Sensing Assembly

Abstract

The present disclosure provides a sensing assembly for sensing a property of a fluid sample, the sensing assembly comprising at least one working electrode provided in a primary fluidic channel configured to sense a property of the fluid sample in the primary fluidic channel, a secondary fluidic channel adjacent to and fluidly connected to the primary fluidic channel along a primary flow path, and a reference electrode element provided in the secondary fluidic channel. The secondary fluidic channel is arranged as a branch from the primary fluidic channel so as to restrict flow of the fluid sample from the primary fluidic channel to the reference electrode element. Alternatively or additionally, a method includes determining a property of the sample comprising providing such a sensing assembly.

Description

[Technical field]

[0001] The present disclosure relates to a sensing assembly, a system including a sensing assembly, and a method for determining a property of a fluid sample. [Background technology]

[0002] Various sensor assemblies are known for determining the properties of a sample. Electronic sensors can use electrodes to measure the properties of a sample. For example, electrochemical sensors can be used to detect the presence of a particular analyte or to make measurements such as conductivity or pH. These systems use a reference electrode, which has a relatively stable, analyte-independent potential, to provide a benchmark against which the potential of the working electrode can be compared.

[0003] A reference electrode typically comprises an enclosure in which a reference electrolyte (e.g., a reference solution) is held, an electrode immersed in the reference electrode solution, and an interface with the sample to be measured. If the sample and reference solution are both liquids, this can be a liquid junction. Often, this separates the sample and reference electrolyte by a frit (e.g., a porous member) and / or a salt bridge. Typically, a reference electrode is a combination of a slowly dissolving conductive salt in a defined reference electrolyte (with a diffusion bond to the main electrolyte), as an example, an AgCl salt. The reference electrolyte contains a high enough concentration of Cl to keep the potential stable. - ions, for example, a 3M KCl solution in water is commonly used.

[0004] However, such reference electrodes are complex to integrate, especially into smaller sensing assemblies. This type of reference electrode may also be incompatible with the need to store some systems in a dry state (i.e., without electrolyte or sample) for months / years before their first use.

[0005] Furthermore, in many modern sensing systems, such as in-line sensing systems that acquire multiple samples over extended periods of time, it is important that the reference electrode maintain a stable potential to ensure accurate measurements of potentiometric and amperometric sensors. Summary of the Invention [Means for solving the problem]

[0006] The present disclosure provides a sensing assembly for sensing a property of a fluid sample, the sensing assembly comprising at least one working electrode provided in a primary fluidic channel configured to sense a property of the fluid sample in the primary fluidic channel, a secondary fluidic channel adjacent to and fluidly connected to the primary fluidic channel along a primary flow path, and a reference electrode element provided in the secondary fluidic channel. The secondary fluidic channel is arranged as a branch from the primary fluidic channel so as to restrict flow of the fluid sample from the primary fluidic channel to the reference electrode element. Alternatively or additionally, a method includes determining a property of the sample comprising providing such a sensing assembly.

[0007] In one embodiment, a sensing assembly for sensing a property of a fluid sample comprises a primary fluid channel providing a primary flow path for the fluid sample, at least one working electrode provided in the primary fluid channel configured to sense a property of the fluid sample in the primary fluid channel, a secondary fluid channel adjacent to and fluidly connected to the primary fluid channel along the primary flow path, and a reference electrode element provided in the secondary fluid channel, the secondary fluid channel arranged as a branch from the primary fluid channel so as to restrict flow of the fluid sample from the primary fluid channel to the reference electrode element into the primary fluid channel.

[0008] In one embodiment, a system for sensing a property of a fluid sample comprises a sensing assembly according to any of the embodiments disclosed herein and a fluid delivery assembly configured to deliver fluid to a primary fluid channel along a primary flow path.

[0009] In one embodiment, a method for determining a property of a sample comprises: providing a sensing assembly for sensing a property of a fluid sample, the sensing assembly comprising: a primary fluid channel providing a primary flow path for the fluid sample; at least one working electrode provided in the primary fluid channel configured to sense a property of the fluid sample in the primary fluid channel; a secondary fluid channel adjacent to and fluidly connected to the primary fluid channel along the primary flow path; and a reference electrode element for providing a reference electrode signal provided in the secondary fluid channel, the secondary fluid channel being arranged as a branch from the primary fluid channel so as to restrict flow of the fluid sample from the primary fluid channel to the reference electrode element into the primary fluid channel; Providing a fluid sample into a primary fluid channel; and determining a property of the fluid sample based at least in part on the sensor signal received from the sensing assembly.

[0010] The invention will now be described in more detail with reference to the accompanying drawings, which are not intended to be limiting. [Brief description of the drawings]

[0011] [Figure 1] 1 is a schematic plan view of a sensing assembly according to one embodiment; [Diagram 2] FIG. 2 is a schematic plan view of a system according to one embodiment. [Diagram 3] 1 is a schematic plan view of a sensing assembly according to one embodiment. [Figure 4] 1 is a schematic plan view of a sensing assembly according to one embodiment; [Diagram 5] 1 is a schematic plan view of a sensing assembly according to one embodiment; [Figure 6A] 1A-1D are schematic plan views of a sensing assembly according to one embodiment in two different configurations. [Figure 6B] 1A-1D are schematic plan views of a sensing assembly according to one embodiment in two different configurations. [Figure 7] 1 is a schematic diagram of a method according to one embodiment. [Figure 8] 8A-8D are diagrams showing the results of Example 1; 8E is a graph of the pulse cycle of Example 1; and 8F is a plan view of the detection assembly used in Example 1. [Figure 9] 1 is a graph showing the results of Example 2. [Figure 10A] FIG. 1 shows a plan view of the sensing assembly used in Example 3 and the results of Example 3. [Figure 10B] FIG. 1 shows a plan view of the sensing assembly used in Example 3 and the results of Example 3. [Figure 10C] FIG. 1 shows a plan view of the sensing assembly used in Example 3 and the results of Example 3. [Figure 10D] FIG. 1 shows a plan view of the sensing assembly used in Example 3 and the results of Example 3. [Figure 11A] 1 is a graph showing the results of Example 4. [Figure 11B] 1 is a graph showing the results of Example 4. [Figure 12] 1 is a graph showing the results of Example 5. [Figure 13] 1 is a schematic plan view of a sensing assembly according to one embodiment; DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0012] A conventional reference electrode is, for example, a combination of an AgCl salt and a conducting salt that dissolves slowly in a defined reference electrolyte (with a diffusion bond to the main electrolyte). The reference electrolyte contains a sufficiently high concentration of Cl to keep the potential stable. -ions, for example, 3M KCl in water is commonly used. However, such reference electrodes are complicated to integrate, especially into smaller sensing assemblies. This type of reference electrode may also be incompatible with the need to store some systems in a dry state (i.e., without electrolyte or sample) for months / years before their first use. Miniaturizing these systems is also difficult, and traditional designs are not suitable for mass production, such as the semiconductor processing used for most of the rest of modern sensor systems. Furthermore, in many modern sensing systems, such as in-line sensing systems that acquire multiple samples over long periods of time, it is important that the reference electrode maintains a stable potential to ensure accurate measurements for potentiometric and amperometric sensors.

[0013] In one embodiment, a sensing assembly for sensing a property of a fluid sample (e.g., a parameter of the liquid sample or an analyte within the liquid sample) comprises a primary fluidic channel providing a primary flow path for the fluid sample, at least one working electrode provided within the primary fluidic channel configured to sense a property of the fluid sample (e.g., a parameter of the liquid sample or an analyte within the liquid sample) within the primary fluidic channel, a secondary fluidic channel adjacent to and fluidly connected to the primary fluidic channel along the primary flow path, and a reference electrode element provided within the secondary fluidic channel, the secondary fluidic channel being arranged as a branch from the primary fluidic channel to restrict flow of the fluid sample from the primary fluidic channel to the reference electrode element.

[0014] The embodiments advantageously provide a reference electrode that provides a stable potential but avoids the drawbacks associated with existing reference electrode designs.

[0015] A reference electrode element is an electrode that functions as a reference electrode when exposed to a fluid, and can in particular be exposed to a reference solution or calibration fluid to provide a stable reference potential. The reference electrode element can therefore provide a reference electrode signal indicative of the potential. Providing a secondary fluid channel in which the reference electrode element is provided means that the reference electrode element is separated from the primary flow path, thereby limiting the exposure of the reference electrode element (and the entire reference electrode once formed) to the fluid sample. This reduces degradation of the reference electrode as a result of contact with the sample fluid, as will be explained in more detail below. This combination of reference electrode element structure and channel structure avoids the need to incorporate a conventional reference electrode into the structure, allowing for the miniaturization of a stable reference electrode.

[0016] More specifically, by placing the reference electrode element in a secondary fluid channel that is fluidly connected to the primary fluid channel, the reference electrode element is still in communication with the rest of the system so that it can function as a reference electrode. However, the structure of the primary and secondary fluid channels means that the reference electrode is shielded from the primary fluid flow. In other words, the primary and secondary fluid channels are arranged with the secondary fluid channel branched from the primary fluid channel so that at least a portion of the primary flow does not enter the secondary fluid channel. The branching can be configured or angled to reduce this influx of fluid into the secondary fluid channel. Thus, the secondary fluid channel can form a conduit, enclosure, or cove into which a reference solution (e.g., a calibration fluid or a reference electrolyte that functions as a reference electrode solution) can be provided. This is shielded from the primary fluid so as to reduce the displacement of the reference solution held in the secondary fluid channel and to reduce contact of the reference electrode element itself with the sample fluid. This ensures that the potential is defined by the reference electrode element and the fluid (e.g., a reference solution) that is purposely provided above the reference electrode element, thereby providing a balanced and stable potential. Contact with the sample fluid that could disrupt this equilibrium and cause changes in the reference electrode element structure is reduced or prevented altogether (e.g., by dissolving in the sample fluid salts, particularly salts of the same anion as the reference electrode, or anions that would otherwise interact with the reference electrode element surface and modify its electrochemical potential). In other words, these structures and the positioning of the reference electrode within the secondary fluidic channel essentially replace the traditional concept of a frit or bridge. This replacement allows for the scale-down of the reference electrode and manufacturing using semiconductor fabrication processes and other more efficient manufacturing processes.

[0017] This configuration also has particular advantages when used with intermittent measurement systems, such as in-line measurement systems, configured to make measurements at specific intervals and otherwise remain immersed in the reference solution. For example, many in-line measurement systems make measurements after intervals of minutes or hours. Measurements in such systems can be as little as one or a few seconds to one minute. In such systems, the electrodes, including the working electrode, are typically placed in the calibration fluid during the intervals when not measuring. The structure of the primary and secondary fluid channels is particularly suited to such systems, with the secondary fluid channel being configured to hold a reference solution therein (where this reference solution can be combined with the calibration fluid typically used), reducing the possibility of the sample fluid being displaced as it passes through the primary fluid channel, but the fluid communication means that the reference electrode element can still provide a reference potential measurement to the entire sensing assembly.

[0018] Furthermore, the use of the reference electrode element improves the durability of the system, since it essentially becomes a conventional reference electrode when exposed to a reference solution (electrolyte), allowing for long-term storage without degradation. Specifically, this construction allows the reference electrode element to be maintained as a dry electrode, which is covered with a fluid (e.g., reference solution) upon first use. This has a significant advantage over conventional reference electrodes, which are manufactured in a sealed enclosure with a fluid provided therein during manufacture.

[0019] By branching, it is meant that the secondary fluidic channel is connected to the primary fluidic channel but extends or branches off from the primary fluidic channel in a different direction (i.e., the primary flow path defined by the primary fluidic channel) than the primary fluidic channel. In one embodiment, at least a portion of the secondary fluidic channel extends tangentially to the primary flow path. Such a configuration can reduce fluid flow from the primary flow path (i.e., the flow path defined by the primary flow path) to the secondary flow path. The secondary fluidic channel is fluidly connected to the primary fluidic channel and therefore has an opening associated with it (i.e., there is an opening in a sidewall of the primary fluidic channel). This opening may define a pane that is tangential to the primary flow path in some embodiments. In other or additional embodiments, the secondary fluidic channel is fluidly connected to the primary fluidic channel via an inlet portion of the secondary fluidic channel, the inlet portion comprising an opening in a sidewall of the primary fluidic channel. The inlet portion of the secondary fluidic channel may be tangential to the primary flow path. The primary flow channel may define a central axis (e.g., at the opening to the secondary flow channel) to which the tangent is relative, and the secondary flow channel defines a secondary flow channel that defines a central axis. In one embodiment, the inlet portion of the secondary fluid channel is substantially perpendicular to the primary flow channel. In other or additional embodiments, portions of the secondary fluid channel other than the opening (such as a mid-section or end portion) or the entire secondary fluid channel may extend tangentially to the primary fluid channel. In some embodiments, at least a portion (such as an opening or inlet) extends at an angle of 25 degrees to 180 degrees from the central axis defined by the primary fluid channel. In some embodiments, this may be 30 degrees to less than 180 degrees, 45 degrees to less than 180 degrees, 45 degrees to 135 degrees, 60 degrees to 135 degrees, or 60 degrees to 120 degrees. The greater the divergence from the primary flow channel, the less the fluid sample will enter the secondary flow channel.

[0020] The secondary fluid channel defines a secondary flow path where the relative configuration of the primary and secondary flow paths is configured to reduce the flow of fluid from the primary flow path to the secondary flow path. In some embodiments, less than 20% of the fluid flowing through the primary flow path upstream of the secondary fluid channel enters the secondary fluid channel. In some embodiments, this is less than 10%, or less than 5%. In embodiments, these amounts are determined by flow rate or volume.

[0021] As mentioned above, in some embodiments, the secondary fluid channel is fluidly connected to the primary fluid channel through an inlet portion of the secondary fluid channel, the inlet portion comprising an opening in a sidewall of the primary fluid channel. In further embodiments, the inlet portion of the secondary fluid channel is tapered to reduce the diameter of the secondary fluid channel over at least a portion of the length of the secondary fluid channel. Such a configuration can reduce turbulence at the opening of the secondary fluid channel and reduce the risk of bubble formation. This can, for example, be a taper from a larger diameter at the opening to a reduced diameter at a downstream point of the secondary fluid channel (such as the end of the inlet). Thus, the taper can be a straight taper or can define a neck portion, which may, for example, incorporate rounded corners. In some embodiments, the opening defines an edge or corner (or edge and corner) with the sidewall of the primary fluid channel, the edge or corner being rounded or blunt.

[0022] In an embodiment, the reference electrode element is spaced apart from the opening of the secondary fluid channel. In other words, the reference electrode element is located in the secondary fluid channel and spaced apart from the primary fluid channel, so that the reference electrode element is set back from the opening and the primary fluid channel, thereby reducing the possibility of contact with the fluid sample. In some embodiments, the reference electrode is spaced apart from the opening of the secondary fluid channel by at least 0.5 mm. For example, at least 1 mm, at least 2 mm, at least 3 mm, at least 4 mm, or at least 5 mm from the opening of the secondary fluid channel. For example, 0.5 mm to 100 mm, 1 mm to 100 mm, 2 mm to 100 mm, 3 mm to 100 mm, 4 mm to 100 mm, or 5 mm to 100 mm. For example, 0.5 mm to 20 mm, 1 mm to 20 mm, 0.5 mm to 10 mm, or 1 mm to 10 mm from the opening of the secondary fluid channel. The greater the distance, the less likely the fluid in contact with the reference electrode element in the secondary fluid channel will be contaminated with the fluid sample. In some embodiments, the reference electrode is contained entirely within the secondary fluid channel.

[0023] Separating or spacing the reference electrode element from the aperture can also reduce the possibility of diffusion of components into the channel that could disrupt the stable electrode potential. For example, if the reference electrode element contains a salt, the same ions that make up the salt may be present in the fluid sample and may diffuse into the secondary fluidic channel, disrupting the equilibrium. Other modes of diffusion are possible. While sample fluid flow is one mode of transport of components (such as ions), diffusion can affect the stable electrode potential. The path length may be based on how fast the component diffuses, i.e., the diffusion coefficient. For example, if the reference electrode element contains AgCl or Cl from the fluid sample to the secondary fluidic channel, the diffusion of the components may be dependent on the diffusion of the components. - The reduction in diffusion of ions depends on the diffusion coefficient and the time the fluid sample is in the primary fluid channel. +The same is true for ions. The distance from the aperture to the reference electrode element can be greater than the distance that the ions can diffuse while the fluid sample is in the channel. That is, in embodiments, the distance of the reference electrode element from the primary fluid channel (or aperture) for a particular exposure time is L for that exposure time (i.e., the time that the primary fluid channel is exposed to the component). D 成分 That's all. D 成分 is the diffusion length for the component (e.g., ion) of interest. D 成分 is SQRT(D 成分· The diffusion coefficient is calculated by the diffusion time (time of exposure). Of course, the fluid must be taken into consideration as is the diffusion coefficient of the component (e.g., ion) in the fluid medium in which it exists. One skilled in the art can determine this and other facts based on normal operating parameters (e.g., temperature).

[0024] For example, returning to the example of the AgCl reference electrode element, Cl - Take the diffusion coefficient of Cl for a 60 s exposure time (i.e., - Assuming that the ion-containing fluid sample passes through the primary fluid channel over a period of 60 seconds, the distance is L D Cl- (60s)=SQRT(D Cl- This can be calculated as 1.38E -09 m 2 The diffusion constant is based on a diffusion constant of 1 / s, which provides a reasonable estimate for diffusion in solutions of the type used in typical devices, such as blood and water, and in the concentrations expected (such as body fluids). - A typical diffusion constant value of 1.38E provides a useful baseline for calculating distances. -9 ~2.03E -9The former is typically used for solutions with higher ion concentrations, and the latter for very dilute solutions. These values ​​are particularly useful for estimating the distance for embodiments in which the assembly is for bodily fluid measurements (e.g., blood) and / or embodiments with high water content. These values ​​are at 25° C. Thus, the above distances can eliminate or reduce destabilization of the reference electrode through diffusion of components such as ions into the secondary fluid channel.

[0025] Thus, in one embodiment, the reference electrode element comprises a salt capable of forming at least two ions in solution, the reference electrode element being spaced from the primary fluid channel by a distance greater than the diffusion length for at least one of the ions in one second. As described in more detail below, the reference electrode element typically comprises a metal whose surface facing the fluid is covered with a salt of the metal. These are selected so that the salt is slightly soluble or dissolves slowly. When the electrode is immersed in an (aqueous) reference solution containing at least one of the ions of the salt, the following occurs: The salt layer serves as a medium between the electronic conductor (metal) and the ionic conductor (aqueous electrolyte). On the metal (electronic) side, charge transfer occurs by electronic interactions between the metal atoms, while the ionic interaction is through dissolution and diffusion from the salt layer into the aqueous solution of one of the salt ions (usually anion). Using the example of an Ag-AgCl system (wherein the reference electrode element comprises an Ag metal electrode with an AgCl layer on its surface), AgCl serves as a medium between the electronic conductor (Ag) and the ionic conductor (aqueous electrolyte). On the Ag (electron) side, charge transfer occurs through electronic interactions between Ag atoms, while ionic interactions occur through Cl from the AgCl salt. - Through the dissolution and diffusion of ions into an aqueous solution. The dissolution / diffusion potential is Cl -It is constant only if the ion concentration is constant in the electrolyte surrounding the AgCl salt (forming the reference electrolyte). This contributes to achieving stability of the reference potential by keeping the metal of the reference electrode element in the reference electrolyte at least a characteristic diffusion length away from the primary fluid channel where ion (e.g. anion) concentrations can change.

[0026] In an embodiment, the secondary fluid channel is closed to define a recess. In other words, the secondary fluid channel can form an enclosure or cove. In this way, flow through the secondary fluid channel is further reduced by preventing flow through the secondary fluid channel. In additional or alternative embodiments, the secondary fluid channel can comprise an outlet. In an embodiment in which the secondary fluid channel comprises an outlet, the outlet is closed to define a recess and the sensing assembly comprises a movable closure element, such as a valve for closing the outlet. The outlet can be used to drain the fluid in the secondary fluid channel. Such a closure element can be opened when necessary to help fill the secondary fluid channel. For example, during the first use of the sensing assembly and / or after the sample fluid has passed through the primary fluid channel, the sensing assembly is refilled with a reference solution (e.g., a reference electrolyte). The presence of an outlet can make filling more efficient and reduce the risk of bubble formation. Thus, in some embodiments, the secondary fluid channel comprises an outlet and a valve that seals the outlet.

[0027] The reference electrode element functions as an electrode within the reference electrode, i.e., the reference electrode is formed by the electrode element and by a reference solution provided to the secondary fluid channel, e.g., in a filling operation. This element thus becomes a reference electrode when exposed to a fluid that functions as a reference solution (e.g., a calibration fluid or a reference electrolyte).

[0028] The reference electrode in the embodiment can be based on known reference electrode systems such as an Ag / AgCl reference electrode system, a saturated calomel (Hg / Hg2Cl2) reference electrode system, or a copper (II) sulfate (Cu / CuSO4) reference electrode system. The reference electrode element can include or be formed from any material that can function as the electrode portion of a reference electrode. In some embodiments, the reference electrode element includes or is formed from a metal and a metal salt. For example, it is a metal core on which a metal salt layer is provided. In such cases, the fluid that functions as the reference solution or electrolyte (e.g., calibration fluid or reference electrolyte) includes at least one of a metal salt (or an ion that forms a metal salt) or a metal in a salt or a corresponding ion. In some embodiments, the metal salt can be a metal halide such that the reference electrode element includes or is formed from a metal and a metal halide. For example, it is a metal core on which a metal salt layer is provided. In such cases, the fluid that functions as the reference solution or reference electrolyte (e.g., calibration fluid) can include a halide, such as an excess of halide, in some embodiments. In some embodiments, the metal and metal halide salt pair can be selected from (i) Ag and AgCl, or (ii) Hg and Hg2Cl2. In these, the fluids that serve as reference electrolytes (e.g., calibration fluids or electrolytes) can include chloride ions, e.g., AgCl and / or KCl-containing solutions. These can be saturated solutions. In other embodiments, the metal and metal salt can be selected from copper sulfate and copper (II) sulfate. In these, the fluids that serve as reference solutions or reference electrolytes (e.g., calibration fluids) can include sulfate ions (e.g., copper (II) sulfate, e.g., saturated copper (II) sulfate solutions). The concentrations of these solutions (i.e., reference solutions or calibration fluids) are configured to provide a stable reference electrode potential when the reference electrode element is immersed in the solution.

[0029] The combination of these materials allows for the provision of a stable reference electrode potential while allowing for variations in the structure and operation of the reference electrode as described herein. For example, as described above, a reference solution may be provided to the secondary fluidic channel during use (e.g., during first wetting and / or measurement), with mixing of the fluid sample with the reference solution being minimized by the structure of the secondary fluidic channel relative to the primary fluidic channel and the positioning of the reference electrode element within the secondary fluidic channel. Thus, relevant ions or components in the reference solution in contact with the reference electrode element remain in sufficient concentration to provide a stable reference electrode potential.

[0030] The working electrodes present in the primary fluid channel may be electrodes that include or are formed of copper, nickel, platinum, silver, silver chloride, gold, or other precious metals, or titanium nitride. In one embodiment, at least one working electrode is an electrode configured to detect the concentration of chloride in the fluid sample. The working electrode in this embodiment may include AgCl. For example, it may be an Ag metal electrode provided thereon with an AgCl layer. In some embodiments, the reference electrode comprises an Ag metal electrode provided thereon with an AgCl layer, and at least one working electrode comprises an Ag metal electrode provided thereon with an AgCl layer.

[0031] In an embodiment, the sensing assembly is configured to detect at least one property or analyte in a bodily fluid. In an embodiment, this may be blood, urea or saliva. In some further embodiments, the at least one working electrode is an electrode configured to detect the concentration of chloride in a fluid sample, and the reference electrode element comprises a metal and a chloride-based metal halide, such as Ag and AgCl. Ion concentrations (such as chloride concentrations) in bodily fluids are important measurements, and the structures defined herein have been found to be advantageous when used in this context. For example, measurements in such systems do not require long exposure times, and the effect on the reference electrode element located in the secondary fluid channel is negligible to the extent that the Ag / AgCl reference electrode formed by the element and the electrolyte (or calibration fluid) provides a stable potential. Once the measurement is completed, the primary fluid channel can be refilled with electrolyte or calibration fluid.

[0032] The contents of the reference solution associated with the reference electrode and the reference electrode element are discussed above. However, the reference solution may further include components unrelated to the reference electrode. For example, in some embodiments, it may further include an analyte or may have a specific measurable parameter that serves to calibrate the working electrode. For example, the reference solution may include additional components such as other analytes, or may have a specific pH or conductivity. The reference solution referred to herein may be a calibration fluid or a reference electrolyte.

[0033] In one embodiment, the sensing assembly further includes a calibration fluid provided in the secondary fluid channel, the calibration fluid and the reference electrode element forming a reference electrode, i.e., together they provide a stable reference potential, the reference electrode element being addressable to determine the reference potential.

[0034] More generally, the sensing assembly in the embodiment may measure pH (H +The system may be used in a system or method for determining the -log10 molar concentration of an ion), conductivity, or analyte concentration. As used herein, the term "analyte concentration" or "concentration of an analyte" may refer to the activity of the analyte in certain embodiments. The system may further comprise a working electrode and a counter electrode.

[0035] In some non-limiting examples, at least one working electrode and the reference electrode element can be mounted on a common substrate, e.g., a semiconductor substrate (e.g., a silicon wafer) or a plastic substrate. In alternative examples, at least one working electrode is mounted on a first substrate, e.g., a first semiconductor substrate, and the reference electrode element is mounted on a second substrate, e.g., a second semiconductor substrate, such as a (second) silicon wafer.

[0036] The sensing assembly may be compatible with any suitable electrochemical sensing principle. In some embodiments, the sensing assembly comprises an electrochemical cell including a working electrode assembly and a counter electrode. The counter electrode may function as a cathode or anode relative to the working electrode.

[0037] In one embodiment, a system for sensing a property of a fluid sample (e.g., a parameter of the fluid sample or an analyte in the fluid sample) comprises a sensing assembly as defined in any of the embodiments described herein, a signal processing unit configured to process sensor signals received from the reference electrode element and the at least one working electrode, and a property determination unit configured to determine a property of the fluid sample based at least in part on the processed sensor signals from the at least one working electrode and the reference electrode element.

[0038] In one embodiment, a system for sensing a property of a fluid sample (e.g., a parameter of the fluid sample or an analyte in the fluid sample) comprises a sensing assembly as defined in any of the embodiments described herein and a fluid delivery assembly configured to deliver a fluid to a primary fluid channel along a primary flow path. In an embodiment, the system may further comprise a signal processing unit configured to process sensor signals received from the reference electrode element and the at least one working electrode, and a property determination unit configured to determine a property of the fluid sample based at least in part on the processed sensor signals from the at least one working electrode and the reference electrode element.

[0039] In embodiments, the system further comprises a calibration fluid or reference solution reservoir, and the fluid delivery assembly is configured to deliver a reference solution from the calibration fluid reservoir to the primary fluid channel. In embodiments, the fluid delivery assembly may also or alternatively be configured to deliver a reference solution to the secondary fluid channel during an initial filling phase and / or a refilling phase between fluid sample measurements. In embodiments where a valve and an outlet are provided in the filling channel, the fluid delivery assembly may be configured to operate the valve and outlet to assist in filling the secondary fluid channel. This may be done directly to the secondary fluid channel or indirectly via the primary fluid channel. In some embodiments, a reference solution is provided to the working electrode to monitor a readout (e.g., drift) from the working electrode, such that it may be advantageous to provide a reference solution to the secondary fluid channel via the primary fluid channel. In other embodiments, it may be advantageous to flush the secondary fluid channel directly.

[0040] In some embodiments, the sensing assembly further comprises an inlet to the secondary fluid channel, which may be fluidically connected to a fluid reservoir. A secondary fluid channel with an additional inlet (relative to the opening from the primary fluid channel) advantageously allows for fluid to be provided to the secondary fluid channel without the need for the fluid to first pass through the primary fluid channel. This may avoid potential contamination of the reference electrode element by contaminants located elsewhere in the sensing assembly or in associated devices upstream of the secondary channel (e.g., in the primary fluid channel) or in the region between the primary fluid channel and the reference electrode element. In some cases, such as when there is repeated use of the sensing assembly, when significant periods of time pass between measurements, and / or when there is a particularly persistent sample type (e.g., blood clotting), sample or contaminants may remain and then be flushed so that they reach the reference electrode element. In some cases, even if the flow of contaminants over the reference electrode element is temporary, it has been found that this may interfere with the performance of the reference electrode element. By providing an inlet, the secondary fluid channel may be provided with only fresh, uncontaminated solution, and the fluid flow direction may be from the reference electrode element 860 to the primary fluid channel. In some embodiments, the inlet may be further positioned such that the fluid does not pass through the region between the reference electrode element and the opening before reaching the reference electrode element. In other words, the reference electrode element is positioned between the inlet and the opening to the primary fluid channel. In other embodiments, the reference electrode element is positioned between the inlet and any outlet from this secondary channel.

[0041] In some embodiments, the fluid delivery assembly is configured to deliver the fluid sample to the primary fluid channel. Thus, in some embodiments, the fluid delivery assembly may be configured to deliver both the reference solution and the fluid sample to the fluid channel. That is, it is configured to deliver the fluid sample to the primary fluid channel and, in some embodiments, the reference solution to the secondary fluid channel via the primary fluid channel. In some embodiments, the fluid delivery assembly is configured to alternate delivery of the reference solution and the fluid sample. This intermittent delivery can improve the stability of the reference electrode by rebalancing the equilibrium in the secondary fluid channel. In some embodiments, the fluid delivery assembly is configured to deliver the reference solution in a flush operation and the fluid sample in a measurement operation, the ratio of the measurement operation to the flush operation being at least 1:2. In some embodiments, this is 1:5, 1:10, 1:25, 1:50, or 1:1000. The ratio is determined by the time the fluid delivery assembly exposes the fluid channel to the fluid. Thus, any operation may include a delivery phase where fluid is actively delivered into the channel and there is flow, and a holding phase where fluid is held in the channel. In some embodiments, the measurement operation may be 5 seconds or less, 10 seconds or less, or 60 seconds or less, or may be 1 second or less. It will be appreciated that a minimum measurement time is required, but this will depend on the measurement and system characteristics. In some embodiments, this is at least 0.5 seconds, such as at least 1 second, or at least 0.1 seconds. In some embodiments, the flush operation is 2 seconds or more, such as 5 seconds or more, 10 seconds or more, 60 seconds or more, 5 minutes or more, 30 minutes or more, or 60 minutes or more. In some embodiments, the fluid delivery assembly is configured to deliver an initial reference solution to the secondary fluid channel via the primary fluid channel in some embodiments. This initial filling can bring the sensing assembly from a dry state to a ready-to-use state.

[0042] The fluid delivery assembly may include a controller configured to control the delivery of fluid to the fluid channel. This may control the duration of the measurement, flush, and fill operations as required. The controller may be a processor. The processor may be implemented in any suitable manner using software and / or hardware to perform the various functions required. One or all of the units may use one or more microprocessors, for example, programmed using software (e.g., microcode), to perform the functions required. Examples of processor components that may be used in various embodiments of the present disclosure include, but are not limited to, conventional microprocessors, application specific integrated circuits (ASICs), and field programmable gate arrays (FPGAs).

[0043] In one embodiment, the system is an in-line measurement system. For example, the sensing assembly may be provided as an in-line sensing assembly configured to measure a property of a fluid sample in a separate system flow path. This may be, for example, directly in-line in the separate system flow path, or the system may include a sampling path that is intermittently filled with the fluid sample with the sensing assembly provided in the sensing path.

[0044] In one embodiment, the system is a body fluid analysis system configured to measure a property of a body fluid. In an embodiment, the body fluid is selected from blood, urine, mucus, or saliva. In some embodiments, the body fluid analysis system is an in-line measurement system as described above. For example, the body fluid analysis system may be a dialysis system.

[0045] In an embodiment, the system may be configured to receive a signal from the reference electrode element, which provides an indication (or a property of) the potential at the reference electrode, and indeed at other electrodes in the system. The system may further comprise a property determining unit for determining the property being measured based on the processed signal. These may take the form of, for example, a processor, or may consist of several processors. The processors may be implemented in any suitable manner, using software and / or hardware, to perform the various functions required. One or all of the units may use one or more microprocessors, for example, programmed using software (e.g., microcode), to perform the various functions required. Examples of processor components that may be used in various embodiments of the present disclosure include, but are not limited to, conventional microprocessors, application specific integrated circuits (ASICs), and field programmable gate arrays (FPGAs).

[0046] In various implementations, the signal processing unit, the property determination unit and / or the processor may be associated with one or more non-transitory storage media, such as volatile and non-volatile computer memories, such as RAM, PROM, EPROM, and EEPROM. The non-transitory storage media may be encoded with one or more programs that, when executed on the one or more processors and / or controllers, perform the necessary functions. The various storage media may be fixed within the processor or controller, or may be transportable, such that one or more programs stored on the storage media can be loaded into the signal processing unit, the particular determination unit and / or the processor.

[0047] In some non-limiting examples, the system includes a user interface, such as a display, for communicating the property determined by the property determination unit. Alternatively or additionally, the system may include a communication interface device, such as a wireless transmitter, configured to transmit the analyte concentration determined by the property determination unit to an external device, such as a personal computer, tablet, smartphone, remote server, etc.

[0048] In one embodiment, a method for determining a property of a sample includes providing a sensing assembly for sensing a property of a fluid sample (e.g., a parameter of the liquid sample or an analyte in the liquid sample), the sensing assembly including a primary fluidic channel providing a primary flow path for the fluid sample, at least one working electrode provided in the primary fluidic channel configured to sense a property of the fluid sample (e.g., a parameter of the liquid sample or an analyte in the liquid sample) in the primary fluidic channel, a secondary fluidic channel adjacent to and fluidly connected to the primary fluidic channel along the primary flow path, and a reference electrode element provided in the secondary fluidic channel. The secondary fluidic channel is arranged as a branch from the primary fluidic channel to restrict flow of the fluid sample from the primary fluidic channel to the reference electrode element. The method further includes providing the fluid sample to the primary fluidic channel and determining a property of the fluid sample based at least in part on a sensor signal received from the sensing assembly.

[0049] The method may utilize any of the sensing assemblies or systems disclosed herein.

[0050] In some embodiments, the method further comprises providing both the reference solution and the fluid sample to the fluidic channels, i.e., providing the fluid sample to the primary fluidic channel and, in some embodiments, providing the reference solution to the secondary fluidic channel via the primary fluidic channel. In some embodiments, the method comprises alternating delivery or provision of the reference solution and the fluid sample. This intermittent delivery can improve the stability of the reference electrode by rebalancing the equilibrium in the secondary fluidic channel. In some embodiments, the method comprises delivering or providing the reference solution in a flush operation and delivering or providing the fluid sample in a measurement operation, the ratio of the measurement operation to the flush operation being at least 1:2. In some embodiments, this is 1:5, 1:10, 1:25, 1:50, or 1:1000. The ratio is determined by the time the fluidic channel (in some embodiments, particularly the primary fluidic channel) is exposed to the fluid. Thus, either operation may comprise a delivery phase in which the fluid is actively delivered into the channel and there is flow, and a retention phase in which the fluid is retained in the channel. In some embodiments, the measurement operation may be 1 second or less, such as 5 seconds or less, 10 seconds or less, or 60 seconds or less. It will be appreciated that a minimum measurement time is required, but this will depend on the measurement and system characteristics. In some embodiments, this is at least 0.1 seconds, such as at least 0.5 seconds, or at least 1 second. In some embodiments, the flush operation is 2 seconds or more, such as 5 seconds or more, 10 seconds or more, 60 seconds or more, 5 minutes or more, 30 minutes or more, or 60 minutes or more. In some embodiments, the method includes, in some implementations, delivering an initial reference solution to the secondary fluid channel via the primary fluid channel. This initial filling can bring the sensing assembly from a dry state to a ready-to-use state.

[0051] 1 provides a schematic plan view of a sensing assembly 100. The sensing assembly 100 comprises a primary fluid channel 110, a plurality of working electrodes 120, 120A provided within the primary fluid channel 110, a secondary fluid channel 150 having an opening 155, and a reference electrode element 160 provided within the secondary fluid channel 150.

[0052] The sensing assembly 100 is for sensing a property such as a parameter of a fluid sample or an analyte within the fluid sample. In this embodiment, there are multiple working electrodes 120, 120A, each of which can be used to sense a different parameter or analyte such that the sensing assembly can be used to simultaneously determine multiple properties for the same fluid sample. In an embodiment, the working electrodes include pH (H + The working electrodes 120A may be configured to determine the concentration of a particular analyte, such as ions (chloride, potassium, sodium, calcium, and / or magnesium ions), conductivity, temperature, and / or the presence of a particular analyte, such as ions (chloride, potassium, sodium, calcium, and / or magnesium ions), glucose, urea, and / or creatinine. In this particular embodiment, one of the working electrodes 120A is configured to measure the concentration of chloride ions in solution and is comprised of a silver body provided thereon with a silver chloride layer. The silver chloride coating is positioned so as to be exposed to fluid in the primary fluid channel.

[0053] The primary fluid channel 110 of the sensing assembly 100 is provided as the main flow path for fluid passing through the sensing assembly 100, and thus defines a primary flow path along its central axis. In this embodiment, the primary fluid channel 110 defines a linear path extending from an inlet to an outlet. A fluid sample can be provided along this flow path such that it contacts the working electrodes 120, 120A. This can be a continuous flow of the fluid sample (e.g., a liquid sample), or the fluid sample can be provided to the primary fluid channel 110 and the fluid flow is stopped or reduced to allow the fluid sample to be in contact with the working electrodes 120, 120A. In FIG. 1, the direction of fluid flow is indicated by arrows.

[0054] 1, the primary fluid channel 110 may take the form of a closed fluid channel having a base and working electrodes 120, 120A extending through the base, the working electrodes 120, 120A having sidewalls extending from the base and defining a fluid passageway. A top cover may also be provided. The working electrodes 120, 120A may be electrically connected to each other and / or to external system components, for example, via wires or traces extending below the base.

[0055] The secondary fluidic channel 150 branches off from and is fluidly connected to the primary fluidic channel 110 at a point along the primary flow path. In this embodiment, the secondary fluidic channel 150 is provided at a midpoint along the array of working electrodes 120, 120A located within the primary fluidic channel 110. The secondary fluidic channel 150 is fluidly connected to the primary fluidic channel 110 via an opening 155 in a sidewall of the primary fluidic channel 110. The region of the secondary fluidic channel 150 that extends from the opening 155 defines an inlet inwardly. In this embodiment, the secondary fluidic channel 150 is positioned such that the entirety of the secondary fluidic channel 150 extends perpendicular to the primary fluidic channel 110. That is, it branches off from the primary flow path 110 such that the secondary fluidic channel 150 (and the central axis / fluid flow path defined by the secondary fluidic channel) is at 90 degrees to the primary flow path defined by the primary fluidic channel 110. This has been found to significantly reduce ingress of fluid passing along the primary flow path into the secondary fluid channel 150. In this embodiment, the secondary fluid channel 150 is sealed except for an opening 155 so as to define an enclosure. This has been found to further reduce ingress of fluid from the primary fluid channel 110 into the secondary fluid channel 150.

[0056] In this embodiment, the reference electrode element 160 is located at the end of the secondary fluid channel 150 opposite the opening 155. In this manner, it is spaced apart from the opening 155 and thus from the primary fluid channel 110. This reduces the likelihood that fluid in contact with and adjacent to the reference electrode element 160 will be displaced or contaminated by components (such as ions) in the fluid passing through the primary fluid channel 110. In this embodiment, the reference electrode element 160 comprises a silver metal base having a silver chloride coating thereon. The silver chloride coating is positioned to contact the fluid located in the secondary fluid channel 150.

[0057] It has been found that this configuration can provide a protected area around the reference electrode element 160 where minimal fluid disturbance occurs, thereby minimizing displacement of fluid located in the secondary fluidic channel 150. More specifically, by placing the reference electrode element 160 at the end of the secondary fluidic channel 150 and branching the secondary fluidic channel 150 from the primary fluidic channel 110 in the manner shown, the reference electrode element 160 (which together with the reference solution forms the reference electrode) is shielded from the primary fluidic channel 110, while still being in communication with the remainder of the sensing assembly 100 (specifically, the working electrode) so that it can function as a reference electrode. This means that a potential is defined by the reference electrode element, and a fluid is purposefully provided over the reference electrode element 160 in the secondary fluidic channel 150 (e.g., the reference solution), thereby providing a balanced and stable potential. Contact with the sample fluid, which could disrupt this equilibrium and cause changes to the structure of the reference electrode element 160 (e.g., by dissolving salts in the sample fluid), is reduced or prevented entirely.

[0058] Similar to the primary fluidic channel 110, the secondary fluidic channel 150 may take the form of a closed fluidic channel having a base and sidewalls extending from the base and defining a flow path, with a reference electrode element 160 extending through the base. A top cover may also be provided. The reference electrode element 160 may be electrically connected to an external system, for example, via a wire or trace extending below the base.

[0059] During use, a first filling operation may be performed whereby a calibration fluid is provided to the primary fluid channel 110. The calibration fluid is formulated such that when in contact with the reference electrode element 160 it can form a reference electrode having a stable reference potential. In this particular embodiment, the calibration fluid is a saturated AgCl / KCl solution. The calibration fluid further comprises components for calibrating the working electrode 120. The first filling operation may include flowing the calibration fluid through the primary fluid channel 110 until the secondary fluid channel 150 is also filled with the calibration fluid, thus forming a reference electrode. The sensing assembly 100 may be left for a settling period to allow for the establishment of a stable reference potential.

[0060] A measurement operation can then be performed whereby a fluid sample is provided to the primary fluidic channel 110. The fluid sample passes over the working electrodes 120, 120A so that the properties of the fluid sample can be determined (e.g., by interrogating these electrodes). The configuration and arrangement of the secondary fluidic channel 150 and the primary fluidic channel 110 are such that there is minimal ingress of the fluid sample into the secondary fluidic channel 150 during this operation. The flow rate may also be controlled to minimize this. Furthermore, the position of the reference electrode element 160 and the spacing of the reference electrode element 160 from the opening 155 minimizes the possibility of measurable changes occurring in the calibration fluid surrounding the reference electrode element (e.g., diffusion of ions from the fluid sample and / or changes in the concentration of the calibration fluid). This may also be further minimized by minimizing the exposure time of the sensing assembly 100 to the fluid sample.

[0061] A flush (or refill) operation can then be performed whereby a calibration fluid is provided to the primary fluidic channel 110 to flush away any fluid sample and return the sensing assembly 100 to its pre-measurement state. This may include a delivery phase where the calibration fluid is actively delivered to the primary fluidic channel 110 and there is flow, and a holding phase where the calibration fluid is retained within the primary fluidic channel 110 and the secondary fluidic channel 150. This operation is typical of an intermittent measurement process and / or in-line measurement, and the positioning of the sensing assembly 100 in this embodiment allows for the use of a flush or refill operation; that is, it provides an opportunity to return the secondary fluidic channel 150 to a state where the fluid in the secondary fluidic channel 150 is the calibration fluid (or at least to the extent that a stable reference electrode potential is maintained).

[0062] In embodiments, the flush or refill operation may be longer in duration than the measurement operation, or the delivery phase of the flush or refill operation may be longer in duration than the measurement operation. In this way, the effect of the arrangement of channels 110, 150 is less impacted on the flush or refill operation that allows the secondary fluid channel 150 to be restored.

[0063] In some embodiments, the measurement and flush (or refill) operation can be repeated several times. This intermittent delivery can improve the stability of the reference electrode by rebalancing the equilibrium in the secondary fluid channel.

[0064] 2 provides a schematic diagram of a system 101 for determining a property of a fluid sample. The system 101 in this embodiment comprises the sensing assembly 100 of FIG. 1 together with a fluid delivery assembly 105, an inlet conduit 106, a calibration fluid reservoir 107, a waste reservoir 108, a signal processing unit 102, and a property determination unit 103.

[0065] The fluid delivery assembly 101 is configured to deliver fluid to the primary fluid channel 110 of the sensing assembly 100. In this embodiment, an inflow conduit 106 is provided to receive the fluid sample. The fluid delivery assembly 101 controls the passage of the fluid sample through the inflow conduit 106 to the sensing assembly 100. In this embodiment, the fluid delivery assembly 101 is also configured to deliver fluid from a calibration fluid reservoir 107 to the sensing assembly 100. This may be in accordance with the operations described above with respect to claim 1. A waste container 108 is provided to receive the fluid after it has passed through the sensing assembly 100.

[0066] The system 101 further includes components for addressing the electrodes 120, 120A, 160 of the sensing assembly 100. In particular, it includes a signal processing unit 102 configured to process sensor signals (e.g., a working electrode signal indicative of a reference electrode potential) received from the reference electrode element 160 and the working electrodes 120, 120A. The property determination unit 103 is configured to determine a property of the fluid sample based at least in part on the sensor signals processed by the signal processing unit 102.

[0067] Figure 3 provides a schematic plan view of a sensing assembly 100'. The sensing assembly 100' incorporates the same components as the sensing assembly 100 of Figure 1, but has a different configuration of secondary fluid channels. Thus, the sensing assembly 100' of Figure 3 comprises a primary fluid channel 110', a plurality of working electrodes 120', 120A' provided within the primary fluid channel 110', a secondary fluid channel 150' having an opening 155', and a reference electrode element 160' provided within the secondary fluid channel 150'.

[0068] The sensing assembly 100' of Figure 3 shows an alternative configuration of the secondary fluid channels 150'. In this embodiment, the secondary fluid channels 150' are provided with openings 155' provided in the sidewalls of the primary fluid channels 110 at points downstream of the working electrodes 120', 120A'. This can reduce the effects of diffusion from the secondary fluid channels 150' on the working electrodes 120', 120A', particularly downstream of these secondary fluid channels 150'. Otherwise, the structure can be the same as that described with respect to the sensing assembly 100 of Figure 1.

[0069] FIG. 4 provides a schematic plan view of a portion of a sensing assembly 100″. The sensing assembly 100′ incorporates the same components as the sensing assembly 100 of FIG. 1, but has a different configuration of secondary fluid channels. Thus, the sensing assembly 100″ of FIG. 4 comprises a primary fluid channel 110″, a plurality of working electrodes 120″ provided within the primary fluid channel 110″, a secondary fluid channel 150″ having an opening 155″, and a reference electrode element 160″ provided within the secondary fluid channel 150″.

[0070] In this embodiment, a secondary fluid channel 150'' is provided at a midpoint along the array of working electrodes 120'' located within the primary fluid channel 110''. The secondary fluid channel 150'' is fluidly connected to the primary fluid channel 110'' via an opening 155'' in a sidewall of the primary fluid channel 150''. The region of the secondary fluid channel 150'' extending from the opening 155'' defines an inlet inwardly. In this embodiment, the secondary fluid channel 150 is positioned such that the entirety of the secondary fluid channel 150'' extends at an angle of 135 degrees to the primary fluid channel 110'' (the angle being defined relative to the direction of fluid flow). That is, the secondary fluid channel 150'' (and the central axis / fluid flow path defined by the secondary fluid channel 150'') branches off from the primary flow path 110 such that it is angled back relative to the primary flow path defined by the primary fluid channel 110''. This has been found to significantly reduce ingress of fluid passing along the primary flow path into the secondary fluid channel 150''. In this embodiment, the secondary fluid channel 150'' is sealed except for an opening 155'' to define an enclosure. This has been found to further reduce ingress of fluid from the primary fluid channel 110'' into the secondary fluid channel 150''.

[0071] Otherwise, the structure may be the same as that described with respect to the sensing assembly 100 of FIG.

[0072] FIG. 5 provides a schematic plan view of a sensing assembly 100'''. The sensing assembly 100''' incorporates the same components as the sensing assembly 100 of FIG. 1, but has a different configuration of secondary fluid channels. Thus, the sensing assembly 100''' of FIG. 5 comprises a primary fluid channel 110''', a plurality of working electrodes 120''', 120A'''' provided within the primary fluid channel 110''', a secondary fluid channel 150'''' having an opening 155'''', and a reference electrode element 160''' provided within the secondary fluid channel 150'''.

[0073] In this embodiment, the inlet portion 156''' of the secondary fluid channel 150'' incorporates an opening 155'''' in the sidewall of the primary fluid channel 110''' and a portion of the secondary fluid channel 150'' adjacent to the opening 155''. In this embodiment, the inlet portion 156''' is tapered such that the diameter of the secondary fluid channel 150''' decreases from the opening 155'''' over a portion of the length of the inlet portion 156'''. This also incorporates a shaping that eliminates the 90 degree corner from the opening 155'''. This reduces turbulence at the opening of the secondary fluid channel and may reduce the risk of air bubble formation.

[0074] 6A and 6B provide a schematic plan view of a sensing assembly 200. The sensing assembly 200 has the same basic structure as the sensing assembly 100 of FIG 1, including a primary fluid channel 210, a plurality of working electrodes 220 provided within the primary fluid channel 210, a secondary fluid channel 250 having an opening 255, and a reference electrode element 260 provided within the secondary fluid channel 250. The sensing assembly 200 further includes an outlet 251 from the secondary fluid channel 250 leading to a drain channel 252, and a valve 270 capable of closing the outlet 251.

[0075] Similar to the sensing assembly 100 of FIG. 1, the sensing assembly 200 includes multiple working electrodes 220, each of which can be used to sense a different parameter or analyte such that the sensing assembly can be used to simultaneously determine multiple properties for the same fluid sample. The primary fluid channel 210 of the sensing assembly 200 is provided as a main flow path for fluid passing through the sensing assembly 200, and thus defines a primary flow path along its central axis. In this embodiment, the primary fluid channel 210 defines a linear path extending from an inlet to an outlet. A fluid sample can be provided along this flow path such that it contacts the working electrodes 220.

[0076] 1, the secondary fluid channel 250 of the sensing assembly 200 branches off and is fluidly connected to the primary fluid channel 210 at a point along the primary flow path. In this embodiment, the secondary fluid channel 250 is provided at a midpoint along the array of working electrodes 220. The secondary fluid channel 250 is fluidly connected to the primary fluid channel 210 through an opening 255 in a sidewall of the primary fluid channel 250. The secondary fluid channel 250 is disposed perpendicular to the primary fluid channel 210.

[0077] In this embodiment, the secondary fluid channel 250 also includes an outlet 251 for draining the secondary fluid channel 250. In this particular embodiment, this is located opposite the opening 255. Having the outlet 251 can be advantageous for filling the secondary fluid channel 250 and replacing any fluid within the secondary fluid channel 250 (e.g., during an initial filling operation, or during a refilling or flushing operation). This can also help reduce the formation of air bubbles.

[0078] However, as mentioned above, having an open outlet may encourage fluid flow through the secondary fluid channel 250, which may be disadvantageous during a measurement operation, i.e., when desired, to reduce fluid flow from the primary fluid channel 210 to the secondary fluid channel 250. Therefore, the sensing assembly 200 further includes a valve 270 that can selectively open or close the outlet 251. In this way, when required, the secondary fluid channel 250 may be closed at the outlet 251 by the valve 270 creating an enclosure that can hold the calibration fluid when desired (e.g., during a measurement operation). However, by opening the valve 270, it may be easily drained via the drain channel 252, if desired.

[0079] FIG. 7 depicts a method 302 for determining a property of a sample 300, the method 302 including providing a sensing assembly for sensing a property (e.g., a parameter or an analyte) of the fluid sample. The sensing assembly includes a primary fluidic channel providing a primary flow path for the fluid sample, at least one working electrode provided in the primary fluidic channel configured to sense a property of the fluid sample in the primary fluidic channel (e.g., a parameter of the liquid sample or an analyte in the liquid sample), a secondary fluidic channel adjacent to and fluidly connected to the primary fluidic channel along the primary flow path, and a reference electrode element provided in the secondary fluidic channel for providing a reference electrode signal. The secondary fluidic channel is arranged as a branch from the primary fluidic channel to restrict flow of the fluid sample from the primary fluidic channel to the reference electrode element. The method 302 further includes providing (304) the fluid sample to the primary fluidic channel and determining (306) the property of the fluid sample based at least in part on the sensor signal received from the sensing assembly.

[0080] FIG. 13 demonstrates a schematic plan view of the sensing assembly 800. The sensing assembly 800 has the same basic structure as the sensing assembly 100 of FIG. 1, including a primary fluid channel 810, a plurality of working electrodes 820 provided within the primary fluid channel 810, a secondary fluid channel 850 having an opening 855, and a reference electrode element 860 provided within the secondary fluid channel 850. The primary fluid channel 810 of the sensing assembly 800 is provided as a main flow path for fluid passing through the sensing assembly 800, and thus defines a primary flow path along its central axis. In this embodiment, the primary fluid channel 810 defines a linear path extending from an inlet to an outlet. A fluid sample can be provided along this flow path such that it contacts the working electrode 820.

[0081] 1, the secondary fluid channel 850 of the sensing assembly 800 branches and is fluidly connected to the primary fluid channel 810 at a point along the primary flow path. In this embodiment, the secondary fluid channel 850 is provided at a midpoint along the array of working electrodes 820. The secondary fluid channel 850 is fluidly connected to the primary fluid channel 810 through an opening 855 in a sidewall of the primary fluid channel 810. The secondary fluid channel 850 is disposed perpendicular to the primary fluid channel 810.

[0082] The sensing assembly 800 further comprises an inlet 851 to the secondary fluid channel 850. In this particular embodiment, it is located opposite the opening 855. It can be connected, for example, to a reservoir (not shown), or to another fluid channel. The secondary fluid channel 850 with the further inlet 851 (relative to the opening 855 from the primary fluid channel 810) advantageously allows the fluid to be provided to the secondary fluid channel 850 without the fluid having to first pass through the primary fluid channel 810. In this particular embodiment, it is also located such that the fluid does not pass through the area between the reference electrode element 860 and the opening 855 before reaching the reference electrode element 860. In other words, the reference electrode element 860 is located between the inlet 851 and the only outlet from this secondary fluid channel 850, i.e. the opening 855. In other embodiments, the reference electrode element 860 is located between the inlet 851 and any outlet from this secondary fluid channel 850. These configurations may be advantageous because they may avoid potential contamination of the reference electrode element 860 by contaminants located elsewhere in the sensing assembly 800 or associated devices upstream of the secondary fluid channel 850 (e.g., in the primary fluid channel 810) or in the region between the primary fluid channel 810 and the reference electrode element 860. In some cases, such as when there is repeated use of the sensing assembly 800, when significant periods of time pass between measurements, and / or when there is a particularly persistent sample type (e.g., blood clotting), sample or contaminants may remain and then be flushed to reach the reference electrode element. In some cases, even if the flow of contaminants on the reference electrode element 860 is temporary, it has been found that this may interfere with the performance of the reference electrode element 860. By providing an inlet, the secondary fluid channel 850 may be provided with only fresh, uncontaminated solution, and the fluid flow direction may be from the reference electrode element 860 to the primary fluid channel 810.

[0083] The sensing assembly 800 can also include a valve 870 that can selectively open or close the inlet 851 . EXAMPLES

[0084] Example 1 The results of Example 1 are depicted in FIG. 8 (8A-8D), in which a sensing assembly 400 having the same structure as that of the sensing assembly 100 of FIG. 1 (like reference numbers refer to like parts) is used to monitor the ingress of chloride ions into a secondary fluidic channel 450 that branches in a vertical fashion from a primary fluidic channel 410. A reference electrode element 460 is provided in the secondary fluidic channel 450, and a plurality of working electrodes 420 are provided in the primary fluidic channel 410. FIG. 8F (FIG. 8) depicts the sensing assembly 400 without fluid. In this example, the reference electrode element 460 is positioned 3.0 mm away from the opening of the secondary fluidic channel 450 (i.e., no part of the reference electrode element 460 is closer than 3.0 mm). The entire depth of the secondary fluidic channel 450 is 4.0 mm.

[0085] In this example, Figures 8A-8D depict the progression of changes in chloride ion concentration as a simulated fluid sample is supplied to sensing assembly 400. In Figure 8A, primary fluid channel 410 and secondary fluid channel 450 are filled with 96 mM Cl. - The primary sensing assembly is filled with a fluid (calibration fluid) having a chloride concentration of 107 mM. An inflow of fluid (corresponding to the fluid sample) having a chloride concentration of 107 mM is provided to the primary sensing assembly in a series of pulses. Specifically, in this example, five equal fluid pulses were provided with a total volume of fluid equal to three times the total volume of the sensing structure. FIG. 8E (FIG. 8) depicts fluid delivery to the sensing assembly 400, with the five pulses occurring at approximately 0, 18, 33, 48, and 65 seconds. The peak fluid flow rate (velocity magnitude at inlet (m / s)) was 0.013.

[0086] 8A shows the chloride ion concentration at 0 seconds; 8B shows the chloride ion concentration at 10 seconds; 8C shows the chloride ion concentration at 60 seconds; and 8D shows the chloride ion concentration at 95 seconds. As can be seen, the intrusion of higher concentration fluid into the secondary fluid channel 450 is negligible after 10 seconds and is minimal after 30 seconds. The chloride concentration further into the secondary fluid channel 450 in the region of the reference electrode element 460 remains substantially constant over 95 seconds, such that the reference electrode potential remains stable. In fact, many measurement operations are significantly shorter than 95 seconds.

[0087] Example 2 Example 1 was repeated with varying dimensions for the secondary fluid channel 450, specifically the length of the secondary fluid channel 450 (from the opening 455 to the end of the secondary fluid channel 450 opposite the terminal). The dimensions for the length of the secondary fluid channel 450 were 1 mm, 2 mm, 3 mm, and 4 mm. The reference electrode element 460 is approximately 0.8 mm in diameter.

[0088] FIG. 9 is a graph depicting chloride ion concentration over time at the reference electrode element 460. FIG. 9 shows chloride ion concentration over time (up to 100 seconds) for secondary reference electrode 460 depths of 1 mm (595), 2 mm (596), 3 mm (597), and 4 mm (598). As can be seen, for the 1 mm example, the pulse of higher concentration fluid causes some change in chloride ion concentration at the reference electrode 460 over time. For the 2 mm secondary fluid channel 450 length, there was no significant change in chloride ion concentration at the reference electrode element 460 for more than 30 seconds. For the 3 mm and 4 mm secondary fluid channel 450 lengths, there was no significant change in chloride concentration at the reference electrode element 460 over the duration of the experiment. The total change at 3 mm after 90 seconds was less than 0.01% and the total change at 4 mm was less than 0.0005%. This demonstrates that even at short lengths, stability of chloride ion concentration can be maintained within the secondary fluid channel 450, even when pulses are used, over significant exposure periods that far exceed the time required to make several measurements in which the reference electrode element is completely removed from the primary fluid channel (e.g., 2 mm cove depth).

[0089] Example 3 10A-10D depict the results of the same experiment as in Example 1, with the difference that only a single fluid pulse was used. The total volume delivered was the same. The peak fluid flow (velocity magnitude at the inlet (m / s)) was 0.067. The sensing assembly structure was the same as that used in Example 1.

[0090] FIG 10A shows the chloride ion concentration at 0 seconds. FIG 10B shows the chloride ion concentration at 1 second. FIG 10C shows the chloride ion concentration at 15 seconds. FIG 10D shows the chloride ion concentration at 31 seconds. As can be seen, intrusion of higher concentration fluid into the secondary fluid channel 450 is minimal even after 31 seconds. The chloride concentration further into the secondary fluid channel 450 in the region of the reference electrode element 460 remains substantially constant over the entire period such that the reference electrode potential remains stable.

[0091] Example 4 Example 3 was repeated with varying dimensions for the secondary fluid channel 450. Specifically, the length of the secondary fluid channel 450 (from the opening 455 to the end of the secondary fluid channel 450 opposite the terminal). The dimensions of the length of the secondary fluid channel 450 were 1 mm, 2 mm, 3 mm, and 4 mm. The reference electrode element 460 was approximately 0.8 mm in diameter.

[0092] FIG. 11A is a graph depicting chloride ion concentration over time at the reference electrode element 460. FIG. 11A shows chloride ion concentration over time (up to 100 seconds) for the secondary reference electrode 460 at a depth of 1 mm (695), 2 mm (696), 3 mm (697), and 4 mm (698). As can be seen, for the 1 mm example, the pulse of higher concentration fluid causes some change in chloride ion concentration at the reference electrode 460. For the 2 mm secondary fluid channel 450 length, the level remained stable after the initial shift. For the 3 mm and 4 mm secondary fluid channel 450 lengths, there was no significant change in chloride concentration at the reference electrode element 460 over the duration of the experiment. The total change at 3 mm after 30 seconds was about 0.002%, and the total change at 4 mm was less than 0.0001%. This demonstrates that even at a short length of 2 mm, stability of chloride ion concentration can be maintained within the secondary fluid channel 450 over significant periods of exposure, far beyond that required to make several measurements. Even at 1 mm, there was some resistance compared to that seen by the reference electrode element located within the primary fluid channel.

[0093] Example 5 Example 5 provides a comparison of three separate reference electrode configurations when exposed to several different solutions with the signal obtained from each depicted in the graph of FIG. 12 (signal (μV) versus time (arbitrary time units)). The baseline configuration 795 is a standard REFET in the form of a silver chloride layer covered by a membrane and where the signal generated receives compensation. This represents a comparative example of a typical pseudo reference electrode used in electrochemical sensors. The second configuration 796 is a silver chloride reference electrode located in a secondary fluid channel according to the invention but without any compensation. The third configuration 797 is a silver chloride reference electrode located in a secondary fluid channel according to the invention and with compensation.

[0094] In this example, three electrode configurations were each exposed sequentially to different solutions over time, as depicted across the x-axis. For example, each was first exposed to a calcium ion-containing solution for a period of time, followed by a sodium chloride solution for a period of time, followed by a sodium acetate solution, then a sodium bicarbonate solution, then a sodium lactate solution, then a magnesium sulfate solution, and finally a lactated Ringer's solution. These provide a useful indication of the types of ions found in a typical sample, such as blood, as well as the concentration ranges used in the experiment for each analyte span of physiological fluids. The graph depicts the response of each of the reference electrode configurations to these solutions.

[0095] As can be seen, the third configuration 797 with a silver chloride reference electrode located in the secondary fluid channel provides much more stable performance, especially for sodium ion containing solutions where the comparative REFET 795 has wide fluctuations and drift. Even the uncompensated second configuration 796 with a silver chloride reference electrode located in the secondary fluid channel has significantly improved performance for sodium ion containing solutions and provides stability even with some drift.

[0096] It should be understood that the detailed description and specific examples, while showing exemplary embodiments of the devices, systems, and methods, are for purposes of illustration only and are not intended to be limiting in scope. These and other features, aspects, and advantages of the devices, systems, and methods of the present invention may be better understood from the following description, appended claims, or aspects, and the accompanying drawings. It should be understood that the drawings are merely schematic and are not drawn to scale. It should also be understood that the same reference numbers are used throughout the figures to denote the same or similar parts.

[0097] Other variations of the embodiments of the present disclosure can be understood and effected by those skilled in the art, from a study of the drawings, the disclosure, and the accompanying aspects or claims, and by practicing the present disclosure. In the aspects or claims, the word "comprising" does not exclude other elements or steps, and the indefinite article "a" or "an" does not exclude a plurality. The mere fact that certain measures are recited in mutually different dependent aspects or claims does not indicate that a combination of these measures cannot be used to advantage. Any reference signs in the claims should not be construed as limiting the scope.

Claims

1. 1. A sensing assembly for sensing a property of a fluid sample, said sensing assembly comprising: a primary fluid channel providing a primary flow path for the fluid sample; at least one working electrode provided in the primary fluid channel configured to sense a property of a fluid sample in the primary fluid channel; a secondary fluid channel adjacent to and fluidly connected to the primary fluid channel along the primary flow path; a reference electrode element provided within the secondary fluid channel; A sensing assembly, wherein the secondary fluid channel is disposed as a branch from the primary fluid channel so as to restrict flow of a fluid sample from the primary fluid channel to the reference electrode element.

2. The sensing assembly of claim 1 , wherein at least a portion of the secondary fluid channel extends tangentially to the primary fluid flow path.

3. 3. The detection assembly of claim 1 or 2, wherein the secondary fluid channel is fluidly connected to the primary fluid channel via an inlet portion of the secondary fluid channel, the inlet portion comprising an opening in a side wall of the primary fluid channel.

4. The sensing assembly of claim 3 , wherein the inlet portion of the secondary fluid channel is tangential to the primary fluid flow path.

5. The sensing assembly of claim 4 , wherein the inlet portion of the secondary fluid channel is substantially perpendicular to the primary fluid flow path.

6. A sensing assembly according to any one of claims 3 to 5, wherein the inlet portion of the secondary fluid channel is tapered to reduce a diameter of the secondary fluid channel over at least a portion of the length of the secondary fluid channel.

7. A sensing assembly according to any one of claims 3 to 5, wherein the reference electrode element is spaced apart from an opening of the secondary fluid channel.

8. A sensing assembly according to any preceding claim, wherein the secondary fluid channel is enclosed to define a recess.

9. A sensing assembly according to any preceding claim, wherein the secondary fluid channel comprises an outlet and a movable closure element for closing the outlet.

10. The sensing assembly of any one of claims 1 to 9, wherein the reference electrode element comprises a metal and a metal salt.

11. The reference electrode element is: (i) Ag and AgCl; (ii) Hg and Hg ２ C ２ and (iii) Cu and CuSO ４ The sensing assembly of claim 10 comprising a metal and metal salt selected from:

12. The sensing assembly of any one of claims 1 to 11, wherein the at least one working electrode is an electrode configured to detect a concentration of chloride in a fluid sample.

13. The sensing assembly of any one of claims 1 to 12, further comprising a calibration fluid provided in the secondary fluid channel, the calibration fluid and the reference electrode element forming a reference electrode.

14. 1. A system for sensing a property of a fluid sample, comprising: A sensing assembly according to any one of claims 1 to 13; a fluid delivery assembly configured to deliver fluid along the primary flow path to the primary fluid channel.

15. a signal processing unit configured to process sensor signals received from the reference electrode element and the at least one working electrode; 15. The system of claim 14, further comprising: a property determining unit configured to determine a property of the fluid sample based at least in part on the processed sensor signal from the at least one working electrode and the reference electrode element.

16. 16. The system of claim 14 or 15, further comprising a calibration fluid reservoir, the fluid delivery assembly being configured to deliver a reference solution from the calibration fluid reservoir to the primary fluid channel.

17. 17. The system of claim 16, wherein the fluid delivery assembly is configured to deliver a fluid sample to the primary fluid channel during a measurement operation and to deliver a calibration fluid during a flush operation, the ratio of the measurement operation to the flush operation being at least 1:

2.

18. 1. A method for determining a property of a sample, comprising: providing a sensing assembly for sensing a property of a fluid sample, the sensing assembly comprising: a primary fluid channel providing a primary flow path for the fluid sample; at least one working electrode provided in the primary fluid channel configured to sense a property of the fluid sample in the primary fluid channel; a secondary fluid channel adjacent to and fluidly connected to the primary fluid channel along the primary flow path; and a reference electrode element for providing a reference electrode signal provided in the secondary fluid channel, the secondary fluid channel being arranged as a branch from the primary fluid channel so as to restrict flow of the fluid sample from the primary fluid channel to the reference electrode element; providing the fluid sample to the primary fluid channel; and determining the property of the fluid sample based at least in part on a sensor signal received from the sensing assembly.

19. The method of claim 18 , further comprising providing a calibration fluid to the secondary fluid channel.

20. 20. The method of claim 19, wherein the ratio of the provision of the fluid sample to the provision of the calibration fluid is at least 1:2.

Images