and the reversible terminator from the sstDNA. The sstDNA is then ready for another cycle.
[0131] Referring now to the drive assembly 115, in the implementation shown, the drive assembly 115 includes a pump drive assembly 218 and the valve drive assembly 146. The pump drive assembly 218 interfaces with the pump 138 to pump fluid through the liquid reservoir 102 and/or the flow cell 126 and the valve drive assembly 146 interfaces with the valves 140 and/or 216 to control the position of the valves 140 and/or 216.
[0132] Referring to the controller 117, in the implementation shown, the controller 117 includes a user interface 222, a communication interface 224, one or more processors 226, and a memory 228 storing instructions executable by the one or more processors 226 to perform various functions including the disclosed implementations. The user interface 222, the communication interface 224, and the memory 228 are electrically and/or communicatively coupled to the one or more processors 226.
[0133] In an implementation, the user interface 222 receives input from a user and provides information to the user associated with the operation of the system 100 and/or an analysis taking place. The user interface 222 may include a touch screen, a display, a keyboard, 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).
[0134] In an implementation, the communication interface 224 enables communication between the system 100 and a remote system(s) (e.g., computers) via a network(s). The network(s) may include an intranet, a local-area network (LAN), a wide-area network (WAN), the intranet, 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 system 100. Some of the communications provided to the system 100 may be associated with a fluidics analysis operation, patient records, and/or a protocol(s) to be executed by the system 100.
[0135] The one or more processors 226 and/or the system 100 may include one or more of a processor-based system(s) or a microprocessor-based system(s). In some implementations, the one or more processors 226 and/or the system 100 includes a reduced-instruction set computer(s) (RISC), an application specific integrated circuit(s) (ASICs), a field programable
gate array(s) (FPGAs), a field programable logic device(s) (FPLD(s)), a logic circuit(s) , and/or another logic-based device executing various functions including the ones described herein.
[0136] The memory 228 can include one or more of a hard disk drive, a flash memory, a readonly memory (ROM), erasable programable read-only memory (EPROM), electrically erasable programable read-only memory (EEPROM), a random-access memory (RAM), non-volatile RAM (NVRAM) memory, a compact disk (CD), a digital versatile disk (DVD), 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).
[0137] FIG. 2 is an isometric view of an example implementation of a cartridge assembly 300 and a flow cell assembly 302 that can be used to implement the cartridge assembly 104 and the flow cell assembly 106 of FIG. 1 . The cartridge assembly 300 includes the fluidic interface 180 and a plurality of the wells 120. The flow cell assembly 302 is coupled to the cartridge assembly 300 by the snap-fit connection 170. The flow cell assembly 302 also includes a second flow cell 304 supported or otherwise carried by the body 124. The first flow cell 126 and the second flow cell 304 may be substantially identical structures in some implementations. The first flow cell 126 and the second flow cell 304 may be different structures in other implementations. The first flow cell 126 and the second flow cell 304 are shown being in an end-to-end vertical configuration relative to the cartridge assembly 300. The first flow cell 126 and the second flow cell 304 may be considered to be in an end-to-end horizontal configuration relative to the cartridge assembly 300 if the first flow cell 126 and the second flow cell 304 are oriented about 90° to the position shown. The second flow cell 304 has a channel 132 including a flow cell inlet 164 and a flow cell outlet 166. The flow cell 126 may be referred to as a third flow cell and the second flow cell 304 may be referred to as a fourth flow cell. The flow cell 126 and the second flow cell 304 are fluidly coupled in series in the implementation shown. The flow cell outlet 166 of the flow cell 126 is fluidly coupled to the flow cell outlet gasket 150 via the second flow cell 304, for example. The flow cell 126 and the second flow cell 304 may be coupled in different ways, however. The flow cell 126 and the second flow cell 304 may be coupled in parallel and/or oriented differently as examples.
[0138] FIG. 3 is an isometric partially expanded view of the flow cell assembly 302 of FIG. 2. The flow cell assembly 302 shows the first laminate 154 and the second laminate 156 that are used to form the first fluidic channel 158 and the second fluidic channel 160. The body 124 of the flow cell assembly 106 and the flow cell 126 are coupled by a coupling 306. The coupling 306 includes a first snap-fit cantilever 308 and a second snap-fit cantilever 310. The first snap-fit
cantilever 308 is positioned on a first side 312 of the flow cell 126 and the second snap-fit cantilever 310 is positioned on a second side 314 of the flow cell 126. The first snap-fit cantilever 308 biases the flow cell 126 in the x-direction and the second snap-fit cantilever 310 biases the flow cell 126 in the y-direction in the implementation shown. The coupling 306 also includes a pair of hold downs 316 having a lip 318 that is arranged to be positioned overtop of the flow cell 126. Both of the hold downs 316 are positioned on a side 320 of the flow cell 126. The hold downs 316 may be in a different position. The coupling 306 has a x-datum projection 322 and a y-datum projection 324 in the implementation shown against which the flow cell 126 engages. The coupling 306 also includes has a second x-datum projection 326. The first snap-fit cantilever 308 biases the flow cell 126 into engagement with the x-datum projections 322, 326 and the second snap-fit cantilever 310 biases the flow cell 126 into engagement with the y- datum projection 324. The second flow cell 304 and the body 124 of the flow cell assembly 106 are coupled by a coupling 328 that is similar or the same as the coupling 306.
[0139] The body 124 has locating posts 329 in the implementation shown and the second laminate 156 has locating holes 330 that receive the corresponding locating posts 329. The locating holes 330 receiving the locating posts 329 aligns the second laminate 156 relative to the body 124 to form the second fluidic channel 160.
[0140] FIG. 4 is an isometric view of the first flow cell 126 and the second flow cell 304 of the flow cell assembly 302 of FIG. 2. Each of the flow cells 126 includes a corresponding sensor assembly 128 having a plurality of thermal sensors 136, 174. The flow cells 126 have multiple thermal sensors 136, 174 displaced along the length of the fluidic path in the implementation shown. Each sensor assembly 128 is shown including six thermal sensors 136, 174. One of the thermal sensors 136, 174 may be used when heating the flow cell assembly 302 to the threshold temperature and one of the thermal sensors 136, 174 may be used when performing the leak tests disclosed, in some examples. The thermal sensors 136, 174 may be used as desired to implement the teachings of this disclosure, however.
[0141] FIG. 5 is an expanded isometric view of an example implementation of another flow cell assembly 400 having a body 401 that can be used to implement the flow cell assembly 106 of FIG. 1 . The flow cell assembly 400 may be referred to as a second flow cell assembly 400. The flow cell assembly 400 is similar to the flow cell assembly 302 in that both the flow cell assembly 302 and the flow cell assembly 400 mechanically and fluidly couple with the cartridge assembly 300 and/or the system 100 interchangably. The flow cell assembly 302 and the flow cell assembly 400 have cantilevers 402 of the snap-fit connection 170 in the same or substantially
the same location to allow the flow cell assembly 302 and the flow cell assembly 400 to mechanically couple with the cartridge assembly 300 in the same or similar way. The flow cell assembly 302 and the flow cell assembly 400 may also have the flow cell inlet gasket 130 and the outlet gasket 142 in the same or substantially the same location to allow the flow cell assembly 302 and the flow cell assembly 400 to fluidly couple with the cartridge assembly 300 in the same or in a similar way.
[0142] The flow cell assembly 400 includes a flow cell 404 but does not include an additional flow cell in the implementation shown. The flow cell 404 may be referred to as a second flow cell. The flow cell 404 may be different from the flow cell 126 shown in FIG. 2. The flow cell 404 may have different flow cell channel volumes from the flow cell channel volumes of the flow cell 126 shown in FIG. 2, for example. The flow cell outlet gasket 150 is shown positioned closer to the flow cell inlet gasket 130 to allow the flow cell inlet 164 and the flow cell outlet 166 of the flow cell 404 to fluidly couple with the gaskets 142, 150. The flow cell outlet gasket 150 may be positioned closer to the flow cell inlet gasket 130 in the flow cell assembly 400 as compared to the relative position of the flow cell outlet gasket 150 and the flow cell inlet gasket 130 in the flow cell assembly 302 of FIG. 2.
[0143] The flow cell assembly 400 includes the first laminate 154 and the second laminate 156 similar to the laminates 154, 156 used with the flow cell assembly 302 of FIG. 2. The flow cell assembly 400 does not include an additional flow cell so the laminates 154, 156 used with the flow cell assembly 400 have a different configuration from the laminates 154, 156 used with the flow cell assembly 302 of FIG. 2. The first laminate 154 is to be coupled to the body 401 and forms the first fluidic channel 158 between the flow cell outlet gasket 150 and the fluidic aperture 152 and the second laminate 156 is to be coupled to the body 401 and forms the second fluidic channel 160 between the fluidic aperture 152 and the outlet gasket 142. The body 124 also defines a window 406 to allow visual access of the flow cell 126.
[0144] FIG. 6 is an isometric view of the flow cell 404 of the flow cell assembly 400 of FIG. 5. The flow cell 404 includes a sensor assembly 128 having a plurality of thermal sensors 136, 174. The sensor assembly 128 is shown including four thermal sensors 136, 174. One of the thermal sensors 136, 174 may be used when heating the flow cell assembly 302 to the threshold temperature and one of the thermal sensors 136, 174 may be used when performing the leak tests disclosed, in some examples. The thermal sensors 136, 174 may be used as desired to implement the teachings of this disclosure, however.
[0145] FIG. 7 is an expanded isometric view of an example implementation of a flow cell assembly 500 having a body 501 that can be used to implement the flow cell assembly 106 of FIG. 1 . The flow cell assembly 500 is similar to the flow cell assembly 106 and the flow cell assembly 400 in that each of the flow cell assembly 106, the flow cell assembly 400, and the flow cell assembly 500 mechanically and fluidly couple with the cartridge assembly 300 and/or the system 100 interchangeably. The flow cell assembly 106, the flow cell assembly 400, and the flow cell assembly 500 have the cantilevers 402 of the snap-fit connection 170 in the same or substantially the same location to allow the flow cell assembly 106, the flow cell assembly 400, and the flow cell assembly 500 to mechanically couple with the cartridge assembly 300 in the same or similar way. The flow cell assembly 106, the flow cell assembly 400, and the flow cell assembly 500 may also have the flow cell inlet gasket 130 and the outlet gasket 142 in the same or substantially the same location to allow the flow cell assembly 106, the flow cell assembly 400, and the flow cell assembly 500 to fluidly couple with the cartridge assembly 300 in the same or similar way. The system 100 and/or the cartridge assembly 300 may remain the same or substantially the same while allowing the flexibility of using different flow cell assemblies.
[0146] The flow cell assembly 500 includes a flow cell 502 but does not include an additional flow cell in the implementation shown. The flow cell 502 may be the same or different from the flow cell 404 shown in FIG. 5 and/or the flow cell 126 shown in FIG. 2, for example. The flow cell 502 may have different flow cell channel volumes from the flow cell channel volumes of the flow cell 126 shown in FIG. 2, for example
[0147] The flow cell assembly 500 includes the first laminate 154 and the second laminate 156 similar to the laminates 154, 156 used with the flow cell assembly 400 of FIG. 5. The gaskets 130, 150 of FIG. 6 are further spaced apart because of the size of the flow cell 502 as compared to the spacing of the gaskets 130, 150 of FIG. 5. The first laminate 154 of the flow cell assembly 500 is thus longer to accommodate the position of the gaskets 130, 142 , and/or 150 of the flow cell assembly 500 as compared to the length of the first laminate 154 in the flow cell assembly 400.
[0148] FIG. 8 is an isometric view of the flow cell 502 of the flow cell assembly 500 of FIG. 7. The flow cell 502 includes a sensor assembly 128 having a plurality of thermal sensors 136, 174. The sensor assembly 128 is shown including six thermal sensors 136, 174. One of the thermal sensors 136, 174 may be used when heating the flow cell assembly 302 to the threshold temperature and one of the thermal sensors 136, 174 may be used when performing
the leak tests disclosed, in some examples. The thermal sensors 136, 174 may be used as desired to implement the teachings of this disclosure, however.
[0149] FIG. 9 illustrates a flow chart for a method of determining the presence of a leak using the system 100 of FIG. 1 , the cartridge assembly 104 and/or 300 of FIGS. 1 - 2, the flow cell assemblies 106, 302, 400, 500 and sensor assemblies 128 of FIGS. 1 - 8, or any of the other implementations disclosed herein. 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.
[0150] The process 1200 of FIG. 9 starts with the cartridge assembly 104 and the flow cell assembly 106 being primed with reagent 139 (Block 904). The flow cell 126 is heated to a threshold temperature using the heater 134 of a flow cell assembly 106 (Block 906). The flow cell assembly 106 is coupled to the cartridge assembly 104 and may be positioned in the receptacle 1 10 of the system 100. The reagent 139 may be buffer reagent that is drawn into the flow cell assembly 106 using the pump 138 to prime the flow cell assembly 106. The reagent 139 may be pulled directly from the storage chamber 177 through the valve 140 and into the flow cell assembly 106. The reagent 138 may alternatively be flowed to one of the empty wells 120 using positive pressure and the reagent 138 may then be pulled from that empty well 120 across the flow cell 126 using the pump 144. The reagent 138 may alternatively flow across the flow cell 126 under positive pressure.
[0151] Reagent 139 is flowed into the flow cell 126 (Block 908). The reagent flowing into the flow cell 126 may include the reagent 138 flowing from the cartridge assembly 104. The reagent 139 flowing into the flow cell 126 may include the reagent 138 flowing from a well 120 of the cartridge assembly 104. The reagent 139 flowing from the cartridge assembly 104 into the flow cell 126 may include the reagent 139 flowing into the flow cell inlet gasket 130 of the flow cell assembly 106 using the pump 138 of the cartridge assembly 104. The flow cell assembly 106 includes the body 124 carrying the flow cell inlet gasket 130 and the flow cell 126 supported by the body 124. The flow cell inlet gasket 130 is fluidly coupled to the outlet port 122 and the flow cell 126.
[0152] A measured temperature value from a thermal sensor 136 of the flow cell assembly 106 is accessed, using a controller 1 17, (Block 910) and a presence of a leak in at least one of the cartridge assembly 104 or the flow cell assembly 106 is determined, using the controller 117, based on the measured temperature value (Block 910). The presence of the leak may be determined by determining a difference between the measured temperature value and a
reference temperature value using the controller 1 17 and identifying at least one of the cartridge assembly 104 or the flow cell assembly 106 having the leak if the difference is greater than a threshold using the controller 117.
[0153] The presence of the leak may be determined by actuating the valve 140 of the cartridge assembly 104 to a closed position and a vacuum being generated in at least one of the cartridge assembly 104 or the flow cell assembly 106 using the pump 138. The flow cell 126 may be heated to a threshold temperature using the heater 134 of the flow cell assembly 106 and the valve 140 may be actuated to an open position. The reagent 139 may be flowed from the well 120, from the cartridge assembly 104, and/or from another source (e.g., the system 100) to the flow cell 126 and a plurality of temperature values of the flow cell 126 may be determined using the thermal sensor 136. The reagent 139 may be flowed using the pump 139.
[0154] The presence of the leak may be determined using the controller 117 by accessing measured temperature values from the thermal sensor 136 and determining a difference between the measured temperature values using the controller 117. At least one of the cartridge assembly 104 or the flow cell assembly is identified having the leak if the difference between the measured temperature values is greater than a threshold. An alert is generated if the controller 117 determines the presence of the leak in at least one of the cartridge assembly 104 or the flow cell assembly 106 (Block 914).
[0155] FIG. 10 is a graph 10000 showing results of the disclosed implementations including an x-axis 11002 relating to time and a y-axis 1 1004 relating to temperature. A first line 10007 shows the temperature of the flow cell dropping below a threshold level 10008 when reagent flows through the flow cell. The first line 10007 dropping below the threshold level 10008 indicates that the fluid flowing through the flow cell does not include a significant amount of air and, thus, no leak or substantially no leak is present. A second line 10010 shows the temperature of the flow cell not dropping below the threshold level 10008 when reagent flows through the flow cell. The second line 10010 not dropping below the threshold level 10008 indicates that the fluid flowing through the flow cell includes air and, thus, a leak is present.
[0156] FIG. 1 1 is a graph 10050 showing results of the disclosed implementations including an x-axis 10052 relating to time, a first y-axis 10054 relating to pressure and a second y-axis 10056 relating to temperature.
[0157] First lines 10058, 10060 show a segment 16061 where a vacuum is generated and second segments 10062 where the pressure and temperature drop a similar amount when
reagent flows through the flow cell. The second segments 10062 having similar temperature and/or pressure drops indicates that the fluid flowing through the flow cell does not include a significant amount of air and, thus, no leak or substantially no leak is present in the cartridge assembly and/or the flow cell assembly.
[0158] Second lines 10064, 10066 include the segment 16061 where a vacuum is generated and second segments 10062 where the pressure and temperature drop different amount when reagent flows through the flow cell, specifically when reagent is initially flowed through the flow cell after the vacuum is released. The second segments 10062 having different temperature and/or pressure drops indicates that the fluid flowing through the flow cell includes air and, thus, a leak or a minor leak is present.
[0159] - Overview of System for Biological or Chemical Analysis
[0160] Examples described herein may be used in various biological or chemical processes and systems for academic analysis, commercial analysis, or other analysis. More specifically, examples described herein may be used in various processes and systems where it is desired to detect an event, property, quality, or characteristic that is indicative of a designated reaction. Bioassay systems such as those described herein may be configured to perform a plurality of designated reactions that may be detected individually or collectively. For example, bioassay systems may be used to sequence a dense array of nucleic acid features through iterative cycles of enzymatic manipulation and image acquisition. In some examples, nucleic acids can be attached to a surface and amplified. Examples of such amplification are described in U.S.
Pat. No. 7,741 ,463, entitled “Method of Preparing Libraries of Template Polynucleotides,” issued June 22, 2010, the disclosure of which is incorporated by reference herein, in its entirety; and/or U.S. Pat. No. 7,270,981 , entitled “Recombinase Polymerase Amplification,” issued September 18, 2007, the disclosure of which is incorporated by reference herein, in its entirety.
[0161] Components that are used in the bioassay systems may include one or more microfluidic channels that deliver reagents or other reaction components to a reaction site. The reaction sites may be randomly distributed across a substantially planar surface; or may be patterned across a substantially planar surface. Each of the reaction sites may be imaged to detect light from the reaction site. The signals indicating photons emitted from the reaction sites and detected by image sensors may provide illumination values. These illumination values may be combined into an image indicating photons as detected from the reaction sites. These images may be further analyzed to identify compositions, reactions, conditions, etc., at each reaction site.
[0162] FIG. 12 illustrates a schematic diagram of an example of a system (1100) that may be used to perform an analysis on one or more samples of interest. In some implementations, the sample may include one or more clusters of nucleotides (e.g., DNA) that have been linearized to form a single stranded DNA (sstDNA). In the implementation shown, system (1 100) is configured to receive a flow cell cartridge assembly (1 102) including a flow cell assembly (1103) and a sample cartridge (1104). System (1100) includes a flow cell receptacle (1 122) that receives flow cell cartridge assembly (1 102), a vacuum chuck (1 124) that supports flow cell assembly (1103), and a flow cell interface (1126) that is used to establish a fluidic coupling between system (1 100) and flow cell assembly (1103). Flow cell interface (1126) may include one or more manifolds. System (1100) further includes a sipper manifold assembly (1106), a sample loading manifold assembly (1108), and a pump manifold assembly (1110). System (1100) also includes a drive assembly (1112), a controller (1114), an imaging system (1116), and a waste reservoir (1118). Controller (1114) is electrically and/or communicatively coupled to drive assembly (11 12) and to imaging system (1116); and is configured to cause drive assembly (1112) and/or the imaging system (1116) to perform various functions as disclosed herein.
[0163] In the present example, flow cell assembly (1103) includes a flow cell (1128) having a channel (1130) and defining a plurality of first openings (1132), which are fluidically coupled to the channel (1 130) and arranged on a first side (1134) of the channel (1 130). Flow cell (1128) further includes a plurality of second openings (1136) fluidically coupled to the channel (1130) and arranged on a second side (1 138) of the channel (1130). Fluid may thus flow through flow cell (1128) via channel. While the flow cell (1 128) is shown including one channel (1130), flow cell (1128) may include two or more channels (1130). Flow cell assembly (1103) also includes a flow cell manifold assembly (1140) coupled to flow cell (1128) and having a first manifold fluidic line (1142) and a second manifold fluidic line (1144). Flow cell manifold assembly (1140) may be in the form of a laminate including a plurality of layers as discussed in more detail below.
[0164] In the implementation shown, first manifold fluidic line (1142) has a first fluidic line opening (1 146) and is fluidically coupled to each of the first openings (1 132) of flow cell (1 128); and second manifold fluidic line (1 144) has a second fluidic line opening (1148) and is fluidically coupled to each of the second openings (1 136). As shown, flow cell assembly (1 103) includes gaskets (1 150) coupled to flow cell manifold assembly (1 140) and fluidically coupled to fluidic line openings (1 146, 148). In some implementations where flow cell (1128) includes a plurality of channels (1130), flow cell manifold assembly (1 140) may include additional fluidic lines (1152) that couple first fluidic line openings (1146) to a single manifold port (1 154). In such
implementations, a single gasket (1 150) may be coupled to flow cell manifold assembly (1140) that surrounds the manifold port (1154) and is in fluidic communication with a plurality of channels (1130). In operation, flow cell interface (1126) engages with corresponding gaskets (1150) to establish a fluidic coupling between system (1 100) and flow cell (1128). The engagement between flow cell interface (1 126) and gaskets (1 150) reduces or eliminates fluid leakage between flow cell interface (1 126) and flow cell (1128).
[0165] In the implementation shown, first manifold fluidic line (1142) has a portion (1 156) that is substantially parallel to a longitudinal axis (1 158) of channel (1130); and second manifold fluidic line (1144) has a portion (1 160) that is substantially parallel to longitudinal axis (1 158) of channel (1130). Additionally, first manifold fluidic line (1 142) is shown being at least partially adjacent a first end (1162) of flow cell (1128) and spaced from a second end (1 164) of flow cell (1128); and second manifold fluidic line (1144) is shown being at least partially adjacent second end (1164) of flow cell (1128) and spaced from first end (1162). Other arrangements of manifold fluidic lines (1 142, 144) may prove suitable, however.
[0166] In the implementation shown, system (1100) includes a sample cartridge receptacle (1166) that receives sample cartridge (1104) that carries one or more samples of interest (e.g., an analyte). System (1 100) also includes a sample cartridge interface (1 168) that establishes a fluidic connection with sample cartridge (1104). Sample loading manifold assembly (1108) includes one or more sample valves (1170). Pump manifold assembly (1110) includes one or more pumps (1172), one or more pump valves (1174), and a cache (1 176). Valves (1170, 1174) and pumps (1 172) may take any suitable form. Cache (1176) may include a serpentine cache and may temporarily store one or more reaction components during, for example, bypass manipulations of the system (1 100). While cache (1176) is shown being included in pump manifold assembly (11 10), cache (1176) may alternatively be located elsewhere (e.g., in sipper manifold assembly (1106) or in another manifold downstream of a bypass fluidic line (1178), etc.).
[0167] Sample loading manifold assembly (1108) and pump manifold assembly (1110) flow one or more samples of interest from sample cartridge (1104) through a fluidic line (1180) toward flow cell cartridge assembly (1102). In some implementations, sample loading manifold assembly (1108) may individually load or address each channel (1130) of flow cell (1128) with a respective sample of interest. The process of loading channel (1 130) with a sample of interest may occur automatically using system (1 100). As shown in FIG. 12, sample cartridge (1104) and sample loading manifold assembly (1108) are positioned downstream of flow cell cartridge
assembly (1102). In the implementation shown, sample loading manifold assembly (1108) is coupled between flow cell cartridge assembly (1 102) and pump manifold assembly (1110). To draw a sample of interest from sample cartridge (1104) and toward pump manifold assembly (1110), sample valves (1170), pump valves (1174), and/or pumps (1172) may be selectively actuated to urge the sample of interest toward pump manifold assembly (11 10). Sample cartridge (1104) may include a plurality of sample reservoirs that are selectively fluidically accessible via the corresponding sample valves (1 170). To individually flow the sample of interest toward channel (1130) of flow cell (1 128) and away from pump manifold assembly (1110), sample valves (1170), pump valves (1174), and/or pumps (1172) may be selectively actuated to urge the sample of interest toward flow cell cartridge assembly (1102) and into respective channels (1 130) of flow cell (1 128).
[0168] Drive assembly (11 12) interfaces with sipper manifold assembly (1 106) and pump manifold assembly (11 10) to flow one or more reagents that interact with the sample within flow cell (1128). In some scenarios, a reversible terminator is attached to the reagent to allow a single nucleotide to be incorporated onto a growing DNA strand. 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, imaging system (11 16) excites one or more of the identifiable labels (e.g., a fluorescent label) and thereafter obtains 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 system (1100). Examples of features and functionalities that may be incorporated into imaging system (1 116) will be described in greater detail below.
[0169] After the image data is obtained, drive assembly (1112) interfaces with sipper manifold assembly (1106) and pump manifold assembly (1110) to flow another reaction component (e.g., a reagent) through flow cell (1128) that is thereafter received by waste reservoir (1 118) via a primary waste fluidic line (1182) and/or otherwise exhausted by system (1100). Some reaction components may perform a flushing operation that chemically cleaves the fluorescent label and the reversible terminator from the sstDNA. The sstDNA may then be ready for another cycle.
[0170] The primary waste fluidic line (1 182) is coupled between pump manifold assembly (1110) and waste reservoir (1118). In some implementations, pumps (1172) and/or pump valves (1174) of pump manifold assembly (1 110) selectively flow the reaction components from flow cell cartridge assembly (1102), through fluidic line (1 180) and sample loading manifold
assembly (1108) to primary waste fluidic line (1182). Flow cell cartridge assembly (1 102) is coupled to a central valve (1 184) via flow cell interface (1 126). Central valve (1 184) is coupled with flow cell interface (1126) via a fluidic line (1 185). An auxiliary waste fluidic line (1186) is coupled to central valve (1 184) and to waste reservoir (11 18). In some implementations, auxiliary waste fluidic line (1186) receives excess fluid of a sample of interest from flow cell cartridge assembly (1102), via central valve (1 184), and flows the excess fluid of the sample of interest to waste reservoir (11 18) when back loading the sample of interest into flow cell (1128), as described herein.
[0171] Sipper manifold assembly (1 106) includes a shared line valve (1 188) and a bypass valve (1190). Shared line valve (1188) may be referred to as a reagent selector valve. Central valve (1184) and the valves (1188, 190) of sipper manifold assembly (1106) may be selectively actuated to control the flow of fluid through fluidic lines (1192, 1194, 1196). Sipper manifold assembly (1106) may be coupled to a corresponding number of reagent reservoirs (1198) via reagent sippers (1200). Reagent reservoirs (1198) may contain fluid (e.g., reagent and/or another reaction component). In some implementations, sipper manifold assembly (1106) includes a plurality of ports. Each port of sipper manifold assembly (1106) may receive one of the reagent sippers (1200). Reagent sippers (1200) may be referred to as fluidic lines. Some forms of reagent sippers (1200) may include an array of sipper tubes extending downwardly along the z-dimension from ports in the body of sipper manifold assembly (1106). Reagent reservoirs (1 198) may be provided in a cartridge, and the tubes of reagent sippers (1200) may be configured to be inserted into corresponding reagent reservoirs (1198) in the reagent cartridge so that liquid reagent may be drawn from each reagent reservoir (1198) into the sipper manifold assembly (1106).
[0172] Shared line valve (1188) of sipper manifold assembly (1106) is coupled to central valve (1184) via shared reagent fluidic line (1196). Different reagents may flow through shared reagent fluidic line (1196) at different times. In some versions, when performing a flushing operation before changing between one reagent and another, pump manifold assembly (11 10) may draw wash buffer through shared reagent fluidic line (1196), central valve (1184), and flow cell cartridge assembly (1102).
[0173] Bypass valve (1 190) of sipper manifold assembly (1 106) is coupled to central valve (1184) via dedicated reagent fluidic lines (1194, 1196). Each of the dedicated reagent fluidic lines (1 194, 196) may be associated with a single reagent. The fluids that may flow through dedicated reagent fluidic lines (1194, 1196) may 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.
[0174] Bypass valve (1 190) is also coupled to cache (1 176) of pump manifold assembly (11 10) via bypass fluidic line (1178). One or more reagent priming operations, hydration operations, mixing operations, and/or transfer operations may be performed using bypass fluidic line (1 178). The priming operations, the hydration operations, the mixing operations, and/or the transfer operations may be performed independent of flow cell cartridge assembly (1102). Thus, the operations using bypass fluidic line (1 178) may occur during, for example, incubation of one or more samples of interest within flow cell cartridge assembly (1 102). That is, shared line valve (1188) may be utilized independently of bypass valve (1 190) such that bypass valve (1190) may utilize bypass fluidic line (1 178) and/or cache (1176) to perform one or more operations while shared line valve (1 188) and/or central valve (1184) simultaneously, substantially simultaneously, or offset synchronously perform other operations.
[0175] Drive assembly (11 12) includes a pump drive assembly (1202) and a valve drive assembly (1204). Pump drive assembly (1202) may be adapted to interface with one or more pumps (1172) to pump fluid through flow cell (1128) and/or to load one or more samples of interest into flow cell (1128). Valve drive assembly (1204) may be adapted to interface with one or more of the valves (1170, 1174, 1184, 1188, 1190) to control the position of the corresponding valves (1170, 1174, 1184, 1188, 1190).
[0176] FIG. 13 shows an example of a fluidic arrangement (2220) that may be incorporated into a variation of the system (1100) of FIG. 12. Fluidic arrangement (2220) of this example includes a pump manifold assembly (2222), which may operate similar to pump manifold assembly (1110) described above; a sample loading manifold assembly (2228), which may operate similar to sample loading manifold assembly (1108) described above; a flow cell interface (2240), which may operate similar to flow cell interface (1 126) described above; a sipper manifold assembly (2250), which may operate similar to sipper manifold assembly (1106) described above; and a waste reservoir (2270), which may operate similar to waste reservoir (1118) described above. Pump manifold assembly (2222) is coupled with a port assembly (2258) of sipper manifold assembly (2250) via a fluidic line (2224), which may be similar to fluidic line (1178); and with sample loading manifold assembly (2228) via a fluidic line (2226). Sample loading manifold assembly (2228) is coupled with flow cell interface (2240) via fluidic line (2230), which may be similar to fluidic line (1180); and with port assembly (2258) via fluidic lines (2232, 234). Flow cell interface (2240) is coupled with sipper manifold assembly (2250) via fluidic line (2242), which
may be similar to fluidic line (1185). Sipper manifold assembly (2250) includes a manifold body (2252) and a common output port (2256), which provides fluid communication via fluidic line (1185). A valve assembly (2254) controls fluid flow through common output port (2256) and may operate similar to central valve (1184). Port assembly (2258) of sipper manifold assembly (2250) is coupled with waste reservoir (2270) via fluidic line (2272), which may be similar to fluidic line (1 186).
[0177] A plurality of reagent sippers (2260) extend from manifold body (2252) and are flu idically coupled with valve assembly (2254) via respective fluid channels (2262) in manifold body (2252). Reagent sippers (2260) may operate similar to reagent sippers (2200). Valve assembly (2254) is operable to selectively couple fluid channels (2262) with flow cell interface (2240) via common output port (2256) and fluidic line (2230), to thereby selectively provide various reagents to flow cell interface (2240). In other words, when each reagent sipper (2260) is disposed in a different respective reagent (e.g., in a respective reagent reservoir (1 198)), a flow cell (e.g., like flow cell (1128)) that is coupled with flow cell interface (2240) may selectively receive those different reagents based on control of valve assembly (2254).
[0178] Port assembly (2258) may provide a fluidic interface between pump manifold assembly (2222) and sipper manifold assembly (2250), thereby allowing sipper manifold assembly (2250) to receive pressurized fluid from pump manifold assembly (2222). Port assembly (2258) may also provide a fluidic interface between sample loading manifold assembly (2228) and sipper manifold assembly (2250), thereby allowing sipper manifold assembly (2250) to receive sample fluid from sample loading manifold assembly (2228). In addition, port assembly (2258) may provide a fluidic interface between waste reservoir (2270) and sipper manifold assembly (2250), thereby allowing sipper manifold assembly (2250) to communicate waste fluid to waste reservoir (2270). Communication of fluids via port assembly (2258) may be regulated, at least in part, by valve assembly (2254).
[0179] The following claims recite aspects of certain examples of the disclosed subject matter and are considered to be part of the above disclosure. These aspects may be combined with one another.
[0180] Example 1 . An apparatus comprising: a system, comprising: a receptacle; a cartridge assembly receivable within the receptacle, the cartridge assembly comprising: a well; and an outlet port fluidly coupled to the well; and a flow cell assembly, comprising: a body; a flow cell supported by the body and comprising a channel; and a sensor assembly comprising a heater and a thermal sensor, wherein the outlet port is fluidly coupled to the flow cell, wherein a leak
test is to be performed on the cartridge assembly and the flow cell assembly using the thermal sensor.
[0181] Example 2. The apparatus of Example 1 , wherein the system comprises a controller and wherein the leak test comprisesi ) priming the cartridge assembly and the flow cell assembly, 2) accessing a measured temperature value from the thermal sensor using the controller, 3) determining a difference between the measured temperature value and a reference temperature value using the controller, and 4) identifying at least one of the cartridge assembly or the flow cell assembly having a leak if the difference is greater than a threshold using the controller.
[0182] Example 3. The apparatus of Example 2, wherein the reference temperature is between about 40°C and about 60°C.
[0183] Example 4. The apparatus of any one of Examples 2 - 3, wherein the reference temperature is about 55°C.
[0184] Example 5. The apparatus of any one of the preceding Examples, wherein the leak test comprises the flow cell being heated to a threshold temperature using the heater after the flow cell is primed, reagent being flowed from the cartridge assembly into the flow cell using a pump, and a temperature value of the flow cell being measured using the thermal sensor.
[0185] Example 6. The apparatus of any one of the preceding Examples, wherein the cartridge assembly comprises a pump and wherein the leak test comprises 1 ) a valve being actuated to a closed position, 2) a vacuum being generated in at least one of the cartridge assembly or the flow cell assembly using the pump, 3) the flow cell being heated to a threshold temperature using the heater, 4) the valve being actuated to an open position, 5) reagent being flowed from the cartridge assembly into the flow cell assembly and the channel of the flow cell using the pump, and 6) a plurality of temperature values of the flow cell being measured using the thermal sensor.
[0186] Example 7. The apparatus of any of the preceding Examples, wherein the system comprises a controller and wherein the leak test comprises accessing measured temperature values from the thermal sensor using the controller, determining a difference between the measured temperature values using the controller, and identifying at least one of the cartridge assembly or the flow cell assembly having a leak if the difference between the measured temperature values is greater than a threshold using the controller.
[0187] Example 8. The apparatus of Example 7, wherein the threshold is between about 2 degrees Celsius and about 15 degrees Celsius.
[0188] Example 9. The apparatus of any one of Examples 7 - 8, wherein the threshold is about 3 degrees Celsius.
[0189] Example 10. The apparatus of anyone of the preceding Examples, wherein the cartridge assembly does not include a pressure sensor.
[0190] Example 1 1 . The apparatus of any one of the preceding Examples, wherein the flow cell assembly does not include a pressure sensor.
[0191] Example 12. The apparatus of any one of the preceding Examples, wherein the system comprises a controller and wherein the controller is to generate an alert if the controller identifies at least one of the cartridge assembly or the flow cell assembly as having a leak.
[0192] Example 13. The apparatus of any one of the preceding Examples, wherein the flow cell assembly carries an outlet gasket and wherein the cartridge assembly comprises a pump coupled to at least one of the outlet gasket of the flow cell assembly or between the well and the flow cell assembly.
[0193] Example 14. The apparatus of Example 13, wherein the pump comprises a syringe pump.
[0194] Example 15. The apparatus of any one of the preceding Examples, further comprising dried reagent contained within the well and wherein a pump is used to flow rehydrated dried reagent from the well to the flow cell.
[0195] Example 16. The apparatus of any one of the preceding Examples, wherein the cartridge assembly comprises a valve coupled between the outlet port of the cartridge assembly and the well and wherein the system comprises a valve drive assembly to interface with the valve.
[0196] Example 17. The apparatus of any one of any one of the preceding Examples, wherein the body of the flow cell assembly carries a flow cell outlet gasket and an outlet gasket and comprising a fluidic aperture and wherein the flow cell comprises a flow cell inlet and a flow cell outlet, the flow cell inlet fluidly coupled to the flow cell inlet gasket and the flow cell outlet fluidly coupled to the flow cell outlet gasket.
[0197] Example 18. The apparatus of Example 17, wherein the flow cell assembly comprises a first laminate coupled to the body of the flow cell assembly and forming a first fluidic channel
between the flow cell outlet gasket and the fluidic aperture and a second laminate coupled to the body of the flow cell assembly and forming a second fluidic channel between the fluidic aperture and the outlet gasket.
[0198] Example 19. The apparatus of Example 18, wherein the body comprises a first groove and a second groove, the first laminate covering the first groove to form the first fluidic channel and the second laminate covering the second groove to form the second fluidic channel.
[0199] Example 20. The apparatus of any one of the preceding Examples, wherein the flow cell assembly is coupled to the cartridge assembly by a coupling.
[0200] Example 21 . The apparatus of Example 20, wherein the coupling comprises a snap fit connection.
[0201] Example 22. The apparatus of any one of the preceding Examples, wherein the sensor assembly comprises a die.
[0202] Example 23. The apparatus of Example 22, wherein the die comprises the thermal sensor.
[0203] Example 24. The apparatus of any one of Examples 22 - 23, wherein the die comprises a complementary metal-oxide semiconductor.
[0204] Example 25. The apparatus of any one of Examples 22 - 24, wherein the sensor assembly comprises a printed circuit board and wherein the heater is positioned between the die and the printed circuit board.
[0205] Example 26. The apparatus of any one of the preceding Examples, further comprising a liquid reservoir receivable within the receptacle and having a body comprising a storage chamber, and a fluidic port fluidly coupled to the storage chamber, wherein the cartridge assembly comprises: a fluidic interface couplable to the fluidic port; and a channel fluidly coupled between the fluidic interface and the well.
[0206] Example 27. The apparatus of Example 26, wherein the system comprises a pneumatic interface and the body of the liquid reservoir comprises a pneumatic port fluidly couplable to the storage chamber.
[0207] Example 28. The apparatus of any one of the preceding Examples, wherein the system comprises a dry instrument.
[0208] Example 29. An apparatus, comprising: a cartridge assembly, comprising: a well; and an outlet port fluidly coupled to the well; a flow cell assembly, comprising: a body; a flow cell
supported by the body and comprising a channel; and a sensor assembly comprising a heater and a thermal sensor, wherein the outlet port is fluidly coupled to the flow cell, wherein a leak test is to be performed on the cartridge assembly and the flow cell assembly using the thermal sensor.
[0209] Example 30. The apparatus of Example 29, wherein the cartridge assembly comprises a valve coupled between the outlet port of the cartridge assembly and the well.
[0210] Example 31 . The apparatus of any one of Examples 29 - 30, wherein the cartridge assembly comprises a pump coupled to at least one of the outlet gasket of the flow cell assembly or between the well and the flow cell assembly.
[0211] Example 32. The apparatus of any one of Examples 29 - 31 , wherein the flow cell assembly comprises a second flow cell supported by the body.
[0212] Example 33. The apparatus of Example 32, wherein the flow cell and the second flow cell are fluidly coupled in series.
[0213] Example 34. The apparatus of any one of Examples 32 - 33, wherein the flow cell outlet of the flow cell is fluidly coupled to the flow cell outlet gasket via the second flow cell.
[0214] Example 35. The apparatus of any one of Examples 29 - 34, further comprising a second flow cell assembly comprising a second flow cell different than the flow cell, the second flow cell assembly couplable to the cartridge assembly in place of the flow cell assembly.
[0215] Example 36. The apparatus of Example 35, further comprising a third flow cell assembly comprising a third flow cell and a fourth flow cell, the third flow cell assembly couplable to the cartridge assembly in place of the flow cell assembly and in place of the second flow cell assembly.
[0216] Example 37. An apparatus, comprising: a cartridge assembly; and a first flow cell assembly including a first flow cell and a first sensor assembly comprising a heater and a thermal sensor; and a second flow cell assembly including a second flow cell different than the first flow cell, the second flow cell assembly comprises a second sensor assembly comprising a heater and a thermal sensor, wherein the first flow cell assembly and the second flow cell assembly are interchangeably mechanically and fluidly couplable with the cartridge assembly, wherein a leak test is to be performed on the cartridge assembly and the first flow cell assembly when coupled using the thermal sensor of the first sensor assembly, and wherein a leak test is
to be performed on the cartridge assembly and the second flow cell assembly when coupled using the thermal sensor of the second sensor assembly.
[0217] Example 38. An apparatus comprising: a system, comprising: a receptacle; a liquid reservoir receivable within the receptacle and having: a body comprising a storage chamber, and a fluidic port fluidly coupled to the storage chamber; a cartridge assembly, comprising: a fluidic interface couplable to the fluidic port; a well; a channel fluidly coupled between the fluidic interface and the well; and an outlet port fluidly coupled to the well; and a flow cell assembly, comprising: a body carrying a flow cell inlet gasket and an outlet gasket; a flow cell supported by the body and comprising a channel; and a sensor assembly comprising a heater and a thermal sensor, wherein the outlet port is fluidly coupled to the flow cell inlet gasket, wherein a leak test is to be performed on the cartridge assembly and the flow cell assembly using the thermal sensor.
[0218] Example 39. A method, comprising: heating a flow cell to a threshold temperature using a heater of a flow cell assembly, the flow cell assembly coupled to a cartridge assembly and positioned in a receptacle of a system; flowing reagent into the flow cell; accessing, using a controller, a measured temperature value from a thermal sensor of the flow cell assembly; and determining, using the controller, a presence of a leak in at least one of the cartridge assembly or the flow cell assembly based on the measured temperature value.
[0219] Example 40. The method of Example 39, further comprising priming the cartridge assembly and the flow cell assembly with reagent prior to heating the flow cell to the threshold temperature.
[0220] Example 41 . The method of any one of Examples 39 - 40, wherein determining the presence of the leak comprises determining, using the controller, a difference between the measured temperature value and a reference temperature value and identifying, using the controller, at least one of the cartridge assembly or the flow cell assembly having the leak if the difference is greater than a threshold.
[0221] Example 42. The method of any one of Examples 39 - 41 , wherein determining the presence of the leak comprises actuating a valve of the cartridge assembly to a closed position, generating a vacuum in at least one of the cartridge assembly or the flow cell assembly using the pump, heating the flow cell to a threshold temperature using a heater of the flow cell assembly, actuating the valve to an open position, flowing the reagent from the cartridge
assembly to the flow cell using the pump, and determining a plurality of temperature values of the flow cell using the thermal sensor.
[0222] Example 43. The method any one of Examples 39 - 42, wherein determining, using the controller, the presence of the leak comprises accessing measured temperature values from the thermal sensor, determining, using the controller, a difference between the measured temperature values, and identifying, using the controller, at least one of the cartridge assembly or the flow cell assembly having the leak if the difference between the measured temperature values is greater than a threshold.
[0223] Example 44. The method of any one of Examples 39 - 43, further comprising generating an alert if the controller determines the presence of the leak in at least one of the cartridge assembly or the flow cell assembly.
[0224] Example 45. The method of any one of Examples 39 - 44, further comprising flowing reagent under positive pressure into the cartridge assembly comprising dry reagent to rehydrate the dry reagent, the cartridge assembly comprising a well and an outlet port fluidly coupled to the well, wherein flowing reagent from the cartridge assembly into the flow cell comprises flowing the rehydrated reagent into a flow cell inlet gasket of the flow cell assembly using a pump, the flow cell assembly comprising a body carrying the flow cell inlet gasket and a flow cell supported by the body, the flow cell inlet gasket fluidly coupled to the outlet port and the flow cell.
[0225] Example 46. The method of Example 45, wherein flowing the reagent under positive pressure comprises pressurizing a storage chamber of a liquid reservoir comprising the reagent and flowing the reagent from the storage chamber to the cartridge assembly.
[0226] Example 47. The method of any one of Examples 38 - 46, wherein flowing reagent into the flow cell comprises flowing reagent from the cartridge assembly.
[0227] Example 48. The method of any one of Examples 38 - 47, wherein flowing reagent into the flow cell comprises flowing reagent from a well of the cartridge assembly.
[0228] Example 49. The method of any one of Examples 38 - 48, wherein flowing reagent into the flow cell comprises flowing reagent into the flow cell using a pump of the cartridge assembly.
[0229] Example 50. The method of any one of Examples 38 - 48, wherein flowing reagent into the flow cell comprises flowing reagent into the flow cell under positive pressure.
[0230] Example 51 . An apparatus comprising: a system, comprising: a receptacle; a cartridge assembly receivable within the receptacle, the cartridge assembly comprising: a well comprising reagent; and an outlet port fluidly coupled to the well; and a flow cell assembly, comprising: a body carrying a flow cell inlet gasket; a flow cell supported by the body and comprising a channel; and a sensor assembly comprising a thermal sensor, wherein the outlet port is fluidly coupled to the flow cell inlet gasket, wherein the reagent is preheated prior to entering the channel of the flow cell using a heater of at least one of the system or the cartridge assembly, wherein a leak test is to be performed on the cartridge assembly and the flow cell assembly using the thermal sensor.
[0231] Example 52. The apparatus of Example 51 , wherein the system comprises the heater.
[0232] Example 53. The apparatus of Example 51 , wherein the cartridge assembly comprises the heater.
[0233] Example 54. The apparatus of any one of Examples 51 - 53, wherein the leak test comprises not heating the flow cell.
[0234] Example 55. The apparatus of any one of Examples 51 - 54, wherein the system comprises a controller and wherein the leak test comprises 1 ) flowing the preheated reagent into the flow cell using a pump, 2) accessing a measured temperature value from the thermal sensor using the controller, 3) determining a difference between the measured temperature value and a reference temperature value using the controller, and 4) identifying at least one of the cartridge assembly or the flow cell assembly having a leak if the difference is greater than a threshold using the controller.
[0235] Example 56. A method, comprising: preheating reagent to a threshold temperature using a heater; flowing the pre-heated reagent into a flow cell, the flow cell assembly coupled to a cartridge assembly and positioned in a receptacle of a system; accessing, using a controller, a measured temperature value from a thermal sensor of the flow cell assembly; and determining, using the controller, a presence of a leak in at least one of the cartridge assembly or the flow cell assembly based on the measured temperature value.
[0236] Example 57. The method of Example 56, wherein flowing the preheated reagent into the flow cell comprises flowing the preheated reagent from a well of the cartridge assembly.
[0237] Example 58. The method of Example 57, wherein flowing the preheated reagent into the flow cell comprises flowing the preheated reagent into the flow cell comprises using a pump of the cartridge assembly.
[0238] Example 59. The method of any one of Examples 56 - 57, wherein flowing the preheated reagent into the flow cell comprises flowing the preheated reagent into the flow cell under positive pressure.
[0239] Example 60. The apparatus of any one of Examples 1 - 28, and 38, wherein the system does not include a pressure sensor.
[0240] Example 61 . The apparatus of any one of Examples 1 - 28, wherein the leak test comprises the flow cell being heated to a threshold temperature using the heater after the flow cell is primed, reagent being flowed from the cartridge assembly into the flow cell inlet gasket and the flow cell, and a temperature value of the flow cell being measured using the thermal sensor.
[0241] Example 62. The apparatus of Example 60, wherein the reagent is to be flowed from the cartridge assembly into the flow cell inlet gasket and the flow cell under positive pressure.
[0242] Example 63. The apparatus of Example 60, wherein the cartridge assembly comprises a pump, and wherein the reagent is to be flowed from the cartridge assembly into the flow cell inlet gasket and the flow cell using the pump of the cartridge assembly.
[0243] 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.
[0244] While cartridges and reservoirs are described herein with regard to reagent cartridges and reagent reservoirs, these cartridges or reservoirs may also be used to house other liquids, including without limitation buffers, samples, and washes, either separate from or in combination with reagents or other liquids. For example, a cartridge may have a first chamber housing a reagent, a second chamber housing a buffer, and a third chamber housing a wash.
Furthermore, the cartridges and reservoirs described herein may include one or more additional chambers that may be used, for example, as waste chambers on the cartridge that may or may not include corresponding sipper chambers.
[0245] 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.
[0246] 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%.
[0247] The terms “connect,” “connected,” “contact,” “coupled” and/or the like are broadly defined herein to encompass a variety of divergent arrangements and assembly techniques. These arrangements and techniques include, but are not limited to (1 ) the direct joining of one component and another component with no intervening components therebetween (/.e., the components are in direct physical contact); and (2) the joining of one component and another component with one or more components therebetween, provided that the one component being “connected to” or “contacting” or “coupled to” the other component is somehow in operative communication (e.g., electrically, fluidly, physically, optically, etc.) with the other component (notwithstanding the presence of one or more additional components therebetween). It is to be understood that some components that are in direct physical contact with one another may or may not be in electrical contact and/or fluid contact with one another. Moreover, two components that are electrically connected, electrically coupled, optically connected, optically coupled, fluidly connected or fluidly coupled may or may not be in direct physical contact, and one or more other components may be positioned therebetween.
[0248] 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.
[0249] 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.
[0250] 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.
Claims
1 . An apparatus comprising: a system, comprising: a receptacle; a cartridge assembly receivable within the receptacle, the cartridge assembly comprising: a well; and an outlet port fluidly coupled to the well; and a flow cell assembly, comprising: a body; a flow cell supported by the body and comprising a channel; and a sensor assembly comprising a heater and a thermal sensor, wherein the outlet port is fluidly coupled to the flow cell, wherein a leak test is to be performed on the cartridge assembly and the flow cell assembly using the thermal sensor.
2. The apparatus of claim 1 , wherein the system comprises a controller and wherein the leak test comprisesl ) priming the cartridge assembly and the flow cell assembly, 2) accessing a measured temperature value from the thermal sensor using the controller, 3) determining a difference between the measured temperature value and a reference temperature value using the controller, and 4) identifying at least one of the cartridge assembly or the flow cell assembly having a leak if the difference is greater than a threshold using the controller.
3. The apparatus of claim 2, wherein the reference temperature is between about 40°C and about 60°C.
4. The apparatus of any one of claims 2 - 3, wherein the reference temperature is about 55"C.
5. The apparatus of any one of the preceding claims, wherein the leak test comprises the flow cell being heated to a threshold temperature using the heater after the flow
cell is primed, reagent being flowed from the cartridge assembly into the flow cell using a pump, and a temperature value of the flow cell being measured using the thermal sensor.
6. The apparatus of any one of the preceding claims, wherein the cartridge assembly comprises a pump and wherein the leak test comprises 1) a valve being actuated to a closed position, 2) a vacuum being generated in at least one of the cartridge assembly or the flow cell assembly using the pump, 3) the flow cell being heated to a threshold temperature using the heater, 4) the valve being actuated to an open position, 5) reagent being flowed from the cartridge assembly into the flow cell assembly and the channel of the flow cell using the pump, and 6) a plurality of temperature values of the flow cell being measured using the thermal sensor.
7. The apparatus of any of the preceding claims, wherein the system comprises a controller and wherein the leak test comprises accessing measured temperature values from the thermal sensor using the controller, determining a difference between the measured temperature values using the controller, and identifying at least one of the cartridge assembly or the flow cell assembly having a leak if the difference between the measured temperature values is greater than a threshold using the controller.
8. The apparatus of claim 7, wherein the threshold is between about 2 degrees Celsius and about 15 degrees Celsius.
9. The apparatus of any one of claims 7 - 8, wherein the threshold is about 3 degrees Celsius.
10. The apparatus of anyone of the preceding claims, wherein the cartridge assembly does not include a pressure sensor.
11 . The apparatus of any one of the preceding claims, wherein the flow cell assembly does not include a pressure sensor.
12. The apparatus of any one of the preceding claims, wherein the system comprises a controller and wherein the controller is to generate an alert if the controller identifies at least one of the cartridge assembly or the flow cell assembly as having a leak.
13. The apparatus of any one of the preceding claims, wherein the flow cell assembly carries an outlet gasket and wherein the cartridge assembly comprises a pump coupled to at least one of the outlet gasket of the flow cell assembly or between the well and the flow cell assembly.
14. The apparatus of claim 13, wherein the pump comprises a syringe pump.
15. The apparatus of any one of the preceding claims, further comprising dried reagent contained within the well and wherein a pump is used to flow rehydrated dried reagent from the well to the flow cell.
16. The apparatus of any one of the preceding claims, wherein the cartridge assembly comprises a valve coupled between the outlet port of the cartridge assembly and the well and wherein the system comprises a valve drive assembly to interface with the valve.
17. The apparatus of any one of any one of the preceding claims, wherein the body of the flow cell assembly carries a flow cell outlet gasket and an outlet gasket and comprising a fluidic aperture and wherein the flow cell comprises a flow cell inlet and a flow cell outlet, the flow cell inlet fluidly coupled to the flow cell inlet gasket and the flow cell outlet fluidly coupled to the flow cell outlet gasket.
18. The apparatus of claim 17, wherein the flow cell assembly comprises a first laminate coupled to the body of the flow cell assembly and forming a first fluidic channel between the flow cell outlet gasket and the fluidic aperture and a second laminate coupled to the body of the flow cell assembly and forming a second fluidic channel between the fluidic aperture and the outlet gasket.
19. The apparatus of claim 18, wherein the body comprises a first groove and a second groove, the first laminate covering the first groove to form the first fluidic channel and the second laminate covering the second groove to form the second fluidic channel.
20. The apparatus of any one of the preceding claims, wherein the flow cell assembly is coupled to the cartridge assembly by a coupling.
21 . The apparatus of claim 20, wherein the coupling comprises a snap fit connection.
22. The apparatus of any one of the preceding claims, wherein the sensor assembly comprises a die.
23. The apparatus of claim 22, wherein the die comprises the thermal sensor.
24. The apparatus of any one of claims 22 - 23, wherein the die comprises a complementary metal-oxide semiconductor.
25. The apparatus of any one of claims 22 - 24, wherein the sensor assembly comprises a printed circuit board and wherein the heater is positioned between the die and the printed circuit board.
26. The apparatus of any one of the preceding claims, further comprising a liquid reservoir receivable within the receptacle and having a body comprising a storage chamber, and a fluidic port fluidly coupled to the storage chamber, wherein the cartridge assembly comprises: a fluidic interface couplable to the fluidic port; and a channel fluidly coupled between the fluidic interface and the well.
27. The apparatus of claim 26, wherein the system comprises a pneumatic interface and the body of the liquid reservoir comprises a pneumatic port fluidly couplable to the storage chamber.
28. The apparatus of any one of the preceding claims, wherein the system comprises a dry instrument.
29. An apparatus, comprising: a cartridge assembly, comprising: a well; and an outlet port fluidly coupled to the well; a flow cell assembly, comprising: a body; a flow cell supported by the body and comprising a channel; and a sensor assembly comprising a heater and a thermal sensor, wherein the outlet port is fluidly coupled to the flow cell, wherein a leak test is to be performed on the cartridge assembly and the flow cell assembly using the thermal sensor.
30. The apparatus of claim 29, wherein the cartridge assembly comprises a valve coupled between the outlet port of the cartridge assembly and the well.
31 . The apparatus of any one of claims 29 - 30, wherein the cartridge assembly comprises a pump coupled to at least one of the outlet gasket of the flow cell assembly or between the well and the flow cell assembly.
32. The apparatus of any one of claims 29 - 31 , wherein the flow cell assembly comprises a second flow cell supported by the body.
33. The apparatus of claim 32, wherein the flow cell and the second flow cell are fluidly coupled in series.
34. The apparatus of any one of claims 32 - 33, wherein the flow cell outlet of the flow cell is fluidly coupled to the flow cell outlet gasket via the second flow cell.
35. The apparatus of any one of claims 29 - 34, further comprising a second flow cell assembly comprising a second flow cell different than the flow cell, the second flow cell assembly couplable to the cartridge assembly in place of the flow cell assembly.
36. The apparatus of claim 35, further comprising a third flow cell assembly comprising a third flow cell and a fourth flow cell, the third flow cell assembly couplable to the cartridge assembly in place of the flow cell assembly and in place of the second flow cell assembly.
37. An apparatus, comprising: a cartridge assembly; and a first flow cell assembly including a first flow cell and a first sensor assembly comprising a heater and a thermal sensor; and a second flow cell assembly including a second flow cell different than the first flow cell, the second flow cell assembly comprises a second sensor assembly comprising a heater and a thermal sensor, wherein the first flow cell assembly and the second flow cell assembly are interchangeably mechanically and fluidly couplable with the cartridge assembly, wherein a leak test is to be performed on the cartridge assembly and the first flow cell assembly when coupled using the thermal sensor of the first sensor assembly, and wherein a leak test is to be performed on the cartridge assembly and the second flow cell assembly when coupled using the thermal sensor of the second sensor assembly.
38. An apparatus comprising: a system, comprising: a receptacle; a liquid reservoir receivable within the receptacle and having: a body comprising a storage chamber, and a fluidic port fluidly coupled to the storage chamber; a cartridge assembly, comprising: a fluidic interface couplable to the fluidic port; a well; a channel fluidly coupled between the fluidic interface and the well; and an outlet port fluidly coupled to the well; and a flow cell assembly, comprising:
a body carrying a flow cell inlet gasket and an outlet gasket; a flow cell supported by the body and comprising a channel; and a sensor assembly comprising a heater and a thermal sensor, wherein the outlet port is fluidly coupled to the flow cell inlet gasket, wherein a leak test is to be performed on the cartridge assembly and the flow cell assembly using the thermal sensor.
39. A method, comprising: heating a flow cell to a threshold temperature using a heater of a flow cell assembly, the flow cell assembly coupled to a cartridge assembly and positioned in a receptacle of a system; flowing reagent into the flow cell; accessing, using a controller, a measured temperature value from a thermal sensor of the flow cell assembly; and determining, using the controller, a presence of a leak in at least one of the cartridge assembly or the flow cell assembly based on the measured temperature value.
40. The method of claim 39, further comprising priming the cartridge assembly and the flow cell assembly with reagent prior to heating the flow cell to the threshold temperature.
41 . The method of any one of claims 39 - 40, wherein determining the presence of the leak comprises determining, using the controller, a difference between the measured temperature value and a reference temperature value and identifying, using the controller, at least one of the cartridge assembly or the flow cell assembly having the leak if the difference is greater than a threshold.
42. The method of any one of claims 39 - 41 , wherein determining the presence of the leak comprises actuating a valve of the cartridge assembly to a closed position, generating a vacuum in at least one of the cartridge assembly or the flow cell assembly using the pump, heating the flow cell to a threshold temperature using a heater of the flow cell assembly, actuating the valve to an open position, flowing the reagent from the cartridge assembly to the flow cell using the pump, and determining a plurality of temperature values of the flow cell using the thermal sensor.
43. The method any one of claims 39 - 42, wherein determining, using the controller, the presence of the leak comprises accessing measured temperature values from the thermal sensor, determining, using the controller, a difference between the measured temperature values, and identifying, using the controller, at least one of the cartridge assembly or the flow cell assembly having the leak if the difference between the measured temperature values is greater than a threshold.
44. The method of any one of claims 39 - 43, further comprising generating an alert if the controller determines the presence of the leak in at least one of the cartridge assembly or the flow cell assembly.
45. The method of any one of claims 39 - 44, further comprising flowing reagent under positive pressure into the cartridge assembly comprising dry reagent to rehydrate the dry reagent, the cartridge assembly comprising a well and an outlet port fluidly coupled to the well, wherein flowing reagent from the cartridge assembly into the flow cell comprises flowing the rehydrated reagent into a flow cell inlet gasket of the flow cell assembly using a pump, the flow cell assembly comprising a body carrying the flow cell inlet gasket and a flow cell supported by the body, the flow cell inlet gasket fluidly coupled to the outlet port and the flow cell.
46. The method of claim 45, wherein flowing the reagent under positive pressure comprises pressurizing a storage chamber of a liquid reservoir comprising the reagent and flowing the reagent from the storage chamber to the cartridge assembly.
47. The method of any one of claims 38 - 46, wherein flowing reagent into the flow cell comprises flowing reagent from the cartridge assembly.
48. The method of any one of claims 38 - 47, wherein flowing reagent into the flow cell comprises flowing reagent from a well of the cartridge assembly.
49. The method of any one of claims 38 - 48, wherein flowing reagent into the flow cell comprises flowing reagent into the flow cell using a pump of the cartridge assembly.
50. The method of any one of claims 38 - 48, wherein flowing reagent into the flow cell comprises flowing reagent into the flow cell under positive pressure.
51 . An apparatus comprising: a system, comprising: a receptacle; a cartridge assembly receivable within the receptacle, the cartridge assembly comprising: a well comprising reagent; and an outlet port fluidly coupled to the well; and a flow cell assembly, comprising: a body carrying a flow cell inlet gasket; a flow cell supported by the body and comprising a channel; and a sensor assembly comprising a thermal sensor, wherein the outlet port is fluidly coupled to the flow cell inlet gasket, wherein the reagent is preheated prior to entering the channel of the flow cell using a heater of at least one of the system or the cartridge assembly, wherein a leak test is to be performed on the cartridge assembly and the flow cell assembly using the thermal sensor.
52. The apparatus of claim 51 , wherein the system comprises the heater.
53. The apparatus of claim 51 , wherein the cartridge assembly comprises the heater.
54. The apparatus of any one of claims 51 - 53, wherein the leak test comprises not heating the flow cell.
55. The apparatus of any one of claims 51 - 54, wherein the system comprises a controller and wherein the leak test comprises 1 ) flowing the preheated reagent into the flow cell using a pump, 2) accessing a measured temperature value from the thermal sensor using the controller, 3) determining a difference between the measured temperature value and a reference temperature value using the controller, and 4) identifying at least one of the cartridge assembly or the flow cell assembly having a leak if the difference is greater than a threshold using the controller.
56. A method, comprising: preheating reagent to a threshold temperature using a heater; flowing the pre-heated reagent into a flow cell, the flow cell assembly coupled to a cartridge assembly and positioned in a receptacle of a system; accessing, using a controller, a measured temperature value from a thermal sensor of the flow cell assembly; and
determining, using the controller, a presence of a leak in at least one of the cartridge assembly or the flow cell assembly based on the measured temperature value.
57. The method of claim 56, wherein flowing the preheated reagent into the flow cell comprises flowing the preheated reagent from a well of the cartridge assembly.
58. The method of claim 57, wherein flowing the preheated reagent into the flow cell comprises flowing the preheated reagent into the flow cell comprises using a pump of the cartridge assembly.
59. The method of any one of claims 56 - 57, wherein flowing the preheated reagent into the flow cell comprises flowing the preheated reagent into the flow cell under positive pressure.
60. The apparatus of any one of claims 1 - 28, and 38, wherein the system does not include a pressure sensor.
61 . The apparatus of any one of claims 1 - 28, wherein the leak test comprises the flow cell being heated to a threshold temperature using the heater after the flow cell is primed, reagent being flowed from the cartridge assembly into the flow cell inlet gasket and the flow cell, and a temperature value of the flow cell being measured using the thermal sensor.
62. The apparatus of claim 60, wherein the reagent is to be flowed from the cartridge assembly into the flow cell inlet gasket and the flow cell under positive pressure.
63. The apparatus of claim 60, wherein the cartridge assembly comprises a pump, and wherein the reagent is to be flowed from the cartridge assembly into the flow cell inlet gasket and the flow cell using the pump of the cartridge assembly.
64. The apparatus of claim 1 , wherein the leak test comprises the flow cell being heated to a threshold temperature using the heater after the flow cell is primed, reagent being flowed from the cartridge assembly into the flow cell using a pump, and a temperature value of the flow cell being measured using the thermal sensor.
65. The apparatus of claim 1 , wherein the cartridge assembly comprises a pump and wherein the leak test comprises 1 ) a valve being actuated to a closed position, 2) a vacuum being generated in at least one of the cartridge assembly or the flow cell assembly using the pump, 3) the flow cell being heated to a threshold temperature using the heater, 4) the valve being actuated to an open position, 5) reagent being flowed from the cartridge assembly into the flow cell assembly and the channel of the flow cell using the pump, and 6) a plurality of temperature values of the flow cell being measured using the thermal sensor.
66. The apparatus of claim 1 , wherein the system comprises a controller and wherein the leak test comprises accessing measured temperature values from the thermal sensor using
the controller, determining a difference between the measured temperature values using the controller, and identifying at least one of the cartridge assembly or the flow cell assembly having a leak if the difference between the measured temperature values is greater than a threshold using the controller.
67. The apparatus of claim 1 , wherein the cartridge assembly does not include a pressure sensor.
68. The apparatus of claim 1 , wherein the flow cell assembly does not include a pressure sensor.
69. The method of claim 39, wherein determining the presence of the leak comprises actuating a valve of the cartridge assembly to a closed position, generating a vacuum in at least one of the cartridge assembly or the flow cell assembly using the pump, heating the flow cell to a threshold temperature using a heater of the flow cell assembly, actuating the valve to an open position, flowing the reagent from the cartridge assembly to the flow cell using the pump, and determining a plurality of temperature values of the flow cell using the thermal sensor.
70. The method of claim 39, wherein determining, using the controller, the presence of the leak comprises accessing measured temperature values from the thermal sensor, determining, using the controller, a difference between the measured temperature values, and identifying, using the controller, at least one of the cartridge assembly or the flow cell assembly having the leak if the difference between the measured temperature values is greater than a threshold.
71 . The method of claim 39, further comprising flowing reagent under positive pressure into the cartridge assembly comprising dry reagent to rehydrate the dry reagent, the cartridge assembly comprising a well and an outlet port fluidly coupled to the well, wherein flowing reagent from the cartridge assembly into the flow cell comprises flowing the rehydrated reagent into a flow cell inlet gasket of the flow cell assembly using a pump, the flow cell assembly comprising a body carrying the flow cell inlet gasket and a flow cell supported by the body, the flow cell inlet gasket fluidly coupled to the outlet port and the flow cell.
72. The apparatus of claim 51 , wherein the system comprises a controller and wherein the leak test comprises 1 ) flowing the preheated reagent into the flow cell using a pump, 2) accessing a measured temperature value from the thermal sensor using the controller, 3) determining a difference between the measured temperature value and a reference temperature value using the controller, and 4) identifying at least one of the cartridge assembly or the flow cell assembly having a leak if the difference is greater than a threshold using the controller.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202463650127P | 2024-05-21 | 2024-05-21 | |
| US63/650,127 | 2024-05-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2025244815A1 true WO2025244815A1 (en) | 2025-11-27 |
Family
ID=95895824
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US2025/027429 Pending WO2025244815A1 (en) | 2024-05-21 | 2025-05-02 | Flow cell assemblies and related systems and methods |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2025244815A1 (en) |
-
2025
- 2025-05-02 WO PCT/US2025/027429 patent/WO2025244815A1/en active Pending
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