Sensing assembly

Abstract

The present disclosure provides a sensing assembly for sensing a property of a fluid sample, comprising: at least one working electrode disposed 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; and a reference electrode element disposed in the secondary fluid channel, the secondary fluid channel being arranged as a branch from the primary fluid channel to restrict flow of the fluid sample from the primary fluid channel to the reference electrode element. Alternatively or additionally, a method includes determining a property of a sample, including providing such a sensing assembly.

Description

Technical Field

[0001] The present invention relates to a sensing assembly, a system comprising a sensing assembly and a method for determining a property of a fluid sample. Background Art

[0002] A variety of sensor assemblies are known for determining the characteristics of a sample. Electronic sensors can use electrodes to measure properties of a sample. For example, electrochemical sensors can be used to detect the presence of a specific analyte or to make measurements such as conductivity or pH. These systems use a reference electrode with a relatively stable and analyte-independent potential to provide a baseline to which the potential of the working electrode is compared.

[0003] The reference electrode typically includes a housing for accommodating a reference electrolyte (e.g., a reference solution), an electrode immersed in the reference electrode solution, and an interface with the sample to be measured. If both the sample and the reference solution are liquids, this can be a liquid junction. Typically, the sample and the reference electrolyte will be separated by a glass material (e.g., a porous member) and / or a salt bridge. Typically, the reference electrode is a combination of conductive salts that slowly dissolve in a defined reference electrolyte (with a diffusion junction with the main electrolyte), with AgCl salts as an example. The reference electrolyte must have a sufficiently high Cl- ion concentration to keep the potential stable, for example, a 3M KCl aqueous solution is typically used.

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

[0005] Furthermore, in many modern sensing systems, such as online sensing systems where multiple samples are collected over a long period of time, it is important to ensure that the reference electrode maintains a stable potential to ensure accurate measurements by potentiometric and current sensors. Summary of the invention

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

[0007] In one embodiment, a sensing component for sensing properties of a fluid sample includes: a main fluid channel providing a main flow path for the fluid sample; at least one working electrode disposed in the main fluid channel, configured to sense properties of the fluid sample in the main fluid channel; a secondary fluid channel, adjacent to and fluidically connected to the main fluid channel along the main flow path; and a reference electrode element mixedly disposed in the secondary fluid channel, wherein the secondary fluid channel is arranged as a branch from the main fluid channel to limit the flow of the fluid sample from the main fluid channel to the reference electrode element.

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

[0009] In one embodiment, a method for determining a property of a sample comprises:

[0010] A sensing component for sensing properties of a fluid sample is provided, the sensing component comprising: a main fluid channel providing a main flow path for the fluid sample, at least one working electrode arranged in the main fluid channel, configured to sense properties of the fluid sample in the main fluid channel, a secondary fluid channel, adjacent to and fluidically connected to the main fluid channel along the main flow path; and a reference electrode element for providing a reference electrode signal arranged in the secondary fluid channel, wherein the secondary fluid channel is arranged as a branch from the main fluid channel to restrict the flow of the fluid sample from the main fluid channel to the reference electrode element;

[0011] providing a fluid sample to the main fluid channel; and

[0012] A property of the fluid sample is determined based at least in part on a sensor signal received from the sensing assembly. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] The invention will now be described in more detail with reference to the accompanying drawings, which are not intended to be limiting:

[0014] Figure 1 A schematic plan view of a sensing assembly according to an embodiment is provided;

[0015] Figure 2 A schematic plan view of a system according to an embodiment is provided;

[0016] Figure 3 A schematic plan view of a sensing assembly according to an embodiment is provided;

[0017] Figure 4A schematic plan view of a sensing assembly according to an embodiment is provided;

[0018] Figure 5 A schematic plan view of a sensing assembly according to an embodiment is provided;

[0019] Fig. 6A and 6B Provided are schematic plan views of a sensing assembly in two different configurations according to an embodiment;

[0020] Figure 7 A schematic diagram of a method according to an embodiment is provided;

[0021] Figures 8A to 8D shows a plan view of the sensing assembly used in Example 1 and the results of Example 1;

[0022] Fig. 8E A pulse cycle diagram of Example 1 is provided;

[0023] Fig.8F A plan view of the sensing assembly used in Example 1 is provided;

[0024] Fig. 9 Provides a result diagram of Example 2;

[0025] Figures 10A to 10D shows a plan view of the sensing assembly used in Example 3 and the results of Example 3;

[0026] Fig.11A and 11B Provides a result diagram of Example 4;

[0027] Fig.12 Provides a result diagram of Example 5;

[0028] Fig.13 A schematic plan view of a sensing assembly according to an embodiment is provided. DETAILED DESCRIPTION

[0029] Conventional reference electrodes are typically a combination of slowly dissolving conductive salts in a defined reference electrolyte (with a diffusion junction to the main electrolyte), for example AgCl salts. The reference electrolyte must have a sufficiently high Cl- ion concentration to keep the potential stable, for example, 3M KCl aqueous solution is commonly used. However, such reference electrodes are difficult to integrate, especially into smaller sensing components. This type of reference electrode may also be incompatible with the need to store certain systems in a dry state (i.e. without electrolyte or sample) for several months / years before first use. There are also difficulties in miniaturizing these systems, and conventional designs are not suitable for large-scale production, such as semiconductor processing, which is used for most of the remaining components of modern sensor systems. In addition, in many modern sensing systems, such as online sensing systems where multiple samples are collected over a long period of time, it is important to ensure that the reference electrode maintains a stable potential to ensure accurate measurements of potential and current sensors.

[0030] In one embodiment, a sensing component for sensing properties of a fluid sample (e.g., a parameter of the fluid sample or an analyte therein) includes: a main fluid channel providing a main flow path for the fluid sample; at least one working electrode disposed in the main fluid channel, configured to sense properties of the fluid sample in the main fluid channel (e.g., a parameter of the fluid sample or an analyte therein); a secondary fluid channel, adjacent to and fluidically connected to the main fluid channel along the main flow path; and a reference electrode element disposed in the secondary fluid channel. The secondary fluid channel is arranged as a branch from the main fluid channel to limit the flow of the fluid sample from the main fluid channel to the reference electrode element.

[0031] Embodiments advantageously provide a reference electrode that provides a stable potential but forgoes the disadvantages associated with prior reference electrode designs.

[0032] A reference electrode element is an electrode that acts as a reference electrode when exposed to a fluid, and in particular can be exposed to a reference solution or calibration fluid to provide a stable reference potential. Therefore, the reference electrode element can provide a reference electrode signal indicating the potential. Providing a secondary fluid channel in which the reference electrode element is disposed means that the reference electrode element is separated from the main flow path, thereby limiting the reference electrode assembly (and the reference electrode as a whole once formed) from being exposed to the fluid sample. This in turn reduces the degradation of the reference electrode due to contact with the sample fluid, as explained in more detail below. This combination of the reference electrode element structure and the channel structure avoids the need to incorporate a conventional reference electrode into the structure, thereby achieving miniaturization of a stable reference electrode.

[0033] More specifically, by arranging the reference electrode element in a secondary fluid channel connected to the main fluid channel fluid, the reference electrode element is still connected to the rest of the system, so that it can act 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 so that the secondary fluid channel branches off from the primary fluid channel so that at least a portion of the mainstream does not enter the secondary fluid channel. The branch can be configured or tilted to reduce the flow of fluid into the secondary fluid channel. Therefore, the secondary fluid channel can form a conduit, a housing or a concave shape, in which a reference solution (e.g., a calibration fluid or a reference electrolyte used as a reference electrode solution) can be provided. This is shielded from the mainstream to reduce the displacement of the reference solution maintained in the secondary fluid channel and reduce the contact of the reference electrode element itself with the sample fluid. This ensures that the potential is determined by the reference electrode element and the fluid (e.g., a reference solution) intentionally provided on the reference electrode element, thereby providing a balanced and stable potential. Contact with the sample fluid, which could disrupt this equilibrium and result in changes to the reference electrode element structure (e.g., by causing salts to dissolve in the sample fluid, particularly salts of the same anions as the reference electrode or anions that would otherwise interact with the reference electrode element surface and alter its electrochemical potential), is reduced or completely prevented. In other words, these structures and the positioning of the reference electrode within the secondary fluid channel essentially replace the traditional frit or bridge concept. This replacement enables the reference electrode to be reduced in size and manufactured using semiconductor manufacturing processes and other more efficient manufacturing processes.

[0034] This configuration also has particular benefits when used with intermittent measurement systems, such as online measurement systems, which are configured to make measurements at specific intervals while otherwise remaining immersed in a reference solution. For example, many online measurement systems will make measurements after intervals of several minutes or even hours. Measurements in such systems can range from a second or a few seconds to a minute. In such systems, the electrodes, including the working electrode, typically remain in the calibration fluid for a period of time when not measuring. The construction of the primary and secondary fluid channels is particularly suitable for such systems because the secondary fluid conduit is constructed to retain the reference solution within it (in this case, it can be combined with the commonly used calibration fluid) and reduce the possibility of displacement of the sample fluid as it passes through the primary fluid channel, but the fluid connectivity means that the reference electrode element can still provide a reference potential measurement for the entire sensing assembly.

[0035] Furthermore, when exposed to a reference solution (electrolyte), the reference electrode element essentially becomes a conventional reference electrode, the use of which improves the durability of the system and enables long-term storage without degradation. Specifically, the structure allows the reference electrode element to be maintained as a dry electrode and then covered in a fluid (e.g., a reference solution) between primary and secondary uses. This has significant advantages over conventional reference electrodes, which are manufactured in a sealed housing in which a fluid is provided during manufacture.

[0036] Branching refers to a secondary fluid channel connected to a primary fluid channel, but extending or branching from the primary fluid channel in a different direction from the primary fluid channel (i.e., the main flow path defined by the primary fluid channel). In one embodiment, at least a portion of the secondary fluid channel extends tangentially relative to the main flow path. This configuration can reduce the flow of fluid from the main flow path (i.e., the path defined by the main flow channel) into the secondary fluid channel. The secondary fluid channel is fluidically connected to the primary fluid channel and therefore has an opening connected to the primary fluid channel (i.e., there is an opening in the side wall of the primary fluid channel). In some embodiments, the opening can define a pane tangent to the main flow path. In other or additional embodiments, the secondary fluid channel is fluidically connected to the main fluid channel through an inlet portion of the secondary fluid channel, and the inlet portion includes an opening in the side wall of the main fluid channel. The inlet portion of the secondary fluid channel can be tangent to the main flow path. The main flow path can define a central axis (e.g., at the opening of the secondary fluid channel), the tangent relative to the central axis, the secondary fluid channel defines a secondary flow path, and the secondary flow path defines a central axis. In one embodiment, the inlet portion of the secondary fluid channel is perpendicular to substantially perpendicular to the main flow path. In other or additional embodiments, a portion (e.g., a middle portion or an end) or the entire secondary fluid channel except the opening of the secondary fluid channel can extend tangentially with the primary fluid channel. In some embodiments, at least a portion (e.g., an opening or an inlet) extends away from a central axis defined by the primary fluid channel at an angle of 25 to 180 degrees. In some embodiments, this can be 30 degrees to less than 180 degrees, 45 degrees to less than 80 degrees, 45 degrees to 135 degrees, 60 degrees to 135 degrees, or 60 degrees to 120 degrees. The greater the divergence from the main flow path, the less likely the fluid sample is to enter the secondary fluid channel.

[0037] The secondary fluid channel defines a secondary flow path, wherein the relative configuration of the primary flow path and the secondary flow path is configured to reduce fluid flow 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.

[0038] As described 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, and the inlet portion includes an opening in the side wall of the primary fluid channel. In another embodiment, the inlet portion of the secondary channel is tapered so as to reduce the diameter of the secondary fluid channel over at least a portion of the length of the secondary fluid channel. This configuration can reduce turbulence at the opening of the secondary fluid channel and reduce the risk of bubble formation. For example, this can be a taper from a larger diameter at the opening to a smaller diameter at the downstream of the secondary fluid channel (such as the inlet end). Thus, the taper can define a neck that can be a straight taper or can include rounded corners. In some embodiments, the opening defines an edge or corner (or edge and corner) with the side wall of the primary fluid channel, and the edge or corner is rounded or blunted.

[0039] 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 arranged in the secondary fluid channel and is spaced apart from the primary fluid channel so that the reference electrode element is set backward 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 at least 0.5mm from the opening of the secondary fluid channel. For example, at least 1mm, at least 2mm, at least 3mm, at least 4mm, at least 5mm from the opening of the secondary fluid channel. For example, 0.5mm to 100mm, 1mm to 100mm, 2mm to 100mm, 3mm to 100mm, 4mm to 100mm, 5mm to 100mm. For example, 0.5mm to 20mm, 1mm to 20mm, 0.5mm to 10mm or 1mm to 10mm from the opening of the secondary fluid channel. The greater the distance, the less likely it is that the fluid in contact with the reference electrode element in the secondary fluid channel will be contaminated by the fluid sample. In some embodiments, the reference electrode is completely contained in the secondary fluid channel.

[0040] Separating or isolating the reference electrode element from the opening can also reduce the likelihood of components that could disrupt the stable electrode potential diffusing into the channel. For example, where the reference electrode element comprises a salt, the same ions that make up the salt may be present in the fluid sample and may diffuse into the secondary fluid channel, disrupting the equilibrium. Another mode of propagation is also possible. While the flow of the sample fluid will be one mode of transfer of components (e.g., ions), diffusion will have an effect on the stable electrode potential. The path length can be based on the rate at which the component in question diffuses, i.e., the diffusion coefficient. For example, where the reference electrode element comprises AgCl, reducing the Cl -The diffusion of ions from the fluid sample into the secondary fluid channel will depend on the diffusion coefficient and the time the fluid sample is in the primary fluid channel. This is also true for Ag+ ions. The distance from the opening to the reference electrode element can be greater than the distance the ions can diffuse when the fluid sample is in the channel. That is, in embodiments, the distance between the reference electrode element and the primary fluid channel (or opening) during a particular exposure time is greater than or equal to the LD of the exposure time (i.e., the time the primary fluid channel is exposed to the component). component , where LD component is the diffusion length of the component in question (e.g., an ion). component The component is given by SQRT(D component The diffusion coefficient is calculated based on the exposure time of the component. Of course, the fluid in question needs to be considered so that the diffusion coefficient is the diffusion coefficient of the components (such as ions) present in the fluid medium. A person skilled in the art will be able to determine this fact and other facts based on the usual operating parameters (such as temperature).

[0041] For example, taking the AgCl reference electrode element as an example, taking the diffusion coefficient of Cl-, assuming the exposure time is 60 seconds (i.e., the fluid sample containing Cl- ions will pass through the main fluid channel for 60 seconds), the distance can be calculated as L D Cl- (60s) = SQRT(D Cl- .60s)=0.3mm. This is based on 1.38E -09 m 2 / s, which provides a reasonable estimate of the diffusion of Cl- in typical solutions (e.g., blood and water) and expected concentrations (e.g., body fluids) used in typical devices. Typical diffusion constant values ​​for Cl- in such solutions range from 1.38E -9 To 2.03E -9 , provide a useful baseline for calculating distances. The former is typically used for solutions with higher ion concentrations, and the latter is used for very dilute solutions. These values ​​are particularly useful for estimating distances for embodiments where the assembly is used for body fluid measurements (such as blood) and / or high water content. These values ​​are at 25°C. Therefore, the above distances can eliminate or reduce instability of the reference electrode caused by diffusion of components such as ions into the secondary fluid channel.

[0042] Therefore, in one embodiment, the reference electrode element includes a salt capable of forming at least two ions in the solution, and the distance at which the reference electrode element is spaced from the main fluid channel is greater than the diffusion length of at least one ion within 1 second. As described in more detail below, the reference electrode element will generally include a metal whose surface facing the fluid is covered with a salt of the metal. These salts are selected so that they are only slightly soluble or slowly dissolved. When the electrode is immersed in an (aqueous) reference solution comprising at least one salt ion, the following occurs: the salt layer acts as a medium between an electronic conductor (metal) and an ionic conductor (aqueous electrolyte). On the metal (electronic) side, charge transfer occurs through electronic interactions between metal atoms, while ionic interactions are dissolved and diffused from the salt layer into the aqueous solution by a salt ion (usually an anion). Take the Ag-AgCl system as an example (wherein the reference electrode element includes an Ag metal electrode with an AgCl layer on the surface): AgCl acts as a medium between an electronic conductor (Ag) and an ionic conductor (aqueous electrolyte). On the Ag (electronic) side, charge transfer occurs via electronic interactions between Ag atoms, while ionic interactions occur via dissolution and diffusion of Cl- ions from the AgCl salt into the aqueous solution. The dissolution / diffusion potential remains constant only if the concentration of Cl- ions in the electrolyte surrounding the AgCl salt (forming the reference electrolyte) is constant. This helps achieve stability of the reference potential by maintaining at least a characteristic diffusion length between the metal of the reference electrode element in the reference electrolyte and the main fluid channel where the concentration of ions (e.g. anions) may vary.

[0043] In an embodiment, the secondary fluid channel is closed to define a recess. In other words, the secondary fluid channel can form a shell or a concave shape. In this way, by preventing a straight-through flow through the secondary fluid channel, the flow through the secondary fluid conduit is further reduced. In additional or alternative embodiments, the secondary fluid channel may include an outlet. In an embodiment where the secondary fluid channel includes an outlet that is closed to define a recess, the sensing assembly includes a movable closing element, such as a valve, for closing the outlet. The outlet can be used to discharge the fluid in the secondary fluid channel. This closing element can be opened when auxiliary filling of the secondary fluid channel is required. For example, during the primary and secondary use of the sensing assembly and / or after the sample fluid has passed through the primary fluid channel and the sensing assembly is supplemented with a reference solution (e.g., a reference electrolyte). The presence of an outlet can make the filling more efficient and reduce the risk of bubble formation. Therefore, in some embodiments, the secondary fluid channel includes an outlet and a valve that seals the outlet.

[0044] The reference electrode element acts as an electrode in a reference electrode. That is, the reference electrode is formed by the electrode element and a reference solution provided to the secondary fluid channel, for example, during a filling operation). Thus, when exposed to a fluid serving as a reference solution (e.g., a calibration fluid or a reference electrolyte), the element becomes a reference electrode.

[0045] In an embodiment, the reference electrode can be based on a known reference electrode system, such as an Ag / AgCl reference electrode, a saturated calomel (Hg / Hg2Cl2) reference electrode, or a copper sulfate (Cu / CuSO4) reference circuit. The reference electrode element may include or be formed of any material that can be used as an electrode portion of a reference electrode. In some embodiments, the reference electrode element includes or is formed of a metal and a metal salt. For example, a metal core having a metal salt layer disposed thereon. In this case, the fluid used as a reference solution or electrolyte (e.g., a calibration fluid or a reference electrolyte) includes at least one of a metal salt (or an ion forming a metal salt) or a metal in a salt or a corresponding ion. In some embodiments, the metal salt may be a metal halide, so that the reference electrode element includes or is formed of a metal and a metal halide. For example, a metal core having a metal halide layer disposed thereon. In this case, in some embodiments, the fluid used as a reference solution or reference electrolyte (e.g., a calibration fluid) may include a halide, such as an excess of a halide. In some embodiments, metal and metal halide salt pair can be selected from (i) Ag and AgCl or (ii) Hg and Hg2Cl2. In these, the fluid (e.g., calibration fluid or electrolyte) used as reference electrolyte can include chloride ions, such as solutions containing AgCl and / or KCl. These may be saturated solutions. In other embodiments, metal and metal salt can be selected from copper and copper sulfate (II). In these, the fluid (e.g., calibration fluid) used as reference solution or reference electrolyte can include sulfate ions (e.g., copper sulfate (II), such as saturated copper sulfate (II) solution). The concentration of these solutions (i.e., reference solution or calibration fluid) is configured to provide a stable reference electrode potential when the reference electrode element is immersed in the solution.

[0046] These material combinations can provide a stable reference electrode potential while allowing for changes in the structure and operation of the reference electrode described herein. For example, as described above, a reference solution can be provided to the secondary fluid channel during use (e.g., between primary and secondary wetting and / or measurement), and mixing of the fluid sample with the reference solution is minimized by the structure of the secondary fluid channel relative to the primary fluid channel and the positioning of the reference electrode element within the secondary fluid channel. Thus, the relevant ions or components in the reference solution in contact with the reference electrode element are maintained at a concentration sufficient to provide a stable reference electrode potential.

[0047] The working electrode present in the main fluid channel can be an electrode comprising copper, nickel, platinum, silver, silver chloride, gold or other noble metals or titanium nitride or formed thereof. In one embodiment, the at least one working electrode is an electrode configured to detect chloride concentration in the fluid sample. The working electrode in the present embodiment can include AgCl. For example, this can be an Ag metal electrode with an AgCl layer disposed thereon. In certain embodiments, the reference electrode includes an Ag metal electrode with an AgCl layer disposed thereon, and at least one working electrode includes an Ag electrode with an AgCl layer disposed thereon.

[0048] In an embodiment, the sensing assembly is configured to detect at least one characteristic or analyte in a body fluid. In an embodiment, this can be blood, urea or saliva. In some further embodiments, at least one working electrode is an electrode configured to detect chloride concentration in a fluid sample, and the reference electrode element includes metals and chloride-based metal halides, such as Ag and AgCl. The ion concentration (such as chloride concentration) in body fluids is an important measurement value, and it has been found that the structure defined herein is advantageous when used in this context. For example, measurements in such a system do not require long exposures, and the effects on the reference electrode element located in the secondary fluid channel can be ignored, as long as the Ag / AgCl reference electrode formed by the element and the electrolyte (or calibration fluid) provides a stable potential. After the measurement is completed, the main fluid channel can be refilled with an electrolyte or calibration fluid.

[0049] The content of the reference solution in the context of the reference electrode and reference electrode elements has been discussed above. However, the reference solution may also include components that are not related to the reference electrode. For example, in some embodiments, this may also include an analyte or have a specific measurable parameter for calibrating the working electrode. For example, the reference solution may include other components, such as other analytes, or may have a specific pH value or conductivity. The reference solution referred to herein may be a calibration fluid or a reference electrolyte.

[0050] In one embodiment, the sensing assembly further comprises a calibration fluid disposed in the secondary fluid channel, wherein the calibration fluid and the reference electrode element form a reference electrode. That is, they together provide a stable reference potential. The reference electrode element can be addressed to determine the reference potential.

[0051] More generally, the sensing assembly of the embodiments can be used in a system or method for determining pH (determining the -log 10 molar concentration of H+ ions), conductivity, or analyte concentration. In certain embodiments, the term "analyte concentration" or "analyte concentration" as used herein can refer to the activity of the analyte. The system can also include a working electrode and a counter electrode.

[0052] In some non-limiting examples, at least one working electrode and a reference electrode element may be mounted on a common substrate, such as a common substrate, such as a semiconductor substrate (e.g., a silicon wafer) or a plastic substrate. In alternative examples, the at least one working electrode is mounted on a primary substrate, such as a primary semiconductor substrate, and the reference electrode element is mounted on a secondary substrate, such as a secondary semiconductor substrate, such as a (secondary) silicon wafer.

[0053] The sensing assembly can be compatible with any suitable electrochemical sensing principle. In some embodiments, the sensing assembly includes an electrochemical cell including a working electrode assembly and a counter electrode. The counter electrode can act as a cathode or anode of the working electrode.

[0054] In one embodiment, a system for sensing a property of a fluid sample (e.g., a parameter of the fluid sample or an analyte therein) includes a sensing component as defined in any of the embodiments described herein; and 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 the property of the fluid sample based at least in part on the sensor signals processed from the at least one working electrode and the reference electrode element.

[0055] In one embodiment, a system for sensing a property of a fluid sample (e.g., a parameter of the fluid sample or an analyte therein) comprises a sensing component as defined in any embodiment described herein; and a fluid delivery component configured to deliver the fluid to the main fluid channel along the main flow path. In an embodiment, the system may also include 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 the property of the fluid sample based at least in part on the sensor signals processed from the at least one working electrode and the reference electrode element.

[0056] In an embodiment, the system further comprises: a calibration fluid or reference solution reservoir; and the fluid delivery assembly is configured to deliver the reference solution from the calibration fluid reservoir to the primary fluid channel. In an embodiment, the fluid delivery assembly may also or alternatively be configured to deliver the reference solution to the secondary fluid channel during an initial filling phase and / or a refilling phase between fluid sample measurements. In embodiments where valves and outlets are provided in the filling channel, the fluid delivery assembly may be configured to operate the valves and outlets to assist in filling the secondary fluid channel. This may be directly to the secondary fluid channel or indirectly via the primary fluid channel. In some embodiments, it is advantageous to provide the reference solution to the working electrode so as to monitor data (e.g., drift) read from the working electrode, thereby providing the reference solution to the secondary fluid channel through the primary fluid channel. In other embodiments, it may be advantageous to flush the secondary fluid channel directly.

[0057] In some embodiments, the sensing assembly also includes an inlet to the secondary fluid channel. This can be connected to the fluid reservoir. The secondary fluid channel having another inlet (the inlet from the opening of the main fluid channel) advantageously allows fluid to be provided to the secondary fluid channel without the need for the fluid to first pass through the primary fluid channel. This can avoid the potential contamination of the reference electrode element by contaminants in other places (e.g., in the main fluid channel) in the sensing assembly or related device located upstream of the secondary channel or in the area between the main fluid channel and the reference electrode element. In some cases, such as in the case of repeated use of the sensing assembly, a long time has passed between measurements, and / or there are particularly persistent sample types (e.g., coagulation), which may be sample or contaminant residues, and then flushed to the reference electrode element. In some cases, it has been found that even if the flow of contaminants on the reference electrode element is only temporary, this will interfere with the performance of the reference electrode element. By providing an inlet, the secondary fluid channel can only provide fresh, uncontaminated solution, and the direction of fluid flow can be from the reference electrode element 860 to the primary fluid channel. In some embodiments, the inlet can be further positioned so that the fluid does not pass through the area between the reference electrode element and the opening before reaching the reference electrode element. In other words, the reference electrode element is located between the inlet and the opening of the primary fluid channel. In other embodiments, the reference electrode element is located between the inlet and any outlet of the secondary channel.

[0058] In some embodiments, the fluid delivery component is configured to deliver the fluid sample to the main fluid channel. Therefore, in some embodiments, the fluid delivery component may be configured to deliver the reference solution and the fluid sample to the fluid channel. That is, it is configured to deliver the fluid sample to the main fluid channel, and in some embodiments, the reference solution is delivered to the secondary fluid channel via the main fluid channel. In some embodiments, the fluid delivery component is configured to alternately deliver the reference solution and the fluid sample. This intermittent delivery can improve the stability of the reference electrode by rebalancing the balance in the secondary fluid channel. In some embodiments, the fluid delivery component is configured to deliver the reference solution in the flushing operation and is configured to deliver the fluid sample in the measuring operation, and wherein the ratio of the measuring operation to the flushing operation is 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 component exposes the fluid channel to the fluid in question. Therefore, any operation may include a delivery phase and a holding phase, in which the fluid is actively delivered to the channel and there is a flow phase, and in the holding phase, the fluid is held in the channel. In some embodiments, the measuring operation can be less than or equal to 1 second, such as less than or equal to 5 seconds, less than or equal to 10 seconds, or less than or equal to 60 seconds. It should be understood that a minimum measuring time is necessary, 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 for example at least 1 second. In some embodiments, the flushing operation is greater than or equal to 2 seconds, such as greater than or equal to 5 seconds, greater than or equal to 10 seconds, greater than or equal to 60 seconds, greater than or equal to 5 minutes, greater than or equal to 30 minutes, or greater than or equal to 60 minutes. In some embodiments, the fluid delivery assembly is configured to deliver the initial reference solution to the secondary fluid channel, in some embodiments, through the primary fluid channel. This initial filling can change the sensing assembly from a dry state to a ready-to-use state.

[0059] 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 measurement, flushing and filling operations as required. The controller may be a processor. The processor may be implemented in software and / or hardware in any suitable manner to perform the desired various functions. For example, one or all units may use one or more microprocessors programmed using software (e.g., microcode) to perform the desired functions. Examples of processor assemblies that may be used for 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).

[0060] In one embodiment, the system is an online measurement system. For example, the sensing component can be arranged as an online sensing component, which is configured to measure a characteristic of a fluid sample in a fluid path of a separate system. For example, this can be directly connected in series in the fluid path of the separate system, or the system can include a sampling path that is intermittently filled with a fluid sample, wherein the sensing component is arranged in the sensing path.

[0061] In one embodiment, the system is a body fluid analysis system configured to measure body fluid properties. In an embodiment, the body fluid is selected from blood, urine, mucus or saliva. In some embodiments, the body fluid analysis system is an online measurement system as described above. For example, the body fluid analysis system can be a dialysis system.

[0062] In an embodiment, the system can be configured to receive a signal from a reference electrode element, which provides an indication (or property indication) of the potential at the reference electrode and, in fact, at other electrodes in the system. The system can also include a property determination unit for determining the property being measured based on the processed signal. For example, these can take the form of a processor or can be composed of multiple processors. The processor can be implemented in software and / or hardware in any suitable manner to perform the various functions required. For example, one or all units can use one or more microprocessors programmed using software (e.g., microcode) to perform the required functions. Examples of processor components that can be used for various embodiments of the present disclosure include, but are not limited to, traditional microprocessors, application specific integrated circuits (ASICs), and field programmable gate arrays (FPGAs).

[0063] In various implementations, the signal processing unit, the attribute determination unit, and / or the processor may be associated with one or more non-transient storage media, such as volatile and non-volatile computer memories such as RAM, PROM, EPROM, and EEPROM. The non-transient storage media may be encoded with one or more programs that, when executed on one or fewer processors and / or controllers, may perform the desired functions. The various storage media may be fixed within the processor or controller, or may be removable, such that one or more programs stored thereon may be loaded into the signal processing unit, the attribute determination unit, and / or the processor.

[0064] 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, a tablet computer, a smart phone, a remote server, etc.

[0065] In one embodiment, a method for determining a property of a sample includes: providing a sensing component for sensing a property of a fluid sample (e.g., a parameter of the fluid sample or an analyte therein), the sensing component including a main fluid channel providing a main flow path for the fluid sample, at least one working electrode disposed in the main fluid channel, configured to sense a property of the fluid sample in the main fluid channel (e.g., a parameter or an analyte therein), a secondary fluid channel adjacent to and fluidically connected to the main fluid channel along the main flow path; and a reference electrode element for providing a reference electrode signal disposed in the secondary fluid channel. The secondary fluid channel is arranged as a branch from the main fluid channel to restrict the flow of the fluid sample from the main fluid channel to the reference electrode element. The method also includes: providing a fluid sample to the main fluid channel; and determining the property of the fluid sample based at least in part on a sensor signal received from the sensing component.

[0066] The method may utilize any sensing assembly or system disclosed herein.

[0067] In some embodiments, the method also includes providing a reference solution and a fluid sample to the fluid channel. That is, in some embodiments, the fluid sample is provided to the main fluid channel by the main fluid channel, and the reference solution is provided to the secondary fluid channel. In some embodiments, the method includes alternately delivering or providing a reference solution and a fluid sample. This intermittent delivery can improve the stability of the reference electrode by rebalancing the balance in the secondary fluid channel. In some embodiments, the method includes delivering or providing a reference solution in a flushing operation, and delivering or providing a fluid sample in a measuring operation, and wherein the ratio of the measuring operation to the flushing operation is at least 1:2. In some embodiments, the ratio is 1:5, 1:10, 1:25, 1:50 or 1:1000. The ratio is determined by the time when the fluid channel (in some embodiments, particularly the main fluid channel) is exposed to the fluid in question. Therefore, any operation may include a delivery phase and a holding phase, in which the fluid is actively delivered to the channel, and there is a flow phase, and in the holding phase, the fluid is held in the channel. In some embodiments, the measuring operation can be less than or equal to 1 second, for example, less than or equal to 5 seconds, less than or equal to 10 seconds or less than or equal to 60 seconds. It should be understood that a minimum measurement time is necessary, 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 such as at least 1 second. In some embodiments, the flushing operation is greater than or equal to 2 seconds, such as greater than or equal to 5 seconds, greater than or equal to 10 seconds, greater than or equal to 60 seconds, greater than or equal to 5 minutes, greater than or equal to 30 minutes or greater than or equal to 60 minutes. In some embodiments, the method includes delivering the initial reference solution to the secondary fluid channel, in some embodiments via the primary fluid channel. This initial filling can make the sensing assembly from a dry state to a ready-to-use state.

[0068] Figure 1 A schematic plan view of a sensing assembly 100 is provided. The sensing assembly 100 includes a primary fluid channel 110, a plurality of working electrodes 120, 120A disposed in the primary fluid channel 110, a secondary fluid channel 150 having an opening 155, and a reference electrode element 160 disposed in the secondary fluid channel 150.

[0069] Sensing assembly 100 is used to sense properties in fluid samples, such as parameters or analytes. In this embodiment, there are multiple working electrodes 120, 120A, each of which can be used to sense different parameters or analytes, so that the sensing assembly can be used to simultaneously determine the multiple properties of the same fluid sample. In an embodiment, these working electrodes can be configured to determine the presence of pH (H+ ions), conductivity, temperature and / or specific analytes, such as ions (chloride ions, potassium ions, sodium ions, calcium ions 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 the solution, and is composed of a silver body having a silver chloride layer disposed thereon. The silver chloride coating is arranged to be exposed to the fluid in the main fluid channel.

[0070] The main fluid channel 110 of the sensing component 100 is configured as a main fluid path for fluid to pass through the sensing component, thereby defining a main fluid path along its central axis. In this embodiment, the main fluid channel 110 defines a straight path extending from an inlet to an outlet. A fluid sample can be provided along this flow path so that it contacts the working electrodes 120, 120A. This can be a continuous flow of a fluid sample (e.g., a liquid sample), or a fluid sample can be provided to the main fluid channel 110 and the fluid flow can be stopped or reduced to allow the fluid sample to contact the working electrodes 120, 120A. Figure 1 , the direction of fluid flow is indicated by arrows.

[0071] Despite Figure 1 Although not visible in the drawings, the main fluid channel 110 can take the form of a closed fluid channel having a base and sidewalls extending from the base and defining a fluid path, and the working electrodes 120, 120A extending through the base. A top cover can also be provided. The working electrodes 120, 120A can be electrically connected to each other and / or external system components by, for example, wires or traces extending below the base.

[0072] The secondary fluid channel 150 is bifurcated at a point along the main flow path and fluidically connected to the primary fluid channel 110. In this embodiment, the secondary fluid channel 150 is arranged at the midpoint of the array of working electrodes 120, 120A located in the primary fluid channel 110. The secondary fluid channel 150 is fluidically connected to the primary fluid channel 110 via an opening 155 in the side wall of the primary fluid channel 110. The area of ​​the secondary fluid channel 150 extending inward from the opening 155 defines the inlet. In this embodiment, the secondary fluid channel 150 is arranged so that the entire secondary fluid channel 150 extends perpendicular to the main fluid channel 110. That is, it bifurcates from the main fluid channel 110 so that the secondary fluid channel 150 (and the central axis / fluid flow path defined by the secondary fluid channel) is 90 degrees to the main fluid path defined by the primary fluid channel 110. It has been found that this significantly reduces the entry of fluids entering the secondary fluid channel 150 along the main flow path. In this embodiment, except for the opening 155, the secondary fluid channel 150 is sealed to define a housing. It has been found that this further reduces the flow of fluid from the primary fluid channel 110 into the secondary fluid channel 150 .

[0073] 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 way, it is separated from the opening 155 and thus from the main fluid channel 110. This reduces the possibility that the fluid in contact with and adjacent to the reference electrode element 160 is displaced or contaminated by components (such as ions) in the fluid passing through the main fluid channel 110. In this embodiment, the reference electrode element 160 includes a silver metal substrate having a silver chloride coating thereon. The silver chloride coating is arranged to contact the fluid located in the secondary fluid channel 150.

[0074] It has been found that such a configuration is able to provide a protected area near the reference electrode element 160 in which minimal fluid disturbance occurs, thereby minimizing the displacement of the fluid located in the secondary fluid channel 150. More specifically, by arranging the reference electrode element 160 at the end of the secondary fluid channel 150 and having the secondary fluid channel 150 branch off from the primary fluid channel 110 in the manner shown, the reference electrode unit 160 is still in communication with the rest of the sensing assembly 100 (particularly the working electrode) so that it can be used as a reference electrode; however, the reference electrode element 160 (which together with the reference solution forms the reference electrode) is shielded from the primary fluid channel 110. This means that the potential is determined by the reference electrode element and the fluid (e.g., the reference solution) that is intentionally provided on the reference electrode element 160 in the secondary fluid channel 150, thereby providing a balanced and stable potential. Contact with the sample fluid, which could disrupt this balance and cause changes in the structure of the reference electrode element 160 (e.g., by dissolving salts in the sample fluid), is reduced or completely prevented.

[0075] As with the primary fluid channel 110, the secondary fluid channel 150 may take the form of a closed fluid channel having a base and sidewalls extending from the base and defining a fluid 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 by wires or traces, such as those extending below the base.

[0076] In use, a main filling operation can be performed, whereby a calibration fluid is provided to the primary fluid channel 110. The calibration fluid is formulated so that a reference electrode having a stable reference potential can be formed when in contact with the reference electrode element 160. In this particular embodiment, the calibration fluid is a saturated AgCl / KCl solution. The calibration fluid also includes components for calibrating the working electrode 120. The main filling operation can include flowing the calibration fluid through the primary fluid channel 110 until the secondary fluid channel 150 is also filled with the calibration fluid, thereby forming a reference electrode. The sensing assembly 100 can be placed for a stabilization period to allow a stable reference potential to be established.

[0077] A measurement operation can then be performed, whereby a fluid sample is provided to the primary fluid channel 110. The fluid sample passes through the working electrodes 120, 120A so that these electrodes can determine the properties of the fluid sample (e.g., by interrogating these electrodes). The configuration and arrangement of the secondary fluid channel 150 and the primary fluid channel 110 minimizes the likelihood that the fluid sample will enter the secondary fluid channel 150 during this operation. The flow rate can also be controlled to minimize this situation. In addition, the position of the reference electrode element 160 and its spacing from the opening 155 minimize the likelihood of measurable changes in the calibration fluid around the reference electrode element (e.g., through ion diffusion in the fluid sample and / or changes in the concentration of the calibration fluid). This can also be further minimized by minimizing the exposure time of the sensing assembly 100 to the fluid sample.

[0078] A flushing (or refilling) operation may then be performed, whereby a calibration fluid is provided to the primary fluid channel 110 to flush out any fluid sample and return the sensing assembly 100 to its pre-measured state. This may include a delivery phase in which the calibration fluid is actively delivered into the primary fluid channel 110, and there is a flow and holding phase in which the calibration fluid is held in the primary fluid channel 110 and the secondary fluid channel 150. This operation is typical of an intermittent measurement process and / or an online measurement, and the arrangement of the sensing assembly 100 in this embodiment is able to take advantage of a flushing or refilling operation. That is, this provides an opportunity to return the secondary fluid channel 150 to a state in which the fluid in the secondary fluid channel 150 is a calibration fluid (or at least to the extent that a stable reference electrode potential is maintained).

[0079] In an embodiment, the duration of the flushing or refilling operation may be longer than the measuring operation, or the duration of the delivery phase of the flushing or refilling operation may also be longer than the measuring operation. In this way, the arrangement of the channels 110, 150 has less impact on the flushing or refilling operation, thereby allowing the secondary fluid channel 150 to be restored.

[0080] In some embodiments, the measurement and flushing (or refilling) 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.

[0081] Figure 2 A schematic diagram of a system 101 for determining a property of a fluid sample is provided. The system 101 in this embodiment includes Figure 1 The sensing component 100, as well as the fluid delivery component 105, the inflow conduit 106, the calibration fluid reservoir 107, the waste reservoir 108, the signal processing unit 102 and the characteristic determination unit 103.

[0082] The fluid delivery assembly 101 is configured to deliver fluid to the main fluid channel 110 of the sensing assembly 100. In this embodiment, an inflow conduit 106 is provided to receive a fluid sample. The fluid delivery assembly 101 controls the fluid sample to pass through the inflow conduit 106 and enter the channel of the sensing assembly 100. In this embodiment, the fluid delivery assembly 106 is also configured to deliver fluid from a calibration fluid reservoir 107 to the sensing assembly 100. This may be consistent with the above-mentioned operation with respect to claim 1. A waste container 108 is provided for receiving the fluid after the fluid passes through the sensing assembly 100.

[0083] The system 101 also 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 received from the reference electrode element 160 (e.g., a reference electrode signal indicating a reference electrode potential) and the working electrode 120, 120A (e.g., a working electrode signal representing a property of the fluid sample). The characteristic determination unit 103 is configured to determine the characteristic of the fluid sample based at least in part on the sensor signal processed by the signal processing unit 102.

[0084] Figure 3 A schematic plan view of a sensing assembly 100' is provided. The sensing assembly 100' includes Figure 1 The sensing assembly 100 has the same components, but the configuration of the secondary fluid channel is different. Figure 3 The sensor assembly 100' comprises a primary fluid channel 110', a plurality of working electrodes 120', 120A' disposed in the primary fluid channel 110', a secondary fluid channel 150' having an opening 155', and a reference electrode element 160' disposed in the secondary fluid channel 150'.

[0085] Figure 3 The sensor assembly 100' shows another configuration of the secondary fluid channel 150'. In this embodiment, the secondary fluid channel 150' is provided with an opening 155', which is provided in the side wall of the primary fluid channel 110, and is located downstream of the working electrode 120', 120A'. This can reduce the effect of diffusion outward from the secondary fluid channel 150' on the working electrode 120', 120A', especially the electrode downstream of the secondary fluid channel 150'. Otherwise, this structure can be similar to Figure 1 The structure of the sensing component 100 is the same.

[0086] Figure 4 A schematic plan view of a portion of a sensing assembly 100' is provided. The sensing assembly 100' includes Figure 1 The sensing assembly 100 has the same components, but the configuration of the secondary fluid channel is different. Figure 4 The sensing assembly 100" includes a main fluid channel 110", a plurality of working electrodes 120" disposed in the main fluid channel 110", a secondary fluid channel 150" having an opening 155", and a reference electrode element 160" disposed in the secondary fluid channel 150".

[0087] In this embodiment, the secondary fluid channel 150" is disposed at the midpoint of the array of working electrodes 120" located in the primary fluid channel 110". The secondary fluid channel 150" is fluidically connected to the primary fluid channel 110" through an opening 155" in the side wall of the primary fluid channel 150". The area of ​​the secondary fluid channel 150" extending inward from the opening 155" defines an inlet. In this embodiment, the secondary fluid channel 150 is arranged so that the entire secondary fluid channel 150" extends at an angle of 135 degrees relative to the main fluid channel 110" (the angle is defined relative to the direction of fluid flow). That is, it branches off from the main fluid channel 110", so that the secondary fluid channel 150" (and the central axis / fluid flow path defined by the secondary fluid channel 150") is tilted backward relative to the main fluid path defined by the primary fluid channel 110". It has been found that this significantly reduces the entry of fluid into the secondary fluid channel 150" along the main flow path. In this embodiment, the secondary fluid channel 150" is sealed except for the opening 155" to define a housing. It has been found that this further reduces the flow of fluid from the primary fluid channel 110" into the secondary fluid channel 150".

[0088] Otherwise, the structure can be Figure 1 The structure of the sensing component 100 is the same.

[0089] Figure 5 A schematic plan view of a sensing assembly 100'' is provided. The sensing assembly 100'' includes Figure 1 The sensing assembly 100 is the same assembly as the sensing assembly 100, but the configuration of the secondary fluid channel is different. Figure 5 The sensing assembly 100'' includes a primary fluid channel 110'', a plurality of working electrodes 120'', 120A'' disposed in the primary fluid channel 110'', a secondary fluid channel 150'' having an opening 155'', and a reference electrode element 160'' disposed in the secondary fluid channel 150''.

[0090] In this embodiment, the inlet portion 156'' of the secondary fluid channel 150'' combines an opening 155'' in the side wall 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 so that the diameter of the secondary fluid channel 150'' decreases over a portion of the length of the inlet portion 156'' starting from the opening 155'' over a length of the secondary fluid channel 150''. This also adopts a shape that eliminates the 90 degree angle of the opening 155''. This can reduce turbulence at the opening of the secondary fluid channel and reduce the risk of bubble formation.

[0091] Fig. 6A and 6B A schematic plan view of a sensing assembly 200 is provided. The sensing assembly 200 has Figure 1 The sensing assembly 200 has the same underlying structure as the sensing assembly 100, including a main fluid channel 210, a plurality of working electrodes 220 disposed in the main fluid channel 210, a secondary fluid channel 250 having an opening 255, and a reference electrode element 260 disposed in the secondary fluid channel 250. The sensing assembly 200 also includes an outlet 251 leading from the secondary fluid channel 250 to a drain channel 252 and a valve 270 that can close the outlet 251.

[0092] and Figure 1 Like the sensing assembly 100 of the present invention, the sensing assembly 200 includes a plurality of working electrodes 220, each of which can be used to sense a different parameter or analyte, so that multiple properties of the same fluid sample can be determined simultaneously using the sensing assembly. The main fluid channel 210 of the sensing assembly 200 is configured as a main fluid path for the fluid to pass through the sensing assembly 200, and thus defines the main fluid path along its central axis. In this embodiment, the main fluid channel 210 defines a straight path extending from an inlet to an outlet. A fluid sample can be provided along the flow path so that it contacts the working electrode 220.

[0093] and Figure 1Like the sensing assembly 100 of the present invention, the secondary fluid channel 250 of the sensing assembly 200 branches off at a point of the main flow path and is fluidically connected to the primary fluid channel 210. In this embodiment, the secondary fluid channel 250 is disposed at a midpoint along the array of working electrodes 220. The secondary fluid channel 250 is fluidically connected to the primary fluid channel 210 via an opening 255 in a sidewall of the primary fluid channel 250. The secondary fluid channel 250 is arranged perpendicular to the primary fluid channel 210.

[0094] In this embodiment, the secondary fluid channel 250 also includes an outlet 251 for draining the secondary fluid channel 250. In this particular embodiment, it is located opposite the opening 255. Having the outlet 251 is advantageous in filling the secondary fluid channel 250 and replacing any fluid within the secondary fluid channel 250 (e.g., during an initial filling operation or a refilling or flushing operation). This also helps reduce the formation of bubbles.

[0095] However, as described above, having an open outlet can promote fluid flow through the secondary fluid channel 250, which may be disadvantageous during measurement operations, i.e., when it is necessary to reduce the fluid flow from the primary fluid channel 210 to the secondary fluid channel 250. Therefore, the sensing assembly 200 also includes a valve 270 that can selectively open or close the outlet 251. In this way, when necessary, the secondary fluid channel 250 can be closed at the outlet 251 by the valve 270, thereby forming a housing that can contain the calibration fluid when needed (e.g., during measurement operations). However, as needed, it can be easily discharged through the drain channel 252 by opening the valve 270.

[0096] Figure 7 A method 302 for determining a property of a sample 300 is depicted, the method 302 comprising providing a sensing assembly for sensing a property of a fluid sample (e.g., a parameter of the fluid sample or an analyte therein). The sensing assembly comprises: a primary fluid channel providing a primary flow path for the fluid sample, at least one working electrode disposed in the primary fluid channel, configured to sense a property of the fluid sample in the primary fluid channel (e.g., a parameter or an analyte therein), a secondary fluid channel adjacent to and fluidically connected to the primary fluid channel along the primary flow path; and a reference electrode element for providing a reference electrode signal disposed in the secondary fluid channel. The secondary fluid channel is arranged as a branch from the primary fluid channel to restrict flow of the fluid sample from the primary fluid channel to the reference electrode element. The method 302 also comprises providing the fluid sample to the primary fluid channel 304; and determining a property of the fluid sample 306 based at least in part on a sensor signal received from the sensing assembly.

[0097] Fig.13 800 is a schematic plan view of a sensing assembly 800. The sensing assembly 800 has Figure 1 The sensing assembly 100 of the present invention has the same underlying structure, including a main fluid channel 810, a plurality of working electrodes 820 disposed in the main fluid channel 810, a secondary fluid channel 850 having an opening 855, and a reference electrode element 860 disposed in the secondary fluid channel 850. The main fluid channel 810 of the sensing assembly 800 is configured as a main fluid path for fluid passing through the sensing assembly 800, and thus defines the main fluid path along its central axis. In this embodiment, the main fluid channel 810 defines a straight path extending from an inlet to an outlet. A fluid sample can be provided along the flow path so that it contacts the working electrode 820.

[0098] and Figure 1 Like the sensing assembly 800 of the present invention, the secondary fluid channel 850 of the sensing assembly 800 branches off at a point of the main flow path and is fluidically connected to the primary fluid channel 810. In this embodiment, the secondary fluid channel 850 is disposed at a midpoint along the array of working electrodes 820. The secondary fluid channel 850 is fluidically connected to the primary fluid channel 810 via an opening 855 in the side wall of the primary fluid channel 810. The secondary fluid channel 850 is arranged perpendicular to the primary fluid channel 810.

[0099] The sensing assembly 800 also includes an inlet 851 leading to the secondary fluid channel 850. In this particular embodiment, it is located opposite the opening 855. This can be connected to, for example, a reservoir (not shown) or other fluid channel. The secondary fluid channel 850 having another inlet 851 (the inlet from the main fluid channel 810 to the opening 855) advantageously allows the fluid to be provided to the secondary fluid channel 850 without the need for the fluid to first pass through the main fluid channel 810. In this particular embodiment, this is also positioned so 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 of the secondary fluid channel 850, namely the opening 855. In other embodiments, the reference electrode element 860 is located between the inlet 851 and any outlet of the secondary fluid channel 850. These arrangements may be advantageous because they avoid potential contamination of the reference electrode element 860 by contaminants located elsewhere in the sensing assembly 800 or in an associated device upstream of the secondary fluid channel 850 (e.g., within the primary fluid channel 810) or in the area between the primary fluid channel 810 and the reference electrode element 860. In some cases, such as where the sensing assembly 800 is reused, significant time has passed between measurements, and / or there are particularly persistent sample types (e.g., coagulation), it may be that sample or contaminants remain and are then flushed to the reference electrode element 860. In some cases, it has been found that even if the flow of contaminants over the reference electrode element 860 is only temporary, this can interfere with the performance of the reference electrode element 860. By providing an inlet, the secondary fluid channel 850 can be provided with only fresh, uncontaminated solution, and the direction of fluid flow can be from the reference electrode element 860 to the primary fluid channel 810.

[0100] The sensing assembly 800 may also include a valve 870 that may selectively open or close the inlet 851 .

[0101] Example

[0102] Example 1

[0103] The results of Example 1 are as follows Figures 8A to 8D As shown, using Figure 1 The sensor assembly 100 has the same structure as the sensor assembly 400 (the same reference numerals refer to the same components) to monitor the entry of chloride ions into the secondary fluid channel 450, which is vertically branched from the primary fluid channel 410. The reference electrode element 460 is disposed in the secondary fluid channel 450, and the plurality of working electrodes 420 are disposed in the primary fluid channel 410. Fig.8FThe sensing assembly 400 is depicted without fluid. In this example, the reference electrode element 460 is positioned 3.0 mm from the opening of the secondary fluid channel 450 (ie, no portion of the reference electrode element 460 is less than 3.0 mm). The total depth of the secondary fluid channel 450 is 4.0 millimeters.

[0104] In this example, Figures 8A to 8D The change in chloride ion concentration when a fluid sample is supplied to the sensing assembly 400 in the simulation is depicted. Fig. 8A In the example, the primary and secondary fluid channels 410, 450 are filled with a fluid having a Cl- concentration of 96 mM (calibration fluid). A fluid having a chloride concentration of 107 mM (equivalent to the fluid sample) is provided to the main sensing assembly in a series of pulses. Specifically, in this example, five equal fluid pulses are provided, with a total volume of the fluid equal to three times the total volume of the sensing structure. Fig. 8E The fluid delivered to the sensing assembly 400 is depicted with five pulses occurring at approximately 0, 18, 33, 48 and 65 seconds. The peak fluid flow rate (the velocity magnitude at the inlet in m / s) is 0.013.

[0105] Fig. 8A The chloride ion concentration at 0 seconds is shown. Figure 8B The chloride ion concentration at 10 seconds is shown. Figure 8C The chloride ion concentration at 60 seconds is shown. Fig.8D The chloride concentration at 95 seconds is shown. As shown, after 10 seconds, the higher concentration fluid enters the secondary fluid channel 450 and is negligible, and after 30 seconds it is reduced to a minimum. The chloride concentration further entering the secondary fluid channel 450 in the region of the reference electrode element 460 remains substantially constant within 95 seconds, so that the reference electrode potential will remain stable. In fact, many measurement operations are much less than 95 seconds.

[0106] Example 2

[0107] Example 1 was repeated, but with different dimensions of the secondary fluid channel 450. Specifically, the length of the secondary fluid channel 450 (from the opening 455 to the opposite end of the secondary fluid channel 450). The length dimensions of the secondary fluid channel 450 were 1 mm, 2 mm, 3 mm, and 4 mm. The diameter of the reference electrode element 460 was approximately 0.8 mm.

[0108] Fig. 9 is a graph depicting the change in chloride ion concentration at reference electrode element 460 over time. Fig. 9The change in chloride ion concentration over time (up to 100 seconds) is shown for a secondary reference electrode 460 depth of 1 mm (595), 2 mm (596), 3 mm (597) and 4 mm (598). As shown, for 1 mm as an example, a pulse of high concentration fluid causes some change in chloride ion concentration over time at the reference electrode 460. For a secondary fluid channel 450 length of 2 mm, there was no significant change in chloride ion concentration at the reference electrode element 460 for more than 30 seconds. For secondary fluid channel 450 lengths of 3 mm and 4 mm, there was no significant change in chloride concentration at the reference electrode element 460 during the experiment. The total change after 90 seconds was <0.01% for 3 mm and <0.0005% for 4 mm. This shows that stability of chloride ion concentration can be maintained in the secondary fluid channel 450 even at shorter lengths, and this far exceeds the exposure time required for certain measurements (e.g., a 2 mm depression depth) when the reference electrode element is completely removed from the primary fluid channel, even when pulses are used.

[0109] Example 3

[0110] Figures 10A to 10D Depicts the same experimental results as Example 1, except that only one fluid pulse was used. The total volume delivered was exactly the same. The peak fluid flow rate (the magnitude of the velocity at the inlet in m / s) was 0.067. The sensing assembly structure was the same as that used in Example 1.

[0111] Fig. 10A The chloride ion concentration at 0 seconds is shown. Fig. 10B The chloride ion concentration at 1 second is shown. Fig. 10C The chloride ion concentration at 15 seconds is shown. Fig. 10D The chloride concentration at 31 seconds is shown. As shown, even after 31 seconds, the possibility of high concentration fluid entering the secondary fluid channel 450 is very small. The chloride concentration in the region of the reference electrode element 460 further entering the secondary fluid channel 450 remains substantially constant throughout the period, so that the reference electrode potential remains stable.

[0112] Example 4

[0113] Example 3 was repeated, but with different dimensions of the secondary fluid channel 450. Specifically, the length of the secondary fluid channel 450 (from the opening 455 to the opposite end of the secondary fluid channel 450). The length dimensions of the secondary fluid channel 450 were 1 mm, 2 mm, 3 mm, and 4 mm. The diameter of the reference electrode element 460 was approximately 0.8 mm.

[0114] Fig.11A is a graph depicting the change in chloride ion concentration at reference electrode element 460 over time. Fig.11AThe change of chloride ion concentration over time (up to 100 seconds) when the depth of the secondary reference electrode 460 is 1mm (695), 2mm (696), 3mm (697) and 4mm (698) is shown. As shown in the figure, taking 1mm as an example, the pulse of high concentration fluid causes some changes in the chloride ion concentration at the reference electrode 460. For the secondary fluid channel 450 length of 2mm, the liquid level remains stable after the initial movement. For the secondary fluid channel 450 length of 3mm and 4mm, there is no significant change in the chloride concentration at the reference electrode element 460 during the experiment. The total change of 3mm after 30 seconds is ~0.002%, and the total change of 4mm is less than 0.0001%. This shows that even at a short length of 2mm, the stability of the chloride ion concentration in the secondary fluid channel 450 can be maintained during the exposure time that significantly exceeds the time required for some measurements. Even at 1mm, there is some resistance compared to what is seen with the reference electrode element located in the main fluid channel.

[0115] Example 5

[0116] Example 5 provides a comparison of three separate reference electrode configurations when subjected to several different solutions. The signals obtained from each configuration are as follows: Fig.12 1 and 2 (Signal (pV) vs. Time (arbitrary time units)). The baseline configuration 795 is a standard REFET in the form of a silver chloride layer covered by a membrane, the signal produced being compensated. This represents a comparative example of a typical pseudo reference electrode used in electrochemical sensors. The secondary configuration 796 is a silver chloride reference electrode in the secondary fluid channel according to the present invention, but without any compensation. The third configuration 797 is a silver chloride reference electrode in the secondary fluid channel with compensation according to the present invention.

[0117] In this example, three electrode configurations are sequentially exposed to different solutions over time, as shown on the x-axis. For example, each solution is first exposed to a solution containing calcium ions for a period of time, then to a sodium chloride solution for a short period of time, followed by a sodium acetate solution, then a sodium bicarbonate solution, then a sodium lactate solution, followed by a magnesium sulfate solution, and finally a lactated Ringer's solution. These provide a useful indication of the types of ions found in typical samples such as blood, as the concentration range used for each analyte in the experiment spans pathological values ​​from physiological fluids. The graph depicts the response of each reference electrode configuration to these solutions.

[0118] It can be seen that the third configuration 797 with the silver chloride reference electrode in the secondary fluid channel provides by far the most stable performance, particularly for solutions containing sodium ions where the comparative REFET 795 has large variations and drift. Even the uncompensated secondary configuration 796 with the silver chloride reference electrode in the secondary fluid channel has greatly improved performance for solutions containing sodium ions, providing stability even in the presence of some drift.

[0119] It should be understood that the detailed description and specific examples, although indicating exemplary embodiments of the device, system and method, are for illustrative purposes only and are not intended to limit the scope. These and other features, aspects and advantages of the device, system and method of the present invention can be better understood from the specification, the attached claims or aspects and the accompanying drawings. It should be understood that the drawings are only schematic and are not drawn to scale. It should also be understood that the same reference numerals are used throughout the drawings to indicate the same or similar parts.

[0120] By studying the drawings, the present disclosure and the attached aspects or claims, those skilled in the art can understand and implement other variations to the disclosed embodiments when 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 multiple elements or steps. The mere fact that certain measures are cited 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 interpreted as limiting the scope.

Claims

1. A sensing assembly for sensing a property of a fluid sample, the sensing assembly comprising: a main fluid channel providing a main flow path for a fluid sample; at least one working electrode disposed in the main fluid channel, configured to sense a property of a fluid sample in the main 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 disposed in the secondary fluid channel, The secondary fluid channel is arranged as a branch from the primary fluid channel to restrict the flow of the 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 relative to the primary flow path.

3. A sensing assembly according to claim 1 or 2, wherein the secondary fluid channel is fluidically connected to the primary fluid channel through an inlet portion of the secondary fluid channel, the inlet portion comprising an opening in a side wall of the primary fluid channel. The sensing assembly of claim 3 , wherein an inlet portion of the secondary fluid channel is tangential to the primary flow path.

5. The sensing assembly of claim 4, wherein an inlet portion of the secondary fluid channel is substantially perpendicular to the primary 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 the diameter of the secondary fluid channel over at least a portion of its length.

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

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

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

10. A sensing assembly according to any preceding claim, wherein the reference electrode element comprises a metal and a metal salt.

11. The sensing assembly of claim 10, wherein the reference electrode element comprises a metal and a metal salt selected from the group consisting of: (i) Ag and AgCl; (ii) Hg and Hg2Cl2; and (iii) Cu and CuSC.

12. A sensing assembly according to any preceding claim, wherein the at least one working electrode is an electrode configured to detect chloride concentration in a fluid sample.

13. A sensing assembly according to any preceding claim, wherein the sensing assembly further comprises a calibration fluid disposed in the secondary fluid channel, wherein the calibration fluid and a reference electrode element form a reference electrode.

14. A system for sensing a property of a fluid sample, comprising: A sensing assembly according to any preceding claim; and A fluid delivery assembly is configured to deliver fluid to the primary fluid channel along the primary flow path.

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

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

17. The system of claim 16, wherein the fluid delivery component is configured to deliver a fluid sample to the main fluid channel in a measurement operation and is configured to deliver the calibration fluid in a flushing operation, wherein the ratio of the measurement operation to the flushing operation is at least 1:

2.

18. A method for determining a property of a sample, comprising: A sensing component for sensing properties of a fluid sample is provided, the sensing component comprising: a main fluid channel providing a main flow path for the fluid sample, at least one working electrode arranged in the main fluid channel, configured to sense properties of the fluid sample in the main fluid channel, a secondary fluid channel, adjacent to and fluidically connected to the main fluid channel along the main flow path; and a reference electrode element for providing a reference electrode signal arranged in the secondary fluid channel, wherein the secondary fluid channel is arranged as a branch from the main fluid channel to restrict the flow of the fluid sample from the main fluid channel to the reference electrode element; providing a fluid sample to the main fluid channel; and A property of the fluid sample is determined 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. The method of claim 19, wherein the ratio of providing the fluid sample to providing the calibration fluid is at least 1:2.

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