Solid-state reference electrode

Abstract

A solid state reference electrode configured to provide a reference potential in an electrochemical analyzer. The solid state reference electrode comprises a conductor element, the conductor element comprises a metal and a coating, and the coating comprises a solid salt of the metal; and a solid polymer composition disposed in contact with the conductor element. The solid polymer composition includes a mixture of a cured resin, a salt that produces substantially isotactic ions, and a polyol that promotes the curing of ionic conductivity within the solid polymer composition.

Description

Technical Field

[0001] The present disclosure relates to solid-state reference electrodes. Background Art

[0002] Reference electrodes are an important part of electrochemical sensing devices and are used to provide a stable, accurate, and reproducible reference potential required for analyzing fluid samples such as blood, plasma, or water samples. Liquid electrolytes (which have long been used in such reference electrodes) require careful setup and often suffer from problems such as leakage and evaporation. Solid-state reference electrodes (which use solid materials such as polymers instead of liquid electrolytes in traditional reference electrodes) are considered to have advantages such as position independence, high mechanical strength, ease of manufacturing, miniaturization, integration with other electrochemical components, and greater resistance to sample contamination compared to liquid electrolytes. Summary of the Invention

[0003] In one aspect, this document describes a solid-state reference electrode configured to provide a reference potential in an electrochemical analyzer. The solid-state reference electrode includes a conductor element that includes a metal and a coating, the coating including a solid salt of the metal; and a solid-state polymer composition in contact with the conductor element. The solid-state polymer composition includes a cured resin, a salt that generates substantially equitransferent ions, and a mixture of polyols that promotes the curing of the ion conductivity within the solid-state polymer composition.

[0004] In another aspect, this document describes a module for an electrochemical analyzer that includes a flow path configured to receive a fluid sample, a solid-state reference electrode including a reservoir with a solid-state polymer composition therein, and a joining structure disposed between the reservoir and the flow path. The solid-state polymer composition includes a cured resin, a salt that generates substantially equitransferent ions, and a polyol that promotes ion conductivity within the solid-state polymer composition. The shape of the joining structure is configured to (i) allow the fluid sample in the sample input port to contact the solid-state polymer composition, and (ii) promote a substantially constant ion flux between the fluid sample and the solid-state polymer composition.

[0005] In another aspect, this document describes a method for manufacturing a solid-state reference electrode for an electrochemical analyzer. The method includes forming a fluid composition that includes (i) a cured resin precursor, (ii) a salt that generates substantially equitransferent ions, and (iii) a polyol. The method also includes depositing the fluid composition into a reservoir configured to receive the solid-state reference electrode and curing the fluid composition.

[0006] In another aspect, this document describes a method for analyzing a fluid sample, the method comprising receiving the fluid sample within an electrochemical measurement device and contacting the fluid sample at a junction structure through a solid-state reference electrode of the electrochemical measurement device. The junction structure is disposed between (i) a flow path of the fluid sample and (ii) a reservoir containing a solid polymer composition, the reservoir being configured to support the solid-state reference electrode. The solid polymer composition is configured to provide a substantially constant ionic flux of substantially equi-transporting ions through the junction structure. The method further comprises measuring one or more analytes in the fluid sample using one or more sensors of the electrochemical measurement device, wherein the measurement is based on a reference potential provided by the solid-state reference electrode at the junction structure. The solid polymer composite composition comprises a fixed mixture of: a cured resin, a salt that produces substantially equi-transporting ions, and a polyol that promotes a substantially constant ionic flux within the solid polymer composition.

[0007] Various embodiments of the above aspect may include one or more of the following.

[0008] The fixed mixture may include a nonionic surfactant material. The cured resin may include a polyacrylate. The salt may include potassium chloride (KCl). The fixed mixture may include a second salt that reduces the effect of red blood cells on the junction potential between the solid-state reference electrode and the sample in the electrochemical analyzer. The second salt may be an equi-transporting salt of sodium, including at least one of the following: sodium acetate, sodium bicarbonate, or sodium formate. The polyol may be a triol compound. The triol compound may include glycerol. The nonionic surfactant material may include lauroyl / myristoyl methyl glucamide. The solid polymer composition may include 45 - 65% of the cured resin, 30 - 55% of the salt, 1 - 4% of the polyol, and 0.2 - 2% of the nonionic surfactant material. The metal may be silver (Ag). The solid salt of the metal may be silver chloride (AgCl).

[0009] The reservoir may have an elliptical shape to facilitate a substantially constant ionic flux between the fluid sample and the solid polymer composition. The junction structure may include a first opening at the interface of the reservoir and the junction structure, and a second opening at the interface of the flow path and the junction structure. The size of the first opening may be larger than the size of the second opening, and the junction structure may have a funnel shape. The module may include one or more sensors disposed in the flow path to measure one or more analytes in the fluid sample.

[0010] In some embodiments, the solid-state reference electrodes described herein may provide one or more of the following advantages. By providing a carefully tailored selection / composition of polymers, ion-exchange salts, and other additives (such as triols), the techniques described herein facilitate the realization of solid-state reference electrodes with fast start-up times, substantially constant ion fluxes of ion-exchange ions (thereby generating stable reference potentials), and significantly long service lives. Additives such as non-ionic surfactants provide homogeneity of the mixture, making the reference electrode easy to reproduce and thus potentially widely applicable to various electrochemical measurement systems. In addition, the specific configurations of the reference electrode chamber and the junction where the reference electrode contacts the sample can result in sufficient and substantially stable ion fluxes between the electrode and the sample, thereby allowing a stable reference potential to be maintained throughout the service life of the reference electrode.

[0011] Some or all aspects may be methods, or may further be included in corresponding systems or other devices for performing the functions. Details of these and other aspects and embodiments of the present disclosure are set forth in the drawings and the following description. Other features, objects, and advantages of the present disclosure will be apparent from the description, the drawings, and the claims. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] FIG. 1 illustrates an example system in which the solid-state reference electrode described herein may be used.

[0013] Figure 2 Shows an example of a module including a portion of the system Figure 1 described.

[0014] Figure 3 FIG. 18 shows a flowchart of an example manufacturing process of the solid-state reference electrode described herein.

[0015] FIGS. 4A and 4B respectively show examples of solid-state reference electrodes achieved using the techniques described herein, before use and after one month of use.

[0016] FIG. 5 is a flowchart of an example operating sequence for measuring an analyte in a fluid sample using the solid-state reference electrode described herein.

[0017] Figure 6 FIG. 28 shows a flowchart of an example manufacturing process of the solid-state reference electrode described herein.

[0018] Figure 7 FIG. 32 shows a flowchart of an example process using the solid-state reference electrode described herein.

[0019] Like reference numerals and labels in the various figures represent the same elements. DETAILED DESCRIPTION

[0020] This specification relates to solid-state reference electrodes for use in various electrochemical measurement systems. Compared to other solid-state reference electrodes used in the industry, the solid-state reference electrodes described herein have a significantly longer service life (e.g., one month or longer even with continuous use). For intermittent use (e.g., analyzing a discrete number of samples per day), the service life is significantly more than one month. The disclosed reference electrodes also exhibit stable junction potentials for different fluid samples and a low hydration time (i.e., the time required for the reference electrode to achieve stable ionic communication with the sample, after which the reference electrode reliably provides a stable reference potential). In addition, due to the simple composition, the solid-state reference electrodes described herein are easy to replicate, making it possible to be widely used to improve the reliability and cost-effectiveness of various electrochemical measurement systems. In addition, this document also discusses the specific configurations of the reference electrode chamber and the junction where the reference electrode contacts the sample. Specifically, the disclosed configurations of the chamber and the junction result in sufficient and substantially stable ionic flux between the electrode and the sample through the junction, thereby providing a stable junction potential throughout the service life of the reference electrode.

[0021] Traditional reference electrodes operate based on liquid electrolytes and can include Ag / AgCl half-cells that are connected to the sample through a salt bridge containing an aqueous solution of a transport salt such as KCl. Such traditional reference electrodes can provide fast startup and a long service life, but typically have a complex design that is not conducive to miniaturization. Other methods use flow-through Ag / Ag+ reference electrodes, where a low concentration of silver ions (usually 1 millimole AgNO3) is mixed with a high concentration of a transport salt (usually 1 mole KNO3) to form a liquid flow connection. Such electrodes are generally large in size and have a complex design, and are often subject to contamination of the sample by the reference solution electrolyte. Generally speaking, liquid electrolyte reference electrodes encounter various problems such as leakage, evaporation, sensitivity to temperature and pressure changes, and biological contamination.

[0022] Solid-state reference electrodes are designed to address the disadvantages associated with liquid electrolyte reference electrodes and use solid materials such as polymers, agar, or polymer membranes as ion sources. Solid-state reference electrodes have characteristics such as position independence, high mechanical strength, ease of manufacture, miniaturization, and integration with other electrochemical components, and have strong resistance to sample contamination. However, solid-state reference electrodes also have their own challenges, such as long hydration times, unstable interfacial or junction potentials, and limited lifetimes. Although some currently available reference electrodes do exhibit fast hydration, this comes at the cost of a short service life (in some cases, they are single-use). Due to these disadvantages, despite the advantages of solid-state reference electrodes over liquid electrolyte electrodes, they have not been widely used in electrochemical measurement systems.

[0023] The techniques described herein provide a solid-state reference electrode that may address some of the aforementioned drawbacks of solid-state reference electrodes. Specifically, this document describes a solid-state reference electrode that includes a silver / silver chloride electrode in a housing that contains an inert photocurable polymer matrix (e.g., formed using acrylate monomers that can be cured / polymerized using ultraviolet light) and a salt powder dispersed in the matrix, the salt powder generating equitransfer ions. The polymer matrix contains additional additives to provide specific functions. For example, one or more polyols (e.g., triol compounds such as glycerol) are added to allow for obtaining a target ionic conductivity in the cured polymer material, which in turn results in a fast startup. A nonionic surfactant (e.g., lauroyl / myristoyl methyl glucamide) is included in the polymer / salt mixture to maintain the homogeneity that is closely related to reproducibility.

[0024] In addition, the chamber or reservoir that houses the solid-state reference electrode, and / or the junction or interface through which the electrode contacts the sample in the reservoir, is configured specifically for a particular target function - for example, maintaining a constant ionic flux from the cured polymer / salt mixture through the junction into the sample, thereby maintaining junction potential stability throughout the entire service life of the electrode. In some examples, the reservoir that houses the polymer / salt mixture can have a circular or semi-elliptical configuration and a funnel-shaped junction structure to contact the sample. This configuration can allow for a substantially constant ionic flux through the junction, thereby providing a stable junction potential for at least one month of service life of the disclosed solid-state reference electrode.

[0025] In some examples, the disclosed solid-state reference electrode can be embedded in a sensor card that houses a sensor for analyzing a fluid sample and can replace the reference liquid flow path, reference solution inlet, reference solution bag, and reference pump winding in a liquid flow junction reference electrode.

[0026] Figure 1 An example system 100 for analyzing a fluid sample is shown. System 100 includes an analyzer 20 (also referred to herein as an electrochemical measurement device) that is configured to receive an example cartridge 23 that includes one or more containers 30a to 30d (collectively 30), corresponding conduits 31a to 31d (collectively 31), a sample input 33a and a corresponding conduit 33b, a dispensing valve 34, and a waste container 35. The cartridge 23 can be moved into and out of the analyzer 20 via a corresponding slot 24 provided on the analyzer 20. In some embodiments, the cartridge 23 can be a reusable, disposable cartridge.

[0027] In some embodiments, the cartridge 23 includes a plurality of containers 30. Although Figure 1Four containers 30a - 30d are shown, but cartridge 23 can include fewer than four containers (e.g., one, two, or three containers) or more than four containers (e.g., five, six, seven, eight, etc. containers). In some embodiments, container 30 can be a sealed bag or pouch. The bag or pouch can be made of foil laminate, soft plastic, rubber, or any other type of soft liquid - tight material. In some embodiments, container 30 can be made of hard plastic, glass, or any other type of hard liquid - tight material. Container 30 can be a disposable container or a reusable container. In some embodiments, different containers 30 can hold compositions of different reagents for analyzing a fluid sample. In some embodiments, different containers 30 can hold compositions of the same reagent at different concentrations.

[0028] In some embodiments, cartridge 23 includes conduits 31 that are fluidly connected to the flow path of sensor 21 via conduit 27. Conduits 31a to 31d are configured and arranged to convey the composition from the respective containers 30a to 30d. For example, conduit 31 can include a plastic tube within the cartridge or a channel formed in the cartridge structure. In some embodiments, negative pressure / suction can be applied to move the composition from the respective container 30 into the respective conduit 31 and ultimately to sensor 21. For this purpose, in some embodiments, system 100 can include a pump 28 for introducing suction into conduit 31 via conduit 29, sensor 21, conduit 27, and dispensing valve 34.

[0029] Dispensing valve 34 is in fluid communication with conduit 31 and is in fluid communication with sensor 21 via conduit 27. In some embodiments, dispensing valve 34 can be controlled by control system 22 to selectively apply the pressure from pump 28 to conduit 31, thereby moving the composition from the respective container 30 into the flow channel of sensor 21.

[0030] Sensor 21 can include various types of sensors that are configured to sense the presence of various analytes. In some embodiments, sensor 21 can include one or more sensors that are configured to sense one or more of the following analytes in whole blood or plasma: creatine, creatinine, glucose, lactate, pCO2, pH, potassium, sodium, calcium, chloride, PO2, and hematocrit. In some embodiments, sensor 21 can include one or more hemolysis sensors. In some embodiments, sensor 21 can be similar to the sensor described in U.S. Patent No. 9,658,181, the content of which is incorporated herein by reference. In some embodiments, one or more optical sensors 52 can be disposed within electrochemical measurement device 23 to perform optical measurements on the fluid flowing through the device. Although Figure 1An optical sensor associated with flow path 29 is shown, but the optical sensor can be deployed at another location on the electrochemical measurement device, such as on sensor flow path 27 or waste flow path 26.

[0031] In some embodiments, cartridge 23 includes a sample input 33a. Sample input 33a is configured to receive a test sample (e.g., blood, plasma, or another aqueous sample) to be analyzed by analyzer 20. For example, sample input 33a can be a self-sealing port or other structure into which a pipette or needle can be inserted to inject the test sample into the cartridge. In some embodiments, sample input 33a is fluidly connected to conduit 33b, which can be fluidly connected to the flow path of sensor 21 via dispensing valve 34 and conduit 27. Suction and control of the dispensing valve can move the test sample to sensor 21.

[0032] In some embodiments, cartridge 23 includes a waste container 35 that is in fluid communication with pump 28 via conduit 26. Pump 28 can be controlled by control system 22 to move the contents from the fluid channels of sensor 21 to waste container 35 after use of the contents.

[0033] Control system 22 can include one or more processing devices 39, examples of which are described herein. Control system 22 also includes a memory 40 for storing executable instructions 41 to control various operations of clinical analyzer 20, such as opening and / or closing dispensing valve 34 to move a composition or test sample to sensor 21, and performing the various operations described herein. In this example, control system 22 is shown as a component that communicates locally with analyzer 20. In some examples, control system 22 or portions thereof can be located external to clinical analyzer 20. In some examples, control system 22 can be distributed across multiple hardware platforms. In some examples, control system 22 can be partially embedded in the clinical analyzer and partially distributed across one or more external hardware platforms.

[0034] In some embodiments, control system 22 includes a voltage measurer 44. For example, voltage measurer 44 can be a hardware device, such as a potentiometer. The hardware device can be electrically connected to a conductor of sensor 21 to measure the voltage on the conductor. The hardware device can be configured to obtain a signal output readable by one or more processing devices 39 to obtain a voltage measurement, which can in turn be used to identify an analyte. The voltage measurement can be made for a reference electrode 50 connected to a portion of the flow path (e.g., a portion of sensor flow path 27 or sample input port 33a). While Figure 1An example shows the voltage measurer 44 as part of the control system 22, but in some embodiments, the voltage measurer 44 can be located outside the control system 22. In some embodiments, the voltage measurer can be disposed within the clinical analyzer 20. In some embodiments, the clinical analyzer includes a display device. The control system 22 can be configured to output test results to a user interface (UI) on the display device, such as a graphical UI.

[0035] A solid-state reference electrode according to the techniques described in this document can be used as the reference electrode 50. In some embodiments, the reference electrode 50 can be a solid-state reference electrode that includes a conductor element made of a metal and a coating including a solid salt of the metal. For example, the conductor element can be silver, and the metal solid salt can be silver chloride. The conductor element can be disposed in contact with a solid-state polymer composition that includes a cured mixture of: (i) a polymer that can be thermally polymerized or exhibits a change in structural properties when exposed to at least a portion of the electromagnetic spectrum, and (ii) a first salt powder that produces substantially equitransporting ions (e.g., potassium chloride (KCl)). In some embodiments, the polymer can be an acrylate that changes from a fluid state to a solid state when exposed to the ultraviolet (UV) portion of the spectrum. Other examples of polymers can include epoxy resins, polyurethanes, polyesters, polyimides, amino resins, silicone resins, or other polymers that do not release ions. The conductivity of the polymer composition is supported by the mobility of ions, cations and anions, which flow in opposite directions and together support the flow of current. The movement of ions represents ionic conductivity and together sustains the flow of current. Ions are said to be equitransporting if the portion of the current carried by cations is substantially equal to the portion of the current carried by anions. An equitransporting salt is necessary for the reference electrode because it helps to minimize the diffusion potential at the junction of the reference electrode and the test solution, thereby enabling a stable and reproducible reference potential. Although KCl is used as an example, other equitransporting salts can also be used, such as rubidium chloride (RbCl) or cesium chloride (CsCl).

[0036] In some embodiments, one or more polyols can be mixed with the polymer composition to enhance ionic conductivity, resulting in rapid startup of the electrode 50. In some embodiments, the polyol is a small molecule (e.g., having a molecular weight less than about 1000 g / mol, less than about 500 g / mol). In some embodiments, the polyol has a molecular weight greater than about 70 g / mol. In some embodiments, the polyol has a boiling point greater than 200°C at STP. For example, in some embodiments, a triol compound (e.g., glycerol) can be added—e.g., in a weight ratio of 1% - 4% to the salt mixture under the solid polymer composition—to facilitate rapid startup and stable equitransfer ionic conductivity throughout the lifespan of the electrode. In some embodiments, other wetting polyols (e.g., ethylene glycol, propylene glycol, or sorbitol) can be added to the polymer composition to support ionic conductivity in the electrode 50. The choice of polyol is based in part on the observation that volatile alcohols (e.g., methanol and ethanol) do not persist in the polymer composition over an extended shelf life, resulting in changes in ionic conductivity throughout the polymer composition—particularly around the junction area where the sample contacts the reference. Polyols with high boiling points (e.g., glycerol with a boiling point exceeding 500°F) provide stable performance over the entire shelf life.

[0037] In some embodiments, the polymer composition can further include a second salt powder, e.g., an equitransfer salt of sodium such as sodium acetate, sodium bicarbonate, or sodium formate. In some embodiments, the second salt is added to reduce the effect of red blood cells on the junction potential of the solid reference electrode 50. In some embodiments, the polymer composition can include 50 - 60% polymer, 35 - 45% first salt, and less than 5% second salt.

[0038] In some embodiments, the polymer composition can include a nonionic surfactant (e.g., lauroyl / myristoyl methyl glucamide) to maintain the homogeneity of the mixture and make the polymer composition reusable for large - scale production. The nonionic surfactant can enhance wettability, ensuring better contact between the solid electrode and the sample solution. Improved wettability can result in a more reliable and stable electrode potential.

[0039] Incorporating a nonionic surfactant into the composition of a solid-state reference electrode offers multiple benefits. Notably, it has anti-biofouling properties, which make it particularly advantageous in applications involving biological samples such as whole blood. Additionally, the surfactant can act as an effective bubble inhibitor, preventing bubbles from adhering to the junction surface and ensuring smoother ion transport, thereby enabling more reliable measurements. Moreover, the nonionic surfactant facilitates a reproducible flux of ions through the electrode junction, thus enhancing the accuracy of potential measurements. In summary, the nonionic surfactant enhances the stability, reliability, and performance of various aspects of the solid-state reference electrode. For example, it has been found that adding a nonionic surfactant in a proportion of 0.2% to 2% of the polymer composition can effectively maintain the uniformity of the polymer and first salt mixture, resulting in good reproducibility of the junction potential of the solid-state reference electrode 50.

[0040] In some embodiments, the reference electrode, together with at least a portion of the sensor flow path 27, may be disposed in a separate module or housing that is removably attached to the electrochemical measurement device 23. In some embodiments, one or more sensors 21 may also be disposed within a portion of the sensor flow path such that the reference electrode 50, the sensor flow path 27, and one or more sensors together form a separate module (e.g., a sensor card). Figure 2 An example of such a module 200 is shown. The module 200 includes at least a portion of the sensor flow path 27 and a reservoir 208 for accommodating the polymer composition of the solid-state reference electrode 50. In some embodiments, the reservoir 208 has an oval shape, as Figure 2 shown. In some embodiments, the reservoir 208 can be oval, or have a circular or other shape, to facilitate a substantially constant ion flux between the polymer composition contained in the reservoir and the portion of the sensor flow path 27 to which the reservoir 208 is connected. In Figure 2 a specific example, the reservoir 208 is oval with a minor axis of 9 millimeters, a major axis of 12 millimeters, and a substantially constant depth of 0.6 millimeters. In a particular embodiment, it has been found that an oval junction with a volume of 43 cubic millimeters can extend the stability of the service life by more than 40 days.

[0041] The reservoir is connected to a portion of the sensor flow path 27 via the bonding structure 210 shown in the enlarged view of portion 215. In this example, the bonding structure 210 is a funnel-shaped structure that connects the reservoir 208 to a portion of the sensor flow path 27. The cross-section of the opening at the interface 216 between the reservoir 208 and the bonding structure 210 is generally larger than the cross-section of the opening at the interface 217 between the bonding structure 208 and the sensor flow path 27. For example, the width of the opening at interface 217 can be 0.3 - 0.4 millimeters. In some embodiments, a circular, semi-circular, or semi-elliptical configuration with a diameter of approximately 12 millimeters and a depth of approximately 0.6 millimeters can be used for the reservoir 208 and used with the funnel-shaped bonding structure 210 to make the ion flux through the bonding structure 210 substantially constant and allow for a stable bonding potential during the extended lifespan phase of the solid-state reference electrode 50. Module 200 is covered with a transparent tape to seal and form the flow path 27 and the solid-state reference reservoir 208. After the polymer composition in the reservoir 208 has cured, module 200 can be covered with an additional metal backing with an adhesive to facilitate thermostatic heating of module 200 during sample measurements.

[0042] In some cases, this configuration can provide a lifespan of at least one month for the reference electrode.

[0043] Module 200 also includes a hole or other opening 202 that allows a fluid polymer composition to be injected into the reservoir 208 during manufacture. In some embodiments, the polymer composition of the solid-state reference electrode 50 is injected in fluid form through the hole 202 until the fluid composition fills the reservoir 208 and the bonding structure 210 up to the narrow opening 217 of the junction. A curing process (e.g., by exposure to ultraviolet light) can then be carried out to complete the curing of the polymer composition. Figure 3FIG. 300 is an exemplary flow chart showing a process of depositing a fluid composition into reservoir 208. Specifically, in step 310, an equitransfer salt 302 (e.g., KCl), a polymer 304 (e.g., UV curable acetate), a triol compound 306 (e.g., glycerol), and a nonionic surfactant 308 (e.g., lauroyl / myristoyl methyl glucamide) are mixed without introducing air bubbles to form a homogeneous mixture paste 312. In some embodiments, the weight ratio of the composition of the mixture paste 312 may include 45% to 65% of the polymer 304, 30% to 55% of the salt 302, 1% to 4% of the triol compound 306, and 0.2% to 2% of the nonionic surfactant 308. The fluid composition is for forming a polymer composition of a solid reference electrode in reservoir 208. In step 314, the mixture paste 312 is transferred into a syringe barrel, and in step 316, the mixture paste 312 in the syringe barrel is injected into reservoir 208 through hole 202. The filling process continues until reservoir 208 and engagement structure 210 are filled up to the narrow opening 217 of the joint. Then, the fluid composition in reservoir 208 is cured, for example, using a UV curing process to form a polymer composition of a solid reference electrode.

[0044] The polymer composition is disposed within reservoir 208 such that the polymer composition contacts the metal electrode. In Figure 2 exemplary module 200, reservoir 208 includes an island 204 that supports an Ag / AgCl electrode. These electrodes can be formed, for example, by dripping a chloride solution (e.g., 0.2 molar FeCl3 solution) onto two silver needles (e.g., metal electrodes) disposed on island 204 for a period of time (e.g., ten minutes) and then washing the two needles with deionized water and air drying to obtain chlorinated needles. Although Figure 2 the exemplary description is of an Ag / AgCl electrode, other metal electrodes coated with a corresponding solid salt can also be used, as described in reference Figure 1 stated.

[0045] The solid reference electrode implemented using the techniques described herein has a significantly long service life. For example, although some solid reference electrodes available in the industry have long hydration times (in hours) and / or short service lives (disposable in some cases), the solid reference electrodes described herein can exhibit a service life of more than one month while also having a low hydration time (in minutes). Figure 4A And 4B show the significantly long service life exhibited by the solid reference electrode described herein. Specifically, Figure 4AShows reservoir 208 of the polymer composition before being filled as part of a solid-state reference electrode. The dark gray region 405 indicates that the polymer composition has an ionic potential and can be used to generate an ion flux sufficient to provide a stable junction potential at the junction structure 210. Thus, Figure 4A Indicates that the entire polymer composition within reservoir 208 can be used as part of a solid-state reference electrode. On the other hand, Figure 4B Shows reservoir 208 of the polymer composition one month after being filled as part of a solid-state reference electrode. In this figure, the light gray region 415 represents the portions of the polymer composition where the equitransfer salt has been washed out, such that these portions are unable to provide sufficient ions to maintain a stable junction potential at the junction structure 210. Thus, portion 415 is substantially depleted and cannot be used to support the reference electrode. However, the dark gray region 410 represents the portions of the polymer composition that continue to have sufficient equitransfer salt and are thus able to generate an ion flux sufficient to provide a stable junction potential at the junction structure 210. Thus, Figure 4B Shows that approximately half of the polymer composition in reservoir 208 can continue to be used to support the reference electrode even after one month of use. In a particular experiment, different solid-state reference electrodes were evaluated after a one-month service life, and each electrode showed that half to one-third of the equitransfer salt remained in the reservoir, indicating that its capacity was sufficient to support an even longer service life. The solid-state reference electrodes implemented using the techniques described herein have such a high service life, combined with the low implementation cost and reproducibility of the electrodes, making these reference electrodes attractive for various clinical and industrial applications.

[0046] Figure 5 Shows a flowchart 500 of an example set of operations for measuring one or more analytes using an electrochemical measurement device that includes a solid-state reference electrode implemented using the techniques described herein. At least a portion of process 500 can be performed by a control system 22 described in Figure 1 The following description refers to Figure 5 and Figure 1。At 502, the control system 22 detects and identifies the cartridge 23 inserted into the cell 24 of the analyzer or electrochemical measurement device 20 for analyzing a fluid sample. At 504, the control system 22 receives an input to initiate operation, e.g., via a user interface associated with the analyzer 20. In some embodiments, the control system 22 may be configured to control (at 506) the movement of a composition containing a reagent from one or more containers 30a - 30d to the dispensing valve 34. The control system 22 may also be configured to receive (at 508) signals from one or more sensors 21 and the reference electrode 50. Based on the signals received from the sensors and the reference potential signal received from the solid-state reference electrode 50, the control system 22 determines (at 510) a measurement value indicative of the amount of one or more analytes in the fluid sample being tested. At 512, the control system 22 uses the measurement result determined at 510 to calibrate the readings from one or more sensors 21 or to verify the results from one or more sensors 21.

[0047] Figure 6 is a flowchart showing an exemplary process 600 for manufacturing the solid-state reference electrode described herein. In some embodiments, portions of process 600 may be performed / controlled by one or more processing devices implementing a computer-aided manufacturing (CAM) process. Process 600 includes forming (at 602) a fluid composition that includes (i) a curable resin, such as a polymer that can be thermally polymerized or exhibits a change in structural properties upon exposure to at least a portion of the electromagnetic spectrum, (ii) a salt that produces substantially equivalent transport ions, and (iii) a polyol, such as a triol. Each of these components can be of various types, as described above with reference to Figure 1 those described. In some embodiments, the ratios at which these components are mixed together are controlled using a CAM process of an automated dispensing instrument that dispenses one or more of the components. In some embodiments, a CAM process can be used to control a mixer that mixes the above components together to form the fluid composition.

[0048] At 604, the fluid composition is deposited into a reservoir configured to receive the solid-state reference electrode and covered with a transparent adhesive film. In some embodiments, step 604 may include portions of process 300 described above with reference to Figure 3 those described. In some embodiments, a CAM process can be used to control a syringe and / or dispenser that injects the fluid composition into the reservoir. At 606, the fluid composition in the reservoir is cured using energy within at least one subset of the electromagnetic spectrum to produce the solid-state reference electrode. In some embodiments, this includes controlling a UV source to expose the fluid composition in the reservoir for a period of time.

[0049] Figure 7Illustrates an example process 700 for measuring one or more analytes in a fluid sample using a solid-state reference electrode. Process 700 may include, for example, receiving a fluid sample (702) within an electrochemical measurement device (e.g., analyzer 20 described above with reference to Figure 1 ). The fluid sample may include, for example, blood, plasma, or another aqueous solution that contains one or more analytes to be detected / quantified by the electrochemical measurement device.

[0050] Process 700 also includes contacting the fluid sample with a solid-state reference electrode that includes a solid-state polymer composition that provides a substantially constant isopotential ion flux (704). The solid-state reference electrode can be of various types, as described above with reference to Figure 1 . The fluid sample contacts the solid-state reference electrode at a junction structure that is located between (i) the flow path of the fluid sample and (ii) a reservoir that houses the solid-state polymer composition configured to support the solid-state reference electrode. The solid-state polymer composition can include a cured resin, a salt that produces substantially isopotential ions, and a cured mixture of polyols that facilitate ion movement within the solid-state polymer composition. The curable resin, salt, and polyol compounds (and generally the solid-state polymer composition) can be substantially similar to those described above with reference to Figure 1 .

[0051] Process 700 also includes measuring one or more analytes in the fluid sample (706) using one or more sensors and based on the reference potential provided by the solid-state reference electrode at the junction structure. The one or more sensors can be substantially similar to sensor 21 described above with reference to Figure 1 . Accordingly, the measurement can be performed substantially in the manner described above with reference to Figure 1 .

[0052] Various implementations of the systems and techniques described herein can be implemented in digital electronic circuitry, integrated circuitry, specially designed application specific integrated circuits (ASICs), computer hardware, firmware, software, and / or combinations thereof. These various implementations can include being implemented in one or more computer programs that can be executed and / or interpreted on a programmable system including at least one programmable processor that can be used for special or general purposes, coupled to receive data and instructions from, and to transmit data and instructions to, a storage system, at least one input device, and at least one output device.

[0053] These computer programs (also referred to as programs, software, software applications, or code) include machine instructions for a programmable processor and can be implemented in high-level programming languages, object-oriented languages, assembly languages, and / or machine languages. As used herein, the terms "machine-readable medium" and "computer-readable medium" refer to any computer program product, apparatus, and / or device (e.g., a disk, optical disk, memory, programmable logic device (PLD)) for providing machine instructions and / or data to a programmable processor, including a machine-readable medium that receives the machine instructions as a machine-readable signal. The term "machine-readable signal" refers to any signal for providing machine instructions and / or data to a programmable processor.

[0054] For interaction with a user, the systems and techniques described herein can be implemented on a computer having a display device (for displaying information to the user) and a keyboard and a pointing device (e.g., a mouse or a trackball), by which the user can provide input to the computer. Other types of devices can also be used for interacting with the user; for example, the feedback provided to the user can be any form of sensory feedback (e.g., visual feedback, auditory feedback, or tactile feedback); and the input from the user can be received in any form, including acoustic, speech, or tactile input.

[0055] The systems and techniques described herein can be implemented in a computing system that includes backend components (e.g., as a data server), or includes middleware components (e.g., an application server), or includes frontend components (e.g., a client computer having a GUI or a web browser through which a user can interact with an implementation of the systems and techniques described herein), or any combination of such backend, middleware, or frontend components. The components of the system can be interconnected by any form or medium of digital data communication (e.g., Figure 1 the network 22 in ). Examples of communication networks include LAN, WAN, and the Internet.

[0056] Although this specification contains many specific implementation details, these details should not be construed as limiting the scope of the claims, but rather as descriptions of features of particular implementations. Certain features described herein in the context of separate implementations can also be implemented in combination in a single implementation. Conversely, various features described in the context of a single implementation can also be implemented separately or in any sub-combination in multiple implementations. In addition, although the previously described features may be described as acting in certain combinations and even initially claimed as such, in some cases, one or more features can be removed from the claimed combination, and the claimed combination may be directed to a sub-combination or a variant of a sub-combination.

[0057] As used in this disclosure, the term "substantially" is intended to permit a degree of variation in a value or range, e.g., within 10%, within 5%, or within 1% of a stated value or of a stated limit of a range.

[0058] Specific implementations of the subject matter have been described. It will be apparent to those skilled in the art that other implementations, variations, and permutations of the described implementations are within the scope of the following claims. Although operations are described in a particular order in the figures or claims, it should not be understood that the operations are required to be performed in the particular order shown or in a sequential order, or that all of the operations shown are required to be performed (some operations may be considered optional) to achieve the desired result. In some cases, multitasking or parallel processing (or a combination of multitasking and parallel processing) may be advantageous and may be performed as needed.

[0059] Furthermore, the separation or integration of the various system modules and components in the foregoing implementations should not be construed as required in all implementations, and it should be understood that the described components and systems can generally be integrated together or packaged into multiple products.

[0060] Accordingly, the foregoing example implementations do not define or limit this disclosure. Other changes, substitutions, and variations are possible without departing from the spirit and scope of this disclosure.

Claims

1. A solid reference electrode configured to provide a reference potential in an electrochemical analyzer, the solid reference electrode comprising: A conductive element comprising a metal and a coating comprising a solid salt of the metal; as well as a solid polymer composition disposed in contact with the conductive element, the solid polymer composition comprising a cured mixture of: Curing resin, Salts that produce substantially isotropic ions, and Polyols which promote ionic conductivity in solid polymer compositions.

2. The solid-state reference electrode according to claim 1, wherein the solidified mixture further comprises a non-ionic surfactant material.

3. The solid-state reference electrode according to claim 1, wherein the curing resin comprises polyacrylate.

4. The solid-state reference electrode of claim 1, wherein the salt comprises potassium chloride (KCl).

5. The solid state reference electrode of claim 1, wherein the solidified mixture further comprises a second salt that reduces the effect of red blood cells on the junction potential between the solid state reference electrode and the sample in the electrochemical analyzer.

6. The solid-state reference electrode of claim 5, wherein the second salt is an isotropic salt of sodium, comprising at least one of the following: sodium acetate, sodium bicarbonate, or sodium formate.

7. The solid-state reference electrode according to claim 1, wherein the polyol is a triol compound.

8. The solid-state reference electrode of claim 7, wherein the triol compound comprises glycerol.

9. The solid state reference electrode of claim 2, wherein the nonionic surfactant material comprises lauroyl / myristoyl methyl glucamide.

10. The solid reference electrode of claim 2, wherein the solid polymer composition comprises 45-65% of a curing resin, 30-55% of a salt, 1-4% of a polyol, and 0.2-2% of a nonionic surfactant material.

11. The solid-state reference electrode of claim 1, wherein the metal is silver (Ag).

12. The solid-state reference electrode according to claim 11, wherein the solid salt of the metal is silver chloride (AgCl).

13. A module for an electrochemical analyzer, the module comprising: a flow path configured to receive a fluid sample; A solid-state reference electrode comprising a reservoir having disposed therein a solid polymer composition comprising: Curing resin, Salts that produce substantially isotropic ions, and A polyol compound that promotes ionic conductivity within a solid polymer composition; and A junction structure is disposed between the reservoir and the flow path, the junction structure being shaped and configured to (i) allow a fluid sample in the sample input port to contact the solid polymer composition, and (ii) promote a substantially constant ion flux between the fluid sample and the solid polymer composition.

14. The module of claim 13, wherein the solid polymer composition further comprises a nonionic surfactant.

15. The module of claim 13, wherein the reservoir has an elliptical shape to promote a substantially constant ion flux between the fluid sample and the solid polymer composition.

16. The module of claim 13, wherein the engagement structure comprises: a first opening at an interface of the reservoir and the engagement structure; as well as a second opening at the interface of the flow path and the engagement structure; wherein: The size of the first opening is larger than the size of the second opening; and The engagement structure has a funnel shape.

17. The module of claim 13, wherein the module further comprises one or more sensors disposed in the flow path to measure one or more analytes in the fluid sample.

18. A method for manufacturing a solid reference electrode for an electrochemical analyzer, the method comprising: forming a fluid composition of: (i) a curing resin precursor, (ii) a substantially isotropic ion-generating salt, and (iii) a polyol; depositing the fluid composition into a reservoir configured to receive a solid reference electrode; as well as The fluid composition is cured.

19. The method of claim 18, wherein the fluid composition further comprises a nonionic surfactant material.

20. A method for analyzing a fluid sample, comprising: receiving a fluid sample within an electrochemical measurement device; contacting a solid-state reference electrode for an electrochemical measurement device with a fluid sample at a junction structure disposed between (i) a flow path of the fluid sample and (ii) a reservoir containing a solid polymer composition configured to support the solid-state reference electrode, wherein the solid polymer composition is configured to provide a substantially constant ion flux of substantially isotropic ions through the junction structure; and measuring one or more analytes in the fluid sample using one or more sensors of the electrochemical measuring device, wherein the measurement is based on a reference potential provided by a solid-state reference electrode at the junction structure, wherein the solid polymer composition comprises a cured mixture of: Curing resin, Salts that produce substantially isotropic ions, and A polyol which promotes substantially constant ion mobility within a solid polymer composition.

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