Sensing system with improved fluidics control

Abstract

A method and apparatus for a fluid sensing system is disclosed. The method can include providing a first portion of a sample fluid in a sensing channel, retaining the first portion of the sample fluid in the sensing channel for a first diffusion period, providing a second portion of the sample fluid in the sensing channel after the first diffusion period, retaining the second portion of the sample fluid in the sensing channel for a second diffusion period, and sensing the second portion of the sample fluid in the sensing channel by a sensing element after the second diffusion period. Providing a pulse of sample with an intervening diffusion period can produce a more uniform analyte concentration across the sensor with a smaller overall volume of sample fluid.

Description

[Technical field]

[0001] Related Applications This application claims the benefit of U.S. Provisional Patent Application No. 63 / 280,496, entitled "SENSING SYSTEM WITH IMPROVED FLUIDICS CONTROL," filed November 17, 2021, the entire disclosure of which is incorporated herein by reference for all purposes.

[0002] This application is also related to U.S. Patent Application No. 17 / 654,177, filed March 9, 2022 (U.S. Patent Application Publication No. 2022 / 0291165), the entire disclosure of which is incorporated herein by reference for all purposes.

[0003] The technical field relates to methods for controlling fluid sensor systems and systems with fluidics control. [Background technology]

[0004] 2. Description of Related Art Many medical treatment procedures are performed in hospitals or outpatient facilities, so patients typically must be admitted to the facility to receive treatment. Treatment procedures, such as kidney dialysis procedures, are often performed on a regular basis, which can be inconvenient, time-consuming, and economically expensive for patients and clinicians. Allowing such treatment procedures to be performed in one location (e.g., the patient's home) can advantageously improve the convenience, efficiency, and affordability of the procedures. Summary of the Invention

[0005] For purposes of summarizing the disclosure, certain aspects, advantages, and novel features of the invention are described herein. It is to be understood that not all such advantages may necessarily be achieved in accordance with any particular embodiment. Thus, the invention described herein may be embodied or performed in a manner that achieves or optimizes one advantage or a group of advantages as taught herein, but does not necessarily achieve other advantages that may be taught or suggested herein.

[0006] In one aspect, a method of operating a fluid sensing system is disclosed that can include providing a first portion of a sample fluid in a sensing channel, retaining the first portion of the sample fluid in the sensing channel for a first diffusion period, providing a second portion of the sample fluid in the sensing channel after the first diffusion period, retaining the second portion of the sample fluid in the sensing channel for a second diffusion period, and sensing the second portion of the sample fluid in the sensing channel by a sensing element after the second diffusion period.

[0007] In one embodiment, the method further includes calibrating a sensing element in the sensing channel using a calibration fluid. The calibration fluid can be provided to the sensing channel in multiple pulses. Calibrating the sensing element can further include retaining at least a portion of the calibration fluid such that diffusion occurs. Calibrating the sensing element can include providing the calibration fluid in 2-6 portions and sequentially providing the portions with diffusion periods between them.

[0008] In one embodiment, the method further includes providing a third portion of the sample fluid in the sensing channel after the first diffusion period and prior to providing the second portion of the sample fluid, and retaining the third portion of the sample fluid in the sensing channel for a third diffusion period. The method can further include providing a fourth portion of the sample fluid in the sensing channel after the third diffusion period and prior to providing the second portion of the sample fluid, and retaining the fourth portion of the sample fluid in the sensing channel for a fourth diffusion period.

[0009] In one embodiment, each subsequent portion of the sample fluid directly replaces the previous portion after a diffusion period for the previous portion.

[0010] In one embodiment, the sensing element includes an optical sensing element or an electrochemical sensing element.

[0011] In one embodiment, the method further comprises providing an air segment prior to providing the first portion of the sample fluid.

[0012] In one embodiment, the first diffusion period is in the range of 5 seconds to 20 seconds.

[0013] In one embodiment, the volume of the first portion is between 25% and 200% of the volume of the sensing channel.

[0014] In one embodiment, the sensing element includes between 3 and 15 electrodes, a first electrode of the sensing element capable of detecting a first component in the second portion of the sample fluid, and a second electrode of the sensing element capable of detecting a second component in the second portion of the sample fluid that is different from the first component.

[0015] In one aspect, a method of operating a fluid sensing system is disclosed. The method can include flushing at least a portion of a first fluid in a sensing channel with a second fluid, retaining the second fluid in the sensing channel for a diffusion period, flushing at least a portion of the second fluid in the sensing channel with a third fluid after the diffusion period, and sensing the third fluid in the sensing channel with a sensing element. The first fluid and the second fluid are different fluids. The second fluid and the third fluid are from the same fluid sample or calibration fluid.

[0016] In one embodiment, the diffusion period is in the range of 5 seconds to 20 seconds.

[0017] In one embodiment, the method further includes flushing the third fluid with a fourth fluid and retaining the fourth fluid in the sensing channel for a second diffusion period.

[0018] In one embodiment, the apparatus includes a control module for implementing the method, The control module may be electrically and mechanically coupled to a sensor module comprising a sensing channel and a transmitting element.

[0019] In one aspect, a sensing system is disclosed. The sensing system can include a sensing module having a sensing element positioned between an inlet valve and an outlet valve, and a reader including a controller. The controller is configured to open the inlet and outlet valves to provide a first portion of a sample fluid in the sensing channel, close the inlet and outlet valves to hold the first portion of the sample fluid in the sensing channel for a first diffusion period, open the inlet and outlet valves to provide a second portion of the sample fluid in the sensing channel after the first diffusion period, close the inlet and outlet valves to hold the second portion of the sample fluid in the sensing channel for a second diffusion period, and operate the sensing element to sense the second portion of the sample fluid in the sensing channel after the second diffusion period.

[0020] In one embodiment, the sensing element includes a plurality of electrodes.

[0021] In one embodiment, the sensing element is configured to transmit a signal indicative of each constituent of the second portion of the sample fluid.

[0022] Specific embodiments will now be described with reference to the following drawings, which are provided by way of example and not by way of limitation, and in which: [Brief description of the drawings]

[0023] [Figure 1] FIG. 1 is a block diagram of a fluid sensing system 1. [Diagram 2] 2 is a system diagram of the fluid sensing system of FIG. 1. [Diagram 3] FIG. 2 is a top plan schematic view of a sensing element. [Figure 4A] FIG. 2 is a timing diagram for operating a sensor module of the sensor system. [Figure 4B] 4B is a diagram illustrating an example timing of various states in the operation of the sensor module of FIG. 4A. [Figure 5A] FIG. 2 is a timing diagram for operating a sensor module of a sensor system according to one embodiment. [Figure 5B] 5B is a diagram illustrating an example timing of various states in the operation of the sensor module of FIG. 5A. [Figure 6A] 1 is a graph showing the timing of five pulses (flushes) of a particular fluid to replace an existing fluid in a simulation. [Figure 6B] 4 shows the concentration distribution of the sample fluid on the sensing element at different times. [Figure 6C] 4 shows the concentration distribution of the sample fluid on the sensing element at different times. [Figure 6D] 4 shows the concentration distribution of the sample fluid on the sensing element at different times. [Figure 6E] 4 shows the concentration distribution of the sample fluid on the sensing element at different times. [Figure 6F] 4 shows the concentration distribution of the sample fluid on the sensing element at different times. [Figure 7A] 4 shows the sodium concentration on the surface of one electrode at various times. [Figure 7B] 4 shows the sodium concentration on the surface of another electrode at various times. [Figure 8A] 4 shows the average concentration of calibration fluid on the surface of one electrode measured over time. [Figure 8B] 4 shows the average concentration of the calibration fluid on the surface of the different electrodes measured over time. [Figure 8C] FIG. 8B is an enlarged view of FIG. 8A across a smaller concentration scale on the y-axis. [Figure 8D] FIG. 8B is an enlarged view of FIG. 8A across a smaller concentration scale on the y-axis. [Figure 9A] 1 is a graph showing three simulated time points during replacement of a particular fluid with an existing fluid using a single pour. [Figure 9B] 4 shows the concentration distribution of a particular fluid on a sensing element at various times. [Figure 9C] 4 shows the concentration distribution of a particular fluid on a sensing element at various times. [Figure 9D] 4 shows the concentration distribution of a particular fluid on a sensing element at various times. [Figure 10A] 9A-9D show the sodium concentration on the surface of the first electrode measured at 1 second, 5 seconds, and 62.5 seconds in the simulation. [Figure 10B] In the simulation of Figures 9A-9D, the sodium concentration on the surface of the twelfth electrode measured at 1 second, 5 seconds, and 62.5 seconds is shown. [Figure 11A] 4 shows the average concentration of calibration fluid on the surface of a first electrode in a series of electrodes measured over time. [Figure 11B] 1 shows the average concentration of calibration fluid on the surface of the 12th electrode in a series of electrodes measured over time. [Figure 12A] This is a combination of the simulation results of Figures 8A and 11A. [Figure 12B] This is a combination of the simulation results of Figures 8B and 11B. [Figure 13] 1 shows a mesh illustration of a fluid in a cross-sectional side view of a portion of a sensing channel near a sensing element. [Figure 14A] 13 is a graph showing simulation results of sensed voltage over time of a second fluid in a fluid exchange process using a continuous flow of the second fluid to replace a first fluid. [Figure 14B] 13 is a graph showing simulation results of sensed voltage over time of a second fluid in a fluid exchange process using a continuous flow of the second fluid to replace a first fluid. [Figure 14C] 13 is a graph showing simulation results of sensed voltage over time of a second fluid in a fluid exchange process using a continuous flow of the second fluid to replace a first fluid. [Figure 14D] 13 is a graph showing simulation results of sensed voltage over time of a second fluid in a fluid exchange process using a continuous flow of the second fluid to replace a first fluid. [Figure 15A] 13 is a graph showing simulation results including sensed voltage over time of a second fluid in a fluid exchange process using a continuous flow of the second fluid for a portion of time to replace a first fluid followed by a steady state for measurement. [Figure 15B] 13 is a graph showing simulation results including sensed voltage over time of a second fluid in a fluid exchange process using a continuous flow of the second fluid for a portion of time to replace a first fluid followed by a steady state for measurement. [Figure 15C] 13 is a graph showing simulation results including sensed voltage over time of a second fluid in a fluid exchange process using a continuous flow of the second fluid for a portion of time to replace a first fluid followed by a steady state for measurement. [Figure 15D]13 is a graph showing simulation results including sensed voltage over time of a second fluid in a fluid exchange process using a continuous flow of the second fluid for a portion of time to replace a first fluid followed by a steady state for measurement. [Figure 16A] 13 is a graph showing simulation results including sensed voltage over time of a second fluid in a fluid exchange process using a pulsed flow of a second fluid to replace a first fluid. [Figure 16B] 13 is a graph showing simulation results including sensed voltage over time of a second fluid in a fluid exchange process using a pulsed flow of a second fluid to replace a first fluid. [Figure 16C] 13 is a graph showing simulation results including sensed voltage over time of a second fluid in a fluid exchange process using a pulsed flow of a second fluid to replace a first fluid. [Figure 16D] 13 is a graph showing simulation results including sensed voltage over time of a second fluid in a fluid exchange process using a pulsed flow of a second fluid to replace a first fluid. [Figure 17A] 1 illustrates the concentration distribution and flow direction of a first and a second fluid in a sensing channel. [Figure 17B] 1 illustrates the concentration distribution and flow direction of a first and a second fluid in a sensing channel. [Figure 17C] 1 illustrates the concentration distribution and flow direction of a first and a second fluid in a sensing channel. [Figure 17D] 1 illustrates the concentration distribution and flow direction of a first and a second fluid in a sensing channel. [Figure 18A] 1A and 1B illustrate a schematic process of replacing a first fluid with a second fluid using an air segment between the first and second fluids. [Figure 18B] 1A and 1B illustrate a schematic process of replacing a first fluid with a second fluid using an air segment between the first and second fluids. [Figure 18C]1A and 1B illustrate a schematic process of replacing a first fluid with a second fluid using an air segment between the first and second fluids. [Figure 18D] 10A-10C are schematic diagrams illustrating another process for replacing a first fluid with a second fluid using an air segment between the first and second fluids; [Figure 18E] 10A-10C are schematic diagrams illustrating another process for replacing a first fluid with a second fluid using an air segment between the first and second fluids; [Figure 18F] 10A-10C are schematic diagrams illustrating another process for replacing a first fluid with a second fluid using an air segment between the first and second fluids; DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0024] In medical treatment procedures, it is desirable to monitor the content of fluids, such as the electrolyte content of dialysate or blood. Biological fluid content sensors can include sensor devices or chips that operate on optical or electrochemical sensing principles. In either case, it is desirable to calibrate the sensor between fluid samples.

[0025] When replacing a first fluid (e.g., a calibration fluid or an analyte) in a sensing channel of a sensor module with a second fluid (e.g., an analyte or a calibration fluid), a relatively large amount of the second fluid may need to be provided to adequately measure the second fluid because residues of the first fluid may remain in the channel. However, using a relatively large amount of the second fluid to effectively (e.g., completely) replace the first fluid may not be desirable. For example, when only a limited amount of the second fluid is present, it may be important to efficiently replace the first fluid with the second fluid. In some embodiments, one of the fluids may be an inert fluid (e.g., air or distilled water). However, embodiments described herein may be advantageous to replace one active fluid with another active fluid (e.g., an analyte with a calibration fluid or vice versa), thereby avoiding the time and fluid volume required to provide an inert fluid (e.g., air or distilled water) between the analyte and the calibration fluid.

[0026] Various embodiments disclosed herein relate to a fluid sensor module configured to connect in series with a treatment system. The treatment system can comprise a medical device such as a dialysis treatment system. Various embodiments disclosed herein relate to a fluid sensing system that can effectively replace a first fluid in a sensing channel with a second fluid in the sensing channel. In some embodiments, the total amount of the second fluid can be divided into multiple portions, and each portion can be provided to the channel separately in sequence. This process of providing portions of the second fluid separately can flush or directly replace the fluid (e.g., the first fluid, or a portion of the second fluid) previously present in the sensing channel. At each flush, the flow is paused to allow the second fluid to remain in the sensing chamber for diffusion to occur and equilibrate the concentration in the active fluidics portion of the sensing element. Each portion can have a volume equal to or close to the volume of the sensing channel. For example, the volume of the sensing channel can be 25 μL to 100 μL in an example utilizing 12 different sensors along the channel (i.e., about 2 μL to 8 μL on average for each sensor).

[0027] FIG. 1 shows a block diagram of a fluid sensing system 1 according to an embodiment. FIG. 2 is a system diagram of the fluid sensing system 1 according to an embodiment. The fluid sensing system 1 can include a sensor module 10 and a reader 12. The sensor module 10 can be disposable. The sensor module 10 can also be referred to as a sensor cartridge. In some embodiments, the sensor module 10 can be removably coupled to the reader 12. The sensor module 10 can include one or more optical or electrochemical sensors, or a combination of optical and electrochemical sensors. For example, the sensor module 10 can include a sensing assembly including a sensing element 14. The sensor system 1 can include an interface unit 16. The interface unit 16 can function as an interface between the sensor module 10 and the reader 12 and can be part of the sensor module 10 and / or the reader 12 (shown as part of the reader 12 in FIG. 1). The reader 12 can include a controller 18. In some embodiments, the reader 12 and the sensor module 10 can communicate via the interface unit 16.

[0028] The sensing element 14 can include multiple functionalized electrodes 20 (e.g., 12 electrodes as shown in FIG. 3) that transmit a signal indicative of a particular constituent of the sample fluid when exposed to the sample fluid. In some embodiments, the sensing element 14 can include any suitable number of transducers or electrodes 20 (FIG. 2). For example, the sensing element 14 can include 3 or more, 4 or more, 6 or more, 11 or more, or even more transducers or electrodes 20. For example, the sensing element 14 can include 3-15 electrodes, 6-15 electrodes, or 10-15 electrodes. In some embodiments, all or some of the electrodes 20 can be configured (with the electronic circuitry of the reader 12) to sense the same constituent. In some other embodiments, each electrode 20 can be configured to sense a different component (in conjunction with the electronic circuitry of the reader 12. Examples of sensors can be ion sensors (both anions and cations such as Na+, K+, Ca++, pH, Mag++, Cl-, NH3-), metabolite sensors (e.g., creatinine, glucose, urea), dissolved gas sensors (e.g., pO2, pCO2), genetic labeling sensors (e.g., IL-6, MMPs, and cytokines in general), and can be configured to function as a reference potential and counter electrode (to enable accurate potentiometric and amperometric sensor measurements). The sensing element 14 can be positioned within a sensing channel 22 that is configured to receive a calibration fluid and / or a sample fluid. The inlet valve 24a can be positioned at an upstream end of the sensing channel 22, and the outlet valve 24b can be positioned at a downstream end of the sensing channel 22.

[0029] During operation of the fluid sensing system 1, the inlet valve 24a and the outlet valve 24b can be controlled to allow fluid to enter and exit the sensing channel 22. In some embodiments, a valve motor 26 disposed in the reader 12 can be connected to the valves 24a, 24b via a valve connector (e.g., a valve opening) configured to operably connect to a motor shaft of the valve motor 26. The processing electronics 28 in the reader 12 can be configured to send commands to the valve motor 26 to open and close the inlet valve 24a and the outlet valve 24b. In some embodiments, the outlet valve 24b can be positioned between the sensing element 14 and the waste compartment 34. The outlet valve 24b can separate the sensing channel 22 and the waste channel 36. In some embodiments, a user (e.g., a patient or clinician) can manually operate the inlet and outlet valves 24a, 24b by moving a user interface (UI) 38 of the reader 12. The UI 38 of the reader 12 can include a touch screen and / or buttons that allow a user and / or clinician to interact with the reader 12. In some embodiments, the UI 38 can include a display that indicates the level of a constituent in the fluid.

[0030] The fluid path 42 of the sensor module 10 can be coupled to a tubing set 44 of a treatment system, such as a dialysis treatment system. For example, the fluid path 42 can be connected in series with the tubing set 44 of the treatment system. The inlet valve 24a can separate the sensing channel 22 and the fluid path 42. In some embodiments, the inlet valve 24a can be a multi-way (e.g., three-way) valve having a closed state that blocks fluid from entering the sensing channel 22, a first open state that provides fluid communication between the sensing channel 22 and a calibration container 32 that stores a calibration fluid, and a second open state that provides fluid communication between the sensing channel 22 and the fluid path 42.

[0031] FIG. 3 is a top plan schematic diagram of the sensing element 14. In the illustrated embodiment, the sensing element 14 includes first through twelfth electrodes 20a-20l. As described herein, the sensing element 14 may include any suitable number of transducers or electrodes. The sample fluid may interact with the first through twelfth electrodes 20a-20l, and in response, the sensor module 10 may transmit a signal to the reader 12 indicative of the respective constituent of the sample fluid. In some embodiments, all or some of the electrodes 20a-20l may be configured (together with the electronic circuitry of the reader 12) to sense the same constituent. In some other embodiments, each electrode 20a-20l may be configured (together with the electronic circuitry of the reader 12) to sense a different constituent.

[0032] In the illustrated embodiment, the length of the sensing element 14 may be about 17 mm. The length of the sensing element 14 may depend at least in part on the number of electrodes included in the sensing element 14. In some embodiments, the length of the sensing element 14 may range from 10 mm to 30 mm, 15 mm to 30 mm, 10 mm to 25 mm, or 15 mm to 20 mm. For example, each electrode may have a diameter of about 0.75 mm and an inter-electrode spacing relative to adjacent electrodes of about 0.5 mm. The various measurements disclosed herein are obtained using the sensing element 14 of FIG. 3. However, any suitable sensing element for measuring the respective constituents of a sample fluid may be implemented in the sensor module disclosed herein.

[0033] FIG. 4A shows a timing diagram for operating a sensor module of a sensor system. FIG. 4B is a diagram showing an example timing of various states in the operation of a sensor module. In some embodiments, the operation of a sensor module (e.g., sensor module 10) can be at least partially controlled by a reader 12. In a first state (start state 60), the sensing element or electrodes of the sensing element 14 can be dry and free of liquid. In the start state 60, the sensor module 10 can be in a bypass mode in which no sample fluid enters the sensor channel 22. The duration t1 of the start state 60 can be about 30 seconds.

[0034] A second state, a calibration flush state 62, may follow the start state 60. In the calibration flush state 62, the electrodes of the sensing element 14 may be flushed with a calibration fluid via the sensing channel 22. The duration t2 of the calibration flush state 62 may be about 1 second. The calibration fluid may include, for example, water with known concentrations of species (e.g., sodium, potassium, pH, calcium, etc.) to calibrate the sensing element 14.

[0035] A third state (standby state 64) may follow the calibration flush state 62. In the standby state 64, the calibration fluid may remain in the sensing channel 22 until a measurement request is received. In the standby state 64, the sensor module 10 may be in a bypass mode. The duration t3 of the standby state 64 may be between about 1 minute and 120 minutes.

[0036] A fourth state (sample flush state 66) may follow the standby state 64. In the sample flush state 66, a sample fluid or analyte may be provided. The sensor module 10 may be in a sample flush mode with the inlet valve 24a and the outlet valve 24b open to allow sample fluid to flow into the sensing channel 22. The inlet valve 24a may be a three-way valve with a closed state that blocks fluid from entering the sensing channel 22, a first open state that provides fluid communication between the sensing channel 22 and the calibration reservoir 32, and a second open state that provides fluid communication between the sensing channel 22 and the fluid path 42. For example, the calibration fluid in the sensing channel 22 may be flushed and replaced with the sample fluid. In some embodiments, excess fluid may be directed to the waste compartment 34. The duration t4 of the sample flush state 66 may be about 1 second.

[0037] A fifth state (measurement state 68) may follow the sample flush state 66. In the measurement state 68, sample fluid may remain in the sensing channel 22 and interact with the electrodes of the transducer chip 14 for measurement. In the measurement state 68, the sensor module 10 may be in a bypass mode with the inlet valve 24a and the outlet valve 24b closed. The duration t5 of the fifth state 68 may be about 30 seconds.

[0038] The measurement state 68 may be followed by a cleaning process (calibration flush and standby states 62, 64) to clean the sensing channel 22 and the surfaces of the electrodes 20 of the sensing element 14. After cleaning the sensing channel 22 and the surfaces of the electrodes 20, another measurement may be taken if desired and the measurement process (sample flush and measurement states 66, 68) may be repeated. The cleaning and measurement cycle 70 may be repeated any number of times. The total number (N) of cleaning and measurement cycles 70 may be determined at least in part based on the size of the calibration container 32 and / or the size of the waste compartment 34. The total operating lifetime t6 may be about 72 hours.

[0039] In the operation described with respect to Fig. 4A and 4B, the sample fluid is provided in one dose. Similarly, the calibration fluid is provided in one dose. A significant amount of sample fluid or calibration fluid may be required to achieve a sufficiently high concentration of the sample fluid or to sufficiently clean the electrode 20 by the calibration fluid in such a one-dose process. Also, if a limited amount of sample fluid is available, a sufficiently high concentration of the sample fluid may not be obtained in the sensing channel 22, and the accuracy of the measurement may not be ideal. Also, the total number of measurements that can be performed by the sensor module 10 over its lifetime may depend on the total amount of calibration fluid. Therefore, using more calibration fluid in each cleaning process may reduce the total number of measurements that can be performed by the sensor module 10.

[0040] In Figures 5A and 5B, an improved operation of the sensor module 10 is described that overcomes the shortcomings of the operation of Figures 4A and 4B. Figure 5A shows a timing diagram for operating a sensor module of a sensor system, according to one embodiment. Figure 5B is a diagram showing an example timing of various states in the operation of the sensor module. In a first state (start state 60), the channel can be dry. In some applications, the duration t1 of the start state 60 can be about 30 seconds. For example, the duration t1 of the start state 60 can be 5 seconds to 10 minutes, 10 seconds to 5 minutes, or 20 seconds to 1 minute.

[0041] In the second (calibration flush) state 62, the inlet valve 24a and the outlet valve 24b can be opened to flush a first portion of the calibration fluid into the sensing channel 22. A calibration liquid or fluid (also referred to as a quality control fluid, or QC fluid, e.g., a biocompatible fluid such as water, saline, etc.) can be provided to the calibration reservoir 32 of the sensor module 10. In some embodiments, there can be multiple calibration reservoirs, including the calibration reservoir 32. The multiple calibration reservoirs can store different calibration fluids. For example, each reservoir of the multiple calibration reservoirs can be configured to store a different calibration fluid having a known amount of one or more constituents to be sensed that is suitable for a particular sensor (e.g., an ion sensor, a metabolite sensor, a dissolved gas sensor, or a genetic labeling sensor) implemented by the sensing element 14. The calibration liquid or fluid can include, for example, water with a known concentration of a species (e.g., sodium, potassium, pH, calcium, etc.) to calibrate the sensor. In some embodiments, the calibration fluid can help reset the sensor module 10 by flushing older sample fluid and / or other debris from the sensing element 14. In this manner, the calibration fluid can also be considered a purge fluid. The processing electronics 28 can be configured to recognize that the sample fluid is in fluid communication with each of the bare or functionalized electrodes 20. In some applications, the duration t2 of the second state 62 can be about 1 second. For example, the duration t2 of the second state 62 can be 0.5 seconds to 5 seconds, 0.5 seconds to 3 seconds, or 0.75 seconds to 3 seconds.

[0042] In the third (calibration diffusion) state 72, the inlet valve 24a and the outlet valve 24b can be closed and the calibration fluid can remain in the sensing channel 22. In some embodiments, the calibration flush state 62 and the calibration diffusion state 72 can be repeated. When the calibration flush state 62 and the calibration diffusion state 72 are repeated, it is not necessarily repeating the exact same process. For example, the amount of sample fluid in the calibration flush state 62 and / or the calibration diffusion state 72 and / or the duration of those states can be changed in a series of repeated processes. For example, the total amount of calibration fluid for one calibration process can be divided into x portions including the first portion to the xth portion, and the second state and the third state can be performed x times in sequence in the first cycle (or subcycle). In some embodiments, x can be 2 to 10. In some embodiments, x can be 3 to 6. In some applications, the duration t7 of the calibration diffusion state 72 can be about 10 seconds. For example, duration t7 of calibration diffusion state 72 can be 5 seconds to 20 seconds, or 5 seconds to 15 seconds. In some embodiments, multiple calibration flush states 62 can occur without an intervening calibration diffusion state 72. In some embodiments, the volume of one of the x portions of calibration fluid can be 25% to 200%, 50% to 150%, or 75% to 125% of the volume of sensing channel 22. In some embodiments, the volume of one of the x portions of calibration fluid can be approximately the same as the volume of sensing channel 22, about twice the volume of sensing channel 22, or about three times the volume of the sensing channel.

[0043] In the fourth (standby) state 64, a measurement of the calibration fluid may be performed for calibration. The calibration may ensure proper functioning of the sensing element 14. In some embodiments, the sensing element 14 may include an optoelectronic signal converter. The inlet valve 24a and the outlet valve 24b may remain closed and the calibration fluid may remain in the sensing channel 22 until the measurement of the sample fluid (analyte) is started. The second state to the fourth state may constitute a calibration process. In some applications, the duration t3 of the standby state 64 may be about 1 minute to 90 minutes. For example, the duration t3 of the standby state 64 may be 1 minute to 60 minutes, 30 minutes to 90 minutes, or 10 minutes to 60 minutes.

[0044] In a fifth (sample flush) state 66, the inlet valve 24a and the outlet valve 24b may be opened to flush a first portion of the sample fluid into the sensing channel 22. In some embodiments, a portion of the calibrant fluid may be directed to the waste compartment 34 via the waste channel 36. In some applications, the duration t4 of the sample flush state 66 may be about 1 second. For example, the duration t4 of the sample flush state 66 may be between 0.5 seconds and 5 seconds, between 0.5 seconds and 3 seconds, or between 0.75 seconds and 3 seconds.

[0045] In the sixth (sample diffusion) state 74, the inlet valve 24a and the outlet valve 24b can be closed for a time (e.g., a first diffusion period) to allow diffusion to occur and equilibrate the concentrations in the active fluidics portion of the sensing element 14. In some embodiments, the sample flush state 66 and the sample diffusion state 74 can be repeated with a second portion replacing the first portion and a subsequent diffusion period (e.g., a second diffusion period) to equilibrate the concentrations in the active fluidics portion of the sensing element 14. When the sample flush state 66 and the sample diffusion state 74 are repeated, it does not necessarily repeat the exact same process. For example, the amount of sample fluid in the sample flush state 66 and / or the sample diffusion state 74 and / or the duration of those states can vary in a series of repeated processes. For example, the total amount of sample fluid for a particular measurement can be divided into y portions, including the first portion through the yth portion, and the sample flush state 66 and the sample diffusion state 74 can be performed y times in sequence in the second cycle (or subcycle). In some embodiments, y can be between 2 and 10. In some embodiments, y can be between 3 and 6. In some applications, the duration t8 of the sample diffusion state 74 can be about 10 seconds. For example, the duration t8 of the sample diffusion state 74 can be between 5 seconds and 20 seconds, or between 5 seconds and 15 seconds. In some embodiments, multiple sample wash states 66 can be performed without an intervening sample diffusion state 74. In some embodiments, the volume of the portion of the sample fluid can be between 25% and 200%, between 50% and 150%, or between 75% and 125% of the volume of the sensing channel 22.

[0046] In a seventh (final sample flush) state 66y, the inlet valve 24a and the outlet valve 24b may be opened to flush the yth portion of sample fluid into the sensing channel 22. As a portion of sample fluid is flushed more and more times, the concentration of the sample fluid in the sensing channel 22 may increase. For example, after flushing, the concentration of the sample fluid may be greater than 80%, greater than 85%, greater than 90%, greater than 95%, or greater than 97.5%.

[0047] In an eighth (measurement) state 68, the inlet valve 24a and the outlet valve 24b may be briefly closed, as in a sample diffusion state 74, and a measurement of the sample fluid may be taken. The sensor module 10 may send a signal to the reader 12 indicative of a particular constituent of the sample fluid. The processing electronics 28 of the reader 12 may control the operation of the sensor module 10.

[0048] The above operation (cycle or super cycle) 76, including the calibration flush state 62, the calibration diffusion state 72, the standby state 64, the sample flush state 66, the sample diffusion state 74, the final sample flush state 66y, and the measurement state 68) can be repeated N times for different sample fluids. The total number of times (N) can depend at least in part on, for example, the size of the calibration container 32 and / or the size of the waste compartment 34. N can range from 10 to 2000 depending at least in part on the application requirements. In one example, a sensing system for incorporation into a dialysis system can be configured for N=95 samples over about 3 days. Thus, the total operational lifetime t6 of the sample module 10 over N samples can be about 72 hours. For example, the total operational lifetime t6 of the sample module 10 over N samples can range from 24 hours to 240 hours, 36 hours to 168 hours, 48 ​​hours to 144 hours.

[0049] As explained above, both the calibration flush state 62 and the calibration diffusion state 72 (calibration process) and the sample flush state 66 and the sample diffusion state 74 (measurement process) can be repeated in the first and second subcycles, respectively. However, in some embodiments, only the calibration flush state 62 and the calibration diffusion state 72 (calibration process) can be repeated, or only the sample flush state 66 and the sample diffusion state 74 (measurement process) can be repeated.

[0050] FIG. 6A is a graph showing the timing of five pulses (washes) of a particular fluid (e.g., sample fluid) to replace an existing fluid (e.g., calibration fluid) in a simulation. Referring to FIG. 5A, in FIG. 6A, the sample fluid is divided into y=5 portions including the first portion to the fifth portion, and the process includes four sample wash states 66 followed by a sample diffusion state 74 each, and a final sample wash state 66y. FIG. 6B shows the concentration distribution of the sample fluid on the sensing element 14 having 12 electrodes 20a-20l at 1 second (just before the first pulse). FIG. 6C shows the concentration distribution of the sample fluid on the sensing element 14 at 20 seconds (just before the second pulse). FIG. 6D shows the concentration distribution of the sample fluid on the sensing element 14 at 45 seconds (just after the third pulse). FIG. 6E shows the concentration distribution of the sample fluid on the sensing element 14 at 90 seconds (just after the fifth pulse). FIG. 6F shows the concentration distribution of the sample fluid on the sensing element 14 at 145 seconds (well after the fifth pulse). In the simulation, the sample fluid used can be water with a known sodium content. The sodium concentration in the sample fluid is about 250 mol / m 3 The sodium concentration of the calibration fluid used in the simulation is about 40 mol / m 3 In a real measurement, the concentration of a particular component in the sample fluid may be unknown, and the concentration of a particular component in the calibration fluid is known. The total amount of sample fluid used in the simulation is twice the volume of the sensing channel 22.

[0051] Figures 6A and 6B show that at 1 second (just after the first pulse), the calibration fluid is partially replaced by sample fluid on the first three electrodes 20a-20c with a relatively high concentration. Figures 6A and 6C show that at 20 seconds (just before the second pulse), the calibration fluid is partially replaced by sample fluid on the first seven electrodes 20a-20g with a lower sample concentration (sodium in this example) than that in Figure 6B. Figure 6C shows that the sample fluid diffuses into the calibration fluid over time. Figures 6A and 6D show that at 45 seconds (just after the third pulse), the calibration fluid is partially replaced by sample fluid on the eight electrodes 20a-20h with a relatively high concentration. Figures 6A and 6E show that at 90 seconds (just after the fifth pulse) the concentration of the sample fluid is relatively high on the twelve electrodes 20a-20l. Figures 6A and 6F show that at 145 seconds (about 60 seconds after the fifth pulse) the concentration of the sample fluid is even higher than in Figure 6E.

[0052] FIG. 7A shows the sodium concentration on the surface of the first electrode 20a (near the upstream end of the sensing channel 22) measured at 20, 45, 90, and 145 seconds in the simulation of FIGS. 6A-6F. FIG. 7B shows the sodium concentration on the surface of the twelfth electrode 20l (near the downstream end of the sensing channel 22) measured at 20, 45, 90, and 145 seconds in the simulation of FIGS. 6A-6F. FIG. 8A shows the average concentration of the calibration fluid on the surface of the first electrode 20a measured over time. FIG. 8B shows the average concentration of the calibration fluid on the surface of the twelfth electrode 20l measured over time. FIGS. 8C and 8D are enlarged views of portions of FIGS. 8A and 8B.

[0053] 7A and 7B show that the concentration of the sample fluid (in this embodiment, the sodium concentration) approaches 100% (about 250 mol / m 3) and the concentration of the sample fluid approaches 100% at a slower rate at the twelfth electrode 20l. Figures 8A-8D show that the average concentration of the calibrator fluid approaches zero relatively quickly and the concentration of the sample fluid approaches zero at a slower rate at the twelfth electrode 20l.

[0054] FIG. 9A is a graph showing three simulated time points during the replacement of a particular fluid (e.g., a sample fluid) with an existing fluid (e.g., a calibration fluid) using a single pulse. FIG. 9B shows the concentration distribution of the sample fluid on the sensing element 14 having 12 electrodes 20a-20l at 1 second (just before the single pulse). FIG. 9C shows the concentration distribution of the sample fluid on the sensing element 14 at 5 seconds (just after the single pulse). FIG. 9D shows the concentration distribution of the sample fluid on the sensing element 14 at 62.5 seconds (well after the single pulse). In the simulation, water with a known sodium content can be used when using the sample fluid. For the purposes of the simulation, the sodium concentration in the sample fluid is about 250 mol / m 3 and the sodium concentration in the calibration fluid is about 40 mol / m 3 The amount of sample fluid used in a single pulse is twice the volume of sensing channel 22 (the same amount as the total amount of sample fluid used in the five-pulse simulations of FIGS. 6A-8D).

[0055] FIG. 10A shows the sodium concentration on the surface of the first electrode 20a measured at 1 second, 5 seconds, and 62.5 seconds in the simulation of FIGS. 9A-9D. FIG. 10B shows the sodium concentration on the surface of the twelfth electrode 20l measured at 1 second, 5 seconds, and 62.5 seconds in the simulation of FIGS. 9A-9D. FIG. 11A shows the average concentration of the calibration fluid on the surface of the first electrode 20a measured over time. FIG. 11B shows the average concentration of the calibration fluid on the surface of the twelfth electrode 20l measured over time.

[0056] Figure 12A combines the simulation results of Figures 8A and 11A. Figure 12B combines the simulation results of Figures 8B and 11B. Figures 12A and 12B show that for electrodes positioned downstream of sensing channel 22, it may be more difficult to displace fluid within the channel. Figures 12A and 12B also show that in both the single pulse and multiple pulse examples, a single pulse may give a measurement error of about 15% and multiple pulses may give an error of less than about 5%, even though the total amount of sample fluid is the same.

[0057] The calibration diffusion state 72 and / or sample diffusion state 74 can provide sufficient time for the calibration fluid and / or sample fluid to diffuse, thereby improving the performance efficiency of the sensor module 10. For example, compared to a single flush process, five flush processes with 15 seconds between each flush can result in a 3 to 13 times improvement in final concentration accuracy. Also, to achieve the same final concentration accuracy, a multiple pulse process may use a smaller amount of fluid compared to a single pulse process.

[0058] There may be non-uniformities, such as large surface roughness, crevices, pockets, etc., at or near each of the first through twelfth electrodes 20a-20l, for example, due to the manufacturing process thereof. Such non-uniformities may impede fluid displacement within the sensing channel 22. In some embodiments, the advantages disclosed herein may be pronounced when the shape, contour, or geometry of the sensing channel deviates from an ideal circular pipe.

[0059] FIG. 13 shows a mesh illustration of a fluid 80 in a cross-sectional side view of a portion of a sensing channel near a sensing element (e.g., an electrode). The sensing channel 22 can include a well 82. The portion of the sensing channel 22 can be positioned between an inlet valve and an outlet valve. A surface of the well 82 can include a sensing surface 82a. In some embodiments, the depth d of the well 82 can range from 50 μm to 250 μm. For example, the depth d of the well 82 can range from 50 μm to 200 μm, 100 μm to 250 μm, or 100 μm to 200 μm. The fluid 80 can interact with the sensing element at the sensing surface 82a, and the sensing element can output a signal indicative of the respective constituent of the sample fluid. In some embodiments, the sample fluid can include calcium. In the sensing channel 22, the sample fluid can flow from an inlet side (IN) to an outlet side (OUT) in a generally laminar flow. In the simulations shown in Figures 14A-17E, a first fluid with a calcium content of 1.165 mM is replaced with a second fluid with a calcium content of 0.2 mM. The calcium content can be calculated based on the voltage measured by the sensing element using the static Nernst equation. Also, in the simulations shown in Figures 14A-17E, the depth d of the well 82 is set to 135 μm.

[0060] 14A-14D are graphs showing simulation results including sensed voltage, fluid flow rate, calcium concentration, and exchange efficiency over time of the second fluid in a fluid exchange process using a continuous flow of the second fluid to replace the first fluid. FIGs. 15A-15D are graphs showing simulation results including sensed voltage, fluid flow rate, calcium concentration, and exchange efficiency over time of the second fluid in a fluid exchange process using a continuous flow of the second fluid to replace the first fluid followed by a steady state of the second fluid for measurement. FIGs. 16A-16D are graphs showing simulation results of a fluid exchange process using a pulsed flow of the second fluid to replace the first fluid.

[0061] In the simulations of Figs. 14A-14D, the second fluid is given a constant flow rate of about 1.302 mm / s. In the simulations of Figs. 14A-14D, there is no steady state of the second fluid for measurement. Fig. 14C shows that to reach a concentration change of 97.5% on the sensing surface 82a, a volume of the second fluid 22 times the volume of the sensing channel 22 is required. In the simulations of Figs. 14A-14D, the potential is not defined and is expected to vary with the flow rate and geometry of the sensing channel 22. Thus, the simulation results show that a fluid exchange process using continuous flow may not be reliable for accurate measurements.

[0062] In the simulations of Figures 15A-15D, the second fluid is given a constant flow rate of about 1.302 mm / s until the concentration change on the sensing surface 82a reaches 97.5%. After providing the second fluid, the measurement is taken for 30 seconds. Unlike the simulations of Figures 14A-14D, where the second fluid continues to flow after the concentration change on the sensing surface 82a reaches 97.5%, in the simulations of Figures 15A-15D, the flow of the second fluid is stopped after the concentration change on the sensing surface 82a reaches 97.5% for the measurement. Figure 15C shows that a volume of the second fluid 22 times the volume of the sensing channel 22 is required to reach a concentration change of 97.5% on the sensing surface 82a. After the flow of the second fluid is terminated, the potential can be defined, allowing the sensing element to make an accurate measurement.

[0063] In the simulations of Figures 16A-16D, the second fluid is provided in four pulses or washes, each pulse having a volume equal to the volume of the sensing channel. The approach used in the simulations of Figures 16A-16D may be referred to as a flat flow and diffusion approach. In the simulations, a single wash time of 1 second and a soaking time (diffusion time) of 30 seconds after each wash is used. Figure 16C shows that a volume of the second fluid that is only three times the volume of the sensing channel 22 (i.e., after three pulses) can allow the concentration change on the sensing surface 82a to reach 97.5%. When the flow of the second fluid stops (i.e., after each pulse), the potential can be defined, allowing the sensing element to make an accurate measurement. For example, an accurate measurement can be made after the fourth pulse of the second fluid. Since the concentration change reaches 97.5% after the third pulse, making the measurement after the fourth pulse can ensure that the measurement is accurate.

[0064] 14A-16D show that a fluid exchange process using pulsed flow can significantly reduce the amount of fluid required to allow for a sufficiently high (e.g., 97.5%) concentration change on the sensing surface 82a. In some applications, a concentration change of more than 80%, more than 85%, more than 90%, or more than 95% may be considered high enough to make an accurate measurement.

[0065] 17A-17D illustrate the concentration distribution and flow or diffusion direction of the first and second fluids in the sensing channel 22. FIG. 17A shows the concentration distribution and flow direction of the first and second fluids in the sensing channel 22 during the first pulse of the simulation of FIGS. 16A-16D. A generally laminar flow of the second fluid is visible in the sensing channel 22 in FIG. 17A. Also, a relatively high concentration of the first fluid can be observed in the well 82.

[0066] 17B shows the concentration distribution and diffusion direction of the first and second fluids in the sensing channel 22 during a diffusion period after the first pulse. During the diffusion period, diffusion can occur between the first and second fluids in the sensing channel 22. The diffusion period can allow the first fluid in the well 82 to diffuse into the second fluid above the well 82. In FIGS. 17C and 17B, another pulse and diffusion period can be repeated to achieve a higher concentration of the second fluid in the sensing channel 22.

[0067] 18A-18C generally illustrate a process of displacing a first fluid 90 with a second fluid 92 using an air segment 94 between the first and second fluids. As shown in FIG. 18C, an air pocket 96 may be formed in the well 82.

[0068] 18D-18F generally illustrate another process for displacing a first fluid 90 with a second fluid 92 using an air segment 94 between the first and second fluids. As shown in FIG. 19C, a trapped first fluid portion 98 can be formed in well 82.

[0069] Using air to help replace the first fluid with the second fluid can be beneficial because air may be easily accessible and it does not consume the second fluid or reduces the amount of the second fluid for replacement due to the drawbacks described with respect to Figures 18A-18F (formation of air pockets 96 or trapped portions of the first fluid 98), but it may not provide sufficient reliability. However, the combination of the air segment 94 and one or more fluid replacement methods disclosed herein may enable a sufficiently reliable sensing process. For example, the use of the air segment 94 can be combined with the process described with respect to Figures 15A-15D and / or the process described with respect to Figures 16A-16D.

[0070] Although pulsed delivery of sample fluid is primarily discussed herein, the principles and advantages disclosed herein may be used to deliver any suitable fluid to replace existing fluid in the sensing channel, for example, a calibration fluid may be provided in multiple pulses to replace the sample fluid in the manner described above with respect to reverse replacement.

[0071] Unless the context clearly requires otherwise, throughout the description and claims, the words "comprise," "comprising," "include," "including," and similar words are to be interpreted in an inclusive sense, i.e., "including, but not limited to," as opposed to an exclusive or exhaustive sense. The word "coupled," as used generally herein, refers to two or more elements that may be directly connected or that may be connected via one or more intermediate elements. Similarly, the word "connected," as used generally herein, refers to two or more elements that may be directly connected or that may be connected via one or more intermediate elements. Additionally, the words "herein," "above," "below," and words of similar import, when used in this application, shall refer to this application as a whole and not to any particular portions of this application. Furthermore, as used herein, when a first element is described as being "on" or "over" a second element, the first element can be directly on or above the second element, such that the first and second elements are in direct contact, or the first element can be indirectly on or above the second element, such that one or more elements are interposed between the first and second elements. Where the context permits, words in the above Detailed Description using the singular or plural can also include the plural or singular, respectively. The word "or" in reference to a list of two or more items includes all of the following interpretations of that word: any of the items in the list, all of the items in the list, and any combination of the items in the list.

[0072] Additionally, conditional terms used herein, such as "can," "could," "might," "may," "eg," "for example," "such as," among others, are generally intended to convey that certain embodiments include certain features, elements, and / or conditions, while other embodiments do not, unless specifically indicated otherwise or understood otherwise within the context when used. Thus, such conditional terms are generally not intended to imply that features, elements, and / or conditions are in any way required for one or more embodiments.

[0073] While certain embodiments have been described, these embodiments are presented as examples only and are not intended to limit the scope of the present disclosure. Indeed, the novel apparatus, methods, and systems described herein may be embodied in other various forms, and further, various omissions, substitutions, and modifications may be made in the form of the methods and systems described herein without departing from the spirit of the present disclosure. For example, although blocks are presented in a given arrangement, alternative embodiments may implement similar functionality with different components and / or circuit topologies, and some blocks may be deleted, moved, added, subdivided, combined, and / or modified. Each of these blocks may be implemented in a variety of different ways. Any suitable combination of elements and acts of the various embodiments described above may be combined to provide further embodiments. The appended claims and their equivalents are intended to cover such forms or modifications as are within the scope and spirit of the present disclosure. [Explanation of symbols]

[0074] 1. Fluid sensing system 10 Sensor Module 12 Leader 14 Sensing Elements 16 Interface Unit 18 Controller 20 electrodes 22 Sensing Channel 24a Inlet valve 24b Outlet valve 26 Valve motor 28 Processing Electronics 32 Calibration vessel 34 Waste Area 36 Waste Channel 38 User Interface (UI) 42 Fluid Path 44 Piping set 80 fluid 82 Vertical Hole 82a Sensing surface 90 First Fluid 92 Second Fluid 94 Air Segments 96 Air Pocket

Claims

1. 1. A method of operating a fluid sensing system, the method comprising: Providing a first portion of a sample fluid in a sensing channel; retaining the first portion of the sample fluid in the sensing channel for a first diffusion period; providing a second portion of the sample fluid into the sensing channel after the first diffusion period; retaining the second portion of the sample fluid in the sensing channel for a second diffusion period; sensing the second portion of the sample fluid in the sensing channel with a sensing element after the second diffusion period.

2. The method of claim 1 , further comprising calibrating the sensing element in the sensing channel using a calibration fluid.

3. The method of claim 2 , wherein the calibration fluid is provided into the sensing channel in multiple pulses.

4. The method of claim 3 , wherein calibrating the sensing element further comprises retaining at least a portion of the calibration fluid so that diffusion occurs.

5. 3. The method of claim 2, wherein calibrating the sensing element comprises providing the calibration fluid in two to six portions and sequentially providing the portions with diffusion periods therebetween.

6. 6. The method of claim 1, further comprising providing a third portion of the sample fluid in the sensing channel after the first diffusion period and prior to providing the second portion of the sample fluid, and retaining the third portion of the sample fluid in the sensing channel for a third diffusion period.

7. 7. The method of claim 6, further comprising providing a fourth portion of the sample fluid in the sensing channel after the third diffusion period and prior to providing the second portion of the sample fluid, and retaining the fourth portion of the sample fluid in the sensing channel for a fourth diffusion period.

8. A method according to any one of claims 1 to 7, wherein each subsequent portion of the sample fluid directly replaces the preceding portion after a diffusion period of the preceding portion.

9. The method of any one of claims 1 to 8, wherein the sensing element comprises an optical sensing element or an electrochemical sensing element.

10. The method of any one of claims 1 to 9, further comprising providing an air segment before providing the first portion of the sample fluid.

11. The method of any one of claims 1 to 10, wherein the first diffusion period is in the range of 5 seconds to 20 seconds.

12. The method of any one of claims 1 to 11, wherein the volume of the first portion is between 25% and 200% of the volume of the sensing channel.

13. The method of any one of claims 1 to 12, wherein the sensing element comprises between 3 and 15 electrodes.

14. 14. The method of claim 13, wherein a first electrode of the sensing element detects a first component in the second portion of the sample fluid and a second electrode of the sensing element detects a second component in the second portion of the sample fluid that is different from the first component.

15. 1. A method of operating a fluid sensing system, the method comprising: flushing at least a portion of the first fluid in the sensing channel with a second fluid, the first fluid and the second fluid being different fluids; retaining the second fluid in the sensing channel for a diffusion period; after the diffusion period, flushing at least a portion of the second fluid in the sensing channel with a third fluid, the second fluid and the third fluid being from the same fluid sample or calibration fluid; sensing the third fluid in the sensing channel with a sensing element.

16. The method of claim 15, wherein the diffusion period is in the range of 5 seconds to 20 seconds.

17. 17. The method of claim 15 or 16, further comprising flushing the third fluid with a fourth fluid and retaining the fourth fluid in the sensing channel for a second diffusion period.

18. Apparatus comprising a control module for carrying out the method according to any one of claims 15 to 17.

19. The apparatus of claim 18 , wherein the control module is electrically and mechanically coupled to a sensor module that includes the sensing channel and transmitting element.

20. 1. A sensing system, comprising: a sensing module having a sensing element positioned between the inlet valve and the outlet valve; A reader including a controller, the controller comprising: opening the inlet and outlet valves to provide a first portion of sample fluid into the sensing channel; closing the inlet and outlet valves to retain the first portion of the sample fluid within the sensing channel for a first diffusion period; after the first diffusion period, opening the inlet and outlet valves to provide a second portion of the sample fluid into the sensing channel; closing the inlet and outlet valves to retain the second portion of the sample fluid within the sensing channel for a second diffusion period; a reader configured to operate a sensing element to sense the second portion of the sample fluid in the sensing channel after the second diffusion period.

21. The sensing system of claim 20 , wherein the sensing element comprises a plurality of electrodes.

22. 22. A sensing system according to claim 20 or 21, wherein the sensing element is configured to transmit a signal indicative of a respective constituent of the second portion of the sample fluid.

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