Systems and related methods for monitoring fluids in a reagent cartridge

By using sensor modules and controller systems in the sequencing platform to monitor and adjust the pressure of the reagent reservoir, the problem of inaccurate reagent flow rate and volume monitoring is solved, the efficiency and accuracy of fluid operation are improved, and the stability of the sequencing process is ensured.

CN114072234BActive Publication Date: 2024-12-20ILLUMINA INC
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Patent Information

Application Number
CN202080048292.X
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Priority Date
2019-12-30
Filing Date
2020-12-08
Publication Date
2024-12-20
Estimated Expiration
2040-12-08

AI Technical Summary

Technical Problem

The existing sequencing platforms have inaccuracy and control difficulties in reagent flow rate and volume monitoring, resulting in limited fluid operation efficiency and accuracy.

Method used

Using a system including a sensor module and a controller, by generating signals related to the volume and flow rate of the reagent in the reagent reservoir, comparing the flow rate value with the reference threshold, adjusting the pressure applied to the reagent reservoir to keep the flow rate within the threshold range, and passing through The connection between the sensor electrode and the kit enables real-time monitoring and control of reagent flow.

Benefits of technology

It improves the accuracy and efficiency of reagent flow, ensures the stability and accuracy of reagents during sequencing, reduces the uncertainty of operating parameters, and improves the reliability of fluid analysis.

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Abstract

The present invention provides a system and a related method for monitoring a fluid in a test kit. The device includes a system comprising a test kit receptacle and a circulation cell assembly. The device includes a test kit that can be received in the test kit receptacle and is suitable for carrying the circulation cell assembly. The test kit includes a reagent reservoir that is fluidically coupled to the circulation cell assembly. The device includes a sensor module that is suitable for positioning adjacent to the reagent reservoir. The sensor module is suitable for generating a signal associated with the volume of a reagent contained in the reagent reservoir.
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Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This patent application claims the benefit of U.S. Provisional Application No. 62 / 955,160, filed on December 30, 2019, the contents of which are incorporated herein by reference in their entirety and for all purposes. Background Art

[0003] The sequencing platform may include valves and pumps. The valves and pumps may be used to perform various fluid operations. Summary of the invention

[0004] According to a first specific implementation, the device includes a system that includes a test kit receptacle. The device includes a circulation cell assembly. The device includes a test kit that can be received in the test kit receptacle and is suitable for carrying the circulation cell assembly. The test kit includes a reagent reservoir that is suitable for being fluidically coupled to the circulation cell assembly. The device includes a sensor module that is suitable for being positioned adjacent to the reagent reservoir. The sensor module is suitable for generating a signal associated with the volume of the reagent contained in the reagent reservoir.

[0005] According to a second specific implementation, the device includes a circulation cell assembly. The device includes a test kit suitable for carrying the circulation cell assembly. The test kit includes a reagent reservoir suitable for being fluidically coupled to the circulation cell assembly. The test kit includes a sensor electrode, which is associated with generating a signal associated with at least one of the volume of reagent in the reagent reservoir, the presence of reagent, or the reagent flow rate value.

[0006] According to a third specific implementation, the device includes a flow cell assembly and a test kit suitable for carrying the flow cell assembly. The test kit includes a reagent reservoir suitable for being fluidically coupled to the flow cell assembly. The device includes a sensor electrode that is associated with generating a signal associated with at least one of the volume of reagent in the reagent reservoir, the presence of reagent, or a reagent flow rate value.

[0007] According to a fourth embodiment, the method includes flowing a reagent from a reagent reservoir to a flow cell assembly and generating a signal associated with the reagent contained in the reagent reservoir. The method includes determining a volume of the reagent in the reagent reservoir based on the signal.

[0008] According to the fifth specific implementation, the device includes a system, which includes a test kit receptacle; a sensor module; and a controller, which is operably connected to the sensor module. The device includes a circulation cell assembly. The device includes a test kit that can be received in the test kit receptacle and is suitable for carrying the circulation cell assembly. The test kit includes a reagent reservoir containing reagents and a fluid line connected to the reagent reservoir and the circulation cell assembly. The device includes a pressure source suitable for applying pressure to the reagent reservoir. The sensor module is suitable for generating a signal associated with the reagent flow rate value, and the controller is suitable for comparing the determined reagent flow rate value with the reference flow rate value. When the determined reagent flow rate value exceeds the threshold range of the reference flow rate value, the controller can change the pressure applied to one or more reagent reservoirs, so that subsequent reagent flow rate values ​​can be within the threshold value of the reference flow rate value.

[0009] According to a sixth specific implementation, the apparatus includes a circulation cell assembly and a reagent box capable of being received in a reagent box receptacle of the system and adapted to carry the circulation cell assembly. The reagent box includes a plurality of reagent reservoirs; a common fluid line; and a plurality of reagent fluid lines. Each reagent fluid line is coupled to a corresponding reagent reservoir. The reagent box includes a portion of a sensor module adapted to interface with another portion of the sensor module of the system and associated with the generation of a signal associated with a reagent flow rate value.

[0010] According to a seventh specific implementation, the method includes pressurizing a reagent reservoir containing a reagent; allowing the reagent to flow to a common fluid line through a reagent fluid line; determining a reagent flow rate value; comparing the determined reagent flow rate value with a reference flow rate value; and when the determined reagent flow rate value exceeds a threshold range of the reference flow rate value, changing the pressure applied to the reagent reservoir so that subsequent reagent flow rate values ​​are within the threshold range of the reference flow rate value.

[0011] According to an eighth specific implementation, the device includes a test kit suitable for carrying a circulation cell assembly. The test kit includes a reagent reservoir suitable for being fluidically coupled to the circulation cell assembly. The device includes a sensor electrode associated with generating a signal associated with at least one of the volume of reagent in the reagent reservoir, the presence of reagent, or a reagent flow rate value.

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

[0013] In one implementation, the system includes a controller adapted to access the signal from the sensor module. The controller is adapted to determine a flow rate from the reagent reservoir based on the volume within the reagent reservoir over time.

[0014] In another specific implementation, the controller is adapted to compare the determined reagent flow rate value with a reference flow rate value. When the determined reagent flow rate value exceeds a threshold range of the reference flow rate value, the controller is adapted to change an operating parameter of the system.

[0015] In another embodiment, the operating parameter includes the amount of time that the reagent flows from the reagent reservoir.

[0016] In another specific implementation, the operating parameter includes a pressure applied to the reagent reservoir.

[0017] In another specific implementation, a pressure source suitable for applying pressure to the reagent reservoir is also included.

[0018] In another specific implementation, the invention further comprises a regulator connected between the pressure source and the reagent reservoir. The controller is adapted to cause the regulator to change the pressure applied to the reagent reservoir.

[0019] In another implementation, a system includes a sensor module.

[0020] In another specific implementation, a sensor electrode adapted to be communicatively coupled to a sensor module is also included.

[0021] In another implementation, the sensor electrodes are wirelessly coupled to the sensor module.

[0022] In another specific implementation, a connector suitable for connecting the sensor module and the sensor electrode is also included.

[0023] In another specific implementation, the connector includes a male portion and a female portion, one of the male portion or the female portion is carried by the reagent kit, and the other of the male portion or the female portion is carried by the system.

[0024] In another specific implementation, the sensor electrode includes a pair of plates with the reagent reservoir positioned between the pair of plates.

[0025] In another specific implementation, the sensor electrode includes a pair of plates, and the reagent reservoir is adapted to be positioned between the pair of plates.

[0026] In another specific implementation, the sensor electrode is a ring electrode and surrounds the reagent reservoir.

[0027] In another specific implementation, the sensor electrode is a ring electrode and is adapted to surround the reagent reservoir.

[0028] In another specific implementation, the sensor electrodes are carried by a reagent cartridge.

[0029] In another specific implementation, the sensor electrode includes a contact connecting the sensor module and the sensor electrode.

[0030] In another specific implementation, the sensor module includes contacts adapted to interface with the sensor electrodes.

[0031] In another specific implementation, the contact comprises a leaf spring contact.

[0032] In another specific implementation, the cartridge includes a fluid line, and the sensor electrode is positioned adjacent to the fluid line.

[0033] In another specific implementation, a flow cell assembly is also included, wherein the reservoir is fluidly coupled to the flow cell assembly.

[0034] In another specific implementation, the sensor electrodes include conductive tape coupled to the reagent cartridge.

[0035] In another implementation, the sensor electrode comprises a portion of a reagent reservoir or reagent kit.

[0036] In another implementation, the sensor electrode includes a well filled with a conductive fluid and adjacent to a reagent reservoir.

[0037] In another specific implementation, the reagent reservoir includes a tapered portion.

[0038] In another embodiment, the reagent reservoir includes an elongated portion.

[0039] In another specific implementation, the sensor module includes a capacitive sensor.

[0040] In another specific implementation, the method further includes determining a reagent flow rate value based on the volume of the reagent over time.

[0041] In another specific implementation, the step further includes pressurizing the reagent reservoir.

[0042] In another specific implementation, the method further includes comparing the determined reagent flow rate value with a reference flow rate value; and when the determined reagent flow rate value exceeds a threshold range of the reference flow rate value, changing the pressure applied to the reagent reservoir so that subsequent reagent flow rate values ​​can be within the threshold range of the reference flow rate value.

[0043] In another embodiment, the signal is correlated to the level of reagent contained within the reagent reservoir.

[0044] In another specific implementation, the signal is associated with an electrode of an electrode array, each electrode in the electrode array is positioned adjacent to the reagent reservoir and is associated with a different volume of reagent within the reagent reservoir.

[0045] It should be understood that all combinations of the foregoing concepts and the additional concepts discussed in more detail below (assuming such concepts are not mutually inconsistent) are contemplated as being part of the subject matter disclosed herein and / or can be combined to achieve specific benefits of specific aspects. In particular, all combinations of claimed subject matter appearing at the end of this disclosure are contemplated as being part of the subject matter disclosed herein. BRIEF DESCRIPTION OF THE DRAWINGS

[0046] Figure 1A A schematic diagram showing a specific implementation of a system according to a first embodiment of the present disclosure is shown.

[0047] Figure 1B Shows Figure 1A A schematic diagram of another specific implementation of the system.

[0048] Figure 1C Shows Figure 1A Another specific implementation of the flow cell assembly and kit of the system.

[0049] Figure 2 is a schematic diagram of a specific implementation of the sensor module and sensor electrode of FIG. 1 , including a pair of plates.

[0050] Figure 3 is a schematic diagram of another specific implementation of the sensor module and sensor electrode of FIG. 1 , including a ring electrode.

[0051] Figure 4 is a schematic diagram of another specific implementation of the sensor module and sensor electrode of FIG. 1 , including conductors and contacts.

[0052] Figure 5 is a schematic diagram of another specific implementation of the sensor module and the sensor electrode of FIG. 1 , including a pair of conductors and a pair of contacts.

[0053] Figure 6 is a schematic diagram of the reagent reservoir, sensor module and sensor electrode of FIG. 1 , wherein the reagent reservoir includes a tapered portion.

[0054] Figure 7 is a schematic diagram of another specific implementation of the reagent reservoir, sensor module, and sensor electrode of FIG. 1 , wherein the reagent reservoir includes an elongated portion.

[0055] Figure 8 is a specific implementation of the reagent reservoir of FIG. 1 having a flat portion.

[0056] Fig. 9 is another specific implementation of the reagent reservoir of FIG. 1 .

[0057] Fig.10A pair of sensor electrodes are shown spaced apart and positioned adjacent the common fluid line implementation of FIG. 1 .

[0058] Fig.11 shows an array of sensor electrodes, which are connected to Fig.10 The common fluid pipelines are positioned adjacent to each other.

[0059] Fig.12 Another array of sensor electrodes is shown, which is similar to Fig.10 The common fluid pipelines are positioned adjacent to each other.

[0060] Fig.13 Another arrangement of sensor electrodes is shown. Fig.10 The common fluid pipelines are adjacent to each other.

[0061] Fig.14 An arrangement of sensor electrodes is shown adjacent to the reagent reservoir implementation of FIG. 1 .

[0062] Fig.15 An array of sensor electrodes is shown, the array comprising Fig.14 The reagent reservoir is adjacent to the reference sensor electrode.

[0063] Fig.16 shows the arrangement of sensor electrodes, which is Fig.14 The reagent reservoir 136 is adjacent.

[0064] Fig.17 A flow chart of a method for determining the volume of a reagent within the reagent reservoir of any of FIG. 1 or other implementations disclosed herein is shown.

[0065] Fig.18 Another flow chart of a method for determining the volume of a reagent within the reagent reservoir of any of FIG. 1 or other implementations disclosed herein is shown. DETAILED DESCRIPTION

[0066] Although the following text discloses a detailed description of a specific implementation of the method, apparatus and / or article of manufacture, it should be understood that the legal scope of the property rights is defined by the text of the claims set forth at the end of this patent. Therefore, the following detailed description should be understood to be merely exemplary and does not describe every possible specific implementation, because it is impractical, if not impossible, to describe every possible specific implementation. Many alternative specific implementations can be implemented using current technology or technology developed after the filing date of this patent. It is contemplated that such alternative specific implementations will still fall within the scope of the claims.

[0067] The present disclosure relates to a sensor module for determining a reagent flow rate and / or a reagent volume in a reagent reservoir. In one embodiment, a system (e.g., a sequencing system) includes a sensor module and a controller operably coupled to the sensor module. The system is adapted to receive a reagent kit.

[0068] The test kit is suitable for carrying a circulation cell assembly and includes a plurality of reagent reservoirs containing reagents, a common fluid line and a plurality of reagent fluid lines. Each reagent fluid line is suitable for being connected to a corresponding reagent reservoir. The sensor module may be suitable for being positioned adjacent to the reagent reservoir.

[0069] In operation, the sensor module is adapted to generate a signal associated with the volume of the reagent contained in the reagent reservoir. In some implementations, the controller is adapted to determine the flow rate from the reagent reservoir based on the volume in the reagent reservoir over time.

[0070] In some such examples, the controller is suitable for comparing determined reagent flow rate value with a reference flow rate value. The reference flow rate value may be stored in a memory. The threshold range may be stored in a memory. When determined reagent flow rate value exceeds the threshold range of the reference flow rate value, the controller is suitable for changing the operating parameters of the system. Changing operating parameters may be associated with changing the amount of time that reagent flows out of the reagent reservoir to allow the reagent of the pumping threshold amount. In the specific implementation of the reagent reservoir pressurized, changing operating parameters may be associated with changing the pressure applied to the reagent reservoir to allow subsequent reagent flow rate value to be within the threshold range of the reference flow rate value.

[0071] Figure 1A A schematic diagram of a specific implementation of a system 100 according to a first embodiment of the present disclosure is shown. The system 100 can be used to perform analysis on one or more samples of interest. The sample may include one or more DNA clusters that have been linearized to form single-stranded DNA (sstDNA). In the specific implementation shown, the system 100 includes a reagent box receptacle 102 suitable for receiving a reagent box 104. The reagent box 104 carries a circulation pool assembly 106.

[0072] In the illustrated implementation, the system 100 includes, in part, a sensor module 108 and a controller 110 operably coupled to the sensor module 108. The sensor module 108 may include an integrated circuit (IC) 111. When the reagent box 104 is carried by the system 100, the sensor module 108 may be positioned on the top of the reagent box 104, on one side of the reagent box 104, and / or on the bottom of the reagent box 104. The sensor module 108 may include a non-contact sensor, such as a capacitive sensor and / or a non-contact capacitive level sensor. However, other types of sensors may prove suitable. For example, the sensor module 108 may include an optical sensor or a flow sensor.

[0073] Sensor module 108 may be suitable for generating a signal associated with the fluid in test kit 104. The signal may be associated with the volume of reagent in test kit 104. The flow rate of reagent may be associated with the volume of reagent over time. Some factors that may affect the flow rate of reagent include impedance (e.g., impedance of fluid pipeline), humidity, circulation cell assembly 106, manufacturing tolerance, ambient temperature, creep, water absorption, pressure (e.g., ambient pressure) and / or alignment. For example, different test kits 104 may have different impedances, sometimes referred to as box and box impedance variability. Other factors may also affect the flow rate of reagent.

[0074] The signal may also be associated with bubbles within the system 100, the reagent cartridge 104, and / or the flow cell assembly 106. For example, the signal may be associated with the presence / absence of bubbles within the reagent cartridge 104. For example, the signal may be associated with the presence / absence of reagents within the reagent cartridge 104.

[0075] In some specific implementations, the signal generated by the sensor module 108 can be used to determine the change of humidity, the presence of detection liquid and / or determine the effectiveness of flushing the circulation pool assembly 106 with air (e.g., air flushing) during the flushing operation. If humidity is detected to be higher than a threshold value, it may be associated with a leak. Detection of the presence of liquid in a generally dry region may be associated with a leak. In some specific implementations, the signal generated by the sensor module 108 can be used to determine the remaining reagent amount in one or more fluid lines in the fluid line, the metering of the reagent, to determine whether the reagent flows as expected, to determine whether the reagent is retained at the top of the reagent reservoir 136, and / or the mixing and / or rehydration of the monitoring reagent. Other applications may prove to be suitable.

[0076] In some implementations, a higher signal-to-noise ratio may affect the accuracy of the determined parameter (e.g., volume). In some implementations, the signal-to-noise ratio of the signal can be reduced in a variety of ways. Some methods of reducing the signal-to-noise ratio may include increasing the height of the reagent reservoir, including an array of sensor electrodes (e.g., see Fig.15 ) and / or reducing the spacing of the sensor electrodes and / or the associated voltages. Other approaches may include using capacitance multipliers (pre-ADC capacitance multipliers based on transistors or operational amplifiers), driving the sensor electrodes with sinusoidal voltages, and / or by using lock-in amplifiers. Other approaches may prove suitable.

[0077] In the illustrated implementation, the system 100 also includes a pressure source 112. In some implementations, the pressure source 112 can be used to pressurize the reagent cartridge 104. Pressurizing the reagent can be used to cause the reagent to flow through the system 100, the reagent cartridge 104, and / or the flow cell assembly 106 under positive pressure. Alternatively, the pressure source 112 can be carried by the reagent cartridge 104 or can be external to the system 100.

[0078] Some factors may cause changes in the applied pressure and / or the resulting reagent flow rate values. Some factors that affect flow rate and / or pressure include the height of the circulation pool, manufacturing tolerances, lane reduction, ambient pressure and / or temperature. Other factors may affect the applied pressure and / or the resulting reagent flow rate values.

[0079] The system also includes a regulator 113, an imaging system 114, a drive assembly 115, and a waste reservoir 116. Alternatively, the system may not include the regulator 113. The drive assembly 115 includes a pump drive assembly 118, a valve drive assembly 120, and a pressure drive assembly 122. The controller 110 can be electrically and / or communicatively coupled to the drive assembly 115 and the imaging system 114, and is adapted to cause the drive assembly 115 and / or the imaging system 114 to perform various functions as disclosed herein. The waste reservoir 116 can be selectively received in a waste reservoir receptacle 124 of the system 100.

[0080] The reagent cartridge 104 carries one or more samples of interest. The drive assembly 115 interfaces with the reagent cartridge 104 to flow one or more reagents (eg, A, T, G, C nucleotides) that interact with the sample through the reagent cartridge 104 and / or the flow cell assembly 106 .

[0081] In one embodiment, a reversible terminator is attached to a reagent to allow each cycle to be incorporated into a single nucleotide by sstDNA. 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 embodiment shown, the imaging system 114 is suitable for exciting one or more identifiable labels (e.g., fluorescent labels) and then obtaining image data of the identifiable labels. The label can be excited by incident light and / or laser, and the image data may include one or more colors emitted by the corresponding label in response to the excitation. The image data (e.g., detection data) can be analyzed by the system 100. The imaging system 114 can be a fluorescence spectrophotometer including an objective lens and / or a solid-state imaging device. The solid-state imaging device may include a charge coupled device (CCD) and / or a complementary metal oxide semiconductor (CMOS).

[0082] After obtaining the image data, the drive assembly 115 interfaces with the reagent box 104 to allow another reaction component (e.g., a reagent) to flow through the reagent box 104, which is then received by the waste reservoir 116 and / or otherwise consumed by the reagent box 104. The reaction components undergo a flushing operation that chemically cuts the fluorescent label and reversible terminator from the sstDNA. The flushing operation can also be performed using air. The sstDNA is then ready for another cycle.

[0083] The circulation cell assembly 106 includes a housing 126 and a circulation cell 128. The circulation cell 128 includes at least one channel 130, a circulation cell inlet 132, and a circulation cell outlet 134. The channel 130 may be U-shaped or may be straight and extend across the circulation cell 128. Other configurations of the channel 130 may prove suitable. Each channel in the channel 130 may have a dedicated circulation cell inlet 132 and a dedicated circulation cell outlet 134. Alternatively, a single circulation cell inlet 132 may be fluidically coupled to more than one channel 130 (via, for example, an inlet manifold). Alternatively, a single circulation cell outlet 134 may be coupled to more than one channel (via, for example, an outlet manifold).

[0084] In the specific implementation shown, the test kit 104 includes a plurality of reagent reservoirs 136, a common fluid line 138 and a plurality of reagent fluid lines 140. Alternatively, a reagent reservoir 136 and a reagent fluid line 140 may be included. The reagent reservoir 136 may contain fluid (e.g., reagent and / or another reaction component). The pressure source 112 may apply pressure to the reagent reservoir 136. Therefore, the positive pressure of the pressure source 112 can be used to push the reagent through the system 100, the test kit 104 and / or the circulation cell assembly 106.

[0085] Each reagent fluid line 140 can be coupled to a corresponding reagent reservoir 136. The reagent cartridge 104 also includes a flow cell receptacle 142 and a manifold assembly 144. In other implementations, the manifold assembly 144 is part of the flow cell assembly 106 and / or part of the system 100.

[0086] In operation, the sensor module 108 may generate a signal associated with the volume of reagent contained within the reagent reservoir 136. The controller 110 may be adapted to access the signal from the sensor module 108 and determine a flow rate value from the reagent reservoir 136 based on the volume within the reagent reservoir 136 over time.

[0087] Controller 110 can compare determined reagent flow rate value with reference flow rate value.In some specific implementations, when determined reagent flow rate value exceeds the threshold range of reference flow rate value, controller 110 can change the operating parameters of system 100.Operating parameters can include the amount of time that reagent flows out from reagent reservoir 136.For example, if determined reagent flow rate value is less than reference flow rate value, controller 110 can increase the amount of time that reagent flows out from reagent reservoir 136, to allow the reagent of pumping threshold amount.Alternatively, if determined reagent flow rate value is greater than reference flow rate value, controller 110 can increase the amount of time that reagent flows out from reagent reservoir 136, to allow the reagent of pumping threshold amount.In a specific implementation, the threshold range is between about 100 microliters (μL) and about 6000 μL.Other flow rates can prove to be suitable.

[0088] In other specific implementations, operating parameters include the pressure applied to the reagent reservoir. Pressure can be applied using a pressure source 112. In this type of specific implementation, the controller 110 can change the pressure applied to one or more reagent reservoirs 136 so that subsequent reagent flow rate values ​​can be within the threshold range of the reference flow rate value. For example, the controller 110 can make the valve drive assembly 120 that is suitable for interfacing with the regulator 113 control the pressure applied to the reagent reservoir 136. Therefore, the controller 110 can make the regulator 113 change the pressure applied to one or more reagent reservoirs 136. The regulator 113 is positioned between the pressure source 112 and the reagent reservoir 136. However, the regulator 113 can be in different positions or omitted completely.

[0089] In the illustrated implementation, the reagent cartridge 104 includes the sensor electrodes 145. Thus, the sensor electrodes 145 may be carried by the reagent cartridge 104. The sensor electrodes 145 are communicatively coupled to the sensor module 108. The sensor electrodes 145 may be coupled to the sensor module 108 via a physical connection or a wireless connection. In other implementations, the sensor electrodes 145 may be carried by the system 100 (e.g., see Figure 2 and Figure 3 In such implementations, the sensor electrodes 145 may be a pair of prongs or plates (see Figure 2 ), or may be annular (see Figure 3 ).

[0090] In the illustrated implementation, connector 146 couples sensor module 108 and sensor electrode 145. Connector 146 may be an edge connector, a plug / socket connector, or a spring pin. When connector 146 is a two-part connector (e.g., a plug / socket connector), connector 146 may include a recess 148 and a protrusion 150. One of the protrusion 150 or the recess 148 may be carried by reagent box 104, and the other of the protrusion 150 or the recess 148 may be carried by system 100.

[0091] In another embodiment, the reagent cartridge 104 carries the sensor electrodes 145 and the system 100 carries the connector 146 (see, e.g., Figure 4 and Figure 5 In such implementations, the sensor electrode 145 may include a conductor 152 (see Figure 4 and Figure 5 ), and the connector 146 includes a contact 154 (see Figure 4 and Figure 5 ). The contact 154 may be adapted to interface with the conductor 152. The contact 154 may be a leaf spring contact connector. Other types of contacts 154 may prove suitable.

[0092] The test kit 104 includes a test kit body 156. The test kit body 156 can carry the sensor electrodes 145. For example, the sensor electrodes 145 can be housed within the test kit body 156, can be coupled to the exterior of the test kit body 156, or can be embedded within the test kit body 156. An adhesive or clamp can be used to couple the sensor electrodes 145 to the exterior of the test kit body 156 or otherwise couple them. If the sensor electrodes 145 are carried on the exterior of the test kit body 156, the test kit body 156 can define a sensor electrode receptacle 158. The sensor electrode receptacle 158 can be adapted to receive the sensor electrodes 145. The sensor electrode receptacle 158 can be a groove.

[0093] The reagent box body 156 can be formed of solid plastic using injection molding technology and / or additive manufacturing technology. In some specific implementations, the reagent reservoir 136 is formed integrally with the reagent box body 156. In other specific implementations, the reagent reservoir 136 is formed separately and is connected to the reagent box body 156.

[0094] In the specific implementation shown, manifold assembly 144 includes a plurality of valves 160. Valve 160 may include pinch valves, rotary valves, diaphragm valves, Belleville valves and / or linear valves. Other types of valves 160 may prove suitable. Manifold assembly 144 fluidically couples common fluid line 138 with each reagent fluid line in reagent fluid lines 140. Each valve 160 is coupled between common fluid line 138 and corresponding reagent fluid line 140. In operation, valve drive assembly 120 is adapted to interface with valve 160 to control the flow of reagent between reagent fluid line 140 and common fluid line 138.

[0095] The manifold assembly 144 includes a manifold body 162. The manifold body 162 may be formed of polypropylene. The manifold body 162 defines a portion 164 of the common fluid line 138 and a portion 166 of the reagent fluid line 140.

[0096] The flow cell receptacle 142 is adapted to receive the flow cell assembly 106. Alternatively, the flow cell assembly 106 may be integrated into the reagent cartridge 104. In such implementations, the flow cell receptacle 142 may not be included in the reagent cartridge 104, or at least the flow cell assembly 106 may be non-removably received in the reagent cartridge.

[0097] Referring now to the drive assembly 115, in the illustrated implementation, the drive assembly 115 includes a pump drive assembly 118, a valve drive assembly 120, and a pressure drive assembly 122. The pump drive assembly 118 is adapted to interface with one or more pumps 168 to pump fluid through the reagent cartridge 104. The pump 168 may be implemented by a syringe pump, a peristaltic pump, a diaphragm pump, etc. While the pump 168 may be positioned between the flow cell assembly 106 and the waste reservoir 116, in other implementations, the pump 168 may be positioned upstream of the flow cell assembly 106 or omitted entirely.

[0098] Referring to the controller 110, in the illustrated implementation, the controller 110 includes a user interface 170, a communication interface 172, one or more processors 174, and a memory 176 that stores instructions executable by the one or more processors 174 to perform various functions, including the disclosed implementation. The user interface 170, the communication interface 172, and the memory 176 are electrically and / or communicatively coupled to the one or more processors 174.

[0099] In one implementation, the user interface 170 is adapted to receive input from a user and provide information to the user associated with the operation of the system 100 and / or the analysis performed. The user interface 170 may include a touch screen, a display, a keyboard, a speaker, a mouse, a trackball, and / or a voice recognition system. The touch screen and / or the display may display a graphical user interface (GUI).

[0100] In one implementation, the communication interface 172 is adapted to enable communication between the system 100 and a remote system (e.g., a computer) via a network. The network may include the Internet, an intranet, a local area network (LAN), a wide area network (WAN), a coaxial cable network, a wireless network, a wired network, a satellite network, a digital subscriber line (DSL) network, a cellular network, a Bluetooth connection, a near field communication (NFC) connection, etc. Some communications provided to the remote system may be associated with analysis results, imaging data, etc. generated or otherwise obtained by the system 100. Some communications provided to the system 100 may be associated with fluid analysis operations, patient records, and / or protocols to be executed by the system 100.

[0101] The one or more processors 174 and / or the system 100 may include one or more of a processor-based system or a microprocessor-based system. In some implementations, the one or more processors 174 and / or the system 100 include one or more of a programmable processor, a programmable controller, a microprocessor, a microcontroller, a graphics processing unit (GPU), a digital signal processor (DSP), a reduced instruction set computer (RISC), an application specific integrated circuit (ASIC), a field programmable gate array (FPGA), a field programmable logic device (FPLD), a logic circuit, and / or another logic-based device that performs various functions, including the functions described herein.

[0102] The memory 176 may store one or more reference flow rate values, threshold ranges, and other related data. The memory 176 may include one or more semiconductor memories, magnetically readable memories, optical memories, hard disk drives (HDDs), optical storage drives, solid-state storage devices, solid-state drives (SSDs), flash memory, read-only memories (ROMs), erasable programmable read-only memories (EPROMs), electrically erasable programmable read-only memories (EEPROMs), random access memories (RAMs), non-volatile RAM (NVRAM) memories, compact disks (CDs), compact disk read-only memories (CD-ROMs), digital versatile disks (DVDs), Blu-ray disks, redundant arrays of independent disks (RAID) systems, caches, and / or any other storage devices or storage disks in which information is stored for any duration (e.g., permanently, temporarily, for a long period of time, for buffering, for caching).

[0103] Figure 1B Shows Figure 1A 100 is a schematic diagram of another specific implementation of the system 100. In the specific implementation shown, the system 100 includes a reagent box receptacle 102. A circulation cell assembly 106 is included. A reagent box 104 is also included. The reagent box 104 can be received in the reagent box receptacle 102 and is suitable for carrying the circulation cell assembly 106. The reagent box 104 includes a reagent reservoir 136 and is fluidically connected to the circulation cell assembly 106. A sensor module 108 is also included. The sensor module 108 can be carried by the system 100 and / or by the reagent box 104. The sensor module 108 can be positioned adjacent to the reagent reservoir 136. In operation, the sensor module 108 can generate a signal associated with the volume of the reagent contained in the reagent reservoir 136.

[0104] Figure 1C Shows Figure 1AAnother specific implementation of the circulation cell assembly 106 and the test kit 104 of the system 100. In the specific implementation shown, the circulation cell assembly 106 and the test kit 104 are included. The test kit 104 is suitable for carrying the circulation cell assembly 106. The test kit 104 includes a reagent reservoir 138 that is fluidically connected to the circulation cell assembly 106. The sensor electrode 145 is associated with generating a signal associated with at least one of the volume, the presence of the reagent or the reagent flow rate value of the reagent in the reagent reservoir 136. The presence of the reagent can be identified in the reagent fluid path 140, the common fluid path 138 and / or in the area outside the reagent reservoir 136, the reagent fluid path 140 and / or the common fluid path 138. The presence of the reagent outside the reservoir or the fluid path may be associated with a leak.

[0105] Figure 2 1 is a schematic diagram of a specific implementation of the sensor module 108 and the sensor electrode 145 of FIG. The sensor module 108 and the sensor electrode 145 can be carried by the system 100. In the specific implementation shown, the sensor electrode 145 includes a pair of plates 177. The plates 177 are spaced apart by a distance 178. One of the reagent reservoirs 136 is shown as being positioned between the plates 177. The plates 177 can be positioned above or below the reagent reservoir 136, or the plates 177 can be positioned around the reagent reservoir 136. When the plates 177 are positioned around the reagent reservoir 136, the plates 177 can be positioned on the sides of the reagent reservoir 136, or the plates 177 can be positioned above and below the reagent reservoir 136.

[0106] Regardless of the relative positions of the plate 177 and the reagent reservoir 136, the sensor module 108 and the plate 177 can be adapted to generate a signal associated with the amount of reagent (or other fluid) within the reagent reservoir 136. The determined amount of reagent within the reagent reservoir 136 can be used to determine the flow rate (e.g., volume over time) of the reagent.

[0107] Figure 3 1 is a schematic diagram of another specific implementation of the sensor module 108 and the sensor electrode 145 of FIG. The sensor module 108 and the sensor electrode 145 can be carried by the system 100. In the specific implementation shown, the sensor electrode 145 includes an annular electrode 179. The annular electrode 179 can be referred to as a ring electrode. The annular electrode 179 is shown as surrounding a reagent reservoir in the reagent reservoir 136. Due to the symmetry of the annular electrode 179, the alignment between the annular electrode 179 and the reagent reservoir 136 can be consistently achieved. Therefore, the annular electrode 179 can take into account manufacturing tolerances, including manufacturing tolerances of the reagent reservoir 136.

[0108] The ring electrode 179 may be positioned above or below the reagent reservoir 136, or the ring electrode 179 may be positioned around the reagent reservoir 136. When the ring electrode 179 is positioned around the reagent reservoir 136 (e.g., when the reagent cartridge 104 is locked and / or loaded within the system 100), the ring electrode 179 may be directed around the reagent reservoir 136. Other methods of positioning the ring electrode 179 relative to the reagent reservoir 136 may prove suitable for positioning the ring electrode 179 in such a manner that the sensor module 108 and the ring electrode 179 are able to generate a signal associated with the amount of reagent (or other fluid) within the reagent reservoir 136.

[0109] Figure 4 1 is a schematic diagram of another implementation of the sensor module 108 and the sensor electrode 145. In the implementation shown, the sensor electrode 145 includes a conductor 152, and the connector 146 includes a contact 154. In one implementation, the conductor 152 is a conductive tape, and the contact 154 is a leaf spring electrical contact. The conductive tape may include aluminum.

[0110] In another specific implementation, the conductor 152 comprises a portion of the reagent reservoir 136, and the contact 154 is a leaf spring electrical contact. The portion may be a conductive plastic. In such specific implementations, the reagent reservoir 136 may be formed in a two-step injection molding process. Other methods of forming the reagent reservoir 136 may prove suitable. Alternatively, the test kit 104 may include the portion. Regardless of how the conductor 152 and / or the contact 154 are formed, the contact 154 may be adapted to contact the conductor 152, thereby coupling the conductor 152 and the contact 154 in a communication manner.

[0111] Figure 5 FIG. 1 is a schematic diagram of another specific implementation of the sensor module 108 and the sensor electrode 145. In the specific implementation shown, the sensor electrode 145 includes a pair of conductors 152, and the connector 146 includes a pair of contacts 154. The electric field generated by the pair of conductors 152 may be different from the electric field generated by the pair of conductors 152. Figure 4 The electric field generated by a single conductor 152.

[0112] Conductor 152 may be a pair of holes 180 coupled to and / or adjacent to reagent reservoir 136. Holes 180 may be filled with a conductive fluid 182. Conductive fluid 182 may include adhesive, adhesive in a hardened state, gallium, mercury, conductive adhesive, silver epoxy adhesive, conductive gel, aluminum oxide adhesive, thermal adhesive, and / or conductive adhesive gel. Other conductive fluids may prove suitable.

[0113] Figure 61 is a schematic diagram of a reagent reservoir 136, a sensor module 108 and a sensor electrode 145. In the illustrated implementation, the reagent reservoir 136 includes a tapered portion 184. The sensor module 108 is arranged to determine the characteristics of the reagent in the reagent reservoir 136. The first volume 186 of the reagent adjacent to the tapered portion 184 is less than the second volume 188 in the reagent reservoir 136 remainder. The tapered portion 184 reduces the amount of reagent in the first volume 186. Therefore, the height of the reagent in the first volume 186 changes faster than in the second volume 188, thereby allowing the reagent flow rate value to be determined relatively quickly by monitoring the first volume 186. Therefore, in some implementations, the system 100 can perform a calibration process during normal operating conditions, rather than performing a separate calibration process before starting normal operation.

[0114] Figure 7 1 is a schematic diagram of another specific implementation of the reagent reservoir 136, sensor module 108 and sensor electrode 145 of Fig. 1. In the specific implementation shown, the reagent reservoir 136 includes an extension 190. The sensor module 108 is arranged to determine the characteristics of the reagent in the reagent reservoir 136. The first volume 186 of the reagent adjacent to the extension 190 is less than the second volume 188 in the rest of the reagent reservoir 136, thereby allowing the controller 110 to determine and adjust the flow rate by monitoring the reagent flow rate value from the first volume 186 during normal operating conditions. However, a separate calibration process can be performed here or in any specific implementation of other disclosed specific implementations.

[0115] Figure 8 1 is a specific implementation of the reagent reservoir 136. In the specific implementation shown, the reagent reservoir 136 includes a curved portion 192 and a flat portion 194. The sensor electrode 145 and / or the sensor module 108 can be positioned adjacent to the flat portion 194. Positioning the conductor 152 and / or the conductor 185, the sensor electrode 145 and / or the sensor module 108 adjacent to the flat portion 194 can increase the accuracy of the determined volume and / or the determined reagent flow rate value because such positioning can more easily monitor the height of the reagent at the flat portion 194 compared to the curved portion 192.

[0116] Fig. 9 1 is another embodiment of the reagent reservoir 136. In the embodiment shown, the reagent reservoir 136 has a circular cross-section. Other cross-sections may prove suitable.

[0117] Figures 10 to 12Implementations of different exemplary arrangements of sensor electrodes 145 are depicted positioned adjacent to implementations of common fluid line 138 of FIG. 1. Alternatively, sensor electrodes 145 may be positioned adjacent to one or more of reagent fluid lines 140.

[0118] Fig.10 A pair of sensor electrodes 145 are shown spaced apart and positioned adjacent to a specific implementation of the common fluid line 138 of Figure 1. The volume 196 between the sensor electrodes 145 is known. When a reagent within the common fluid line 138 is adjacent to a corresponding sensor electrode 145, the capacitance value associated with the sensor electrode 145 may change.

[0119] To determine the reagent flow rate value, the amount of time that has elapsed is determined between the time at which the capacitance value of the first electrode 198 changes and the time at which the capacitance value of the second electrode 200 changes. The capacitance value may change when the reagent within the common fluid line 138 is adjacent to the corresponding sensor electrode 145. To determine the flow rate within the common fluid line 138, the volume 196 between the sensor electrodes 145 is divided by the time associated with the changed capacitance value. Other methods of determining flow rate may prove suitable.

[0120] In addition, the sensor electrode 145 can be used to detect the presence of a reagent or another fluid. For example, when the capacitance value of the first electrode 198 changes, the presence of a reagent can be detected.

[0121] Fig.11 Shown with Fig.10 An array of sensor electrodes 145 is positioned adjacent to a common fluid line 138. The sensor electrodes 145 can be coupled to the reagent cartridge 104 and / or the system 100.

[0122] To determine the volume of fluid flowing in the common fluid line 138, in one embodiment, the capacitance values ​​of the corresponding sensor electrodes 145 are monitored. For example, if the capacitance values ​​of the first two sensor electrodes 145 change, the controller 110 can determine that the relevant volume of the reagent has been pumped and / or flowed through a portion of the common fluid line 138. Similarly, if the capacitance values ​​of the first three sensor electrodes 145 change, the controller 110 can determine that the relevant volume of the reagent has been pumped and / or flowed through another portion of the common fluid line 138. Although four sensor electrodes 145 are shown, any number of electrodes may be included. Determining the volume of the reagent can be used to ensure that the reagent is mixed in a threshold amount, a threshold volume of the reagent is provided, a threshold amount of the reagent is rehydrated (e.g., reagent initialization), and / or a threshold concentration of the reagent is reached.

[0123] In a specific implementation, the controller 110 can compare signals from different sensor electrodes 145 to monitor the operating status of the fluid analysis operation when the sensor electrodes 145 are also positioned adjacent to the reagent reservoir 136. For example, the controller 110 can determine whether the fluid analysis operation is proceeding as expected.

[0124] Fig.12 Shown with Fig.10 138. Although ten sensor electrodes 145 are shown, any other number of sensor electrodes 145 may be included. Capacitance values ​​associated with the sensor electrodes 145 may be used to determine reagent flow rate values, reagent volume within the common fluid line 138, and / or pumped reagent volume. However, the capacitance values ​​may be used in other ways.

[0125] Fig.13 Shown with Fig.10 138. In the illustrated implementation, the sensor electrodes 145 include a longer electrode 202 and a pair of reference sensor electrodes 204. One of the reference sensor electrodes 204 may be spaced apart from the common fluid line 138, and another of the reference sensor electrodes 204 may be positioned above the top of or otherwise adjacent to the common fluid line 138. The reference sensor electrodes 204 may be used to allow the controller 110 to determine a reference capacitance value when the reference sensor electrodes 204 are not exposed to or otherwise spaced apart from reagents that may flow through the common fluid line 138.

[0126] The capacitance value associated with the longer electrode 202 can be used to determine the volume of the reagent within the common fluid line 138. The change in capacitance value over time can be correlated to the value of the reagent flow rate through the common fluid line 138.

[0127] Fig.14 An arrangement of sensor electrodes 145 adjacent to the embodiment of the reagent reservoir 136 of FIG. 1 is shown. In the embodiment shown, the longer electrode 202 has a relatively thin width. Providing the longer electrode 202 with a relatively thin width can reduce the possibility of misalignment of the longer electrode 202 relative to the reagent reservoir 136. One of the reference sensor electrodes 204 is spaced apart from the reagent 206, and another of the reference sensor electrodes 204 is positioned adjacent to the reagent 206.

[0128] Fig.15 Shown includes Fig.14An array of sensor electrodes 145 is provided adjacent to a reference sensor electrode 204 positioned adjacent to the reagent reservoir 136. Some of the sensor electrodes 145 positioned toward the top 208 of the reagent reservoir 136 may be used to determine whether the reagent 206 has flowed downward and / or whether the reagent 206 is suspended / stuck at the top 208 of the reagent reservoir 136.

[0129] In the illustrated implementation, the capacitance values ​​of different sensor electrodes 145 may be associated with the volume of the reagent 206 in the reagent reservoir 136. For example, the first electrode 210 may be associated with the first volume of the reagent contained in the reagent reservoir 136; the second electrode 212 may be associated with the second volume of the reagent contained in the reagent reservoir 136; the third electrode 214 may be associated with the third volume of the reagent contained in the reagent reservoir 136, etc. In other words, each electrode 145 in the array of electrodes 145 and its position relative to the reagent reservoir 136 may be associated with a specific volume of the reagent. Therefore, when the capacitance values ​​of electrodes 210 to 214 change and the capacitance values ​​of the remaining electrodes 216, 218, 220, 222, 224, 226 do not change, the controller 110 can determine that a specific volume of the reagent 206 is contained in the reagent reservoir 136 associated with the first three electrodes 210, 212, 214. In such implementations, the electrodes 145 can act as an on / off switch or can be automatically disconnected in other ways when a reagent or fluid is sensed. Additionally, the capacitance values ​​may indicate that the reagent 206 is stuck on and / or on the top 208 of the reagent reservoir 136. For example, when the capacitance value of the top electrode 226 indicates that the reagent is present and the capacitance values ​​of the other electrodes of the electrodes 220, 222, and 224 indicate that the reagent is not present, the controller 110 may determine that some reagent is stuck on the top 208 of the reagent reservoir 136 or that there is another error in determining and / or dispensing the reagent.

[0130] Fig.16 Shown with Fig.14 The reagent reservoir 136 is arranged adjacent to the sensor electrode 145. Fig.16 The arrangement is similar to Fig.14 , but the sensor electrode 145 is wider. Other widths and / or shapes of the sensor electrode 145 may prove suitable. In addition, Fig.14 The lower reference sensor electrode 204 shown in FIG. Fig.16 However, the lower reference sensor electrode 204 may alternatively be included in Fig.16 in the specific implementation.

[0131] Fig.17 and Fig.18 Shows the use of Figure 1AA flow chart of a method for determining the volume of a reagent in a reagent reservoir 136 in any of the system 100 or other embodiments disclosed herein. Fig.17 In the flowchart of FIG. 1700 , the box surrounded by a solid line may be included in the specific implementation of process 1700, while the box surrounded by a dashed line may be optional in the specific implementation of the process. Fig.17 and Fig.18 No matter how the box boundaries are presented, the order of execution of the boxes may be changed, and / or some of the boxes described may be changed, eliminated, combined, and / or subdivided into multiple boxes.

[0132] See also Fig.17 , process 1700 begins by pressurizing reagent reservoir 136 (frame 1702). Pressure source 112 can be used to pressurize reagent reservoir 136. Reagent flows from reagent reservoir 136 to circulation cell assembly 106 (frame 1704). A signal associated with the reagent contained in reagent reservoir 136 is generated (frame 1706). The signal can be generated by sensor module 108. The volume of reagent in reagent reservoir 136 is determined based on the signal (frame 1708).

[0133] A reagent flow rate value is determined based on the volume of the reagent over time (box 1710). The determined reagent flow rate value is compared with a reference flow rate value (box 1712). When the determined reagent flow rate value exceeds a threshold range of the reference flow rate value, the pressure applied to the reagent reservoir 136 is changed so that subsequent reagent flow rate values ​​can be within the threshold range of the reference flow rate value (box 1714).

[0134] In another specific implementation, the reagent flow rate value is determined based on the volume of the reagent over time. The determined reagent flow rate value is compared with a reference flow rate value. The pressure applied to the reagent reservoir is changed so that subsequent reagent flow rate values ​​can be closer to the reference flow rate value.

[0135] See also Fig.18 , process 1800 begins with the flow of reagent from reagent reservoir 136 to flow cell assembly 106 (block 1802). A signal associated with the reagent contained in reagent reservoir 136 is generated (block 1804). The signal may be generated by sensor module 108. The volume of the reagent in reagent reservoir 136 is determined based on the signal (block 1806).

[0136] A device comprises: a system comprising a reagent cartridge receptacle; a circulation cell assembly; a reagent cartridge capable of being received in the reagent cartridge receptacle and adapted to carry the circulation cell assembly, the reagent cartridge comprising a reagent reservoir adapted to be fluidically coupled to the circulation cell assembly; and a sensor module adapted to be positioned adjacent to the reagent reservoir, wherein the sensor module is adapted to generate a signal associated with a volume of a reagent contained in the reagent reservoir.

[0137] The apparatus of any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below, wherein the system comprises a controller adapted to access signals from the sensor module, and wherein the controller is adapted to determine a flow rate from the reagent reservoir based on a volume within the reagent reservoir over time.

[0138] The device according to any one or more of the foregoing specific embodiments and / or any one or more of the specific embodiments disclosed below, wherein the controller is suitable for comparing the determined reagent flow rate value with a reference flow rate value, and wherein when the determined reagent flow rate value exceeds a threshold range of the reference flow rate value, the controller is suitable for changing an operating parameter of the system.

[0139] 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 operating parameter includes an amount of time for the reagent to flow from the reagent reservoir.

[0140] 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 operating parameter includes the pressure applied to the reagent reservoir.

[0141] According to the device of any one or more of the foregoing embodiments and / or any one or more of the embodiments disclosed below, the device further comprises a pressure source adapted and capable of applying pressure to the reagent reservoir.

[0142] According to the device described in any one or more of the foregoing specific embodiments and / or any one or more of the specific embodiments disclosed below, the device also includes a regulator connected between the pressure source and the reagent reservoir, and wherein the controller is suitable for and can cause the regulator to change the pressure applied to the reagent reservoir.

[0143] The device according to any one or more of the foregoing implementations and / or any one or more of the implementations disclosed below, wherein the system includes a sensor module.

[0144] According to the device of any one or more of the foregoing specific implementations and / or any one or more of the specific implementations disclosed below, the device also includes a sensor electrode, which is suitable for being communicatively coupled and can be communicatively coupled to the sensor module.

[0145] The device according to any one or more of the foregoing implementations and / or any one or more of the implementations disclosed below, wherein the sensor electrodes are wirelessly coupled to the sensor module.

[0146] According to the device described in any one or more of the foregoing specific implementations and / or any one or more of the specific implementations disclosed below, the device also includes a connector, which is suitable for connecting and can connect the sensor module and the sensor electrode.

[0147] According to any one or more of the foregoing specific embodiments and / or any one or more of the specific embodiments disclosed below, the connector includes a protrusion and a recess, one of the protrusion or the recess is carried by the reagent kit, and the other of the protrusion or the recess is carried by the system.

[0148] The device according to any one or more of the foregoing implementations and / or any one or more of the implementations disclosed below, wherein the sensor electrode comprises a pair of plates, and the reagent reservoir is positioned between the pair of plates.

[0149] The device according to any one or more of the foregoing implementations and / or any one or more of the implementations disclosed below, wherein the sensor electrode is a ring electrode and is adapted to and does surround the reagent reservoir.

[0150] The device according to any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the sensor electrodes are carried by the reagent cartridge.

[0151] The device according to any one or more of the foregoing implementations and / or any one or more of the implementations disclosed below, wherein the sensor module includes contacts adapted to interface with the sensor electrodes.

[0152] The device according to any one or more of the foregoing implementations and / or any one or more of the implementations disclosed below, wherein the contact comprises a leaf spring contact.

[0153] A device comprises: a circulation cell assembly; a reagent kit, which is suitable for carrying and actually carries the circulation cell assembly, and the reagent kit includes: a reagent reservoir suitable for being fluidically connected to the circulation cell assembly; and a sensor electrode, which is associated with generating a signal associated with at least one of the volume of reagent in the reagent reservoir, the presence of reagent, or the value of the reagent flow rate.

[0154] The device according to any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the cartridge comprises a fluid line, and the sensor electrode is positioned adjacent to the fluid line.

[0155] The device according to any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the sensor electrode comprises a conductive tape coupled to the reagent cartridge.

[0156] The device according to any one or more of the preceding implementations and / or any one or more of the implementations disclosed below, wherein the sensor electrode comprises a part of a reagent reservoir or a reagent kit.

[0157] The device according to any one or more of the foregoing implementations and / or any one or more of the implementations disclosed below, wherein the sensor electrode comprises a hole filled with a conductive fluid and adjacent to the reagent reservoir.

[0158] 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 reagent reservoir comprises a tapered portion.

[0159] 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 reagent reservoir comprises an elongated portion.

[0160] A method includes: flowing a reagent from a reagent reservoir to a flow cell assembly; generating a signal associated with the reagent contained in the reagent reservoir; and determining a volume of the reagent in the reagent reservoir based on the signal.

[0161] According to any one or more of the foregoing specific implementations and / or any one or more of the specific implementations disclosed below, the method further includes determining a reagent flow rate value based on the volume of the reagent over time.

[0162] The method according to any one or more of the foregoing implementations and / or any one or more of the implementations disclosed below, the method further comprising pressurizing the reagent reservoir.

[0163] According to the method described in any one or more of the aforementioned specific implementations and / or any one or more of the specific implementations disclosed below, the method also includes comparing the determined reagent flow rate value with a reference flow rate value; and when the determined reagent flow rate value exceeds a threshold range of the reference flow rate value, changing the pressure applied to the reagent reservoir so that subsequent reagent flow rate values ​​can be within the threshold range of the reference flow rate value.

[0164] The method according to any one or more of the foregoing implementations and / or any one or more of the implementations disclosed below, wherein the signal is associated with a level of a reagent contained in the reagent reservoir.

[0165] The method according to any one or more of the foregoing implementations and / or any one or more of the implementations disclosed below, wherein the signal is associated with the volume of the reagent contained in the reagent reservoir.

[0166] The method according to any one or more of the foregoing implementations and / or any one or more of the implementations disclosed below, wherein the signal is associated with a flow rate of the reagent dispensed from the reagent reservoir.

[0167] According to any one or more of the foregoing specific embodiments and / or any one or more of the methods described in the specific embodiments disclosed below, the signal is associated with an electrode of an electrode array, each electrode in the electrode array is positioned adjacent to a reagent reservoir and is associated with a different volume of reagent in the reagent reservoir.

[0168] The above description is provided to enable those skilled in the art to practice the various configurations described herein. Although the subject technology has been described in detail with reference to various drawings and configurations, it should be understood that these drawings and configurations are only for illustrative purposes and should not be considered to limit the scope of the subject technology.

[0169] While certain implementations describe a single reagent reservoir, other implementations contemplated herein include multiple reagent reservoirs. Likewise, multiple sensor modules and / or sensor electrodes may be used with a single or multiple reagent reservoirs to determine one or more flow rates, as may prove appropriate.

[0170] As used herein, an element or step recited in the singular and preceded by the word "one" or "a kind of" should be understood not to exclude a plurality of said elements or steps, unless such exclusion is expressly indicated. In addition, reference to "a specific implementation" is not intended to be interpreted as excluding the existence of additional specific implementations that also include the described features. In addition, unless expressly stated to the contrary, a specific implementation that "includes" or "has" one or more elements having a particular property may include additional elements, whether or not they have that property. In addition, the terms "includes," "has," etc. are used interchangeably herein.

[0171] The terms "substantially", "approximately" and "about" used throughout this specification are used to describe and illustrate small fluctuations, such as small fluctuations caused by variations in processing. For example, 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%.

[0172] There may be many other ways to realize the subject technology. Without departing from the scope of the subject technology, the various functions and elements described herein may be divided differently from those shown and elements. Various modifications to these specific implementations may be apparent to those skilled in the art, and the general principles defined herein may be applied to other specific implementations. Therefore, without departing from the scope of the subject technology, those of ordinary skill in the art may make many changes and modifications to the subject technology. For example, different numbers of given modules or units may be adopted, one or more different types of given modules or units may be adopted, given modules or units may be added or given modules or units may be omitted.

[0173] Underlined and / or italicized headings and subheadings are used for convenience only, do not limit the subject technology, and are not referenced in conjunction with the explanation of the description of the subject technology. All structural and functional equivalents of the elements of the various specific implementations described throughout this disclosure that are known or will later be known to those of ordinary skill in the art are expressly incorporated herein by reference and are intended to be covered by the subject technology. In addition, nothing disclosed herein is intended to be dedicated to the public, regardless of whether such disclosure is explicitly recited in the above description.

[0174] It should be understood that all combinations of the foregoing concepts and the additional concepts discussed in more detail below (assuming such concepts are not mutually inconsistent) are contemplated as being part of the subject matter disclosed herein. In particular, all combinations of the claimed subject matter appearing at the end of this disclosure are contemplated as being part of the subject matter disclosed herein.

Claims

1. A reagent monitoring device, comprising: A system comprising a reagent cartridge receptacle; Flow cell assembly; a reagent cartridge receivable within the reagent cartridge receptacle and adapted to carry the flow cell assembly, the reagent cartridge comprising a reagent reservoir adapted to be fluidically coupled to the flow cell assembly, the reagent reservoir comprising a first portion having a first volume and a second portion having a second volume greater than the first volume; as well as A sensor module is adapted to be positioned adjacent to the reagent reservoir, wherein the sensor module is adapted to generate a signal correlated to a volume of reagent contained within the first portion of the reagent reservoir.

2. An apparatus according to claim 1, wherein the system includes a controller adapted to access the signal from the sensor module, and wherein the controller is adapted to determine a flow rate from the reagent reservoir based on the volume within the reagent reservoir over time.

3. The apparatus of claim 2, wherein the controller is adapted to compare the determined reagent flow rate value with a reference flow rate value, and wherein the controller is adapted to change an operating parameter of the system when the determined reagent flow rate value exceeds a threshold range of the reference flow rate value.

4. An apparatus according to claim 3, wherein the operating parameter includes the amount of time for the reagent to flow from the reagent reservoir.

5. An apparatus according to any one of claims 3 to 4, wherein the operating parameter includes the pressure applied to the reagent reservoir.

6. The apparatus according to any one of claims 2 to 4, further comprising a pressure source adapted to apply pressure to the reagent reservoir.

7. The apparatus of claim 6, further comprising a regulator coupled between the pressure source and the reagent reservoir, and wherein the controller is adapted to cause the regulator to vary the pressure applied to the reagent reservoir.

8. The apparatus of claim 1, wherein the system comprises the sensor module.

9. The device of claim 1, further comprising a sensor electrode adapted to be communicatively coupled to the sensor module.

10. The apparatus of claim 9, wherein the sensor electrodes are wirelessly coupled to the sensor module.

11. The device of claim 9, further comprising a connector adapted to couple the sensor module and the sensor electrode.

12. The apparatus of claim 11, wherein the connector comprises a male portion and a female portion, one of the male portion or the female portion being carried by the reagent cartridge and the other of the male portion or the female portion being carried by the system.

13. The apparatus of any one of claims 9, 11 and 12, wherein the sensor electrode comprises a pair of plates, the reagent reservoir being positioned between the pair of plates.

14. The device according to any one of claims 9, 11 and 12, wherein the sensor electrode is a ring electrode and surrounds the reagent reservoir.

15. The device according to any one of claims 9, 11 and 12, wherein the sensor electrode is carried by the reagent cartridge.

16. The apparatus of claim 15, wherein the sensor module comprises contacts connecting the sensor module with the sensor electrodes.

17. The apparatus of claim 16, wherein the contacts comprise leaf spring contacts.

18. The apparatus of claim 2, further comprising a pressure source adapted to apply pressure to the reagent reservoir.

19. The apparatus of claim 18, further comprising a regulator coupled between the pressure source and the reagent reservoir, and wherein the controller is adapted to cause the regulator to vary the pressure applied to the reagent reservoir.

20. The apparatus of claim 1, wherein the system comprises the sensor module.

21. The device of claim 1, further comprising a sensor electrode adapted to be communicatively coupled to the sensor module.

22. The apparatus of claim 21, wherein the sensor electrode comprises a pair of plates, the reagent reservoir being positioned between the pair of plates.

23. The apparatus of claim 21, wherein the sensor electrode is a ring electrode and surrounds the reagent reservoir.

24. The device of claim 21, wherein the sensor electrodes are carried by the cartridge.

25. The device of claim 24, wherein the sensor module comprises a contact interface connecting the sensor module with the sensor electrode.

26. A reagent monitoring device comprising: A kit, the kit being suitable for carrying a flow cell assembly, the kit comprising: a reagent reservoir adapted to be fluidly coupled to the flow cell assembly, the reagent reservoir comprising a first portion having a first volume and a second portion having a second volume greater than the first volume; and A sensor electrode is associated with generating a signal associated with at least one of a volume of reagent within the first portion of the reagent reservoir, a presence of reagent, or a reagent flow rate value.

27. The apparatus of claim 26, wherein the reagent cartridge comprises a reagent fluid line, wherein the sensor electrode is positioned adjacent to the reagent fluid line.

28. The apparatus of any one of claims 26 to 27, further comprising a flow cell assembly, wherein the reagent reservoir is fluidly coupled to the flow cell assembly.

29. The device of any one of claims 26 to 27, wherein the sensor electrode comprises a conductive tape coupled to the cartridge.

30. The apparatus of any one of claims 26 to 27, wherein the sensor electrode comprises a portion of the reagent reservoir of the reagent cartridge.

31. The apparatus of any one of claims 26 to 27, wherein the sensor electrode comprises a well filled with a conductive fluid and adjacent to the reagent reservoir.

32. Apparatus according to any one of claims 26 to 27, wherein the signal is associated with the height of the reagent contained within the first portion.

33. An apparatus according to any one of claims 26 to 27, wherein the reagent reservoir comprises an elongated portion.

34. The apparatus of any one of claims 26 to 27, wherein the sensor electrode is adjacent to the reagent reservoir.

35. The apparatus of claim 26, wherein the first portion comprises a tapered portion.

36. A reagent monitoring method comprising: causing a reagent to flow from a reagent reservoir of a reagent cartridge to a flow cell assembly, wherein the reagent cartridge is received in a reagent cartridge receptacle of a sequencing system and the reagent cartridge is connected to and fluidly coupled to the flow cell assembly, the reagent reservoir comprising a first portion having a first volume and a second portion having a second volume greater than the first volume; generating, using a sensor module, a signal associated with a reagent contained within the first portion of the reagent reservoir; and Based on the signal, a volume of the reagent within the reagent reservoir is determined.

37. The method of claim 36, further comprising determining a reagent flow rate value based on the volume of the reagent over time.

38. The method of claim 36, further comprising pressurizing the reagent reservoir.

39. The method according to claim 38 further includes comparing the determined reagent flow rate value with a reference flow rate value; and when the determined reagent flow rate value exceeds a threshold range of the reference flow rate value, changing the pressure applied to the reagent reservoir so that subsequent reagent flow rate values ​​can be within the threshold range of the reference flow rate value.

40. The method of any one of claims 36 to 39, wherein the signal is associated with a level of the reagent contained within the first portion of the reagent reservoir.

41. A method according to any one of claims 36 to 39, wherein the signal is associated with an electrode of an electrode array, each electrode in the electrode array is positioned adjacent to the reagent reservoir and is associated with a different volume of reagent within the reagent reservoir.