System and related temperature calibration method

Abstract

Systems and related temperature calibration methods are provided. According to a first particular implementation, an apparatus includes a flow cell interface, a temperature control device, an infrared sensor, and a controller. The flow cell interface includes a flow cell support, and the temperature control device is for the flow cell support. The controller is to command the temperature control device to cause the flow cell support to reach a temperature value, cause the infrared sensor to measure an actual temperature value of the flow cell support, and calibrate the temperature control device based on a difference between the commanded temperature value and the actual temperature value.

Description

[0001] Related application section

[0002] This application claims the benefit and priority of U.S. Provisional Patent Application No. 63 / 293,294, filed December 23, 2021, the entire contents of which are incorporated herein by reference and used for all purposes. Background Technology

[0003] Instruments such as sequencing instruments may include temperature control components. Summary of the Invention

[0004] By providing the system and associated temperature calibration methods, the disadvantages of the prior art can be overcome, and the benefits described later in this disclosure can be achieved. Various specific embodiments of the apparatus and methods are described below, and these apparatus and methods (including and excluding the additional specific embodiments listed below) in any combination (provided that such combinations are not inconsistent) can overcome these disadvantages and achieve the beneficial effects described herein.

[0005] According to a first embodiment, an apparatus includes a flow cell interface, a temperature controller, an infrared sensor, and a controller. The flow cell interface includes a flow cell support, and the temperature controller is used with respect to the flow cell support. The controller is configured to command the temperature controller to bring the flow cell support to a certain temperature, to cause the infrared sensor to measure the actual temperature of the flow cell support, and to calibrate the temperature controller based on the difference between the commanded temperature value and the actual temperature value.

[0006] According to a second embodiment, a method includes commanding a temperature controller of a system to bring a flow cell support to a temperature value. The method further includes measuring the actual temperature value of the flow cell support using an infrared sensor and calibrating the temperature controller based on the difference between the commanded temperature value and the actual temperature value.

[0007] According to a third embodiment, a method includes commanding a temperature controller of a system to bring a flow cell support to a temperature value, and using an infrared sensor to measure multiple actual temperature values ​​of the flow cell support. The method further includes determining an average actual temperature value based on the multiple actual temperature values, and calibrating the temperature controller based on the difference between the commanded temperature value and the average actual temperature value.

[0008] According to a fourth embodiment, an apparatus includes a flow cell interface, a temperature controller, an infrared sensor, and a controller. The flow cell interface includes a flow cell support, and the temperature controller is used with respect to the flow cell support. The controller commands the temperature controller to bring the flow cell support to a certain temperature, and causes the infrared sensor to measure multiple actual temperature values ​​of the flow cell support.

[0009] According to a fifth embodiment, a method includes commanding a temperature controller to bring a flow cell support to a temperature value; measuring the actual temperature value of the flow cell set on the flow cell support using an infrared sensor; comparing the commanded temperature value with the actual temperature value; and generating an alarm when the difference between the commanded temperature value and the actual temperature value is greater than a threshold.

[0010] According to a sixth embodiment, an apparatus includes a flow cell interface, a temperature controller, an infrared sensor, a temperature sensor, and a controller. The flow cell interface includes a flow cell support, and the temperature controller is used in the flow cell support. The infrared sensor is used to measure a first temperature value adjacent to the temperature sensor; the temperature sensor is used to measure a second temperature value; and the controller is used to calibrate the infrared sensor based on the difference between the first temperature value and the second temperature value.

[0011] According to a seventh embodiment, an apparatus includes a flow cell interface, a temperature controller, an infrared sensor, and a controller. The flow cell interface includes a flow cell support, and the temperature controller is used with respect to the flow cell support. The controller commands the temperature controller to bring the flow cell support to a certain temperature, and causes the infrared sensor to measure multiple actual temperature values ​​of the flow cell support.

[0012] Further according to the aforementioned first, second, third, fourth, fifth, sixth, and / or seventh embodiments, an apparatus and / or method may also include any one or more of the following:

[0013] According to one specific implementation, the temperature control device includes a thermoelectric cooler.

[0014] According to another specific embodiment, the temperature control device includes a resistance temperature detector.

[0015] According to another specific implementation, the controller is used to calibrate the temperature control device by calibrating the resistance temperature detector.

[0016] In another embodiment, the device includes an imaging system. The infrared sensor is coupled to the imaging system.

[0017] According to another specific embodiment, the device includes a bracket that connects the infrared sensor to the imaging system.

[0018] According to another specific implementation, the controller is also used to calibrate the infrared sensor.

[0019] According to another embodiment, the device further includes a temperature sensor. The infrared sensor is used to measure a first temperature value adjacent to the temperature sensor, the temperature sensor is used to measure a second temperature value, and the controller is used to calibrate the infrared sensor based on the difference between the first temperature value and the second temperature value.

[0020] In another embodiment, the flow cell interface also includes a flow cell platform that supports the flow cell support. The temperature sensor is connected to the flow cell platform.

[0021] According to another embodiment, the device includes a printed circuit board coupled to the temperature sensor. The printed circuit board is positioned between the temperature sensor and the flow cell platform.

[0022] According to another embodiment, the device includes a metal layer covering the surface of the temperature sensor.

[0023] According to another specific embodiment, the surfaces of the metal layer and the flow cell support have substantially similar emissivity.

[0024] In another embodiment, the temperature sensor and the metal layer are separated from the flow cell support.

[0025] In another specific embodiment, the metal layer comprises aluminum.

[0026] According to another embodiment, the device includes a thermally conductive epoxy resin that connects the temperature sensor to the metal layer.

[0027] According to another embodiment, the device further includes a temperature sensor. The infrared sensor is used to measure a first temperature value at the flow cell support, the temperature sensor is used to measure a second temperature value at the flow cell support, and the controller is used to calibrate the infrared sensor based on the difference between the first temperature value and the second temperature value.

[0028] In another embodiment, the temperature sensor is connected to the flow cell support.

[0029] According to another embodiment, the device also includes a printed circuit board coupled to the temperature sensor. The temperature sensor is positioned between the flow cell interface and the printed circuit board.

[0030] According to another specific embodiment, the surface of the flow pool support includes a metal layer.

[0031] According to another specific embodiment, the temperature sensor includes a digital temperature sensor.

[0032] According to another specific embodiment, commanding the temperature controller to bring the flow cell support to a temperature value includes: commanding the thermoelectric cooler to bring the flow cell support to the temperature value; and measuring the temperature value using a resistance temperature detector.

[0033] According to another specific embodiment, measuring the actual temperature value of the flow cell support using the infrared sensor includes measuring the actual temperature value of the flow cell support using the infrared sensor while moving the flow cell interface relative to the infrared sensor.

[0034] According to another embodiment, the method further includes commanding the temperature controller to bring the flow cell support to a second temperature value; using the infrared sensor to measure a second actual temperature value of the flow cell set on the flow cell support; comparing the commanded second temperature value with the second actual temperature value; and recalibrating the temperature controller based on the comparison.

[0035] According to another embodiment, the method further includes: causing the system to perform at least a portion of an analysis on one or more samples of interest in a flow cell disposed on the flow cell support; commanding the temperature controller to bring the flow cell support to a second temperature value; using the infrared sensor to measure a second actual temperature value of the flow cell disposed on the flow cell support; comparing the commanded second temperature value with the second actual temperature value; and recalibrating the temperature controller based on the comparison.

[0036] According to another specific implementation, calibrating the temperature controller is in response to receiving a command to calibrate the temperature controller at the controller.

[0037] According to another specific implementation, receiving the command to calibrate the temperature controller at the controller includes receiving the command from a remote computing device.

[0038] According to another specific implementation, receiving the command to calibrate the temperature controller at the controller includes receiving user input at the system's user interface.

[0039] According to another specific implementation, the method includes calibrating the infrared sensor.

[0040] According to another specific embodiment, calibrating the infrared sensor includes: using the infrared sensor to measure a first temperature value of a temperature sensor adjacent to the flow cell interface, using the temperature sensor to measure a second temperature value, and calibrating the infrared sensor with a controller based on the difference between the first temperature value and the second temperature value.

[0041] According to another specific embodiment, calibrating the infrared sensor includes: using the infrared sensor to measure a first temperature value of the flow cell support, using a temperature sensor to measure a second temperature value at the flow cell support, wherein the temperature sensor is carried by the flow cell support, and calibrating the infrared sensor with the controller based on the difference between the first temperature value and the second temperature value.

[0042] According to another specific implementation, calibrating the infrared sensor is in response to receiving a command to calibrate the infrared sensor at the controller.

[0043] According to another specific implementation, receiving the command to calibrate the infrared sensor at the controller includes receiving the command from a remote computing device.

[0044] According to another specific implementation, receiving the command to calibrate the infrared sensor at the controller includes receiving user input at the system's user interface.

[0045] According to another specific embodiment, calibrating the infrared sensor includes generating data associated with the difference between the first temperature value and the second temperature value, and calibrating the infrared sensor with the controller based on the data.

[0046] According to another specific embodiment, commanding the temperature controller of the system to bring the flow cell support to the temperature value includes commanding a first region of the temperature controller of the system to bring a first region of the flow cell support to the temperature value, and wherein measuring the actual temperature value of the flow cell support using an infrared sensor includes measuring the actual temperature value of the first region of the flow cell support.

[0047] According to another specific embodiment, calibrating the temperature controller based on the difference between the commanded temperature value and the actual temperature value includes calibrating the resistance temperature detector of the first region of the temperature controller based on the difference between the commanded temperature value and the actual temperature value.

[0048] According to another specific embodiment, the method further includes: 1) commanding the second region of the temperature controller of the system to bring the second region of the flow cell support to a second temperature value; 2) using the infrared sensor to measure the actual temperature value of the second region of the flow cell support; and 3) calibrating the resistance temperature detector of the second region of the temperature controller based on the difference between the commanded temperature value and the actual temperature value.

[0049] According to another specific implementation, the controller is used to generate a heat map based on the measured multiple actual temperature values.

[0050] In another specific implementation, the controller is used to diagnose anomalies based on the heatmap.

[0051] According to another specific implementation, the controller is used to calibrate the temperature control device based on the thermal map.

[0052] According to another specific implementation, the heatmap includes a 2-D heatmap.

[0053] According to another specific embodiment, the method further includes calibrating the temperature controller based on the difference between the commanded temperature value and the actual temperature value.

[0054] According to another embodiment, the device includes a flow cell that carries the temperature sensor.

[0055] According to another specific implementation, the circulation pool includes a simulated circulation pool.

[0056] It should be understood that all combinations of the foregoing concepts and the additional concepts discussed in more detail below (assuming that such concepts do not contradict each other) are contemplated as part of the subject matter disclosed herein and / or can be combined to achieve specific beneficial effects in particular aspects. Specifically, all combinations of the claimed subject matter appearing at the end of this disclosure are contemplated as part of the subject matter disclosed herein. Attached Figure Description

[0057] Figure 1 A schematic diagram illustrating a specific implementation of a system based on the teachings of this disclosure is shown.

[0058] Figure 2 It can be used to implement Figure 1 Isometric view of the flow pool interface and Figure 1 An isometric view of the imaging system.

[0059] Figure 3 yes Figure 2 A cross-sectional schematic diagram of a portion of the flow cell interface, showing a printed circuit board positioned between the temperature sensor and the flow cell interface.

[0060] Figure 4 It can be used to implement Figure 1 Isometric view of another flow pool interface and Figure 1 An isometric schematic diagram of the imaging system.

[0061] Figure 5 yes Figure 4 A cross-sectional schematic diagram of a portion of the flow cell interface, showing a temperature sensor on the lower surface of the flow cell support attached to the flow cell interface.

[0062] Figure 6 It can be used to implement Figure 1 Top view of the temperature control device.

[0063] Figure 7 Calibration is shown Figure 1 , Figure 2 , Figure 4 and Figure 6 Or a flowchart of the process of a temperature control device in any other specific embodiment disclosed herein.

[0064] Figure 8 Calibration is shown Figure 1 , Figure 2 , Figure 4 and Figure 6 Another flowchart of the process of a temperature control device in any of the other specific embodiments disclosed herein.

[0065] Figure 9 Calibration is shown Figure 1 , Figure 2 , Figure 4 and Figure 6 Another flowchart of the process of a temperature control device in any of the other specific embodiments disclosed herein.

[0066] Figure 10 Calibration is shown Figure 1 , Figure 2 , Figure 4 and Figure 6 Temperature control devices and Figure 1 , Figure 2 and Figure 4 Or a flowchart of the process of an infrared sensor in any of the other specific embodiments disclosed herein. Detailed Implementation

[0067] While the following text discloses a detailed description of specific implementations of the manufacturing methods, apparatus, and / or articles, it should be understood that the legal scope of the property rights is defined by the wording of the claims set forth at the end of this patent. Therefore, the following detailed description should be understood as merely illustrative and does not describe every possible implementation, as describing every possible implementation would be impractical, if not impossible. Many alternative implementations may be implemented using current technology or technology developed after the filing date of this patent. It is contemplated that such alternative implementations will still fall within the scope of the claims.

[0068] The specific implementations disclosed herein relate to the thermal calibration of heating / cooling components and / or temperature sensing components used in sequencing or other systems. Thermal calibration allows for more accurate sequencing performance because the enzymes and sequencing chemistry used in sequencing can be temperature-sensitive, thus requiring greater precision. These systems include a flow cell support, a temperature control device, an infrared sensor oriented to measure the temperature of the flow cell support, and a controller. The controller calibrates the temperature control device by determining the difference between the temperature measured by the infrared sensor and the temperature generated by the temperature control device under command.

[0069] In some implementations, the infrared sensor can be calibrated using a temperature sensor connected to the system. The infrared sensor measures a first temperature value at or near the temperature sensor, and the temperature sensor measures a second temperature value. In some implementations, the system controller calibrates the infrared sensor by determining the difference between the temperature measured by the infrared sensor and the temperature measured by the temperature sensor.

[0070] The disclosed calibration procedure allows for precise calibration of temperature controllers without the need for expensive calibration tools and / or on-site service technicians. It also enables frequent calibrations and rapid, remote anomaly detection and diagnostics. Higher quality temperature calibration is achieved, resulting in less downtime, higher sequencing data quality, and / or less spatial variation in data on and between flow cells.

[0071] Figure 1 A schematic diagram of a specific embodiment of system 100 according to the teachings of this disclosure is shown. System 100 can be used to perform analysis on one or more samples of interest. Samples may include one or more DNA clusters linearized to form single-stranded DNA (sstDNA). System 100 includes a flow cell interface 102 having a flow cell support 104 adapted to support a flow cell assembly 106, which includes a corresponding flow cell 108 in the illustrated embodiment. Flow cell interface 102 may be associated with and / or referred to as a flow cell platform, and flow cell support 104 may be associated with and / or referred to as a flow cell chuck. Flow cell support 104 may include a vacuum channel, latch, snap-fit ​​mechanism, and / or tenon joint for securing flow cell assembly 106 to flow cell support 104.

[0072] System 100 also partially includes a temperature controller 110 for flow cell support 104, an infrared sensor 112, an imaging system 114, a stage assembly 116, a reagent selector valve assembly 118 having a reagent selector valve 120 and a valve actuation assembly 122, and a controller 124. The reagent selector valve assembly 118 may be referred to as a miniature valve assembly. The controller 124 is electrically and / or communicatively coupled to components of system 100, such as the temperature controller 110, infrared sensor 112, imaging system 114, stage assembly 116, and reagent selector valve assembly 118, and is adapted to cause the temperature controller 110, infrared sensor 112, imaging system 114, stage assembly 116, and reagent selector valve assembly 118 to perform the various functions disclosed herein.

[0073] During operation, controller 124 commands temperature controller 110 to bring flow cell support 104 to a specified temperature, and causes infrared sensor 112 to measure the actual temperature of flow cell support 104. Controller 124 may additionally or alternatively cause infrared sensor 112 to measure the actual temperature of flow cell 108 disposed on flow cell support 104. As an example, system 100 can determine the thermal health of sequencing chemistry operations by determining the actual temperature of flow cell 108.

[0074] Controller 124 calibrates temperature controller 110 in this manner based on the difference between the commanded temperature value and the actual temperature value. System 100 can perform calibration procedures in self-diagnostic / self-calibration mode, and / or service technicians can communicate with system 100 to perform maintenance and / or calibration of temperature controller 110. Service technicians can calibrate system 100 remotely by accessing and / or communicating with system 100, either at the same location as system 100 or at a location remote from system 100. System 100 can perform calibration procedures on a schedule, such as, for example, before, during, and / or after analysis. However, calibration procedures can be performed at any time. Controller 124 can additionally or alternatively generate an alarm when the difference between the commanded temperature value and the actual temperature value exceeds a threshold, and / or calibrate temperature controller 110 based on the difference between the commanded temperature value and the actual temperature value. More generally, controller 124 can perform diagnostics based on the actual temperature value.

[0075] When the controller 124 causes the infrared sensor 112 to measure multiple actual temperature values ​​of the flow cell support 104, the controller 124 can generate a thermal map based on the measured multiple actual temperature values. In some embodiments, the controller 124 can diagnose anomalies based on the thermal map and / or calibrate the temperature controller 110 based on the thermal map. The thermal map can be a 2D thermal map.

[0076] Controller 124 may initiate a calibration procedure in response to receiving a command. Controller 124 may receive commands based on the initiation and / or execution of a process by system 100 and / or based on a schedule. However, controller 124 may receive commands from a remote computing device and / or from an individual using system 100. The remote computing device may be used to calibrate system 100 to ensure that system 100 is functioning properly and / or within threshold operating ranges.

[0077] System 100 also allows a remote computing device to perform tests and / or diagnoses of potential anomalies in system 100. In other words, system 100 allows service technicians to perform maintenance on system 100 and identify potential problems with components of system 100 such as temperature controller 110, infrared sensor 112, and / or flow cell interface 102. Controller 124 may automatically report or output any identified problems or other data to notify service technicians of required service. Although this example mentions remote computing device access to system 100 to perform maintenance and / or diagnostics, system 100 may also perform “self-calibration,” in which system 100 calibrates temperature controller 110 and / or infrared sensor 112. Therefore, system 100 can perform the disclosed calibration and / or diagnostic procedures with or without input from service technicians.

[0078] Before system 100 performs analysis, controller 124 may calibrate temperature controller 110 and / or perform diagnostics, and during the calibration process, flow cell assembly 106 may or may not be placed on flow cell support 104. In some embodiments, infrared sensor 112 measures the temperature of flow cell 108 on flow cell support 104, thus not directly measuring the temperature of flow cell support 104. Controller 124 may consider the difference between the temperature determined by resistance temperature detector 128 at temperature controller 110 and the temperature determined by thermoelectric device 110 at flow cell 108. System 100 may also perform calibration procedures and / or perform diagnostics after a portion of the analysis of one or a sample of interest contained in flow cell 108.

[0079] The stage assembly 116 can move the flow cell interface 102 and / or the flow cell support 104 relative to the infrared sensor 112 during the calibration process, regardless of the presence of the flow cell 108, to allow the infrared sensor 112 to acquire temperature data at multiple locations on the flow cell support 104 and / or the flow cell 108. For example, the controller 124 can use the measured temperature values ​​to determine the temperature on the flow cell support 104 or the flow cell 108, and / or to determine whether the temperature gradient on the flow cell support 104 or the flow cell 108 is within an acceptable threshold.

[0080] Temperature control device 110 is shown to include one or more thermoelectric coolers 126 and one or more resistance temperature detectors 128. The thermoelectric cooler 126 may be a Peltier device. Although the inclusion of resistance temperature detector 128 is mentioned, temperature control device 110 may alternatively include any other type of thermometer.

[0081] Temperature control device 110 may be positioned below flow cell support 104 and heat / cool flow cell support 104, thereby heating / cooling flow cell 108 on flow cell support 104. Temperature control device 110 may include different regions 502, 504, 506 (see...) Figure 5 The controller 124 can command the thermoelectric cooler 126 to reach the temperature in one or more of regions 502, 504, and 506. The corresponding resistance temperature detector 128 can determine the actual temperature in regions 502, 504, and 506 and provide feedback to the controller 124 allowing the thermoelectric cooler 126 to reach the commanded temperature value. Therefore, a feedback loop is provided between the controller 124 and the resistance temperature detector 128. In some embodiments, the controller 124 can calibrate the temperature controller 110 by calibrating the resistance temperature detector 128.

[0082] Infrared sensor 112 can acquire multiple actual temperature values ​​of flow cell support 104, and controller 124 can determine an average actual temperature value based on the multiple actual temperature values. Controller 124 can calibrate temperature controller 110 based on the difference between a commanded temperature value and the average actual temperature value. Infrared sensor 112 can additionally or alternatively determine actual temperature values ​​at multiple locations on one or more regions 502, 504, 506 of temperature controller 110, and controller 124 can determine an average actual temperature value for the corresponding regions 502, 504, 506 based on the actual temperature values. Controller 124 can calibrate resistance temperature detectors 128 for the corresponding regions 502, 504, 506 based on the difference between the commanded temperature value and the average actual temperature value. Controller 124 can alternatively calibrate resistance temperature detectors 128 for the corresponding regions 502, 504, 506 based on one or more actual temperature values ​​from infrared sensor 112. Infrared sensor 112 may additionally or alternatively determine the actual temperature values ​​at multiple locations on one or more of regions 502, 504, 506 of temperature controller 110, and controller 124 may generate a heat map and / or perform diagnostics based on the actual temperature values.

[0083] The process of calibrating the temperature control device 110 by the controller 124 may include calibrating the resistance temperature detector 128. The controller 124 may calibrate the resistance temperature detector 128 to more accurately measure the temperature generated by the corresponding thermoelectric cooler 126. In other words, the controller 124 may calibrate the resistance temperature detector 128 to compensate for deviations between the measured temperature value and the actual temperature value. In the specific embodiment shown, the temperature control device 110 includes two thermoelectric coolers 126 and two resistance temperature detectors 128. However, the thermoelectric coolers 126 may include any number of thermoelectric coolers 126 and / or any number of resistance temperature detectors 128.

[0084] The controller 124 can calibrate the resistance temperature detector 128 at any time, so that the resistance temperature detector 128 can more accurately measure the temperature generated by the corresponding thermoelectric cooler 126 and delivered to the flow cell 108. The controller 124 can offset the measurement of the resistance temperature detector 128 or modify the settings of the resistance temperature detector 128 for calibration.

[0085] In the illustrated embodiment, infrared sensor 112 is coupled to imaging system 114. Infrared sensor 112 is positioned to allow measurement of temperature values ​​of flow cell support 104 and / or flow cell interface 102. Stage assembly 116 is movable relative to infrared sensor 112 of flow cell interface 102 and flow cell support 104 to allow temperature values ​​to be obtained.

[0086] A bracket 130 is shown for connecting the infrared sensor 112 to the imaging system 114. The bracket 130 may have apertures allowing the infrared sensor 112 to be attached to the bracket 130. The bracket 130 may additionally or alternatively be an L-shaped bracket. However, other methods of connecting the infrared sensor 112 to the imaging system 114 may also prove suitable. The infrared sensor 112 may alternatively be connected at different locations.

[0087] The controller 124 can also calibrate the infrared sensor 112. The system 100 can calibrate the infrared sensor 112 before calibrating the temperature controller 110, at different schedules, and / or at any time. For this purpose, the system 100 includes a temperature sensor 132. The temperature sensor 132 can be a digital temperature sensor, such as the ADT7422. Other temperature sensors 132 may also prove suitable. In other embodiments, the flow cell 108 can alternatively carry the temperature sensor 132. In a specific embodiment, when the flow cell 108 carries the temperature sensor 132, the flow cell 108 can be considered an analog flow cell. As an example, an analog flow cell can be used for testing and / or calibration purposes.

[0088] The flow cell interface 102 includes a flow cell platform 134 that supports the flow cell support 104, and in the illustrated embodiment, a temperature sensor 132 is coupled to this flow cell platform. However, the temperature sensor 132 may be coupled to different locations.

[0089] Infrared sensor 112 measures a first temperature value from a nearby temperature sensor 132, temperature sensor 132 measures a second temperature value, and controller 124 calibrates infrared sensor 112 based on the difference between the first and second temperature values. Controller 124 can calibrate infrared sensor 112 by offsetting the measurements of infrared sensor 112 or by modifying the settings of infrared sensor 112.

[0090] Temperature sensor 132 may be part of a calibration assembly 135 that includes temperature sensor 132 and printed circuit board 136. Printed circuit board 136 is shown as being coupled to temperature sensor 132 and positioned between temperature sensor 132 and flow cell platform 134. However, temperature sensor 132 and / or printed circuit board 136 may be located in another location. For example, temperature sensor 132 may be coupled to flow cell support 104 and printed circuit board 136 such that temperature sensor 132 is positioned between flow cell support 104 and printed circuit board 136 (e.g., see...). Figure 5 ).

[0091] The calibration assembly 135 may also include a metal layer 138. The metal layer 138 is shown as covering the surface 140 of the temperature sensor 132. Therefore, when the infrared sensor 112 is calibrated, the infrared sensor 112 can measure a first temperature value at the metal layer 138. The metal layer 138 may include aluminum. However, the metal layer 138 may include other or alternative materials. A thermally conductive epoxy resin 142 connects the temperature sensor 132 to the metal layer 138. Due to the presence of the thermally conductive epoxy resin 142, the temperature sensor 132 can measure a second temperature value at the metal layer 138 with relatively high accuracy.

[0092] The surfaces 138 of the metal layer 138 and the flow cell support 104 may have substantially similar emissivity, such as having similar surface finish. The surface 139 of the flow cell support 104 may include a metal layer.

[0093] The stage assembly 116 includes an x-stage 144 and a y-stage 146. The x-stage 144 moves the flow cell interface 102 in the x-direction relative to the imaging system 114 and the infrared sensor 112, and the y-stage 146 moves the flow cell interface 102 in the y-direction relative to the imaging system 114 and the infrared sensor 112. The x-stage 144 and / or the y-stage 146 may be linear stages. However, the x-stage 144 and / or the y-stage 146 may be any other type of motor or actuator. For example, the stage assembly 116 may move the flow cell support 104 to different positions to allow the infrared sensor 112 to measure one or more temperature values ​​of the flow cell support 104.

[0094] Still referencing Figure 1 In the illustrated embodiment, system 100 further includes a sipper manifold assembly 148, a sample loading manifold assembly 150, a pump manifold assembly 152, a drive assembly 154, and a waste reservoir 156. A controller 124 is electrically and / or communicatively connected to the sipper manifold assembly 148, the sample loading manifold assembly 150, the pump manifold assembly 152, and the drive assembly 154, and is adapted to cause the sipper manifold assembly 148, the sample loading manifold assembly 150, the pump manifold assembly 152, and the drive assembly 154 to perform the various functions disclosed herein.

[0095] Referring to flow cell 108, in the illustrated embodiment, each flow cell in flow cell 108 includes a plurality of channels 158, each channel having a first channel opening located at a first end of flow cell 108 and a second channel opening located at a second end of flow cell 108. Depending on the flow direction through the channel 158, any one of the channel openings can serve as an inlet or an outlet. Although flow cell 108 is... Figure 1 The diagram is shown as including two channels 158, but may include any number of channels 158 (e.g., 1, 2, 6, 8).

[0096] The flow cell assembly 106 also includes a flow cell frame 160 and a flow cell manifold 162 coupled to a first end of a corresponding flow cell 108. As used herein, a “flow cell” (also referred to as a flow cell) can include a device having a cap extending over a reaction structure to form flow channels therebetween communicating with a plurality of reaction sites of the reaction structure. Some flow cells may also include a detection device that detects a specified reaction occurring at or near a reaction site. As shown, the flow cell 108, the flow cell manifold 162, and / or any associated gaskets for establishing a fluid connection between the flow cell 108 and the system 100 are coupled to or otherwise carried by the flow cell frame 160. Although the flow cell frame 160 is shown with Figure 1 The flow pool assembly 106 is included together, but the flow pool frame 160 may be omitted. Therefore, the flow pool 108 and the associated flow pool manifold 162 and / or gasket can be used with the system 100 without the flow pool frame 160.

[0097] Reference Figure 1 Before discussing other components of system 100 (such as some fluid components within the fluid components), it should be noted that although some components of system 100 are shown once and coupled to a single flow cell 108, in some specific implementations these components may be duplicated, thereby allowing more flow cells 108 to be used with system 100 (e.g., 2, 3, 4), and thus each flow cell 108 may have its own corresponding components. For example, when more than one flow cell 108 is included with system 100, each flow cell 108 may be associated with a separate sample cassette 164, sample loading manifold assembly 150, pump manifold assembly 152, etc.

[0098] Referring now to sample cartridge 164, sample loading manifold assembly 150, and pump manifold assembly 152, in the illustrated embodiment, system 100 includes a sample cartridge housing 166 that receives sample cartridge 164 carrying one or more samples of interest (e.g., analytes). System 100 also includes a sample cartridge interface 168 that establishes a fluid connection with sample cartridge 164.

[0099] The sample loading manifold assembly 150 includes one or more sample valves 170, and the pump manifold assembly 152 includes one or more pumps 172, one or more pump valves 174, and a buffer 176. One or more of the valves 170 and 174 may be implemented as rotary valves, pinch valves, flat valves, solenoid valves, check valves, piezoelectric valves, and / or three-way valves. However, different types of fluid control devices can be used. One or more of the pumps 172 may be implemented as syringe pumps, peristaltic pumps, and / or diaphragm pumps. However, other types of fluid transfer devices can be used. The buffer 176 may be a serpentine buffer and can be... Figure 1 The system 100 temporarily stores one or more reactive components during bypass operation. Although cache 176 is shown as being included in pump manifold assembly 152, in another embodiment, cache 176 may be located in a different location. In some embodiments, cache 176 may be included in extractor manifold assembly 148 or in another manifold downstream of bypass fluid line 178.

[0100] The sample loading manifold assembly 150 and pump manifold assembly 152 allow one or more samples of interest to flow from the sample cassette 164 to the flow cell assembly 106 via fluid lines 180. In some embodiments, the sample loading manifold assembly 150 can individually load / address each channel 158 of the flow cell 108 with a sample of interest. The process of loading the channels 158 of the flow cell 108 with a sample of interest can be used... Figure 1 The system 100 occurs automatically.

[0101] Sample box 164 and sample loading manifold assembly 150 are positioned in Figure 1 The sample loading manifold assembly 150 is downstream of the flow cell assembly 106 in system 100. The sample loading manifold assembly 150 can load the sample of interest into the flow cell 108 from the rear. Loading the sample of interest from the rear of the flow cell 108 is referred to as "post-loading". Post-loading the sample of interest into the flow cell 108 reduces contamination. The sample loading manifold assembly 50 is connected between the flow cell assembly 106 and the pump manifold assembly 52.

[0102] To draw the sample of interest from sample cartridge 164 into pump manifold assembly 152, sample valve 170, pump valve 174, and / or pump 172 may be selectively actuated to push the sample of interest toward pump manifold assembly 152. Sample cartridge 164 may include multiple sample reservoirs into which fluid can be selectively introduced via corresponding sample valves 170. Thus, each sample reservoir can be selectively isolated from other sample reservoirs using a corresponding sample valve 170.

[0103] To direct the sample of interest toward a corresponding channel in one of the flow cells 108 and away from the pump manifold assembly 152 for individual flow, the sample valve 170, pump valve 174, and / or pump 172 may be selectively actuated to push the sample of interest toward the flow cell assembly 106 and into the corresponding channel 58 of the corresponding flow cell 108. In some embodiments, each channel 158 of the flow cell 108 receives the sample of interest. In other embodiments, one or more channels 158 of the flow cell 108 selectively receive the sample of interest, while other channels 158 of the flow cell 108 do not receive the sample of interest. Channels 158 of the flow cell 108 that do not receive the sample of interest may instead receive a washing buffer.

[0104] A drive assembly 154 interfaces with a picker manifold assembly 148 and a pump manifold assembly 152 to allow flow of one or more reagents that interact with a sample within a corresponding flow cell 108. In one embodiment, a reversible terminator is attached to the reagent to allow individual nucleotides to be incorporated into the growing DNA strand. In some such embodiments, one or more nucleotides have a unique fluorescent label that emits a color when excited. The color (or the absence of color) is used to detect the corresponding nucleotide. In the illustrated embodiment, an imaging system 114 excites one or more identifiable labels (e.g., fluorescent labels) and then acquires image data of these identifiable labels. The labels may be excited by incident light and / or laser light, and the image data may include one or more colors emitted by the corresponding labels in response to excitation. The image data (e.g., detection data) may be analyzed by system 100. The imaging system 114 may be a fluorescence spectrophotometer including objective lenses and / or solid-state imaging devices. Solid-state imaging devices may include electrocoupling devices (CCDs) and / or complementary metal-oxide-semiconductor (CMOS). However, other types of imaging systems and / or optical instruments may be used. In some specific implementations, the imaging system 114 may be a scanning electron microscope, a transmission electron microscope, an imaging flow cytometer, a high-resolution optical microscope, a confocal microscope, a radiation fluorescence microscope, a two-photon microscope, a differential interference contrast microscope, or may be associated with such a microscope.

[0105] After acquiring image data, drive assembly 154 interfaces with absorber manifold assembly 148 and pump manifold assembly 152 to allow another reaction component (e.g., reagent) to flow through flow cell 108. This reaction component is then received by waste reservoir 156 via main waste fluid line 182 and / or otherwise depleted by system 100. Some reaction components undergo a flushing operation, which chemically cleaves the fluorescently labeled and reversible terminator from the sstDNA. The sstDNA is then prepared for another cycle.

[0106] The main waste fluid line 182 is connected between the pump manifold assembly 152 and the waste reservoir 156. In some embodiments, the pump 172 and / or pump valve 174 of the pump manifold assembly 152 selectively directs the reaction components from the flow cell assembly 106 through the fluid line 180 and the sample loading manifold assembly 150 to the main waste fluid line 182.

[0107] Flow cell assembly 106 is connected to central valve 184 via flow cell interface 102. Auxiliary waste fluid line 186 is connected to central valve 184 and waste reservoir 156. As described herein, auxiliary waste fluid line 186 receives excess sample fluid from flow cell assembly 106 via central valve 184 and, in some embodiments, allows excess sample fluid to flow to waste reservoir 156 when a sample is subsequently loaded into flow cell 108. That is, the sample of interest can be loaded from the rear of flow cell 108, and any excess fluid from the sample of interest can exit from the front of flow cell 108. By subsequently loading the sample of interest into flow cell 108, different samples can be loaded into corresponding channels 158 of the corresponding flow cell 108, and a single flow cell manifold 162 connects the front of flow cell 108 to central valve 184 to direct excess fluid from each sample of interest to auxiliary waste fluid line 186. Once the sample of interest is loaded into flow cell 108, flow cell manifold 162 can be used to deliver a common reagent exiting from the rear (e.g., downstream) of flow cell 108 to each channel 158 of flow cell 108 from the front (e.g., upstream) of flow cell 108. In other words, the sample of interest and the reagent can flow in opposite directions through the channels 158 of flow cell 108.

[0108] Referring to the extractor manifold assembly 148, in the illustrated embodiment, the extractor manifold assembly 148 includes a shared line valve 188 and a bypass valve 190. The shared line valve 188 may be referred to as a reagent selector valve. Valve 120 of the reagent selector valve assembly 118, the center valve 184, and / or valves 188 and 190 of the extractor manifold assembly 148 can be selectively actuated to control the flow of fluid through fluid lines 178, 192, 194, 196, and 198. One or more of valves 120, 170, 174, 184, and 188 may be implemented by a rotary valve, pinch valve, flat valve, solenoid valve, check valve, piezoelectric valve, and / or three-way valve. Other fluid control devices may also prove suitable.

[0109] The extractor manifold assembly 148 can be coupled to a corresponding number of reagent reservoirs 200 via reagent extractors 202. The reagent reservoirs 200 may contain fluids (e.g., reagents and / or another reaction component). In some embodiments, the extractor manifold assembly 148 includes multiple ports. Each port of the extractor manifold assembly 148 may receive one reagent extractor from the reagent extractors 202. The reagent extractors 202 may be referred to as fluid lines. Although the system 100 includes the extractor manifold assembly 148, the system 100 may alternatively receive reagent kits; therefore, the extractor manifold assembly 148 may be modified to omit, for example, the reagent extractors 202 and / or include alternative fluid interfaces, or the extractor manifold assembly 148 may be omitted altogether.

[0110] The shared line valve 188 of the aspirator manifold assembly 148 is connected to the central valve 184 via a shared reagent fluid line 192. Different reagents may flow through the shared reagent fluid line 192 at different times. In one embodiment, when a flushing operation is performed before changing between one reagent and another, the pump manifold assembly 152 may aspirate a cleaning buffer via the shared reagent fluid line 192, the central valve 184, and the corresponding flow cell assembly 106. Thus, the shared reagent fluid line 192 can participate in the flushing operation. Although one shared reagent fluid line 192 is shown, any number of shared fluid lines may be included in the system 100.

[0111] The bypass valve 190 of the absorber manifold assembly 148 is connected to the central valve 184 via reagent fluid lines 194, 196. The central valve 184 may have one or more ports corresponding to the reagent fluid lines 194, 196.

[0112] A dedicated reagent fluid line 198 is coupled between the extractor manifold assembly 148 and the reagent selector valve assembly 118. The dedicated reagent fluid line 198 can be associated with a single reagent. The fluid flowing through the dedicated reagent fluid line 198 can be used during sequencing operations and may include cleavage reagents, integration reagents, scan reagents, cleavage wash solution, and / or wash buffer. Because only a single reagent can flow through each reagent fluid line in the dedicated reagent fluid line 198, the dedicated reagent fluid line 198 itself may not be flushed when a flushing operation is performed before changing between reagents. Including the dedicated reagent fluid line 198 can be helpful when the system 100 uses reagents that may react adversely with other reagents. Furthermore, reducing the number of fluid lines flushed or the length of the fluid lines when changing between different reagents reduces reagent consumption and flushing volume, and can reduce the cycle time of the system 100. Although two dedicated reagent fluid lines 198 are shown, any number of dedicated fluid lines may be included in the system 100.

[0113] Bypass valve 190 is also connected to cache 176 of pump manifold assembly 152 via bypass fluid line 178. One or more reagent drainage, hydration, mixing, and / or transfer operations can be performed using bypass fluid line 178. Drainage, hydration, mixing, and / or transfer operations can be performed independently of flow cell assembly 106. Therefore, operations using bypass fluid line 178 can occur during the incubation of one or more samples of interest within flow cell assembly 106. That is, shared line valve 188 can be used independently of bypass valve 190, allowing bypass valve 190 to perform one or more operations using bypass fluid line 178 and / or cache 176, while shared line valve 188 and / or center valve 184 perform other operations simultaneously, substantially simultaneously, or offset synchronously. Therefore, system 100 can perform multiple operations simultaneously, thereby reducing runtime.

[0114] Referring now to drive assembly 154, in the illustrated embodiment, drive assembly 154 includes a pump drive assembly 204 and a valve drive assembly 206. Pump drive assembly 204 may be adapted to interface with one or more pumps 172 to pump fluid through flow cell 108 and / or load one or more samples of interest into flow cell 108. Valve drive assembly 206 may be adapted to interface with one or more valves 120, 170, 174, 184, 188, 190 to control the position of the corresponding valves 120, 170, 174, 184, 188, 190.

[0115] Referring to controller 124, in the illustrated embodiment, controller 124 includes a user interface 208, a communication interface 210, one or more processors 212, and a memory 214 storing instructions executable by the one or more processors 212 to perform various functions, including those disclosed in the illustrated embodiment. The user interface 208, communication interface 210, and memory 214 are electrically and / or communicatively connected to the one or more processors 212.

[0116] In one implementation, the user interface 208 is adapted to receive input from the user and provide the user with information related to the operation and / or analysis performed by the system 100. The user interface 208 may include a touchscreen, display, keyboard, speaker, mouse, trackball, and / or voice recognition system. The touchscreen and / or display may display a graphical user interface (GUI).

[0117] In one implementation, communication interface 210 is adapted to enable communication between system 100 and a remote system (e.g., a computer) via a network. The network may include the Internet, intranet, local area network (LAN), wide area network (WAN), coaxial cable network, wireless network, wired network, satellite network, digital subscriber line (DSL) network, cellular network, Bluetooth connection, near field communication (NFC) connection, etc. Some communications provided to the remote system may be associated with analysis results, imaging data, etc., generated by system 100 or otherwise obtained. Some communications provided to system 100 may be associated with fluid analysis operations, patient records, and / or protocols to be executed by system 100.

[0118] One or more processors 212 and / or system 100 may include one or more of a processor-based system or a microprocessor-based system. In some embodiments, one or more processors 212 and / or system 100 include one or more of a programmable processor, programmable controller, microprocessor, microcontroller, graphics processing unit (GPU), digital signal processor (DSP), reduced instruction set computer (RISC), application-specific integrated circuit (ASIC), field-programmable gate array (FPGA), field-programmable logic device (FPLD), logic circuit, and / or another logic-based device that performs various functions (including those described herein).

[0119] The memory 214 may include one or more of the following: semiconductor memory, magnetically readable memory, optical memory, hard disk drive (HDD), optical storage drive, solid-state storage device, solid-state drive (SSD), flash memory, read-only memory (ROM), erasable programmable read-only memory (EPROM), electrically erasable programmable read-only memory (EEPROM), random access memory (RAM), non-volatile RAM (NVRAM) memory, optical disc (CD), optical disc read-only memory (CD-ROM), digital versatile optical disc (DVD), Blu-ray disc, redundant array of independent disks (RAID) system, cache, and / or any other storage device or storage disk in which information is stored for any duration (e.g., permanently, temporarily, long time period, for buffering, for caching).

[0120] Figure 2 It can be used to implement Figure 1 Isometric view of flow pool interface 102 and flow pool interface 300 and Figure 1 An isometric view of the imaging system 114. The flow cell assembly 300 is similar to... Figure 1 The circulation pool interface 102. However, Figure 2The flow cell interface 300 includes a pair of flow cell supports 104, and therefore includes a pair of temperature controllers 110. Although two flow cell supports 104 are shown, any number of flow cell supports 104 may be included.

[0121] The flow cell interface 300 has a boundary structure 302 adjacent to the flow cell support 104, and a printed circuit board 136 is shown attached to the boundary structure 230. The printed circuit board 136 is positioned between the temperature sensor 132 and the flow cell interface 102, and a metal layer 138 extends over and covers at least a portion of the surface 140 of the temperature sensor 132. In the illustrated embodiment, the metal layer 138 is a metal cap disposed on the temperature sensor 132. The metal layer 138 may be an aluminum sheet of approximately 4x4x4 mm. However, the metal layer 138 may be any other size and may be made of another material.

[0122] Temperature sensor 132, printed circuit board 136, and / or metal layer 138 can be at ambient temperature because they are spaced apart from temperature controller 110 and therefore from flow cell support 104. Therefore, a small temperature gradient may exist between temperature sensor 132, printed circuit board 136, and metal layer 138. Infrared sensor 112 can be calibrated more accurately because components 132, 136, and 138 are at ambient temperature. In other words, the position of components 132, 136, and 138 on boundary structure 302 reduces the amount by which temperature controller 110 affects the temperature of components 132, 136, and 138.

[0123] The metal layer 138 and the temperature sensor 132 also possess low total heat content and good thermal conductivity, which allows the metal layer 138 and the temperature sensor 132 to rapidly track changes in ambient air temperature for consistent measurement and calibration. Since there are no temperature cycles that affect the thermal bonding between the temperature sensor 132 and the metal layer 138, and because the temperature sensor 132 utilizes a semiconductor bandgap, temperature readings from the temperature sensor 132 can be considered accurate within approximately 0.15°C over its lifetime.

[0124] Figure 3 yes Figure 2 A cross-sectional schematic diagram of a portion of the flow cell interface 300 shows a printed circuit board 136 positioned between the temperature sensor 132 and the flow cell interface 102. A metal layer 138 extends over and covers at least a portion of the surface 140 of the temperature sensor 132.

[0125] Figure 4 It can be used to implement Figure 1 Isometric view of another flow pool interface 400 of flow pool interface 102 and Figure 1An isometric schematic diagram of the imaging system 114. The flow cell assembly 400 is similar to... Figure 2 The circulation pool interface is 300. However, Figure 4 The flow cell interface 400 includes a temperature sensor 132 connected to the flow cell support 104, but not to the flow cell interface 102. Therefore, in Figure 4 In this configuration, temperature sensor 132 is not isolated from flow cell support 104. The location of temperature sensor 132 allows it to measure the temperature of flow cell support 104, rather than the temperature at metal layer 138.

[0126] In the specific implementation shown, infrared sensor 112 ( Figure 1 During the calibration procedure of infrared sensor 112, a first temperature value is measured at the flow cell support 104, and temperature sensor 132 can measure a second temperature value at the flow cell support 104. In some specific embodiments, Figure 1 The controller 124 of the system 100 can calibrate the infrared sensor 112 based on the difference between the first temperature value and the second temperature value.

[0127] Temperature sensor 132 may be part of a calibration assembly 402 that includes temperature sensor 132 and printed circuit board 136. Printed circuit board 136 is shown as being coupled to temperature sensor 132. Temperature sensor 132 is positioned between printed circuit board 136 and flow cell platform 134.

[0128] Figure 5 yes Figure 4 A cross-sectional view of a portion of the flow cell interface 400 shows a temperature sensor 132 coupled to the lower surface 404 of the flow cell support 104. A printed circuit board 136 is positioned between the temperature sensor 132 and the flow cell interface 102.

[0129] Figure 6 It can be used to implement Figure 1 Top view of temperature controller 110 and temperature controller 500. Figure 5The temperature control device 500 includes a first region 502, a second region 504, and a third region 506. Each of regions 502, 504, and 506 has a corresponding thermoelectric cooler 126 and a corresponding resistance temperature detector 128. The thermoelectric cooler 126 heats and / or cools the corresponding region 502, 504, and 506, and the resistance temperature detector 128 is positioned to measure the temperature in the corresponding region 502, 504, and 506. The resistance temperature detector 128 allows the controller 124 to acquire the measured temperature value via a feedback loop that allows the commanded temperature to be achieved. However, one thermoelectric cooler 126 can control the temperature of more than one of the regions 502, 504, and 506.

[0130] Figure 7 , Figure 8 , Figure 9 and Figure 10 Calibration is shown Figure 1 , Figure 2 , Figure 4 and Figure 6 Temperature control devices 110, 500 and Figure 1 , Figure 2 and Figure 4 The flowcharts for processes 700, 800, 900, and 100 of the infrared sensor 112 or any other specific embodiment disclosed herein are provided. The execution order of the blocks may be changed, and / or some of the blocks described may be changed, eliminated, combined, and / or subdivided into multiple blocks. Processes 700, 800, 900, and / or 1000 may be executed individually or sequentially in any order.

[0131] Figure 7 The process 700 begins by commanding the temperature controller 110 of the system 100 to bring the flow cell support 104 to a temperature value (box 702). In some embodiments, the temperature controller 110 can be commanded to bring the flow cell support 104 to a temperature value by commanding the thermoelectric cooler 126 to bring the flow cell support 104 to a temperature value and by measuring the temperature value with the resistance temperature detector 128.

[0132] The actual temperature value of the flow cell support 104 is measured using an infrared sensor 112 (box 704). In some embodiments, the actual temperature value of the flow cell support 104 is measured using the infrared sensor 112 while the flow cell interface 102 is moved relative to the infrared sensor 112.

[0133] Temperature controller 110 (box 706) is calibrated based on the difference between the commanded temperature value and the actual temperature value. In some embodiments, temperature controller 110 is calibrated in response to a command to calibrate temperature controller 110 received at controller 124. Controller 124 may receive commands from a remote computing device and / or from user input received at user interface 208 of system 100.

[0134] Figure 8 The process 800 begins by commanding the temperature controller 110 to bring the flow cell support 104 to a specified temperature (box 802). A flow cell 108 may be positioned on the flow cell support 104 and must not contain any sample or reagent. An infrared sensor 112 measures the actual temperature of the flow cell 108 positioned on the flow cell support 104 (box 804) and compares the commanded temperature value with the actual temperature value (box 806). The temperature controller 110 is calibrated based on this comparison (box 808). When calibrating the temperature controller 110, the controller 124 may consider the difference between the temperature determined by the resistance temperature detector 128 at the temperature controller 110 and the temperature determined by the thermoelectric device 110 at the flow cell 108.

[0135] Figure 9 The process 900 begins by enabling the system 100 to perform at least a portion of the analysis on one or more samples of interest within a flow cell 108 disposed on a flow cell support 104 (box 902). The temperature controller 110 is commanded to bring the flow cell support 104 to a second temperature value (box 904). The actual temperature value of the flow cell 108 disposed on the flow cell support 104 is measured using an infrared sensor 112 (box 906), and the commanded temperature value is compared with the actual temperature value (box 908). The temperature controller 110 is calibrated based on this comparison (box 910).

[0136] Figure 10 The process 1000 begins with the calibration of infrared sensor 112 (block 1002). Infrared sensor 112 can be calibrated by generating data associated with the difference between a first temperature value and a second temperature value and calibrating infrared sensor 112 with controller 124 based on that data.

[0137] In some embodiments, the infrared sensor 112 is calibrated by measuring a first temperature value adjacent to a temperature sensor 132 carried by the flow cell interface 102 using the infrared sensor 112, measuring a second temperature value using the temperature sensor 132, and calibrating the infrared sensor 112 using the controller 124 based on the difference between the first and second temperature values. In other embodiments, the infrared sensor 112 is calibrated by measuring a first temperature value at the flow cell support 104 using the infrared sensor 112, measuring a second temperature value at the flow cell support 104 using the temperature sensor 132, and calibrating the infrared sensor 112 using the controller 124 based on the difference between the first and second temperature values. In the second embodiment mentioned above, the temperature sensor 132 may be carried by the flow cell support 104. The infrared sensor 112 may be calibrated in response to a command to calibrate the infrared sensor 112 received at the controller 124. This command may be received from a remote computing device and / or from user input received at the user interface 208 of the system 100.

[0138] The temperature controller 110 of the command system 100 causes the flow cell support 104 to reach a temperature value (box 1004). In some embodiments, the temperature controller 110 can be commanded to cause the flow cell support 104 to reach a temperature value by commanding the thermoelectric cooler 126 to reach the temperature value and by measuring the temperature value with the resistance temperature detector 128.

[0139] The actual temperature value of the flow cell support 104 is measured using an infrared sensor 112 (box 1006). In some embodiments, the actual temperature value of the flow cell support 104 is measured using the infrared sensor 112 while the flow cell interface 102 is moved relative to the infrared sensor 112.

[0140] Temperature controller 110 (block 1008) is calibrated based on the difference between the commanded temperature value and the actual temperature value. In some embodiments, temperature controller 110 is calibrated in response to a command to calibrate temperature controller 110 received at controller 124. Controller 124 may receive commands from a remote computing device and / or from user input received at user interface 208 of system 100.

[0141] The system 100 performs at least a portion of the analysis on one or more samples of interest within a flow cell 108 disposed on a flow cell support 104 (box 1010). The temperature controller 110 is commanded to bring the flow cell support 104 to a second temperature value (box 1012). The actual temperature value of the flow cell 108 disposed on the flow cell support 104 is measured using an infrared sensor 112 (box 1014), and the commanded temperature value is compared with the second actual temperature value (box 1016). The temperature controller 110 is recalibrated based on this comparison (box 1018).

[0142] In specific implementations, the methods and optical systems described herein can be used for nucleic acid sequencing. For example, sequencing-by-synthesis (SBS) protocols are particularly suitable. In SBS, multiple fluorescently labeled modified nucleotides are used to sequence dense clusters (potentially millions) of amplified DNA present on the surface of an optical substrate (e.g., the surface that at least partially defines a channel in a flow cell). The flow cell may contain a nucleic acid sample for sequencing, wherein the flow cell is placed within a suitable flow cell holder. The sample for sequencing may take the form of individual nucleic acid molecules separated from each other and individually recognizable, a group of nucleic acid molecules amplified in the form of clusters or other features, or beads linked to one or more nucleic acid molecules. The nucleic acids may be prepared such that they include oligonucleotide primers adjacent to an unknown target sequence. To initiate a first SBS sequencing cycle, one or more differently labeled nucleotides and DNA polymerase, etc., may be fed into / flow through a flow cell (not shown) via a fluidic flow subsystem. A single type of nucleotide may be added at a time, or the nucleotides used in the sequencing process may be specifically designed to have reversible termination properties, such that each cycle of the sequencing reaction occurs simultaneously in the presence of several types of labeled nucleotides (e.g., A, C, T, G). Nucleotides may include detectable labeled portions, such as fluorophores. When four nucleotides are mixed together, the polymerase is able to select the correct bases to incorporate, and each sequence is extended by a single base. Unincorporated nucleotides can be washed away by passing washing buffer through a flow cell. One or more lasers can excite the nucleic acid and induce fluorescence. The fluorescence emitted from the nucleic acid is based on the fluorophore of the incorporated base, and different fluorophores emit light at different wavelengths. A deblocking reagent can be added to the flow cell to remove reversible terminator groups from the extended and detected DNA strand. This deblocking reagent can be washed away by passing washing buffer through the flow cell. The flow cell is then ready to begin another sequencing cycle starting with the introduction of labeled nucleotides as described above. The fluidization and detection steps can be repeated several times to complete the sequencing run. Exemplary sequencing methods are described in the following references, for example: Bentley et al., Nature 456:53-59 (2008); WO 04 / 018497; U.S. Patent Application No. 7,057,026; WO 91 / 06678; WO 07 / 123,744; U.S. Patent Application No. 7,329,492; U.S. Patent Application No. 7,211,414; U.S. Patent Application No. 7,315,019; U.S. Patent Application No. 7,405,281 and U.S. Patent No. 2008 / 0108082, each of which is incorporated herein by reference.

[0143] The optical system described herein can also be used to scan samples including microarrays. A microarray can include a group of different probe molecules attached to one or more substrates, such that these different probe molecules can be distinguished from each other based on their relative positions. The array can include different probe molecules or groups of probe molecules, each located at a different addressable site on the substrate. Alternatively, the microarray can include individual optical substrates, such as beads, each carrying different probe molecules or groups of probe molecules, which can be identified based on the position of the optical substrate on the surface to which the substrate is attached or based on the position of the substrate in a liquid. Exemplary arrays of separated substrates on a surface include, but are not limited to, the BeadChip Array available from Illumina, Inc. (San Diego, Calif.) or other arrays comprising beads in pores, such as those described in U.S. Patents 6,266,459, 6,355,431, 6,770,441, 6,859,570, and 7,622,294, and PCT Publication WO 00 / 63437, each of which is incorporated herein by reference. Other arrays having particles on a surface include those set forth in US2005 / 0227252, WO 05 / 033681, and WO 04 / 024328, each of which is incorporated herein by reference.

[0144] An exemplary apparatus includes: a flow cell interface including a flow cell support; a temperature controller for the flow cell support; an infrared sensor; and a controller for commanding the temperature controller to bring the flow cell support to a certain temperature, causing the infrared sensor to measure the actual temperature of the flow cell support, and calibrating the temperature controller based on the difference between the commanded temperature and the actual temperature.

[0145] The device according to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below, wherein the temperature control device includes a thermoelectric cooler.

[0146] The device according to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below, wherein the temperature control device further includes a resistance temperature detector.

[0147] The apparatus according to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below, wherein the controller is used to calibrate the temperature control device by calibrating the resistance temperature detector.

[0148] The apparatus according to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below further includes an imaging system to which the infrared sensor is coupled.

[0149] The apparatus according to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below further includes a bracket for connecting the infrared sensor to the imaging system.

[0150] The apparatus according to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below, wherein the controller is further configured to calibrate the infrared sensor.

[0151] The apparatus according to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below further includes a temperature sensor; wherein the infrared sensor is used to measure a first temperature value adjacent to the temperature sensor; the temperature sensor is used to measure a second temperature value; and the controller is used to calibrate the infrared sensor based on the difference between the first temperature value and the second temperature value.

[0152] The apparatus according to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below, wherein the flow cell interface further includes a flow cell platform carrying the flow cell support, and the temperature sensor is coupled to the flow cell platform.

[0153] The apparatus according to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below further includes a printed circuit board coupled to the temperature sensor, the printed circuit board being positioned between the temperature sensor and the flow cell platform.

[0154] The apparatus according to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below further includes a metal layer covering the surface of the temperature sensor.

[0155] The apparatus according to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below, wherein the surfaces of the metal layer and the flow cell support have substantially similar emissivity.

[0156] The apparatus according to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below, wherein the temperature sensor and the metal layer are spaced apart from the flow cell support.

[0157] The apparatus according to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below, wherein the metal layer comprises aluminum.

[0158] The apparatus according to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below further includes a thermally conductive epoxy resin for connecting the temperature sensor to the metal layer.

[0159] The apparatus according to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below further includes a temperature sensor; wherein the infrared sensor is used to measure a first temperature value of the flow cell support; the temperature sensor is used to measure a second temperature value at the flow cell support; and the controller is used to calibrate the infrared sensor based on the difference between the first temperature value and the second temperature value.

[0160] The apparatus according to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below, wherein the temperature sensor is coupled to the flow cell support.

[0161] The apparatus according to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below further includes a printed circuit board coupled to the temperature sensor, the temperature sensor being positioned between the flow cell interface and the printed circuit board.

[0162] The apparatus according to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below, wherein the surface of the flow pool support includes a metal layer.

[0163] The device according to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below, wherein the temperature sensor includes a digital temperature sensor.

[0164] A method comprising: commanding a temperature controller of a system to bring a flow cell support to a temperature value; measuring the actual temperature value of the flow cell support using an infrared sensor; and calibrating the temperature controller based on the difference between the commanded temperature value and the actual temperature value.

[0165] According to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below, the method of commanding the temperature controller to bring the flow cell support to the temperature value includes: commanding the thermoelectric cooler to bring the flow cell support to the temperature value; and measuring the temperature value with one or more resistance temperature detectors.

[0166] According to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below, the method of measuring the actual temperature value of the flow cell support using the infrared sensor includes measuring the actual temperature value of the flow cell support using the infrared sensor while moving the flow cell interface relative to the infrared sensor.

[0167] The method according to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below, further comprising: commanding the temperature controller to bring the flow cell support to a second temperature value; measuring a second actual temperature value of the flow cell disposed on the flow cell support using the infrared sensor; comparing the commanded second temperature value with the second actual temperature value; and recalibrating the temperature controller based on the comparison.

[0168] The method according to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below further includes: causing the system to perform at least a portion of an analysis on one or more samples of interest disposed in a flow cell on the flow cell support; and commanding the temperature controller to bring the flow cell support to a second temperature value; measuring a second actual temperature value of the flow cell disposed on the flow cell support using the infrared sensor; comparing the commanded second temperature value with the second actual temperature value; and recalibrating the temperature controller based on the comparison.

[0169] According to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below, the method of calibrating the temperature controller is in response to receiving a command to calibrate the temperature controller at the controller.

[0170] According to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below, the method wherein receiving the command to calibrate the temperature controller at the controller includes receiving the command from a remote computing device.

[0171] According to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below, the method wherein receiving the command to calibrate the temperature controller at the controller includes receiving user input at the user interface of the system.

[0172] The method according to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below further includes calibrating the infrared sensor.

[0173] According to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below, calibrating the infrared sensor includes: using the infrared sensor to measure a first temperature value adjacent to a temperature sensor carried by the flow cell interface; using the temperature sensor to measure a second temperature value; and calibrating the infrared sensor with a controller based on the difference between the first temperature value and the second temperature value.

[0174] According to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below, calibrating the infrared sensor includes: measuring a first temperature value of the flow cell support using the infrared sensor; measuring a second temperature value at the flow cell support using a temperature sensor carried by the flow cell support; and calibrating the infrared sensor with the controller based on the difference between the first temperature value and the second temperature value.

[0175] According to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below, the method of calibrating the infrared sensor is in response to receiving a command to calibrate the infrared sensor at the controller.

[0176] According to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below, the method wherein receiving the command to calibrate the infrared sensor at the controller includes receiving the command from a remote computing device.

[0177] According to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below, receiving the command to calibrate the infrared sensor at the controller includes receiving user input at the user interface of the system.

[0178] According to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below, calibrating the infrared sensor includes generating data associated with the difference between the first temperature value and the second temperature value, and calibrating the infrared sensor with the controller based on the data.

[0179] According to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below, the method of commanding the temperature controller of the system to bring the flow cell support to the temperature value includes commanding a first region of the temperature controller of the system to bring a first region of the flow cell support to the temperature value, and wherein measuring the actual temperature value of the flow cell support using the infrared sensor includes measuring the actual temperature value of the first region of the flow cell support.

[0180] According to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below, calibrating the temperature controller based on the difference between the commanded temperature value and the actual temperature value includes calibrating a resistance temperature detector of the first region of the temperature controller based on the difference between the commanded temperature value and the actual temperature value.

[0181] The method according to any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below further includes: 1) commanding a second region of the temperature controller of the system to bring the second region of the flow cell support to a second temperature value; 2) measuring the actual temperature value of the second region of the flow cell support using the infrared sensor; and 3) calibrating the resistance temperature detector of the second region of the temperature controller based on the difference between the commanded temperature value and the actual temperature value.

[0182] A method comprising: commanding a temperature controller of a system to bring a flow cell support to a temperature value; measuring multiple actual temperature values ​​of the flow cell support using an infrared sensor; determining an average actual temperature value based on the multiple actual temperature values; and calibrating the temperature controller based on the difference between the commanded temperature value and the average actual temperature value.

[0183] The above description is provided to enable those skilled in the art to practice the various configurations described herein. Although the subject matter has been specifically described with reference to various accompanying drawings and configurations, it should be understood that these drawings and configurations are for illustrative purposes only and should not be considered as limiting the scope of the subject matter.

[0184] As used herein, an element or step described in the singular and preceded by the words "an" or "a" should be understood to not exclude multiple said elements or steps unless such exclusion is expressly indicated. Furthermore, the reference to "an embodiment" is not intended to be interpreted as excluding the existence of additional embodiments that also include the described features. Moreover, unless expressly stated to the contrary, an embodiment that "comprises" or "has" one or more elements having a particular attribute may include additional elements, whether or not they have that attribute. Furthermore, the terms "comprises," "has," etc., are used interchangeably herein.

[0185] The terms “substantially,” “approximately,” and “about” used throughout this specification are used to describe and indicate small fluctuations, such as small fluctuations due to variations in the process. In some specific embodiments, they may 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%.

[0186] Many other ways may exist to implement the subject matter. The various functions and elements described herein may be distinguished differently from those shown without departing from the scope of the subject matter. Various modifications to these specific embodiments will be readily apparent to those skilled in the art, and the general principles defined herein can be applied to other specific embodiments. Therefore, those skilled in the art can make many changes and modifications to the subject matter without departing from its scope. For example, different numbers of given modules or units may be used, one or more different types of given modules or units may be used, given modules or units may be added, or given modules or units may be omitted.

[0187] Underlined and / or italicized headings and subheadings are used for convenience only, do not limit the scope of the subject matter, and are not incorporated into the explanation of the description of the subject matter. All structural and functional equivalents of elements throughout the various specific embodiments described herein, known or later to those skilled in the art, are expressly incorporated herein by reference and are intended to be covered by the subject matter. Furthermore, nothing disclosed herein is intended to be exclusive to the public, regardless of whether such disclosure is expressly set forth in the foregoing description.

[0188] It should be understood that all combinations of the foregoing concepts and the additional concepts discussed in more detail below (assuming that such concepts do not contradict each other) are contemplated as part of the subject matter disclosed herein. Specifically, all combinations of the claimed subject matter appearing at the end of this disclosure are contemplated as part of the subject matter disclosed herein.

Claims

1. A temperature calibration device, the device comprising: A flow cell interface, the flow cell interface including a flow cell support adapted to position a flow cell thereon; A temperature control device, wherein the temperature control device is used in the flow cell support; Infrared sensor; A stage assembly configured to move the flow cell interface relative to the infrared sensor; and The controller is configured to command the temperature control device to bring the flow cell support to a certain temperature value, to cause the infrared sensor to measure the actual temperature value of the flow cell support, and to calibrate the temperature control device based on the difference between the commanded temperature value and the actual temperature value.

2. The apparatus of claim 1, wherein the temperature control device comprises a thermoelectric cooler.

3. The apparatus of claim 2, wherein the temperature control device further comprises a resistance temperature detector.

4. The apparatus of claim 3, wherein the controller is configured to calibrate the temperature control device by calibrating the resistance temperature detector.

5. The apparatus of claim 1, further comprising an imaging system, wherein the infrared sensor is coupled to the imaging system.

6. The apparatus of claim 5, further comprising a bracket for connecting the infrared sensor to the imaging system.

7. The apparatus according to any one of claims 1 to 6, wherein the controller is further configured to calibrate the infrared sensor.

8. The apparatus according to any one of claims 1 to 6, further comprising a temperature sensor; wherein the infrared sensor is used to measure a first temperature value adjacent to the temperature sensor; the temperature sensor is used to measure a second temperature value; and the controller is used to calibrate the infrared sensor based on the difference between the first temperature value and the second temperature value.

9. The apparatus of claim 8, wherein the flow cell interface further includes a flow cell platform supporting the flow cell support, and the temperature sensor is connected to the flow cell platform.

10. The apparatus of claim 9, further comprising a printed circuit board coupled to the temperature sensor, the printed circuit board being positioned between the temperature sensor and the flow cell platform.

11. The apparatus of claim 8, further comprising a metal layer covering the surface of the temperature sensor.

12. The apparatus of claim 11, wherein the temperature sensor and the metal layer are spaced apart from the flow cell support.

13. The apparatus of claim 11, wherein the metal layer comprises aluminum.

14. The apparatus of claim 11, further comprising a thermally conductive epoxy resin connecting the temperature sensor to the metal layer.

15. The apparatus according to any one of claims 1 to 6, further comprising a temperature sensor; wherein the infrared sensor is used to measure a first temperature value of the flow cell support; the temperature sensor is used to measure a second temperature value at the flow cell support; and the controller is used to calibrate the infrared sensor based on the difference between the first temperature value and the second temperature value.

16. The apparatus of claim 15, wherein the temperature sensor is coupled to the flow cell support.

17. The apparatus of claim 15, further comprising a printed circuit board coupled to the temperature sensor, the temperature sensor being positioned between the flow cell interface and the printed circuit board.

18. The apparatus according to any one of claims 1 to 6, wherein the surface of the flow cell support comprises a metal layer.

19. The apparatus of claim 8, wherein the temperature sensor comprises a digital temperature sensor.

20. A temperature calibration method, the method comprising: The temperature controller of the command system brings the flow cell support, which is included in the flow cell interface and is adapted to position the flow cell thereon, to the desired temperature value. The flow cell interface is moved relative to the infrared sensor using the stage assembly; The infrared sensor is used to measure the actual temperature value of the flow cell support. as well as The temperature controller is calibrated based on the difference between the commanded temperature value and the actual temperature value.

21. The method of claim 20, wherein commanding the temperature controller to bring the flow cell support to the temperature value comprises: The thermoelectric cooler is commanded to bring the flow cell support to the stated temperature value. and The temperature value was measured using a resistance temperature detector.

22. The method of claim 20, wherein measuring the actual temperature value of the flow cell support using the infrared sensor comprises measuring the actual temperature value of the flow cell support using the infrared sensor while moving the flow cell support relative to the infrared sensor.

23. The method according to claim 20, further comprising: The temperature controller is commanded to bring the flow cell support to the second temperature value; The infrared sensor is used to measure the second actual temperature value of the flow cell, which is set on the flow cell support. Compare the commanded second temperature value with the second actual temperature value; as well as The temperature controller is recalibrated based on the comparison.

24. The method according to claim 20, further comprising: The system performs at least a portion of the analysis on one or more samples of interest within a flow cell disposed on the flow cell support. The temperature controller is commanded to bring the flow cell support to the second temperature value; The infrared sensor is used to measure the second actual temperature value of the flow cell, which is set on the flow cell support. Compare the commanded second temperature value with the second actual temperature value; as well as The temperature controller is recalibrated based on the comparison.

25. The method according to any one of claims 20 to 24, wherein calibrating the temperature controller is in response to receiving a command to calibrate the temperature controller at the controller.

26. The method of claim 25, wherein receiving the command to calibrate the temperature controller at the controller includes receiving the command from a remote computing device.

27. The method according to any one of claims 20 to 24, wherein receiving the command to calibrate the temperature controller at the controller includes receiving user input at the user interface of the system.

28. The method according to any one of claims 20 to 24, the method further comprising calibrating the infrared sensor.

29. The method of claim 28, wherein calibrating the infrared sensor comprises: The infrared sensor is used to measure a first temperature value of a temperature sensor located near the temperature sensor supported by the flow cell. A second temperature value is measured using a temperature sensor; and The infrared sensor is calibrated using a controller based on the difference between the first temperature value and the second temperature value.

30. The method of claim 29, wherein calibrating the infrared sensor comprises: The infrared sensor is used to measure the first temperature value of the flow cell support. A second temperature value is measured at the flow cell support using a temperature sensor, which is carried by the flow cell support. and The infrared sensor is calibrated using the controller based on the difference between the first temperature value and the second temperature value.

31. The method of claim 28, wherein calibrating the infrared sensor is in response to receiving a command to calibrate the infrared sensor at the controller.

32. The method of claim 31, wherein receiving the command to calibrate the infrared sensor at the controller includes receiving the command from a remote computing device.

33. The method of claim 31, wherein receiving the command to calibrate the infrared sensor at the controller includes receiving user input at the user interface of the system.

34. The method of claim 29, wherein calibrating the infrared sensor comprises generating data associated with the difference between the first temperature value and the second temperature value, and calibrating the infrared sensor with the controller based on the data.

35. The method according to any one of claims 20 to 24, wherein commanding the temperature controller of the system to bring the flow cell support to the temperature value includes commanding a first region of the temperature controller of the system to bring a first region of the flow cell support to the temperature value, and wherein measuring the actual temperature value of the flow cell support using the infrared sensor includes measuring the actual temperature value of the first region of the flow cell support.

36. The method of claim 35, wherein calibrating the temperature controller based on the difference between the commanded temperature value and the actual temperature value comprises calibrating a resistance temperature detector of the first region of the temperature controller based on the difference between the commanded temperature value and the actual temperature value.

37. The method of claim 35, further comprising: 1) The system commands the second region of the temperature controller to bring the second region of the flow cell support to a second temperature value; 2) Use the infrared sensor to measure the actual temperature value of the second region of the flow cell support; And 3) calibrate the resistance temperature detector of the second region of the temperature controller based on the difference between the commanded temperature value and the actual temperature value.

38. A temperature calibration method, the method comprising: The temperature controller of the command system brings the flow cell support, which is included in the flow cell interface and is adapted to position the flow cell thereon, to the desired temperature value. The flow cell interface is moved relative to the infrared sensor using the stage assembly; The infrared sensor was used to measure multiple actual temperature values ​​of the flow cell support. The average actual temperature value is determined based on the multiple actual temperature values; as well as The temperature controller is calibrated based on the difference between the commanded temperature value and the average actual temperature value.

39. A temperature control device, the device comprising: A flow cell interface, the flow cell interface including a flow cell support adapted to position a flow cell thereon; A temperature control device, wherein the temperature control device is used in the flow cell support; Infrared sensor; A stage assembly configured to move the flow cell interface relative to the infrared sensor; and A controller is configured to command the temperature control device to bring the flow cell support to a certain temperature value, and to enable the infrared sensor to measure multiple actual temperature values ​​of the flow cell support.

40. The apparatus of claim 39, wherein the controller is configured to generate a heat map based on the measured plurality of actual temperature values.

41. The apparatus of claim 40, wherein the controller is configured to diagnose anomalies based on the heatmap.

42. The apparatus of claim 40, wherein the controller is used to calibrate the temperature control device based on the thermal map.

43. The apparatus of claim 40, wherein the thermal image comprises a 2-D thermal image.

44. A method for generating an alarm, the method comprising: The command temperature controller causes the flow cell support, included in the flow cell interface and adapted to position the flow cell thereon, to reach the temperature value. The flow cell interface is moved relative to the infrared sensor using the stage assembly; The infrared sensor is used to measure the actual temperature value of the flow cell set on the flow cell support. Compare the commanded temperature value with the actual temperature value; as well as An alarm is generated when the difference between the commanded temperature value and the actual temperature value is greater than a threshold.

45. The method of claim 44, further comprising calibrating the temperature controller based on the difference between the commanded temperature value and the actual temperature value.

46. ​​A temperature calibration device, the device comprising: A flow cell interface, the flow cell interface including a flow cell support adapted to support a flow cell; A temperature control device, wherein the temperature control device is used in the flow cell support; Infrared sensor; Temperature sensor; A stage assembly configured to move the flow cell interface relative to the infrared sensor; and Controller The infrared sensor is used to measure a first temperature value adjacent to the temperature sensor; The temperature sensor is used to measure a second temperature value; and the controller is used to calibrate the infrared sensor based on the difference between the first temperature value and the second temperature value.

47. The apparatus of claim 46, further comprising a flow cell carrying the temperature sensor.

48. The apparatus of claim 47, wherein the flow cell comprises a simulated flow cell.

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