Photocurable compositions for forming chloride ion-selective sensors and methods of production and use thereof

Abstract

Improved formulation(s), device(s), and method(s) for producing ion-selective electrodes (ISEs) that comprise at least one photo-curable, epoxy-based, ion-selective chloride membrane(s) compounds that can be pre-mixed together to form a singularly-dispensed mixture for the formation of an ion-exchange resin membrane(s) for incorporation and use in a chloride ISE. The formulations include one or more ingredients selected from at least one liquid epoxy resin, at least two curing agents, at least two photocurable compounds, at least one rheology modifier, at least one dye, and any combinations thereof. Also disclosed are methods of producing and using the chloride ISEs. In addition, multi-sensor cartridges containing the chloride ISEs are disclosed, along with methods of producing and using same.

Description

PHOTOCURABLE COMPOSITIONS FOR FORMING CHLORIDE ION-SELECTIVE SENSORS AND METHODS OF PRODUCTION AND USE THEREOFCROSS REFERENCE TO RELATED APPLICATIONS

[0001] The subject application claims benefit of US Provisional Patent Application No. 63 / 669,769, filed July 11, 2024. The entire contents of the above-referenced patent application(s) are hereby expressly incorporated herein by reference.STATEMENT REGARDING FEDERALLY FUNDED RESEARCH OR DEVELOPMENT

[0002] Not Applicable.BACKGROUND

[0003] The use of ion selective electrodes (ISEs) to determine the presence and quantity of various analytes in biological samples has become a useful diagnostic technique. For instance, ISEs have been used to detect, by way of example only, analytes such as magnesium, fluoride, sodium, potassium, calcium, and chloride ions. Some of these ISEs are often housed within clinical diagnostic instruments for simultaneous analysis of a large number of analytes.

[0004] ISEs typically comprise at least one ion-selective membrane being constructed of: (1) glass membrane(s) (such as, by way of example, membrane(s) comprising silicate or chalcogenide); (2) crystalline membrane(s) (such as, by way of example, membrane(s) comprising mono- or poly-crystallites of a single substance, such as the use of lanthanum fluoride (La F3) crystals for the detection of fluoride ions); and / or (3) resin-based polymeric membrane(s) with ion-exchange properties.

[0005] Ion-exchange resin membranes are based on special organic polymer membranes made of epoxy resins which contain binding sites to primary ions as well as at least one ionexchange property. The utilization of specific resins allows for the preparation of selective electrodes that detect a wide array of both single-atom and multi-atom ions.

[0006] One such use of the ISEs is for the determination of the amount of chloride ions in a biological sample, specifically blood. The fabrication of ion-exchange resin membranes commonly known in the art involve the mixing of at least two components to form the resin membrane. In one non-limiting embodiment, the at least two components forming the ionexchange resin membrane may comprise at least one resin material, such as resin paste, andat least one hardener material, such as a hardener paste. Because the mixing of the at least one resin material and the at least one hardener may yield a short curing time (i.e., less than about five (5) minutes), it may not be ideal to use the separate materials that cannot be premixed and that require at least two separate dispensers to dispense and mix the materials on a substrate, which may increase the production costs of the resin membrane(s) and ISEs.

[0007] Chloride sensors have previously been fabricated with traditional plasticized PVC based membranes with TDMAC as the binding sites, and an additional top layer of membrane is added for better selectivity. However, this type of design doesn't provide a desired use-life due to leaching of the active ingredients, and the design also increases manufacturing complexity. Epoxy based chloride sensors have been described, for example, in the following publications / patents: Shin et al (Anal. Chem., Vol.76, page 4217-4222); Korean Patent Application No. KR-2004 0032429 A (l-SENS INC); Japanese Patent Application No. JP 2003 215087 A (JOKOH CO LTD); US Patent Application No. 2012 / 077903 Al (SHOWA DENKO KK); US Patent No. 7,384,523 B2 (RADIOMETER MEDICAL APS); and International Patent Application Publication No. WO 2021 / 058206. These epoxy-based chloride sensors are based on reactions between epoxy, an amine compound, and / or a thiol compound, and cured with increased temperatures. However, there is still a need for new designs that exhibit improved manufacturability and sensor performance.BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

[0008] FIG. 1 illustrates one non-limiting embodiment of a formulation of reagents utilized for the creation of a photo-curable, epoxy-based, ion selective chloride membrane for use in a chloride ion-selective sensor in accordance with the present disclosure, as compared to a prior art two-part A-LYTE CL and the prior art formulation disclosed in W02021 / 058206.

[0009] FIG. 2 is a cross-sectional view of one non-limiting embodiment of a sensor constructed in accordance with the present disclosure.

[0010] FIG. 3 is a top plan view of one non-limiting embodiment of a multi-sensor cartridge constructed in accordance with the present disclosure. The cartridge includes a first channel containing functional Na, K, and Cl sensors. The cartridge further includes a second channel containing a reference electrode that has a stable potential.

[0011] FIG. 4. Calibration slopes of Pilot 3 (Lot 211119) single pot chloride sensors made with pastes containing different ratios of BF1. Sensors 1, 3, 4, and 5 are at a stoichiometric ratio of 1:0.3:0.4. Sensors 2 and 6 are at a stoichiometric ratio of 1:0.3:0.4.

[0012] FIG. 5. Precisions of 5 Day ANOVA normalized to design goals of the present disclosure. Sensors 1, 3, 4, and 5 are at a stoichiometric ratio of 1:0.3:0.4. Sensors 2 and 6 are at a stoichiometric ratio of 1:0.3:0.4.

[0013] FIG. 6. Precisions of 5 Day ANOVA normalized to verification limits of the present disclosure. Sensors 1, 3, and 5 are at a stoichiometric ratio of 1:0.3:0.4. Sensors 2 and 6 are at a stoichiometric ratio of 1:0.3:0.4.

[0014] FIG. 7. Sensor sizes measured at a Paste Station after dispensing. Dispensing conditions (gauge and volume in nL) are labeled.

[0015] FIGS. 8A, 8B, and 8C. Distributions of electric signals of mV reads from A-LTYE Standard A and Standard B for sensors made with 50% diameters of the electrodes (FIG. 8A); 75% diameters of the electrodes (FIG. 8B); and regular sized electrodes (FIG. 8C).

[0016] FIG. 9. Fluoresce intensity distribution by sensor conditions summarized in Table 9. The fluorescence intensities were evaluated with MatLab by using sensor images collected at a Paste Station.

[0017] FIG. 10. Change of recovery bias over time from salicylate interference with 50 mg / dL salicylate spiked into normal human serum.

[0018] FIGS. 11A, 11B, and 11C. Calibration slopes of single pot chloride sensors (FIG. 11A), sodium sensors (FIG. 11B), and potassium sensors (FIG. 11C) of pilot lots 221115, 221116, 221117, 221118, and 221120.DETAILED DESCRIPTION

[0019] Before explaining at least one embodiment of the inventive concept(s) in detail by way of exemplary drawings, experimentation, results, and laboratory procedures, it is to be understood that the inventive concept(s) is not limited in its application to the details of construction and the arrangement of the components set forth in the following description or illustrated in the drawings, experimentation and / or results. The inventive concept(s) is capable of other embodiments or of being practiced or carried out in various ways. As such, the language used herein is intended to be given the broadest possible scope and meaning; and the embodiments are meant to be exemplary - not exhaustive. Also, it is to be understoodthat the phraseology and terminology employed herein is for the purpose of description and should not be regarded as limiting.

[0020] Independent of the grammatical term usage, individuals with male, female, or other gender identities are included within the term.

[0021] Unless otherwise defined herein, scientific and technical terms used in connection with the present disclosure shall have the meanings that are commonly understood by those of ordinary skill in the art. Further, unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular. Enzymatic reactions and purification techniques are performed according to manufacturer's specifications or as commonly accomplished in the art or as described herein. The foregoing techniques and procedures are generally performed according to conventional methods well known in the art and as described in various general and more specific references that are cited and discussed throughout the present specification. The nomenclatures utilized in connection with, and the laboratory procedures and techniques of, analytical chemistry, synthetic organic chemistry, and medicinal and pharmaceutical chemistry described herein are those well- known and commonly used in the art. Standard techniques are used for chemical syntheses and chemical analyses.

[0022] All patents, published patent applications, and non-patent publications mentioned in the specification are indicative of the level of skill of those skilled in the art to which the present disclosure pertains. All patents, published patent applications, and non-patent publications referenced in any portion of this application are herein expressly incorporated by reference in their entirety to the same extent as if each individual patent or publication was specifically and individually indicated to be incorporated by reference.

[0023] All of the compositions and / or methods disclosed and / or claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the compositions and methods of the present disclosure have been described in terms of particular embodiments, it will be apparent to those of skill in the art that variations may be applied to the compositions and / or methods and in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit and scope of the present disclosure. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the present disclosure as defined by the appended claims.

[0024] As utilized in accordance with the present disclosure, the following terms, unless otherwise indicated, shall be understood to have the following meanings:

[0025] The use of the word "a" or "an" when used in conjunction with the term "comprising" in the claims and / or the specification may mean "one," but it is also consistent with the meaning of "one or more," "at least one," and "one or more than one." The singular forms "a," "an," and "the" include plural referents unless the context clearly indicates otherwise. Thus, for example, reference to "a compound" may refer to 1 or more, 2 or more, 3 or more, 4 or more, or greater numbers of compounds. The term "plurality" refers to "two or more."

[0026] The use of the term "or" in the claims is used to mean an inclusive "and / or" unless explicitly indicated to refer to alternatives only or unless the alternatives are mutually exclusive. For example, a condition "A or B" is satisfied by any of the following: A is true (or present) and B is false (or not present), A is false (or not present) and B is true (or present), and both A and B are true (or present).

[0027] The use of the term "at least one" will be understood to include one as well as any quantity more than one, including but not limited to, 2, 3, 4, 5, 10, 15, 20, 30, 40, 50, 100, etc. The term "at least one" may extend up to 100 or 1000 or more, depending on the term to which it is attached; in addition, the quantities of 100 / 1000 are not to be considered limiting, as higher limits may also produce satisfactory results. In addition, the use of the term "at least one of X, Y, and Z" will be understood to include X alone, Y alone, and Z alone, as well as any combination of X, Y, and Z. The use of ordinal number terminology (i.e., "first," "second," "third," "fourth," etc.) is solely for the purpose of differentiating between two or more items and is not meant to imply any sequence or order or importance to one item over another or any order of addition, for example.

[0028] As used in this specification and claim(s), the terms "comprising" (and any form of comprising, such as "comprise" and "comprises"), "having" (and any form of having, such as "have" and "has"), "including" (and any form of including, such as "includes" and "include"), or "containing" (and any form of containing, such as "contains" and "contain") are inclusive or open-ended and do not exclude additional, unrecited elements or method steps. For example, unless otherwise noted, a composition, process, method, article, or apparatus that comprises a list of elements is not necessarily limited to only those elements, but may also include other elements not expressly listed or inherently present therein.

[0029] The term "or combinations thereof" as used herein refers to all permutations and combinations of the listed items preceding the term. For example, "A, B, C, or combinations thereof" is intended to include at least one of: A, B, C, AB, AC, BC, or ABC, and if order is important in a particular context, also BA, CA, CB, CBA, BCA, ACB, BAC, or CAB. Continuing with this example, expressly included are combinations that contain repeats of one or more item or term, such as BB, AAA, AAB, BBC, AAABCCCC, CBBAAA, CABABB, and so forth. The skilled artisan will understand that typically there is no limit on the number of items or terms in any combination, unless otherwise apparent from the context.

[0030] As used herein, any reference to "one embodiment," "an embodiment," "some embodiments," "one example," "for example," or "an example" means that a particular element, feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment. The appearance of the phrase "in some embodiments" or "one example" in various places in the specification is not necessarily all referring to the same embodiment, for example. Further, all references to one or more embodiments or examples are to be construed as non-limiting to the claims.

[0031] Throughout this application, the terms "about" and "approximately" are used to indicate that a value includes the inherent variation of error for the composition / apparatus / device, the method being employed to determine the value, or the variation that exists among the study subjects. That is, the terms "about" and "approximately" and variations thereof are intended to include not only the exact value qualified by the term, but to also include some slight deviations therefrom, such as deviations caused by measuring error, manufacturing tolerances, wear and tear on components or structures, and combinations thereof, for example. In particular, for example, but not by way of limitation, when the term "about" is utilized, the designated value may vary by ± 20%, or ± 15%, or ± 12%, or ± 11%, or ± 10%, or ± 9%, or ± 8%, or ± 7%, or ± 6%, or ± 5%, or ± 4%, or ± 3%, or ± 2%, or ±1%, or ± 0.5%, or ±0.1% from the specified value, as such variations are appropriate to perform the disclosed methods and as understood by persons having ordinary skill in the art.

[0032] As used herein, the term "substantially" means that the subsequently described event or circumstance completely occurs or that the subsequently described event or circumstance occurs to a great extent or degree. For example, when associated with a particular event or circumstance, the term "substantially" means that the subsequentlydescribed event or circumstance occurs at least 80% of the time, or at least 85% of the time, or at least 90% of the time, or at least 95% of the time, or at least 98% of the time. The term "substantially adjacent" may mean that two items are 100% adjacent to one another, or that the two items are within close proximity to one another but not 100% adjacent to one another, or that a portion of one of the two items is not 100% adjacent to the other item but is within close proximity to the other item.

[0033] Where a range of numerical values is recited or established herein, the range includes the endpoints thereof and all the individual integers and fractions within the range, and also includes each of the narrower ranges therein formed by all the various possible combinations of those endpoints and internal integers and fractions to form subgroups of the larger group of values within the stated range to the same extent as if each of those narrower ranges was explicitly recited. Where a range of numerical values is stated herein as being greater than a stated value, the range is nevertheless finite and is bounded on its upper end by a value that is operable within the context of the present disclosure. Where a range of numerical values is stated herein as being less than a stated value, the range is nevertheless bounded on its lower end by a non-zero value.

[0034] As used herein, the phrase "associated with" includes both direct association of two moieties to one another as well as indirect association of two moieties to one another. Non-limiting examples of associations include covalent binding of one moiety to another moiety either by a direct bond or through a spacer group, non-covalent binding of one moiety to another moiety either directly or by means of specific binding pair members bound to the moieties, incorporation of one moiety into another moiety such as by dissolving one moiety in another moiety or by synthesis, and coating one moiety on another moiety.

[0035] The term "purified" as used herein means at least one order of magnitude of purification is achieved compared to the starting material or of the natural material, for example but not by way of limitation, two, three, four, or five orders of magnitude of purification of the starting material or of the natural material. Thus, the term "purified" as utilized herein does not necessarily mean that the material is 100% purified, and therefore such term does not exclude the presence of other material(s) present in the purified composition.

[0036] The term "sample" as used herein will be understood to include any type of biological sample that may be utilized in accordance with the present disclosure. Examples ofbiological samples that may be utilized include, but are not limited to, whole blood or any portion thereof (i.e., plasma or serum), saliva, sputum, cerebrospinal fluid (CSF), skin, interstitial fluid, tears, mucus, urine, swabs, combinations, and the like. In one non-limiting embodiment, the sample is a volume of whole blood.

[0037] There is a need in the art for improved formulations, compositions, devices, kits, and methods for producing ISEs that comprise at least one photo-curable, epoxy-based, ion- selective chloride membrane reagent mixture that can be pre-mixed together to form a singularly-dispensed mixture for the formation of an ion-exchange resin membrane for incorporation and use in a chloride ISE. It is to such formulations, compositions devices, kits, and methods that the present disclosure directed.

[0038] It is to such reagents, as well as compositions / formulations, kits, and methods related thereto, that the present disclosure is directed.

[0039] As previously mentioned, the current production process for ion-selective resin membrane(s) for use in ISEs (such as, by way of example only, ISEs that detect chloride ions) requires the use of two separate dispensers— one which dispenses a predetermined amount (for instance, about 10 nanoliters) of a resin paste and another that dispenses a predetermined amount (for instance, about 10 nanoliters) of a hardener paste on a sensor substrate. The present manufacturing method suffers in that the two pastes (the resin paste and the hardener paste) cannot be pre-mixed to be used by a single dispenser because of the fast curing time (less than about five (5) minutes).

[0040] Certain non-limiting embodiments of the present disclosure are directed to formulations for the creation of improved photo-curable, epoxy-based, ion-selective chloride sensor membrane(s) that require only one dispenser for the fabrication of such membranes for use in chloride ISEs. Such new formulation(s) utilize at least one photocurable / photo- initiator compound that allows the formulation to be cured by a particular wavelength or spectrum(s) of light, such as, by way of example, UV-light (i.e., wavelengths from about 100 nanometers to about 400 nanometers).

[0041] The compositions, membranes, kits, and methods of the present disclosure replace the current two-part epoxy A-LYTE IMT Chloride sensor paste design with a pre-mixed, single-pot epoxy formulation. The new formulations of the present disclosure result in extended pot life under ambient conditions and can be quickly cured with UV irradiation and heat. Since there is only one paste, the formulations of the present disclosure can bedeposited on to the electrode of a substrate (such as, but not limited to, a ceramic substrate) as a single dispense. This improves the consistency of dispensing to form more homogeneous sensor membranes, compared to the current two separate dispensing steps process of the prior art A-LYTE product. Therefore, the new formulations and methods of the present disclosure improve manufacturability as well as product quality.

[0042] Turning now to particular (but non-limiting) embodiments of the present disclosure, new and improved compositions, reagents, and kits are provided that can be used to produce chloride sensors such that the chloride sensors exhibit increased stability and improved selectivity over prior art sensor / reagent combinations. The compositions, reagents, and kits of the present disclosure can be used to produce membranes for potentiometric ISEs for ionized chloride, wherein the sensor / reagent combination exhibits improved sensor stability and selectivity as well as decreased production costs associated with the fabrication of such ISEs.

[0043] Epoxy resin has been identified as the next generation chloride sensing material(s) with improved selectivity and increased sensor stability and functional life. Generally, epoxide groups crosslink with polyamine and mercaptan to form a tridimensional high-density polymer network with amine and / or ammonium sites embedded in the polymer backbone. In particular, epoxide reacts with tertiary diamine and forms positively charged quaternary ammonium sites that are able to pair with chloride ions.

[0044] This reversible recognition is suitable to measure chloride ions that generate a potentiometric signal in an ISE sensor. In addition, the cross-linked polymer network creates a hinderance effect on the binding sites to the lipophilic species such as, for instance when the sample is whole blood, salicylate, heparin, and / or protein(s). Accordingly, epoxy-based chloride sensors provide improved selectivity in complex real sample detection.

[0045] Certain non-limiting embodiments of the present disclosure are directed to a mixture / paste composition for forming the improved photo-curable, epoxy-based, ion- selective chloride sensor membrane(s) for use in chloride ISEs. The paste compositions include at least one liquid epoxy resin, at least two polymerization / curing agents, at least two photo-curable / photo-initiator compounds, and at least one rheology modifier; the mixture / paste composition may optionally further include at least one dye. These constituents may be pre-mixed and dispensed from the same, single dispenser onto a sensor substrate (such as, but not limited to, an electrode layer on a ceramic substrate) andsubsequently photocured via the use of a particular wavelength and / or wavelengths of light, for instance, by way of example only, wavelength(s) of light within the ultraviolet (UV) spectrum, along with heating at a plurality of temperatures, as described in further detail herein below. In certain particular (but non-limiting) embodiments, the paste composition is capable of being stored at a temperature of about -70°C or less for at least 14 days, at least one month, at least two months, or at least three months without substantially forming crystals and without substantial polymerization.

[0046] The liquid epoxy resin may be, for example but not by way of limitation, an epoxy resin diglicydyl ether of bisphenol A (DGEBA) commercially offered for sale by Dow Chemical Company (Midland, Ml). A particular (but non-limiting example) of a liquid epoxy resins diglicydyl ether of bisphenol A (DGEBA) that may be utilized in accordance with the present disclosure is Dow Epoxy Resin (D.E.R.™) Grade 331 - a liquid reaction product of epichlorohydrin and bisphenol A. The structure of D.E.R.™ 331 is Propane, 2,2-bis[p- (2,3epoxypropoxy)phenyl]-, polymers liquid epoxy resin, CAS No. 25085-99-8, represented by Formula I below:Formula (I).

[0047] In contrast, prior art compositions have utilized another liquid reaction product of epichlorohydrin and bisphenol A, Dow Epoxy Resin Grade 332, Bisphenol A diglycidyl ether, Epoxy-Resin, 2,2-Bis[4-(glycidyloxy)phenyl]propane, 4,4'-lsopropylidenediphenol diglycidyl ether, BADGE, represented by Formula (II):Formula (II).See, for example, International Patent Application Publication No. WO 2021 / 58206. However, the resin of Formula (I) is utilized in accordance with the present disclosure, as the resin of Formula (II) forms crystals at the desired storage temperature of -70°C or less.

[0048] Note that the resin of Formula (I) (i.e., DER™ 331) differs from the resin of Formula (II) (i.e., DER™ 332) in other ways. For example, the epoxide equivalent weight for the resin of Formula (I) (i.e., DER™ 331) is in a range of from 182-192 g / eq, whereas the epoxide equivalent weight for the resin of Formula (II) (i.e., DER™ 332) is in a range of 171-175 g / ea. Also, the epoxide percentage for the resin of Formula (I) (i.e., DER™ 331) is in a range of from 22.4-23.6%, whereas the epoxide percentage for the resin of Formula (II) (i.e., DER™ 332) is in a range of from 24.6-25.1%. In addition, the epoxide group content for the resin of Formula (I) (i.e., DER™ 331) is in a range of from 5200-5500 mmol / kg, whereas the epoxide group content for the resin of Formula (II) (i.e., DER™ 332) is in a range of from 5710-5850 mmol / kg. Further, the viscosity at 25°C for the resin of Formula (I) (i.e., DER™ 331) is in a range of from 11,000 - 14,000 mPa-s (cP), whereas the viscosity at 25°C for the resin of Formula (II) (i.e., DER™ 332) is in a range of from 4,000 - 6,000 mPa-s (cP).

[0049] The at least one liquid epoxy resin may be present in the paste composition at any concentration that allows the paste composition to function in accordance with the present disclosure. Non-limiting examples of liquid epoxy resin concentrations that may be present in the paste composition include about 20 wt%, about 21 wt%, about 22 wt%, about 23 wt%, about 24 wt%, about 25 wt%, about 26 wt%, about 27 wt%, about 28 wt%, about 29 wt%, about 30 wt%, about 31 wt%, about 32 wt%, about 33 wt%, about 34 wt%, about 35 wt%, about 36 wt%, about 37 wt%, about 38 wt%, about 39 wt%, about 40 wt%, about 41 wt%, about 42 wt%, about 43 wt%, about 44 wt%, about 45 wt%, about 46 wt%, about 47 wt%, about 48 wt%, about 49 wt%, about 50 wt%, about 51 wt%, about 52 wt%, about 53 wt%, about 54 wt%, about 55 wt%, about 56 wt%, about 57 wt%, about 58 wt%, about 59 wt%, about 60 wt%, about 61 wt%, about 62 wt%, about 63 wt%, about 64 wt%, about 65 wt%, about 66 wt%, about 67 wt%, about 68 wt%, about 69 wt%, about 70 wt%, and the like, as well as any range formed from two of the above values (e.g., a range of from about 20 wt% to about 70 wt%, a range of from about 25 wt% to about 65 wt%, a range of from about 26 wt% to about 48 wt%, a range of from about 54 wt% to about 64 wt%, etc.).

[0050] Any polymerization / curing agents known in the art or otherwise contemplated herein may be utilized in accordance with the present disclosure, so long as the paste composition is capable of forming sensors as described herein. In a non-limiting embodiment, the at least two polymerization / curing agents are N1, N1, N5, N6-tetraallylhexane-l,6-diamine (BF1) and Polyamidoamine Generation 0 dendrimer with Ethylenediamine core (PAMAM-G0).PAMAM-GO provides primary amines, secondary amines, and tertiary amine to react with the epoxy. BF1 provides tertiary amines, and BF1 has four allyl groups that can be photo crosslinked. The tertiary diamines form positively-charged quaternary ammonium sites that are able to pair with chloride ions. It has been discovered that instead of conventional commercial epoxy hardener (i.e., mercaptan), diamines (such as BF1 and PAMAM-GO) combined with DMPA create a highly selective chloride sensor with stable long-term use life that be useful for clinical analysis.

[0051] Each of the curing agents may be present in the paste composition at any concentration that allows the paste composition to function in accordance with the present disclosure. Non-limiting examples of curing agent concentrations that may be present in the paste composition include about 0.1 wt%, about 0.2 wt%, about 0.3 wt%, about 0.4 wt%, about 0.5 wt%, about 0.6 wt%, about 0.7 wt%, about 0.8 wt%, about 0.9 wt%, about 1 wt%, about 2 wt%, about 3 wt%, about 4 wt%, about 5 wt%, about 6 wt%, about 7 wt%, about 8 wt%, about 9 wt%, about 10 wt%, about 11 wt%, about 12 wt%, about 13 wt%, about 14 wt%, about 15 wt%, about 16 wt%, about 17 wt%, about 18 wt%, about 19 wt%, about 20 wt%, about 21 wt%, about 22 wt%, about 23 wt%, about 24 wt%, about 25 wt%, about 26 wt%, about 27 wt%, about 28 wt%, about 29 wt%, about 30 wt%, and the like, as well as any range formed from two of the above values (e.g., a range of from about 1 wt% to about 25 wt%, a range of from about 1 wt% to about 11 wt%, a range of from about 5 wt% to about 25 wt%, a range of from about 1 wt% to about 8 wt%, a range of from about 8 wt% to about 18 wt%, a range of from about 3 wt% to about 11 wt%, a range of from about 13 wt% to about 24 wt%, etc.).

[0052] In certain particular (but non-limiting) embodiments, the paste composition comprises BF1 present at a concentration in a range of from about 5 wt% to about 25 wt%, and PAMAM-GO present at a concentration in a range of from about 1 wt% to about 11 wt%.

[0053] The two curing agents may be present in the paste composition at any ratio that allows for proper curing of the sensor. Non-limiting examples of ratios of the two curing agents (such as, but not limited to, a BFl:PAMAM-G0 ratio) include about 0.5:1 about 0.6:1, about 0.7:1, about 0.75:1, about 0.8:1, about 0.85:1, about 0.9:1, about 0.95:1, about 1:1, about 1.05:1, about 1.1:1, about 1.15:1, about 1.2:1, about 1.25:1, about 1.3:1, about 1.35:1, about 1.4:1, about 1.45:1, 1.5:1, and the like, as well as any range formed from two of theabove values (e.g., a range of from about 0.5:1 to about 1.5:1, a range of from about 0.6:1 to about 1.4:1, etc.).

[0054] Each of the two curing agents and the liquid epoxy resin may be present in the paste composition at any ratio that allows for proper curing of the sensor. Non-limiting examples of ratios of individual curing agent to liquid epoxy resin (such as, but not limited to, a BF1:DER331 ratio or a PAMAM-G0:DER331 ratio) include about 0.01:1, about 0.05:1, about 0.1:1, about 0.11:1, about 0.12:1, about 0.13:1, about 0.14:1, about 0.15:1, about 0.16:1, about 0.17:1, about 0.18:1, about 0.19:1, about 0.2:1, about 0.25:1, about 0.3:1, about 0.35:1, about 0.4:1, about 0.45:1, about 0.5:1, about 0.55:1, about 0.6:1, about 0.65:1, about 0.7:1, about 0.75:1, about 0.8:1, about 0.85:1, about 0.9:1, about 0.95:1, about 1:1, , and the like, as well as any range formed from two of the above values (e.g., a range of from about 0.1:1 to about 0.2:1, a range of from about 0.4:1 to about 0.9:1, etc.).

[0055] In a particular (but non-limiting) embodiment, the BF1:DER331 ratio is in a ratio in a range of from about 0.4:1 to about 0.9:1, and the PAMAM-G0:DER331 ratio is in a range of from about 0.1:1 to about 0.2:1.

[0056] In a particular (but non-limiting) embodiment, the DER331:PAMAM-GO:BF1 weight ratio is in a range of from about 1:0.1:0.5 to about 1:0.09:0.3. In a particular (but nonlimiting) embodiment, the DER331:PAMAM-GO:BF1 stoichiometric ratio is about 1:0.3:0.4.

[0057] Any photocurable compounds known in the art or otherwise contemplated herein that are capable of functioning in accordance with the present disclosure may be utilized in the paste compositions and methods disclosed herein. Two non-limiting examples of photocurable compounds that may be utilized include 2,2-dimethoxy-2-phenylacetophenone (DMPA) and 1-hydroxycyclohexyl phenyl ketone (HCPK).

[0058] Each of the photocurable compounds may be present in the paste composition at any concentration that allows the paste composition to function in accordance with the present disclosure. Non-limiting examples of photocurable compound concentrations that may be present in the paste composition include about 0.1 wt%, about 0.2 wt%, about 0.3 wt%, about 0.4 wt%, about 0.5 wt%, about 0.6 wt%, about 0.7 wt%, about 0.8 wt%, about 0.9 wt%, about 1 wt%, about 1.1 wt%, about 1.2 wt%, about 1.3 wt%, about 1.4 wt%, about 1.5 wt%, about 1.6 wt%, about 1.7 wt%, about 1.8 wt%, about 1.9 wt%, about 2 wt%, about 2.1 wt%, about 2.2 wt%, about 2.3 wt%, about 2.4 wt%, about 2.5 wt%, about 2.6 wt%, about 2.7 wt%, about 2.8 wt%, about 2.9 wt%, about 3 wt%, about 3.1 wt%, about 3.2 wt%, about 3.3wt%, about 3.4 wt%, about 3.5 wt%, about 4 wt%, about 4.5 wt%, about 5 wt%, and the like, as well as any range formed from two of the above values (e.g., a range of from about 0.1 wt% to about 5 wt%, a range of from about 1 wt% to about 3 wt%, a range of from about 1 wt% to about 2.5 wt%, a range of from about 2.8 wt% to about 3.2 wt%, etc.).

[0059] In a particular (but non-limiting) embodiment, DMPA is present in the paste composition at a concentration in a range of from about 1 wt% to about 3 wt%, and HCPK is present in the paste composition at a concentration in a range of from about 1 wt% to about 3 wt%.

[0060] Any rheology modifiers known in the art or otherwise contemplated herein that are capable of functioning as described herein may be utilized in the paste compositions of the present disclosure. Non-limiting examples of rheology modifiers that may be utilized include fumed silicas (such as, but not limited to, AEROSIL® R972, AEROSIL® R974, AEROSIL® R976, AEROSIL® R104, AEROSIL® R104, AEROSIL® R106, AEROSIL® R202, AEROSIL® R208, AEROSIL® R805, AEROSIL® R812, AEROSIL® R104, AEROSIL® R816, AEROSIL® R104, AEROSIL® R711, AEROSIL® R7200, AEROSIL® R8200, AEROSIL® R9200, and the like; AEROSIL® is a registered trademark of Evonik Operations GmbH, Essen, Germany); polyurethanes, acrylic polymers, latex, styrene, polyvinyl alcohol, cellulosics (such as, but not limited to, carboxymethyl cellulose, hydroxypropyl cellulose, methyl cellulose, hydroxyethyl cellulose, diethylaminoethyl cellulose, ethyl cellulose, and / or hydroxyethyl methyl cellulose), and the like, as well as any combinations thereof.

[0061] The rheology modifier(s) may be present in the paste composition at any concentration that allows the paste composition to function in accordance with the present disclosure. Non-limiting examples of rheology modifier concentrations that may be present in the paste composition include about 0.001 wt%, about 0.005 wt%, about 0.01 wt%, about 0.02 wt%, about 0.03 wt%, about 0.04 wt%, about 0.05 wt%, about 0.06 wt%, about 0.07 wt%, about 0.08 wt%, about 0.09 wt%, about 0.1 wt%, about 0.15 wt%, about 0.2 wt%, about 0.25 wt%, 0.3 wt%, about 0.35 wt%, about 0.4 wt%, about 0.45 wt%, about 0.5 wt%, about 0.6 wt%, about 0.7 wt%, about 0.8 wt%, about 0.9 wt%, about 1 wt%, about 1.1 wt%, about 1.2 wt%, about 1.3 wt%, about 1.4 wt%, about 1.5 wt%, about 1.6 wt%, about 1.7 wt%, about 1.8 wt%, about 1.9 wt%, about 2 wt%, about 2.1 wt%, about 2.2 wt%, about 2.3 wt%, about 2.4 wt%, about 2.5 wt%, about 2.6 wt%, about 2.7 wt%, about 2.8 wt%, about 2.9 wt%, about 3 wt%, about 3.1 wt%, about 3.2 wt%, about 3.3 wt%, about 3.4 wt%, about 3.5 wt%, about 4wt%, about 4.5 wt%, about 5 wt%, and the like, as well as any range formed from two of the above values (e.g., a range of from about 0.001 wt% to about 5 wt%, a range of from about 0.1 wt% to about 3 wt%, a range of from about 0.001 wt% to about 0.5 wt%, a range of from about 0.001 wt% to about 0.05 wt%, etc.).

[0062] Any dyes known in the art or otherwise contemplated herein that are capable of functioning as described herein may be utilized in the paste compositions of the present disclosure. Non-limiting examples of dyes that may be utilized include Coumarin 6, DCM, Fluorescein (free acid), 4-Di-10-ASP (ASP), Genacryl Pink G, Sypro Orange, Green Fluorescent Protein (GFP), Alexa Fluor 488, Oregon Green 488, NovaFluor Blue 530, NovaFluor Blue 555, NovaFluor Blue 585, NovaFluor Blue 610-30S, NovaFluor Blue 610-70S, NovaFluor Blue 660- 40S, NovaFluor Blue 660-120S, PerCP-Cyanine5.5, PerCP-eFluor 710, NovaFluor Blue 725, NovaFluor Blue 760, and the like, as well as any combinations thereof.

[0063] The dye(s) may be present in the paste composition at any concentration that allows the paste composition to function in accordance with the present disclosure. Nonlimiting examples of dye concentrations that may be present in the paste composition include about 0.001 wt%, about 0.005 wt%, about 0.01 wt%, about 0.02 wt%, about 0.03 wt%, about 0.04 wt%, about 0.05 wt%, about 0.06 wt%, about 0.07 wt%, about 0.08 wt%, about 0.09 wt%, about 0.1 wt%, about 0.15 wt%, about 0.2 wt%, about 0.25 wt%, 0.3 wt%, about 0.35 wt%, about 0.4 wt%, about 0.45 wt%, about 0.5 wt%, about 0.6 wt%, about 0.7 wt%, about 0.8 wt%, about 0.9 wt%, about 1 wt%, about 1.1 wt%, about 1.2 wt%, about 1.3 wt%, about 1.4 wt%, about 1.5 wt%, about 1.6 wt%, about 1.7 wt%, about 1.8 wt%, about 1.9 wt%, about 2 wt%, about 2.1 wt%, about 2.2 wt%, about 2.3 wt%, about 2.4 wt%, about 2.5 wt%, about 2.6 wt%, about 2.7 wt%, about 2.8 wt%, about 2.9 wt%, about 3 wt%, about 3.1 wt%, about 3.2 wt%, about 3.3 wt%, about 3.4 wt%, about 3.5 wt%, about 4 wt%, about 4.5 wt%, about 5 wt%, and the like, as well as any range formed from two of the above values (e.g., a range of from about 0.001 wt% to about 5 wt%, a range of from about 0.1 wt% to about 3 wt%, a range of from about 0.001 wt% to about 0.5 wt%, a range of from about 0.1 wt% to about 1 wt%, etc.).

[0064] Certain non-limiting embodiments of the present disclosure are directed to kits that contain one or more of any of the paste compositions disclosed or otherwise contemplated herein. In a particular (but non-limiting) embodiment, the paste composition(s) is disposed within a sealed packaging that is substantially impermeable to air and / or substantially impermeable to light. The kits may optionally include one or more additionalreagents or components / devices (such as a dispenser with a nozzle and / or one or more substrate or sensor layers) that may be packaged together with or separately from the paste composition. The kits may further optionally include instructions for producing any of the chloride sensors described or otherwise contemplated herein.

[0065] Certain non-limiting embodiments of the present disclosure are directed to a photo-curable, epoxy-based, ion-selective chloride sensor. The sensor includes a polymer layer; an electrode layer; a conductor layer; and a transducer layer. The polymer layer comprises any of the paste compositions disclosed or otherwise contemplated herein, wherein the paste composition is photocured to form the polymer layer.

[0066] In certain particular (but non-limiting) embodiments, the paste composition is photocured via at least one wavelength of light within the ultraviolet spectrum. In certain particular (but non-limiting) embodiments, the paste composition is also exposed to two or more heating temperatures in the formation of the polymer layer.

[0067] Certain non-limiting embodiments of the present disclosure are directed to a method of fabricating a photo-curable, epoxy-based, ion-selective chloride sensor. In the method, two or more of the various components / ingredients described herein above (i.e., liquid epoxy resin(s), curing agents, photocurable compounds, rheology modifier(s), and dye(s)) are mixed together to form any of the photo-curable polymer mixture / paste compositions disclosed or otherwise contemplated herein, and the photo-curable polymer mixture is contained within a single dispenser. An effective amount of the photo-curable polymer mixture / paste composition is then dispensed onto at least a portion of a surface of an electrode substrate. The electrode substrate comprises an electrode layer, a conductor layer, a transducer layer, and a ceramic layer, and the photo-curable polymer mixture / paste composition is dispensed on the electrode layerof the electrode substrate. The photo-curable polymer mixture / paste composition is then irradiated with at least one wavelength of light to thereby form a photo-curable, epoxy-based, ion-selective chloride sensor. The ion-selective chloride sensor is then conveyed through at least two ovens having at least five different temperatures to complete the production of the photo-curable, epoxy-based, ion-selective chloride sensor.

[0068] For example, but not by way of limitation, FIG. 2 illustrates a chloride-selective chloride sensor 10 constructed in accordance with the present disclosure. The ion-selective chloride sensor 10 comprises a base, inert ceramic layer 12 (such as, but not limited to, analumina layer), a silver layer 14, a silver / silver chloride layer 16, two dielectric layers 18a and 18b, and an ion-selective sensing membrane 20. The silver layer 14 is dispensed on at least a portion of the ceramic layer 12. The silver / silver layer 16 is dispensed on a portion of the silver layer 14 between the two dielectric layers 18a and 18b. The sensor membrane 20 is dispensed on the silver / silver layer 16 and between the two dielectric layers 18a and 18b.

[0069] Certain non-limiting embodiments of the present disclosure are directed to a multi-sensor cartridge containing any of the photo-curable, epoxy-based, ion-selective chloride sensors disclosed or otherwise contemplated herein. The multi-sensor cartridge contains one or more channels through which sample flows and one or more other sensors (such as, but not limited to, one or more ion-selective sensors such as potassium and / or sodium sensors) located within the channel(s) so that the sensors come into contact with sample flowing through the channel. The cartridge may further include one or more other components, such as (but not limited to) a reference electrode, ground pins, air detect, etc.

[0070] For example (but not by way of limitation), FIG. 3 illustrates a multi-sensor cartridge 100 containing a first channel 102 and a second channel 104. The first channel 102 includes a sodium sensor 106, a potassium sensor 108, and a chloride sensor 110. The second channel 104 includes a reference electrode 112. In addition, each of the channels 102 and 104 contains a ground pin / air detection well 114. The multi-sensor cartridge 100 is disposed within a receiving space 200 of an automated analyzer that contains pins 202 that provide electric contacts between the automated analyzer and the sensors 106 / 108 / 110 / 112 of the cartridge 100 for sensing signals conducted through the electrodes of the sensors.

[0071] Certain non-limiting embodiments of the present disclosure are directed to a method of fabricating a multi-sensor cartridge containing a photo-curable, epoxy-based, ion- selective chloride sensor. In the method, two or more of the various components / ingredients described herein above (i.e., liquid epoxy resin(s), curing agents, photocurable compounds, rheology modifier(s), and dye(s)) are mixed together to form any of the photo-curable polymer mixture / paste compositions disclosed or otherwise contemplated herein, and the photo-curable polymer mixture is contained within a single dispenser. An effective amount of the photo-curable polymer mixture / paste composition is then dispensed onto at least a portion of a surface of an electrode substrate. The electrode substrate comprises an electrode layer, a conductor layer, a transducer layer, and a ceramic layer, and the photo-curable polymer mixture / paste composition is dispensed on the electrode layer of the electrodeY1substrate. The photo-curable polymer mixture / paste composition is then irradiated with at least one wavelength of light to thereby form a photo-curable, epoxy-based, ion-selective chloride sensor. The ion-selective chloride sensor is then conveyed through at least two ovens having at least five different temperatures to complete the production of the photo-curable, epoxy-based, ion-selective chloride sensor.

[0072] The photo-curable polymer mixture / paste composition may be irradiated with any wavelength(s) of light capable of forming a photo-curable, epoxy-based, ion-selective chloride sensor from the paste compositions. In certain particular (but non-limiting) embodiments, the at least one wavelength of light is within the ultraviolet spectrum. Non-limiting examples of wavelengths that may be utilized in accordance with the present disclosure include about 200 nm, about 225 nm, about 250 nm, about 275 nm, about 300 nm, about 325 nm, about 350 nm, about 375 nm, about 400 nm, and the like, as well as any range formed from two of the above values (e.g., a range of from about 200 nm to about 400 nm, a range of from about 250 nm to about 400 nm, etc.).

[0073] The photo-curable polymer mixture / paste composition may be irradiated at any intensity capable of forming a photo-curable, epoxy-based, ion-selective chloride sensorfrom the paste compositions. Non-limiting examples of intensities that may be utilized in the irradiation step in accordance with the present disclosure include about 1 W / cm2, about 1.5 W / cm2, about 2 W / cm2, about 2.25 W / cm2, about 2.5 W / cm2, about 2.75 W / cm2, about 3 W / cm2, about 3.5 W / cm2, about 4 W / cm2, about 4.5 W / cm2, about 5 W / cm2, about 5.5 W / cm2, about 6 W / cm2, about 6.5 W / cm2, about 7 W / cm2, about 7.5 W / cm2, about 8 W / cm2, about 8.5 W / cm2, about 9 W / cm2, about 9.5 W / cm2, about 10 W / cm2, about 10.5 W / cm2, about 11 W / cm2, about 11.5 W / cm2, about 12 W / cm2, about 12.5 W / cm2, about 13 W / cm2, about 13.5 W / cm2, about 14 W / cm2, about 14.5 W / cm2, about 15 W / cm2, about 15.5 W / cm2, about 16 W / cm2, about 16.5 W / cm2, about 17 W / cm2, about 17.5 W / cm2, about 18 W / cm2, about 18.5 W / cm2, about 19 W / cm2, about 19.5 W / cm2, about 20 W / cm2, and the like, as well as any range formed from two of the above values (e.g., a range of from about 1 W / cm2to about 20 W / cm2, a range of from about 2.5 W / cm2to about 15 W / cm2, a range of from about 2.5 W / cm2to about 14 W / cm2, etc.).

[0074] The photo-curable polymer mixture / paste composition may be irradiated for any period of time capable of forming a photo-curable, epoxy-based, ion-selective chloride sensor from the paste compositions. Non-limiting examples of times that may be utilized inaccordance with the present disclosure include about 1 second, about 2 seconds, about 3 seconds, about 4 seconds, about 5 seconds, about 6 seconds, about 7 seconds, about 8 seconds, about 9 seconds, about 10 seconds, about 11 seconds, about 12 seconds, about 13 seconds, about 14 seconds, about 15 seconds, about 16 seconds, about 17 seconds, about 18 seconds, about 19 seconds, about 20 seconds, about 21 seconds, about 22 seconds, about 23 seconds, about 24 seconds, about 25 seconds, about 26 seconds, about 27 seconds, about 28 seconds, about 29 seconds, about 30 seconds, and the like, as well as any range formed from two of the above values (e.g., a range of from about 1 second to about 30 seconds, a range of from about 5 seconds to about 25 seconds, a range of from about 10 seconds to about 20 seconds, a range of from about 10 seconds to about 17 seconds, etc.).

[0075] In a particular (but non-limiting) embodiment, the irradiating step occurs at a wavelength in a range of from about 250 nm to 450 nm, at an intensity in a range of from about 2.5 W / cm2to about 15 W / cm2, and for a period of time in a range of from about 10 seconds to about 20 seconds.

[0076] In a particular (but non-limiting) embodiment, the irradiating step occurs at a wavelength in a range of from about 250 nm to 450 nm, at an intensity of about 2.5 W / cm2to about 14 W / cm2, and for a period of time in a range of from about 10 seconds to about 17 seconds.

[0077] The various temperatures present in the ovens utilized in the methods of the present disclosure may be within a range of from about 20°C to about 150°C. Non-limiting examples of temperatures that may be utilized in the ovens include about 20°C, about 25°C, about 30°C, about 35°C, about 40°C, about 45°C, about 50°C, about 55°C, about 60°C, about 65°C, about 70°C, about 75°C, about 80°C, about 85°C, about 90°C, about 95°C, about 100°C, about 105°C, about 110°C, about 115°C, about 120°C, about 125°C, about 130°C, about 134°C, about 135°C, about 140°C, about 145°C, about 150°C, and the like, as well as any ranges formed of two of the above values.

[0078] In a particular (but non-limiting) embodiment, a first temperature is in a range of from about 35°C to about 150°C; a second temperature is in a range of from about 45°C to about 150°C; a third temperature is in a range of from about 45°C to about 150°C; a fourth temperature is in a range of from about 55°C to about 150°C; and a fifth temperature is about20°C.

[0079] In a particular (but non-limiting) embodiment, the first temperature is in a range of from about 80°C to about 150°C; the second temperature is in a range of from about 80°C to about 150°C; the third temperature is in a range of from about 100°C to about 150°C; the fourth temperature is in a range of from about 100°C to about 150°C; and there is an additional temperature between the fourth and fifth temperatures that is in a range of from about 100°C to about 150°C.

[0080] In a particular (but non-limiting) embodiment, the conveying step is further defined as conveying the ion-selective chloride sensor through a first oven and a second oven, wherein the first oven has: a first temperature in a range of from about 35°C to about 150°C; a second temperature in a range of from about 45°C to about 150°C; a third temperature in a range of from about 45°C to about 150°C; a fourth temperature in a range of from about 55°C to about 150°C; and a fifth temperature of about 20°C; and the second oven has: a sixth temperature in a range of from about 80°C to about 150°C; a seventh temperature in a range of from about 80°C to about 150°C; an eighth temperature in a range of from about 100°C to about 150°C; a ninth temperature in a range of from about 100°C to about 150°C; a tenth temperature in a range of from about 100°C to about 150°C; and an eleventh temperature of about 20°C.

[0081] The ion-selective chloride sensor may be exposed to each of the above temperatures for any period of time that, when combined, is capable of completing the production of the ion-selective chloride sensor. Non-limiting examples of times that may be utilized include about 5 seconds, about 10 seconds, about 15 seconds, about 20 seconds, about 25 seconds, about 30 seconds, about 35 seconds, about 40 seconds, about 45 seconds, about 50 seconds, about 55 seconds, about 60 seconds, about 65 seconds, about 70 seconds, about 75 seconds, about 80 seconds, about 85 seconds, about 90 seconds, and the like, as well as any range formed from two of the above values (e.g., a range of from about 5 seconds to about 90 seconds, a range of from about 10 seconds to about 80 seconds, a range of from about 15 seconds to about 70 seconds, a range of from about 25 seconds to about 60 seconds, a range of from about 25 seconds to about 35 seconds, etc.).

[0082] In a particular (but non-limiting) embodiment, the conveying step exposes the ion- selective chloride sensor to each of the plurality of temperatures for a period in a range of from about 25 seconds to about 60 seconds.

[0083] The photo-curable polymer mixture may be dispensed using a nozzle having any gauge that will allow for the production of the ion-selective chloride sensor in accordance with the present disclosure without paste overflow. Non-limiting examples of gauges that may be utilized in accordance with the present disclosure include about 20 gauge, about 21 gauge, about 22 gauge, about 23 gauge, about 24 gauge, about 25 gauge, about 26 gauge, about 27 gauge, about 28 gauge, about 29 gauge, about 30 gauge, about 31 gauge, about 32 gauge, about 33 gauge, about 34 gauge, about 35 gauge, and the like, as well as any range formed of two of the above values (e.g., a range of from about 20 gauge to about 35 gauge, a range of from about 23 gauge to about 30 gauge, etc.).

[0084] The photo-curable polymer mixture may be dispensed at any volume that will allow for the production of the ion-selective chloride sensor in accordance with the present disclosure without paste overflow. Non-limiting examples of dispensing volumes that may be utilized in accordance with the present disclosure include about about 1 nL, about 2 nL, about 3 nL, about 4 nL, about 5 nL, about 6 nL, about 7 nL, about 8 nL, about 9 nL, about 10 nL, about 11 nL, about 12 nL, about 13 nL, about 14 nL, about 15 nL, about 16 nL, about 17 nL, about 18 nL, about 19 nL, about 20 nL, about 21 nL, about 22 nL, about 23 nL, about 24 nL, about 25 nL, about 26 nL, about 27 nL, about 28 nL, about 29 nL, about 30 nL, about 31 nL, about 32 nL, about 33 nL, about 34 nL, about 35 nL, about 36 nL, about 37 nL, about 38 nL, about 39 nL, about 40 nL, about 41 nL, about 42 nL, about 43 nL, about 44 nL, about 45 nL, about 46 nL, about 47 nL, about 48 nL, about 49 nL, about 50 nL, and the like, as well as any range formed of two of the above values (e.g., a range of from about 1 nL to about 50 nL, a range of from about 10 nL to about 40 nL, etc.).

[0085] In a particular (but non-limiting) embodiment, the photo-curable polymer mixture is dispensed on the electrode layer of the electrode substrate in a dispensing volume of about 30 nL using a 25 gauge nozzle.

[0086] The electrode layer of the electrode substrate on which the photo-curable polymer mixture is dispensed may have any diameter that allows for the production of the ion-selective chloride sensor in accordance with the present disclosure without paste overflow. Non-limiting examples of diameters that may be utilized in accordance with the present disclosure include about 10 mils, about 11 mils, about 12 mils, about 13 mils, about 14 mils, about 15 mils, about 15.5 mils, about 16 mils, about 16.5 mils, about 17 mils, about 17.5 mils, about 18 mils, about 18.5 mils, about 19 mils, about 19.5 mils, about 20 mils, about21 mils, about 22 mils, about 23 mils, about 24 mils, about 25 mils, about 26 mils, about 27 mils, about 28 mils, about 29 mils, about 30 mils, about 31 mils, about 32 mils, about 33 mils, about 34 mils, about 35 mils, about 36 mils, about 37 mils, about 38 mils, about 39 mils, about 40 mils, about 41 mils, about 42 mils, about 43 mils, about 44 mils, about 45 mils, and the like, as well as any range formed from two of the above values (e.g., a range of from about 10 mils to about 45 mils, a range of from about 18 mils to about 37 mils, a range of from about 10 mils to about 20 mils, a range of from about 16 mils to about 19 mils, etc.).

[0087] In a particular (but non-limiting) embodiment, the electrode layer of the electrode substrate on which the photo-curable polymer mixture is dispensed has a diameter of about 18.5 mils.EXAMPLES

[0088] Examples are provided hereinbelow. However, the present disclosure is to be understood to not be limited in its application to the specific experimentation, results, and laboratory procedures disclosed herein below. Rather, the Examples are simply provided as various embodiments and is meant to be exemplary, not exhaustive.Example 1: Formulations, Curing Conditions, and Substrates and Dispensing Conditions

[0089] The prior art commercial A-LYTE chloride sensor design formulation shown in FIG. 1 (left column) is based on two-part epoxy polymer chemistry. In the presence of tertiary amine, mercaptan reacts fast with epoxide groups to form a crosslinked network within 5 minutes. Therefore, the resin part and the hardener part need to be prepared, stored, and dispensed separately. In contrast, the present disclosure provides a "single pot" formulation (FIG. 1, right column) that has all the components pre-mixed together at a defined ratio and that has a largely extended pot life due to UV-initiated polymerization.

[0090] FIG. 1 compares the single pot formulation of the present disclosure to the prior art commercial A-LYTE Cl two-part formulation and the formulation of International Patent Application Publication No. WO 2021 / 058206.

[0091] To extend the pot life of the paste, mercaptan in the prior art A-LYTE design and DAB in the '206 application are replaced with a dendrimer, PAMAM-G0, and the amount is reduced to limit the fast reactions between the primary amine groups and the epoxide groups. The tertiary diamine TMHA present in the prior art commercial A-LYTE Cl formulationshown in FIG. 1 is replaced with BF1 that also has two tertiary amine groups to react with the resin, and the allyl groups of BF1 can be crosslinked by UV irradiation. Photo initiators are added to activate photopolymerization. DER™ 331 is employed in the new single pot formulation to allow storage under -70°C, as DER™ 332 (primarily used in International Publication No. WO 2021 / 058206) forms crystals at this temperature. In addition, a rheology modifier (such as, but not limited to, Silica R972) is included in the formulation to control spreading of the paste on the substrate after dispensing.

[0092] The new design will have longer pot life, with a target of 24 hours on the IMT production line under ambient conditions. With all chemicals in one paste, a single dispense will provide more homogeneous sensor membranes compared to the separate dispense of two individual pastes in the prior art methods. These features will further result in improved sensor robustness and quality.

[0093] The formulations of the present disclosure utilize chloride sensing chemistry by forming a 3-dimensional crosslinked polymer network with quaternary ammonium sites embedded in the polymer backbone that serve as binding sites for the chloride ions. This allows the chloride ions to reversibly partition between the polymer membrane and the aqueous sample phase, generating potentiometric signals that can be used to quantitively assay chloride ion levels in the samples, governed by the Nernst equation. Because of the similar structures of the monomers, especially that both have the epoxy-amine chemistry, the polymer network is alike to each other. The new design disclosed herein will have the same or better shelf-life and use-life stabilities under the same storage conditions.

[0094] In addition, for better manufacturability purposes, the electrode size is reduced to 50% for ease of dispensing.

[0095] The formulations of the present disclosure possess multiple benefits overthe prior art formulations. The formulations demonstrate improved manufacturability and yield and reduction in scrap. Using a 50% smaller electrode when compared to the prior art electrodes results in more consistent coverage. In addition, a single paste simplifies the dispensing process. The time to manufacture is improved, as the 3-week substrate aging process is removed, and manufacturing throughput is increased by at least 11% with a shorter cycle time. Significant cost savings is also observed based on a reduction in raw material costs as well as a reduction in manufacturing time. In addition, increased customer satisfaction isobserved due to increase Cl recovery, use life, and stability. The on-board stability of the sensors can be increased beyond 14 days or 5,000 samples / 15,000 tests.

[0096] The use of PAMAM-G0 provides costs savings and is more hydrophilic than previously used hardeners / additives such as mercaptan and DAB. The use of the rheology modifier (such as, but not limited to, Silica R972) adjusts the viscosity of the paste and substantially prevents paste overflow and improves manufacturability. The use of the additional photo initiator HCPK yields quicker curing and improved sensor quality. The use of at least one dye provides for better vision system inspection and better manufacturability and sensor quality.

[0097] Table 1 illustrates non-limiting embodiments of formulations and concentration ranges of each component that can be utilized in accordance with the present disclosure.TABLE 1

[0098] Table 2 provides a specific (but non-limiting) formulation produced in accordance with the present disclosure.TABLE 2* The dendrimer PAMAM-GO is sold as a solution in methanol. The wt% of the dendrimer in the solution is 47.5% ± 0.5%. The weight of PAMAM-GO in the formulation is the total weight that includes the methanol.** The wt% in solids are calculated by removing all solvent contents, including DEGMEE from the dispersion and methanol from the dendrimer PAMAM-GO.

[0099] Non-limiting examples of UV curing conditions that can be utilized in accordance with the present disclosure include UV intensities of 2.5, 5, 7.5, 9.1, 10, 11, 12.5, and 14 W / cm2. Non-limiting examples of UV times that can be utilized in accordance with the present disclosure include 10.5, 13.5, and 16.5 seconds. Non-limiting examples of UV wavelengths that can be utilized in accordance with the present disclosure include those in the 250 nm - 450 nm filter range.

[0100] In particular (but not by way of limitation), the specific formulation of Table 2 was exposed to UV with an intensity of 12.5 W / cm2for 13.5 seconds.

[0101] Table 3 explores various non-limiting examples of oven / heating conditions that can be utilized in accordance with the present disclosure.TABLE 3

[0102] In a particular (but non-limiting) embodiment, the formulation of Table 2 was utilized with an oven indexing of 27 seconds, with Oven 2 temperatures (°C) of 55 / 100 / 134 / 100 / 20 / 20, and Oven 3 temperatures (°C) of 80 / 100 / 134 / 134 / 100 / 20.

[0103] In addition, while certain temperatures are shown as associated with Oven 2 or Oven 3, it will be understood that the use of the terms Oven 2 and Oven 3 are for purposesof illustration only and should not be construed as limiting of the order of exposure to temperatures. That is, the order of exposure to the two ovens can be reversed so that components are exposed to Oven 3 temperatures first followed by Oven 2 temperatures.

[0104] Non-limiting examples of nozzle sizes that can be utilized in accordance with the present disclosure include 23 gauge, 25 gauge, 27 gauge, and 30 gauge. Non-limiting examples of dispensing volumes that can be utilized in accordance with the present disclosure include 10 nL, 20 nL, 30 nL, and 40 nL.

[0105] In one non-limiting embodiment, the formulation of Table 2 was utilized with a 25 gauge nozzle and 30 nL dispensing volume.

[0106] Three sizes of electrodes have been tested in accordance with the present disclosure, with electrode diameters of 37 mils (original electrode size), 27.8 miles, and 18.5 mils.

[0107] In one non-limiting embodiment, the 18.5 mils electrode diameter was utilized with the formulation of Table 2.Example 2: Benchtop Development

[0108] All sensors were manually prepared by using an EFD Nordson Ultimus V dispenser and cured with a Spectrolinker UV chamber and either a hotplate or an oven. Sensor inspection was conducted by using a Keyence VHX microscope and / or a Leica Fluorescence microscope.

[0109] These manually prepared sensor cartridges didn't have NA or K sensors and had no NA or K responses.

[0110] A series of feasibility experiments were conducted on the bench to quickly screen formulations, study UV and heat curing conditions, and track pot life. These preliminary benchtop experiments were to gain understanding of the formulations and serve as precursors of experiments on the IMT production line. During the study, the stoichiometry ratios were calculated based on the Equivalent Epoxy Weight of DER™ 331 (187) and possible available reaction sites of BF1 and PAMAM-G0 (2 for BF1 and 10 for PAMAM-GO). This is by taking into account the most reactive amine sites and reaction potential due to the state of the membrane change. In this formulation design, primary amines, secondary amines, and tertiary amines can function as nucleophiles and react with the epoxide groups. Because of the unique resonance structure of amide groups that the lone pair on nitrogen donateselectron density to create a pi bond between carbon and nitrogen, the nucleophilicity of the nitrogen in amide groups is largely reduced, making it unlikely to participate in the ringopening reactions. As a result, the four amide nitrogens in PAMAM-GO are not counted as reaction sites. PAMAM-GO has 2 tertiary amines, 4 primary amines, followed by 4 secondary amines to react with the epoxide groups of DER™ 331, before tertiary amines could become possibly available. On the other hand, the two tertiary amines originally presented in PAMAM- GO and BF1 are readily available to react with epoxide groups under the current curing conditions on the production line. Therefore, the number of reaction sites is counted as 10 for PAMAM-GO and 2 for BF1 which is consistently used throughout the development. Although for the purposes of development the possible reaction sites were counted based on the considerations described above, an alternative theoretical calculation could be performed by using 14 active sites for PAMAM-GO, assuming all possible reactions are 100% complete. It should be noted that the sensor formulation is based on the weight of each component. Regardless of the method of ratio calculation, the weight of each monomer in the sensor formulation remains the same, and the performance of the product was based on an optimized gravimetric formulation.

[0111] Phase separation was observed between DER™ 331 and BF1 in the initial experiments. To obtain an optimal ratio and have a homogeneous solution, a few mixtures of DER™ 331 and BF1 were prepared with ratios ranging from 1:0.9 to 1:0.4 (DER 331:BF1). As the ratio decreased, the less phase separation was observed. When the ratio was reduced to 1:0.5 (DER 331:BF1), the mixture was completely homogeneous. With the addition of dendrimer and a small amount of solvent, there was no observation of phase separation with the ratio of 1:0.6.

[0112] Since the primary amines of PAMAM-GO react quickly with the epoxide groups of the resin at room temperature, the amount of the dendrimer was reduced to obtain longer pot life. Ratios of 1:0.1 and 1:0.2 of DER™ 331 and PAMAM-GO were evaluated. Both could provide greater than 24 hours pot life, but 1:0.2 ratio yielded a more viscous and gel like material than 1:0.1 ratio.

[0113] Sensors were manually prepared with formulations of various ratios of the DER™ 331, PAMAM-GO and BF1. All formulations showed promising results in terms of sensor stability and precision. Sensors exhibited healthy slope values over the sensor life and good precision. Precision results from 5-day ANOVA studies were normalized to either DIR limit (Fb)or UVL limit and presented as margin, meaning that all passing results would be smaller than or equal to 100% margin. DIR limits are for a 20-day precision study. For this shorter period precision study, the Upper Verification Limit (UVL) was also used for evaluation. The UVL represents the upper 95th percentile limit for the acceptance criterion. With consideration of other aspects (e.g., pot life and ease of dispensing), this ratio, 1:0.1:0.5 (DER 331:PAMAM- GO:BF1), was used as interim optimal formulation in the following benchtop experiments.

[0114] The preliminary benchtop curing studies demonstrated that both UV and heat provide benefits to accelerate the curing process. If only heat was involved as the curing method, extensive paste spreading on the substrate was observed, leaving a very thin membrane formed. If only UV was applied, the size of the sensor was more controllable, but the curing process was slower. The optimal process is to apply UV irradiation immediately after dispensing to activate polymerization, followed by heating the sensors with higher temperatures. DMPA was investigated first as a photo initiator. To achieve faster curing and minimize oxygen quenching the radicals, a second photo initiator HCPK was added to the paste formulation, doubling the total amount of photo initiators.

[0115] A small pilot run was conducted on the production line with a spot UV curing unit, OmniCure S2000. Excessive spreading of the paste on the substrate was observed. Silica R972 was added into the paste formulation as the viscosity rheology modifier to control the spreading. Four different concentrations of silica dispersions (A: 6.46 wt%, B: 8.84 wt%, C: 10.93 wt%, and D: 13.30 wt%) were prepared and used to make chloride sensor pastes, which were then manually dispensed on bench to produce chloride sensors. Sensor performance demonstrated feasibility of the addition of silica dispersions.Example 3: Pilot Runs on Production Line

[0116] All Na and K sensors were made by the commercial pastes following production procedures. All chloride sensors were prepared with pastes of single pot formulations that were dispensed at the production line and cured with OmniCure S2000, Oven 2 and Oven 3. The configuration of the multi-sensor cartridge 20 produced is shown in FIG. 3. As can be seen in FIG. 3, the cartridge includes a first channel containing functional Na, K, and Cl sensors, and a second channel containing a reference electrode that has a stable potential. When a sample enters the multi-sensor cartridge, the sample passes through these two channels and over the three functional electrodes. In the method of producing the multi-sensor cartridge, thesodium and potassium membranes are dispensed first and cured (i.e., using "Oven 1"), and then the chloride membrane is dispensed onto the substrate and cured (i.e., using "Oven 2" and "Oven 3"). Therefore, it is important that the preparation of the chloride sensor does not impact the sodium and potassium sensors that are already disposed on the substrate.

[0117] To simultaneously study the impact from multiple factors, the Taguchi approach of Design of Experiments (DOE) was used. A few Taguchi arrays were designed and executed. The first two Taguchi experiments (Pilot 1 and 2) used the paste formulation optimized from the benchtop experiments that had the ratio at 1:0.1:0.5 (DER331:PAMAM-GO:BF1). In the Taguchi experiments, control factors included the type of silica dispersion (A, B, C, D), amounts of each silica dispersion type (low, mid, high), nozzle sizes, dispense volumes, UV intensities, and Oven temperatures (Tables 4 and 5).Table 4: Taguchi array design of Pilot 1Table 5: Taguchi array design of Pilot 2

[0118] Response factors include sensor sizes, calibration slopes, and salicylate interference. It was observed that the amount of dispersion, the dispensed volume, the nozzle size, and oven 2 temperature setting had more impact on the sensor size. Higher amounts of silica dispersion, higher dispensed volume, bigger nozzle size, and lowertemperatures of oven 2 in general tend to produce increased sensor sizes. Although there is a desire to limit paste spreading, it is critical that the entire electrode area is covered by the sensor membrane. Therefore, the optimal condition should be a balanced result. The study found that salicylate interference is more impacted by the dispersion type, the dispersion amount, UV intensities, and oven temperatures. The salicylate interference is evaluated as the biased recovery from a normal human serum sample spiked with 50 mg / dL salicylate compared to a non-spiked control normal human serum sample. The salicylate bias levels didn't vary much, but it seemed dispersion C yielded sensors with smaller interference from salicylate, which was same for higher UV intensities and oven temperatures. In terms of sensor calibration slopes, all conditions gave acceptable slope values. There was some pattern observed of different conditions, but the exact slope values had minimal variation. When combing all the observations and considering the requirements to produce acceptable sensors, dispersion C and D with medium level, 30 nL dispense volume, and 25 gauge nozzle were selected and carried on to future experiments.

[0119] A small benchtop experiment was conducted before the third Taguchi experiments on the production line (Pilot 3). This was to further optimize the PAMAM-G0 and BF1 ratio to shorten curing time post-sensor production. This experiment screened the following ratios: (1) DER™ 331:PAMAM-G0 at 1:0.1, 1:0.2, and 1:0.3; (2) DER™ 331:BF1 at 1:0.2, 1:0.3, and 1:0.4. The combination of 0.3 PAMAM-G0 and 0.4 BF1 cured sooner than other conditions. With 0.3 BF1 and higher UV intensity combined with the same ratio of PAMAM-G0 at 0.3, same curing speed could be achieved. In the first 72 hours, all the pastes within this benchtop experiment were in a liquid state with no gelation observed, indicating greater than 24 hours pot life. This was probably influenced by the additional solvent introduced by the silica dispersion. A third Taguchi experiment on the production line (Pilot 3, sensor Lot 211119) was performed that had the control factors of silica dispersion (C and D), BF1 ratio (0.3 and 0.4), UV intensity (7.5 and 10 W / cm2), and two oven ramping temperatures (Table 6), while PAMAM-G0 ratio remained constantly at 0.3. Sensor size was more impacted by oven temperatures than other factors. Sensor slope values were higherwith dispersion D, but the difference is only about 1 mV / dec between the two dispersion types. Furthermore, lower salicylate bias levels could be obtained with dispersion C, 0.4 BF1, and higher UV intensity and oven temperatures. Use life and precision test results are summarized in FIGS. 4-6.Table 6: Taguchi array design of Pilot 3

[0120] The final optimized conditions from the 3 Taguchi experiments are the following and have been carried on to the future pilot runs: DER™ 331:PAMAM-GO:BF1 stoichiometric ratio at l:0.3:0.4, and 30 nL dispense with 25 gauge nozzle.

[0121] To study the dispensing variation and associated manufacturing capability, different combinations of dispense volumes and nozzle sizes were tested (Table 7). In general, it was observed that the higher the dispensed volume, the bigger the sensor size. Nozzle size was not observed to have a noticeable impact. Results are summarized in FIG. 7, Panel a.Table 7: Taguchi array design of Pilot 4

[0122] The main inspection mechanism is based on the coloration contrast among the sensor membrane, electrode surface, and the dielectric area. In the early phase of vision system development, the major challenge was due to the photobleaching of the dye within the paste and a darkened electrode surface, leading to difficulties in distinguishing the sensor membrane from the electrode and the dielectric surface. This resulted in sensors without full coverage of membranes being accepted by the vision system settings used at the time.

[0123] To increase the contrast between the sensor membrane and the electrode, an optional second dye was introduced to the paste formulation to increase the total amount of dyes. Initially only coumarin 6 was involved. Due to its limited solubility, DCM was employed as the additional dye. The total amount of dye increased to 0.5 wt% with double dyes of the total paste weight from 0.25 - 0.3 wt% of the paste that had coumarin 6 only. When further increasing the dyes amount to 0.8 wt%, it started to show precipitates at the bottom of the syringe barrel. It is worth noting that the paste with 0.8 wt% dyes was used in Pilot 8 (sensor Lot 221116), with no observation of dispense issues or sensor performance issues. With the introduction of the second dye, the contrast between the sensor membrane and the electrode was largely enhanced.

[0124] An additional change to the cartridge design is that the Ag / AgCI electrode area is reduced by reducing the size of the opening on the first layer of dielectric. This is to minimize the possibility of exposed bare electrode area that could cause degradation of sensor performance. Two sizes of smaller chloride electrodes were tested in Pilot 7 (Sensor Lot 221115), with the diameter reduced to 75% and 50% of the current commercial electrode size. This was achieved by reducing the opening of the screen to print the first layer of dielectrics, while the printing screen of the Ag pad was unchanged. The electric signals, mV reads of standard A and standard B, were evaluated for the 3 sizes of electrodes. As predicted by the Nernst equation, no difference was observed (FIGS. 8A-C). The smallest 50% size (FIG. 8A) was selected as the final optimized size due to the ease of covering the Ag / AgCI electrode consistently with the sensor membrane.

[0125] With the smaller electrode and new vision system programs, another pilot (Pilot 11, sensor Lot 221119) was conducted to study the dispensing variation with combinations of different nozzle sizes and dispense volumes. Detailed conditions are summarized in Table 8. It is observed that 40 nL dispense volume yielded noticeably bigger sensors than 30 nL and 20nL dispense volumes. There is no significant difference between 30 nL and 20 nL. Same observation was made for 25 gauge nozzle and 27 gauge nozzle. When a smaller 30 gauge nozzle was used, more variation was introduced when the dispense volume was 20 nL.Table 8: Dispensing conditions of Pilot 11

[0126] When considering the pump capacity and coverage of the electrode, 25 gauge nozzle and 30 nL dispense have been used as the default setting. However, J gauge nozzle and 20 nL dispense volume can be utilized as well (FIG. 7, Panel b).

[0127] A pilot (pilot 5, Lot 221113) was conducted to assess the manufacturability of the pastes with different ages to evaluate the pot life. A bigger batch of paste was prepared and aliquoted into a few syringe barrels. At different time points prior to dispensing, a barrel was taken out from the freezerand started aging on bench under ambient conditions. These paste ages were evaluated: 1 hr (fresh), 14 hours, 25 hours, and 47 hours. All pastes dispensed smoothly, and the sensor sizes seemed consistent among pastes of different ages. No variation of sensor performance was observed from the initial sensor performance testing. Further use life testing indicated good performance of sensors made with fresh paste as well 25 hr and 47 hr aged pastes in terms of calibration slope values, slope stability over sensor use life, and precision. This indicates feasibility of greater than 24 hour paste pot life.

[0128] To study the feasibility of reducingthe oven indexing time to increase productivity, a few pilot runs (Pilot 8, 10, 11, and 12) were conducted with various combinations of oven indexing time, UV intensity, UV time, Oven 2 and Oven 3 temperature setpoints. The conditions are summarized in Table 9. With shorter oven indexing time, the UV time must bereduced accordingly to avoid skipped oven cycles. With shortened UV time, the UV intensities needed to be adjusted to keep the total UV energy the same. A few modifications of oven temperature profiles were also tested to introduce varied amount of total heat energy. It was observed that in general the higher the UV intensity and oven temperatures, the quicker the membranes were cured. However, it was also noticed that NA and K sensor membranes changed to an opaque appearance from being transparent when the oven temperatures increased to 150°C. Those NA and K sensors also exhibited poor calibration slope values, potentially suggesting nonfunctional NA or K sensors. When temperatures didn't exceed 134°C, those two sensors remained transparent and functioned normally. Another observation was the impact on fluorescence signals from different curing conditions. Both UV intensity and oven temperatures influenced the signals in the way that higher curing energies tended to cause lower fluorescence signals (FIG. 9). Initial testing showed acceptable chloride sensor slope values for all conditions (Table 10). Each slope value is the average from the three initial calibrations after automatic onboard sensor hydration. This study demonstrated feasibility of reducing oven indexing time. Taking all factors into account, condition 13 may be more desired (but not by way of limitation) than other conditions. It should be noted that the UV intensity could potentially drift up. In design transfer lot 3, two additional UV intensities were tested, 11 and 14 W / cm2, and no difference was observed comparing to the default setpoint of 12.5 W / cm2. This demonstrates an allowable tolerance of ± 1.0 W / cm2(11.5 to 13.5 W / cm2) during production.Table 9: Conditions of different oven indexing times| 13 | 12 | 27 | 12.5 | 13.5 | 55 / 100 / 134 / 100 / 20 / 20 | 80 / 100 / 134 / 134 / 100 / 20 |Table 10: Calibration slopes of Na, K and Cl sensors with different curing conditions

[0129] A pilot was conducted to assess the paste shelf life. The paste lots that were used in Pilot 8 and Pilot 9 were employed for the shelf-life assessment. The pastes were stored in -70°C freezer for about 3.5 and 2.5 months, respectively. Both pastes were dispensed smoothly on the production line. No variation of sensor performance was observed from the initial sensor performance testing. Detailed sensor performance testing results indicate good performance of sensors in terms of calibration slope values, slope stability over sensor use life, and precision. This indicates feasibility of at least 3 months of paste shelf-life when stored at -70°C.

[0130] Interference from salicylate was evaluated over time after sensor production. Normal human serum samples spiked with 50 mg / dL salicylate was tested along with unspiked normal human serum samples as the control. FIG. 10 summarizes the recovery bias of the spiked sample and control sample on day 6, 10, 13, 34, and 65. The sensor cartridges were pouched on the production line, stored under ambient conditions until day 13, and moved to the fridge on day 13. It is observed that the salicylate interference decreased overtime as the sensor membranes aged, which was likely due to the ongoing polymerization post sensor production. The change was more noticeable within the first two weeks, while the change rate reaches plateau after two weeks. Both old hydration cycles (SW 1.26 and below) and newhydration cycles (SW 1.27 and above) were employed in this study. As shown in FIG. 10, the new hydration cycles noticeably reduced the salicylate interference before day 13, but didn't show advantage over the old hydration cycles after day 13. It is recommended to allow 14 days staging time under room temperature after sensor production. After 14 days, sensors can be transferred to 2-8°C storage.

[0131] Sensors from Lot 221115 (pilot 7), 221116 (pilot 8), 221117 (pilot 9), 221118 (pilot 10), and 221120 (pilot 12) were evaluated for precision and onboard stability. These sensor lots were made with the finalized formulation of the paste (e.g., double dyes, silica dispersion C, and finalized ratio of resin and hardener), and small electrode substrates. Lot 221116 and 221117 were made with shorter oven indexing time accompanied with shorter UV time and higher UV intensities and oven temperatures. Lot 221118 used sensor pastes that were 2.5 (sensor sequence 608) and 3.5 months old (sensor sequence 129). Lot 221120 were produced with the curing conditions 13 from Table 9.

[0132] Sensor in-use life was tested by sensors onboard for at least 14 days or 5000 samples. To extend onboard testing for some sensors (> 14 days or > 5000 samples), the sensor cartridges were renumbered in the middle of the study, allowing them to remain onboard. QC materials were handled according to manufacturer's instructions. Calibrations automatically occur every 4 hours or every 250 samples, whichever comes first.

[0133] P recision was tested consistent with the governing standard CLSI EP05-A3: Evaluation of Precision Performance of Quantitative Measurement Methods. Each day, one run was performed and N=5 replicates were collected on each test sample. Quality control material and human serum were used as samples during the study. Each testing day, new serum pool aliquots were thawed. QC materials were handled according to manufacturer's instructions.

[0134] Data analysis used a nested, two factor (days and runs nested within days) ANOVA model. Repeatability and within-lab precision estimates were calculated using the validated tool: Method Precision: 5 Day ANOVA, Version 2.0.

[0135] I n-use life stability was tested consistent with the governing standard CLSI EP25- A: Evaluation of Stability of In Vitro Diagnostic Reagents. Each test day, one run was performed and N=5 replicates were collected on each test sample. Quality control material and human serum were used as samples during the study. Each testing day, new aliquots were thawed. Over the duration of the study, serum samples were loaded onto theinstrument in order to increase the overall number of total tests performed by the sensor. QC materials were handled according to manufacturer's instructions. Mean results were evaluated with Minitab 19 for statistically significant drift over the use-life using linear regression (result vs time). For linear regression, slopes with p-values > 0.05 are considered as a "Pass" result and there is no significant drift.

[0136] For linear regression slopes with p-values < 0.05, achieved use-life time was estimated from the bisection of the confidence Interval of the linear regression fit and the time where the allowable bias was exceeded. If the linear regression confidence interval and the allowable bias acceptance criteria did not bisect within the study duration, then the outcome is listed as the maximum time tested. The stability duration for each lot was taken as the minimum of the stability durations observed across all test samples.Table 11: Study details

[0137] FIG. 11A shows the calibration slopes of single pot chloride sensors made with the finalized formulation from the pilot lot 221115, 221116, 221117, 221118, and 221120. Sensors demonstrated stable and healthy calibration slopes over the sensor use life with no degradation. Instead, the slope values are more Nernstian, indicating optimal sensitivity and equilibrium state for chloride ions. The data also indicates that the sensor use life can be increased to more than 14 days. Na and K calibration slopes are summarized in FIGS. 11B and 11C, respectively, demonstrating good stability of the whole A-LYTE sensor cartridge.

[0138] The chloride sensors made with the revised formulations demonstrated in use life onboard stability of greater than or equal to 14 days or up to 5,000 samples, with thefollowing allowable drifts: Cl serum, ± 5%; Cl urine, ±5%; Na serum, ±3%; Na urine, ±5%; K serum, ±5%; and K urine, ±5%.

[0139] In summary, chloride sensors made with the revised formulations all have excellent Repeatability and Within-Lab precision. Sodium and Potassium sensors also demonstrated good precision and met design goals. In addition, the chloride sensors made with the new formulations produced stable recovery over the commercial sensor use life of 14 days. QC regression data collected for sodium, potassium, and chloride sensors met the design goals of In Use Stability. All sensors tested demonstrated use life > 20 days and up to 40 days.NON-LIMITING ILLUSTRATIVE EMBODIMENTS

[0140] Illustrative embodiment 1. A paste composition for producing a photocurable, epoxy-based, ion-selective chloride sensor membrane, the paste composition comprising: (1) at least one liquid epoxy resin; (2) at least two curing agents; (3) at least two photocurable compounds; (4) at least one rheology modifier; and (5) at least one dye.

[0141] Illustrative embodiment 2. The paste composition of Illustrative embodiment 1, wherein the at least one liquid epoxy resin comprises an epoxy resin diglicydyl ether of bisphenol A (DGEBA).

[0142] Illustrative embodiment 2A. The paste composition of Illustrative embodiment 2, wherein the DGEBA is represented by Formula (I):Formula (I).

[0143] Illustrative embodiment 2B. The paste composition of Illustrative embodiment 2A, wherein the DGEBA represented by Formula (I) is further defined as having at least one of: an epoxide equivalent weight in a range of from 182-192 g / eq; an epoxide percentage in a range of from 22.4-23.6%; an epoxide group content in a range of from 5200-5500 mmol / kg; and / or a viscosity at 25°C in a range of from 11,000 - 14,000 mPa-s (cP).

[0144] Illustrative embodiment 2C. The paste composition of any of Illustrative embodiments 1-2B, wherein the at least one liquid epoxy resin is present at a concentration in a range of from about 25 wt% to about 65 wt%.

[0145] Illustrative embodiment 3. The paste composition of any of Illustrative embodiments 1-2A, wherein the at least two curing agents comprise Nl, Nl, N6, N6- tetraallylhexane-l,6-diamine (BF1) and Polyamidoamine Generation 0 dendrimer with Ethylenediamine core (PAMAM-GO).

[0146] Illustrative embodiment 3A. The paste composition of any of Illustrative embodiments 1-3, wherein the at least two curing agents are present at a ratio in a range of from about 0.5:1 to about 1.5:1.

[0147] Illustrative embodiment 3B. The paste composition of Illustrative embodiment 3 or 3A, wherein BF1 is present at a concentration in a range of from about 5 wt% to about 25 wt%, and PAMAM-GO is present at a concentration in a range of from about 1 wt% to about 11 wt%.

[0148] Illustrative embodiment 3C. The paste composition of any of Illustrative embodiments 3-3B, wherein BF1 and the liquid epoxy resin are present in a ratio in a range of from about 0.4:1 to about 0.9:1.

[0149] Illustrative embodiment 3D. The paste composition of any of Illustrative embodiments 3-3C, wherein PAMAM-GO and the liquid epoxy resin are present in a ratio in a range of from about 0.1:1 to about 0.2:1.

[0150] Illustrative embodiment 3E. The paste composition of any of Illustrative embodiments 3-3D, wherein the liquid epoxy resin, PAMAM-GO, and BF1 are present at a stoichiometric ratio of about 1:0.3:0.4.

[0151] Illustrative embodiment 4. The paste composition of any of Illustrative embodiments 1-3E, wherein the at least two photocurable compounds comprise 2,2- dimethoxy-2-phenylacetophenone (DMPA) and 1-hydroxycyclohexyl phenyl ketone (HCPK).

[0152] Illustrative embodiment 4A. The paste composition of Illustrative embodiment 4, wherein DMPA is present at a concentration in a range of from about 1 wt% to about 3 wt%, and HCPK is present at a concentration in a range of from about 1 wt% to about 3 wt%.

[0153] Illustrative embodiment 5. The paste composition of any of Illustrative embodiments 1-4A, wherein the at least one rheology modifier is selected from the group consisting of a silica, a polyurethane, an acrylic polymer, latex, styrene, polyvinyl alcohol, carboxymethyl cellulose, hydroxypropyl cellulose, methyl cellulose, hydroxyethyl cellulose, diethylaminoethyl cellulose, ethyl cellulose, and combinations thereof.

[0154] Illustrative embodiment 6. The paste composition of any of Illustrative embodiments 1-5, wherein the at least one dye is selected from the group consisting of Coumarin 6, DCM, Fluorescein (free acid), 4-Di-10-ASP (ASP), Genacryl Pink G, Sypro Orange, Green Fluorescent Protein (GFP), Alexa Fluor 488, Oregon Green 488, NovaFluor Blue 530, NovaFluor Blue 555, NovaFluor Blue 585, NovaFluor Blue 610-30S, NovaFluor Blue 610-70S, NovaFluor Blue 660-40S, NovaFluor Blue 660-120S, PerCP-Cyanine5.5, PerCP-eFluor 710, NovaFluor Blue 725, NovaFluor Blue 760, and combinations thereof.

[0155] Illustrative embodiment 6A. The paste composition of any of Illustrative embodiments 1-6A, wherein the at least one dye is present at a concentration in a range of from about 0.1 wt% to about 1 wt%.

[0156] Illustrative embodiment 7. The paste composition of any of Illustrative embodiments 1-6, further defined as being capable of storage at about -70°C for at least 14 days without substantially forming crystals and without substantial polymerization.

[0157] Illustrative embodiment 7A. The paste composition of any of Illustrative embodiments 1-6, further defined as being capable of storage at about -70°C for at least 1 month, 2 months, or 3 months without substantially forming crystals and without substantial polymerization.

[0158] Illustrative embodiment 8. A paste composition for producing a photocurable, epoxy-based, ion-selective chloride sensor membrane, the paste composition comprising: (1) epoxy resin diglicydyl ether of bisphenol A (DGEBA); (2) Nl, Nl, N6, N6-tetraallylhexane-l,6- diamine (BF1); (3) Polyamidoamine Generation 0 dendrimer with Ethylenediamine core (PAMAM-G0); (4) 2,2-dimethoxy-2-phenylacetophenone (DMPA); (5) 1-hydroxycyclohexyl phenyl ketone (HCPK); (6) at least one rheology modifier; and (7) at least one dye.

[0159] Illustrative embodiment 8A. The paste composition of Illustrative embodiment 8, wherein the DGEBA is represented by Formula (I):Formula (I).

[0160] Illustrative embodiment 8B. The paste composition of Illustrative embodiment 8A, wherein the DGEBA represented by Formula (I) is further defined as having at least one of: an epoxide equivalent weight in a range of from 182-192 g / eq; an epoxide percentage in a rangeof from 22.4-23.6%; an epoxide group content in a range of from 5200-5500 mmol / kg; and / or a viscosity at 25°C in a range of from 11,000 - 14,000 mPa-s (cP).

[0161] Illustrative embodiment 8C. The paste composition of any of Illustrative embodiments 8-8B, wherein: DGEBA is present at a concentration in a range of from about 25 wt% to about 65 wt%; BF1 is present at a concentration in a range of from about 5 wt% to about 25 wt%; PAMAM-G0 is present at a concentration in a range of from about 1 wt% to about 11 wt%; DMPA is present at a concentration in a range of from about 1 wt% to about 3 wt%; HCPK is present at a concentration in a range of from about 1 wt% to about 3 wt%; and the at least one dye is present at a concentration in a range of from about 0.1 wt% to about 1 wt%.

[0162] Illustrative embodiment 8C. The paste composition of any of Illustrative embodiments 8-8B, wherein BF1 and PAMAM-G0 are present at a ratio in a range of from about 0.5:1 to about 1.5:1.

[0163] Illustrative embodiment 8D. The paste composition of any of Illustrative embodiments 8-8C, wherein BF1 and the liquid epoxy resin are present in a ratio in a range of from about 0.4:1 to about 0.9:1.

[0164] Illustrative embodiment 8E. The paste composition of any of Illustrative embodiments 8-8D, wherein PAMAM-G0 and the liquid epoxy resin are present in a ratio in a range of from about 0.1:1 to about 0.2:1.

[0165] Illustrative embodiment 8F. The paste composition of any of Illustrative embodiments 8-8E, wherein the liquid epoxy resin, PAMAM-G0, and BF1 are present at a stoichiometric ratio of about 1:0.3:0.4.

[0166] Illustrative embodiment 9. A kit, comprising: the paste composition of any of Illustrative embodiments 1-8F; and a sealed packaging in which the paste composition is disposed, wherein the sealed packaging is substantially impermeable to air and / or substantially impermeable to light.

[0167] Illustrative embodiment 10. A photo-curable, epoxy-based, ion-selective chloride sensor, comprising: a polymer layer; an electrode layer; a conductor layer; and a transducer layer; wherein the polymer layer comprises the paste composition of any of Illustrative embodiments 1-8F, wherein the paste composition is photocured to form the polymer layer.

[0168] Illustrative embodiment 11. The ion-selective chloride sensor of Illustrative embodiment 10, wherein the paste composition is photocured via at least one wavelength of light within the ultraviolet spectrum.

[0169] Illustrative embodiment 12. A method of fabricating a photo-curable, epoxybased, ion-selective chloride sensor, the method comprising the steps of: mixing effective amounts of at least one liquid epoxy resin, at least two curing agents, at least two photocurable compounds, at least one rheology modifier, and at least one dye to form a photo-curable polymer mixture, wherein the photo-curable polymer mixture is contained within a single dispenser; dispensing an effective amount of the photo-curable polymer mixture onto at least a portion of a surface of an electrode substrate, the electrode substrate comprising an electrode layer, a conductor layer, a transducer layer, and a ceramic substrate layer, wherein the photo-curable polymer mixture is dispensed on the electrode layer of the electrode substrate; irradiating the photo-curable polymer mixture with at least one wavelength of light to thereby form a photo-curable, epoxy-based, ion-selective chloride sensor; and conveying the ion-selective chloride sensor through at least two ovens having at least five different temperatures, wherein: a first temperature is in a range of from about 35°C to about 150°C; a second temperature is in a range of from about 45°C to about 150°C; a third temperature is in a range of from about 45°C to about 150°C; a fourth temperature is in a range of from about 55°C to about 150°C; and a fifth temperature is about 20°C.

[0170] Illustrative embodiment 13. A method of fabricating a multi-sensor cartridge containing a photo-curable, epoxy-based, ion-selective chloride sensor, the method comprising the steps of: mixing effective amounts of at least one liquid epoxy resin, at least two curing agents, at least two photocurable compounds, at least one rheology modifier, and at least one dye to form a photo-curable polymer mixture, wherein the photo-curable polymer mixture is contained within a single dispenser; dispensing an effective amount of the photo-curable polymer mixture onto a surface of an electrode substrate, the electrode substrate comprising an electrode layer, a conductor layer, a transducer layer, and a ceramic substrate layer, wherein the photo-curable polymer mixture is dispensed on the electrode layer of the electrode substrate; irradiating the photo-curable polymer mixture with at least one wavelength of light to thereby form a photo-curable, epoxy-based, ion-selective chloride sensor; and conveying the ion-selective chloride sensor through at least two ovens having at least five different temperatures, wherein: a first temperature is in a range of from about35°C to about 150°C; a second temperature is in a range of from about 45°C to about 150°C; a third temperature is in a range of from about 45°C to about 150°C; a fourth temperature is in a range of from about 55°C to about 150°C; and a fifth temperature is about 20°C.

[0171] Illustrative embodiment 14. The method of Illustrative embodiment 12 or 13, wherein the at least one liquid epoxy resin comprises epoxy resin diglicydyl ether of bisphenol A (DGEBA).

[0172] Illustrative embodiment 14A. The method of Illustrative embodiment 14, wherein the DGEBA is represented by Formula (I):Formula (I).

[0173] Illustrative embodiment 14B. The method of Illustrative embodiment 14A, wherein the DGEBA represented by Formula (I) is further defined as having at least one of: an epoxide equivalent weight in a range of from 182-192 g / eq; an epoxide percentage in a range of from 22.4-23.6%; an epoxide group content in a range of from 5200-5500 mmol / kg; and / or a viscosity at 25°C in a range of from 11,000 - 14,000 mPa-s (cP).

[0174] Illustrative embodiment 15. The method of any of Illustrative embodiments 12- 14A, wherein the at least two curing agents comprise Nl, Nl, N6, N6-tetraallylhexane-l,6- diamine and Polyamidoamine Generation 0 dendrimer with Ethylenediamine core (PAMAM- G0).

[0175] Illustrative embodiment 16. The method of any of Illustrative embodiments 12-15, wherein the at least two photocurable compounds comprise 2,2-dimethoxy-2- phenylacetophenone (DMPA) and 1-hydroxycyclohexyl phenyl ketone (HCPK).

[0176] Illustrative embodiment 17. The method of any of Illustrative embodiments 12-16, wherein the at least one rheology modifier is selected from the group consisting of a silica, a polyurethane, an acrylic polymer, latex, styrene, polyvinyl alcohol, carboxymethyl cellulose, hydroxypropyl cellulose, methyl cellulose, hydroxyethyl cellulose, diethylaminoethyl cellulose, ethyl cellulose, and combinations thereof.

[0177] Illustrative embodiment 18. The method of any of Illustrative embodiments 12-17, wherein the at least one dye is selected from the group consisting of Coumarin 6, DCM,Fluorescein (free acid), 4-Di-10-ASP (ASP), Genacryl Pink G, Sypro Orange, Green Fluorescent Protein (GFP), Alexa Fluor 488, Oregon Green 488, NovaFluor Blue 530, NovaFluor Blue 555, NovaFluor Blue 585, NovaFluor Blue 610-30S, NovaFluor Blue 610-70S, NovaFluor Blue 660- 40S, NovaFluor Blue 660-120S, PerCP-Cyanine5.5, PerCP-eFluor 710, NovaFluor Blue 725, NovaFluor Blue 760, and combinations thereof.

[0178] Illustrative embodiment 18A. The method of any of Illustrative embodiments 12- 18, wherein at least one of: the at least one liquid epoxy resin comprises epoxy resin diglicydyl ether of bisphenol A (DGEBA) present in the photo-curable polymer mixture at a concentration in a range of from about 25 wt% to about 65 wt%; the at least two curing agents comprise Nl, Nl, N6, N6-tetraallylhexane-l,6-diamine (BF1) present in the photo-curable polymer mixture at a concentration in a range of from about 5 wt% to about 25 wt% and Polyamidoamine Generation 0 dendrimer with Ethylenediamine core (PAMAM-G0) present in the photo-curable polymer mixture at a concentration in a range of from about 1 wt% to about 11 wt%; the at least two photocurable compounds comprise 2,2-dimethoxy-2- phenylacetophenone (DMPA) present in the photo-curable polymer mixture at a concentration in a range of from about l wt% to about 3 wt% and 1-hydroxycyclohexyl phenyl ketone (HCPK) present in the photo-curable polymer mixture at a concentration in a range of from about 1 wt% to about 3 wt%; and the at least one dye is present in the photo-curable polymer mixture at a concentration in a range of from about 0.1 wt% to about 1 wt%.

[0179] Illustrative embodiment 18B. The method of any of Illustrative embodiments 12- 18A, wherein BF1 and PAMAM-G0 are present in the photo-curable polymer mixture at a ratio in a range of from about 0.5:1 to about 1.5:1.

[0180] Illustrative embodiment 18C. The method of any of Illustrative embodiments 12- 18B, wherein BF1 and the liquid epoxy resin are present in the photo-curable polymer mixture in a ratio in a range of from about 0.4:1 to about 0.9:1.

[0181] Illustrative embodiment 18D. The method of any of Illustrative embodiments 12- 18C, wherein PAMAM-G0 and the liquid epoxy resin are present in the photo-curable polymer mixture in a ratio in a range of from about 0.1:1 to about 0.2:1.

[0182] Illustrative embodiment 18E. The method of any of Illustrative embodiments 12- 18D, wherein the liquid epoxy resin, PAMAM-G0, and BF1 are present in the photo-curable polymer mixture at a stoichiometric ratio of about 1:0.3:0.4.

[0183] Illustrative embodiment 19. The method of any of Illustrative embodiments 12- 18E, wherein the at least one wavelength of light is within the ultraviolet spectrum.

[0184] Illustrative embodiment 20. The method of any of Illustrative embodiments 12-19, wherein the irradiating step occurs at a wavelength in a range of from about 250 nm to 450 nm, at an intensity in a range of from about 2.5 W / cm2to about 15 W / cm2, and for a period of time in a range of from about 10 seconds to about 20 seconds.

[0185] Illustrative embodiment 20A. The method of Illustrative embodiment 20, wherein the irradiating step occurs at a wavelength in a range of from about 250 nm to 450 nm, at an intensity of about 2.5 W / cm2to about 14 W / cm2, and for a period of time in a range of from about 10 seconds to about 17 seconds.

[0186] Illustrative embodiment 21. The method of any of Illustrative embodiments 12- 20A, wherein the conveying step exposes the ion-selective chloride sensor to each of the plurality of temperatures for a period in a range of from about 25 seconds to about 60 seconds.

[0187] Illustrative embodiment 22. The method of any of Illustrative embodiments 12-21, wherein in the conveying step, the first temperature is in a range of from about 80°C to about 150°C; the second temperature is in a range of from about 80°C to about 150°C; the third temperature is in a range of from about 100°C to about 150°C; the fourth temperature is in a range of from about 100°C to about 150°C; and there is an additional temperature between the fourth and fifth temperatures that is in a range of from about 100°C to about 150°C.

[0188] Illustrative embodiment 23. The method of any of Illustrative embodiments 12-21, wherein the conveying step is further defined as conveying the ion-selective chloride sensor through a first oven and a second oven, wherein the first oven has: a first temperature in a range of from about 35°C to about 150°C; a second temperature in a range of from about 45°C to about 150°C; a third temperature in a range of from about 45°C to about 150°C; a fourth temperature in a range of from about 55°C to about 150°C; and a fifth temperature of about 20°C; and the second oven has: a sixth temperature in a range of from about 80°C to about 150°C; a seventh temperature in a range of from about 80°C to about 150°C; an eighth temperature in a range of from about 100°C to about 150°C; a ninth temperature in a range of from about 100°C to about 150°C; a tenth temperature in a range of from about 100°C to about 150°C; and an eleventh temperature of about 20°C.

[0189] Illustrative embodiment 24. The method of any of Illustrative embodiments 12-23, wherein the photo-curable polymer mixture is dispensed with a nozzle having a gauge in a range of from about 23 gauge to about 30 gauge.

[0190] Illustrative embodiment 25. The method of any of Illustrative embodiments 12-24, wherein the photo-curable polymer mixture is dispensed on the electrode layer of the electrode substrate in a volume in a range of from about 10 nL to about 40 nL.

[0191] Illustrative embodiment 26. The method of any of Illustrative embodiments 12-25, wherein the photo-curable polymer mixture is dispensed on the electrode layer of the electrode substrate in a dispensing volume of about 30 nL using a 25 gauge nozzle.

[0192] Illustrative embodiment 27. The method of any of Illustrative embodiments 12-26, wherein the electrode layer of the electrode substrate on which the photo-curable polymer mixture is dispensed has a diameter in a range of from about 18 mils to about 37 mils.

[0193] Illustrative embodiment 28. The method of any of Illustrative embodiments 12-27, wherein the electrode layer of the electrode substrate on which the photo-curable polymer mixture is dispensed has a diameter of about 18.5 mils.

[0194] Therefore, in accordance with the present disclosure, there have been provided reagents and compositions, as well as kits containing same and methods of use thereof, that fully satisfy the objectives and advantages set forth hereinabove. Although the present disclosure has been described in conjunction with the specific drawings, experimentation, results, and language set forth herein above, it is evident that many alternatives, modifications, and variations will be apparent to those of ordinary skill in the art. Accordingly, it is intended to embrace all such alternatives, modifications, and variations that fall within the spirit and broad scope of the present disclosure.

Claims

What is claimed is:

1. A paste composition for producing a photocurable, epoxy-based, ion-selective chloride sensor membrane, the paste composition comprising:(1) at least one liquid epoxy resin;(2) at least two curing agents;(3) at least two photocurable compounds;(4) at least one rheology modifier; and(5) at least one dye.

2. The paste composition of claim 1, wherein the at least one liquid epoxy resin comprises an epoxy resin diglicydyl ether of bisphenol A (DGEBA) at a concentration in a range of from about 25 wt% to about 65 wt%, and wherein the DGEBA is represented by FormulaFormula (I) wherein the DGEBA represented by Formula (I) is further defined as having at least one of: an epoxide equivalent weight in a range of from 182-192 g / eq; an epoxide percentage in a range of from 22.4-23.6%; an epoxide group content in a range of from 5200-5500 mmol / kg; and / or a viscosity at 25°C in a range of from 11,000 - 14,000 mPa-s (cP).

3. The paste composition of claim 1, wherein the at least two curing agents comprise: N1, N1, N6, N6-tetraallylhexane-l,6-diamine (BF1) at a concentration in a range of from about 5 wt% to about 25 wt%; andPolyamidoamine Generation 0 dendrimer with Ethylenediamine core (PAMAM-G0) at a concentration in a range of from about 1 wt% to about 11 wt%.

4. The paste composition of claim 1, wherein the at least two photocurable compounds comprise:2,2-dimethoxy-2-phenylacetophenone (DMPA) at a concentration in a range of from about 1 wt% to about 3 wt%; and1-hydroxycyclohexyl phenyl ketone (HCPK) at a concentration in a range of from about 1 wt% to about 3 wt%.

5. The paste composition of claim 1, wherein the at least one rheology modifier is selected from the group consisting of a silica, a polyurethane, an acrylic polymer, latex, styrene, polyvinyl alcohol, carboxymethyl cellulose, hydroxypropyl cellulose, methyl cellulose, hydroxyethyl cellulose, diethylaminoethyl cellulose, ethyl cellulose, and combinations thereof.

6. The paste composition of claim 1, wherein the at least one dye is present at a concentration in a range of from about 0.1 wt% to about 1 wt%, and wherein the at least one dye is selected from the group consisting of Coumarin 6, DCM, Fluorescein (free acid), 4-Di- 10-ASP (ASP), Genacryl Pink G, Sypro Orange, Green Fluorescent Protein (GFP), Alexa Fluor 488, Oregon Green 488, NovaFluor Blue 530, NovaFluor Blue 555, NovaFluor Blue 585, NovaFluor Blue 610-30S, NovaFluor Blue 610-70S, NovaFluor Blue 660-40S, NovaFluor Blue 660-120S, PerCP-Cyanine5.5, PerCP-eFluor 710, NovaFluor Blue 725, NovaFluor Blue 760, and combinations thereof.

7. The paste composition of claim 1, further defined as being capable of storage at a temperature of about -70°C for at least 14 days without substantially forming crystals and without substantial polymerization.

8. A kit, comprising: the paste composition of any one of claims 1-7; and a sealed packaging in which the paste composition is disposed, wherein the sealed packaging is substantially impermeable to air and / or substantially impermeable to light.

9. A photo-curable, epoxy-based, ion-selective chloride sensor, comprising: a polymer layer;an electrode layer; a conductor layer; and a transducer layer; wherein the polymer layer comprises the paste composition of any one of claims 1-7, wherein the paste composition is photocured to form the polymer layer.

10. The ion-selective chloride sensor of claim 9, wherein the paste composition is photocured via at least one wavelength of light within the ultraviolet spectrum.

11. A method of fabricating a photo-curable, epoxy-based, ion-selective chloride sensor, the method comprising the steps of: mixing effective amounts of at least one liquid epoxy resin, at least two curing agents, at least two photocurable compounds, at least one rheology modifier, and at least one dye to form a photo-curable polymer mixture, wherein the photo- curable polymer mixture is contained within a single dispenser; dispensing an effective amount of the photo-curable polymer mixture onto at least a portion of a surface of an electrode substrate, the electrode substrate comprising an electrode layer, a conductor layer, a transducer layer, and a ceramic substrate layer, wherein the photo-curable polymer mixture is dispensed on the electrode layer of the electrode substrate; irradiating the photo-curable polymer mixture with at least one wavelength of light to thereby form a photo-curable, epoxy-based, ion-selective chloride sensor; and conveying the ion-selective chloride sensor through at least two ovens having at least five different temperatures, wherein: a first temperature is in a range of from about 35°C to about 150°C; a second temperature is in a range of from about 45°C to about 150°C; a third temperature is in a range of from about 45°C to about 150°C; a fourth temperature is in a range of from about 55°C to about 150°C; and a fifth temperature is about 20°C.

12. The method of claim 11, wherein at least one of:(a) the at least one liquid epoxy resin comprises an epoxy resin diglicydyl ether of bisphenol A (DGEBA) represented by Formula (I):Formula (I), wherein the DGEBA represented by Formula (I) is further defined as having at least one of: an epoxide equivalent weight in a range of from 182-192 g / eq; an epoxide percentage in a range of from 22.4-23.6%; an epoxide group content in a range of from 5200-5500 mmol / kg; and / or a viscosity at 25°C in a range of from 11,000 - 14,000 mPa-s (cP);(b) the at least two curing agents comprise N1, N1, N6, N6-tetraallylhexane-l,6- diamine and Polyamidoamine Generation 0 dendrimer with Ethylenediamine core (PAMAM-G0);(c) the at least two photocurable compounds comprise 2,2-dimethoxy-2- phenylacetophenone (DMPA) and 1-hydroxycyclohexyl phenyl ketone (HCPK);(d) the at least one rheology modifier is selected from the group consisting of a silica, a polyurethane, an acrylic polymer, latex, styrene, polyvinyl alcohol, carboxymethyl cellulose, hydroxypropyl cellulose, methyl cellulose, hydroxyethyl cellulose, diethylaminoethyl cellulose, ethyl cellulose, and combinations thereof; and / or(e) the at least one dye is selected from the group consisting of Coumarin 6, DCM, Fluorescein (free acid), 4-Di-10-ASP (ASP), Genacryl Pink G, Sypro Orange, Green Fluorescent Protein (GFP), Alexa Fluor 488, Oregon Green 488, NovaFluor Blue 530, NovaFluor Blue 555, NovaFluor Blue 585, Nova Fluor Blue 610-30S, NovaFluor Blue 610-70S, NovaFluor Blue 660-40S, NovaFluor Blue 660-120S, PerCP-Cyanine5.5, PerCP-eFluor 710, NovaFluor Blue 725, NovaFluor Blue 760, and combinations thereof.

13. The method of claim 11, wherein the at least one wavelength of light is within the ultraviolet spectrum.

14. The method of claim 11, wherein the irradiating step occurs at a wavelength in a range of from about 250 nm to 450 nm, at an intensity in a range of from about 2.5 W / cm2to about 15 W / cm2, and for a period of time in a range of from about 10 seconds to about 20 seconds.

15. The method of claim 11, wherein the conveying step exposes the ion-selective chloride sensor to each of the plurality of temperatures for a period in a range of from about 25 seconds to about 60 seconds.

16. A method of fabricating a multi-sensor cartridge containing a photo-curable, epoxybased, ion-selective chloride sensor, the method comprising the steps of: mixing effective amounts of at least one liquid epoxy resin, at least two curing agents, at least two photocurable compounds, at least one rheology modifier, and at least one dye to form a photo-curable polymer mixture, wherein the photo- curable polymer mixture is contained within a single dispenser; dispensing an effective amount of the photo-curable polymer mixture onto a surface of an electrode substrate, the electrode substrate comprising an electrode layer, a conductor layer, a transducer layer, and a ceramic substrate layer, wherein the photo-curable polymer mixture is dispensed on the electrode layer of the electrode substrate; irradiating the photo-curable polymer mixture with at least one wavelength of light to thereby form a photo-curable, epoxy-based, ion-selective chloride sensor; conveying the ion-selective chloride sensor through at least two ovens having at least five different temperatures, wherein: a first temperature is in a range of from about 35°C to about 150°C; a second temperature is in a range of from about 45°C to about 150°C; a third temperature is in a range of from about 45°C to about 150°C; a fourth temperature is in a range of from about 55°C to about 150°C; and a fifth temperature is about 20°C.

7. The method of claim 16, wherein at least one of:(a) the at least one liquid epoxy resin comprises an epoxy resin diglicydyl ether of bisphenol A (DGEBA) represented by Formula (I):Formula (I), wherein the DGEBA represented by Formula (I) is further defined as having at least one of: an epoxide equivalent weight in a range of from 182-192 g / eq; an epoxide percentage in a range of from 22.4-23.6%; an epoxide group content in a range of from 5200-5500 mmol / kg; and / or a viscosity at 25°C in a range of from 11,000 - 14,000 mPa-s (cP);(b) the at least two curing agents comprise N1, N1, N6, N6-tetraallylhexane-l,6- diamine and Polyamidoamine Generation 0 dendrimer with Ethylenediamine core (PAMAM-G0);(c) the at least two photocurable compounds comprise 2,2-dimethoxy-2- phenylacetophenone (DMPA) and 1-hydroxycyclohexyl phenyl ketone (HCPK);(d) the at least one rheology modifier is selected from the group consisting of a silica, a polyurethane, an acrylic polymer, latex, styrene, polyvinyl alcohol, carboxymethyl cellulose, hydroxypropyl cellulose, methyl cellulose, hydroxyethyl cellulose, diethylaminoethyl cellulose, ethyl cellulose, and combinations thereof; and / or(e) the at least one dye is selected from the group consisting of Coumarin 6, DCM, Fluorescein (free acid), 4-Di-10-ASP (ASP), Genacryl Pink G, Sypro Orange, Green Fluorescent Protein (GFP), Alexa Fluor 488, Oregon Green 488, NovaFluor Blue 530, NovaFluor Blue 555, NovaFluor Blue 585, Nova Fluor Blue 610-30S, NovaFluor Blue 610-70S, NovaFluor Blue 660-405, NovaFluor Blue 660-120S, PerCP-Cyanine5.5, PerCP-eFluor 710, NovaFluor Blue 725, NovaFluor Blue 760, and combinations thereof.

18. The method of claim 16, wherein the at least one wavelength of light is within the ultraviolet spectrum.

19. The method of claim 16, wherein the irradiating step occurs at a wavelength in a range of from about 250 nm to 450 nm, at an intensity in a range of from about 2.5 W / cm2to about 15 W / cm2, and for a period of time in a range of from about 10 seconds to about 20 seconds.

20. The method of claim 16, wherein the conveying step exposes the ion-selective chloride sensor to each of the plurality of temperatures for a period in a range of from about 25 seconds to about 60 seconds.

21. A composition for a photocurable, epoxy-based, ion-selective chloride sensor membrane, the composition comprising:(1) at least one liquid epoxy resin;(2) at least two curing agents;(3) at least two photocurable compounds;(4) at least one rheology modifier; and(5) at least one dye, wherein the at least one liquid epoxy resin comprises an epoxy resin diglicydyl ether of bisphenol A (DGEBA) at a concentration in a range of from about 25 wt% to about 65 wt%, and wherein the DGEBA is represented by Formula (I):Formula (I) wherein the DGEBA represented by Formula (I) is further defined as having at least one of: an epoxide equivalent weight in a range of from 182-192 g / eq; an epoxide percentage in a range of from 22.4-23.6%; an epoxide group content in a range of from 5200-5500 mmol / kg; and / or a viscosity at 25°C in a range of from 11,000 - 14,000 mPa-s (cP), and wherein the at least two curing agents comprise:N1, N1, N6, Ns-tetraallylhexane-l,6-diamine (BF1) at a concentration in a range of from about 5 wt% to about 25 wt%; andPolyamidoamine Generation 0 dendrimer with Ethylenediamine core (PAMAM-GO) at a concentration in a range of from about 1 wt% to about 11 wt%.

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