A method of continuously manufacturing a template for a reference electrode or a combined counter electrode and reference electrode

Abstract

A method of continuously manufacturing a template (112) for a reference electrode or a combined counter electrode and reference electrode (114), a plurality of reference electrodes or combined counter electrodes and reference electrodes (114), wherein each electrode is based on the template (112) for the respective electrode as produced by the method, and a continuous monitoring system comprising at least one reference electrode or combined counter electrode and reference electrode (114) from the plurality of the reference electrodes or the combined counter electrodes and reference electrodes (114) are disclosed. The method comprises: • i. providing a continuous electrically conductive substrate (116); and • ii. applying a paste composition (122) comprising at least one binder material, silver particles and silver chloride particles to the substrate (116) by using a continuous reel-to-reel coating process, whereby a continuous line (120) having a lateral width (132) of 1 mm to 8 mm and a mean thickness (134) of 1 μm to 100 μm is formed.

Description

[0001] Roche Diabetes Care GmbH September 30, 2025

[0002] RD15692PC ST / GS / KV

[0003] A method of continuously manufacturing a template for a reference electrode or a combined counter electrode and reference electrode

[0004] Technical Field

[0005] The present invention refers to a method of continuously manufacturing a template for a reference electrode or a combined counter electrode and reference electrode, a plurality of reference electrodes or combined counter electrodes and reference electrodes, wherein each electrode is based on the template for the respective electrode as produced by the method, and a continuous monitoring system comprising at least one electrode from the plurality of the reference electrodes or the combined counter electrodes and reference electrodes. The method and the devices, as an example, may be used in the field of medical diagnostics for detecting one or more properties of a sample of a bodily fluid, e.g. a presence and / or a concentration of at least one analyte in the sample of the bodily fluid. Other fields of application of the present invention, however, are also feasible.

[0006] Background art

[0007] Analytical test elements addressed herein are wearable medical devices which comprise at least one electrochemical biosensor being configured for a continuous monitoring of at least one analyte in an interstitial fluid. For example, in the field of medical diagnostics, such in point of care applications and / or in laboratories, samples of a bodily fluid, particularly selected from saliva, blood, interstitial fluid, urine, salvia, sweat, or serum, have to be analyzed, e.g. in order to detect a presence and / or a concentration of an analyte in the sample of the bodily fluid. Examples of analytes to be detected are antigenic proteins of viruses, such as antigenic proteins of the SARS-CoV-2 coronavirus, and other types of analytes, such as glucose, triglycerides, lactate, cholesterol or other types of analytes typically present in these bodily fluids. For this purpose, the electrochemical biosensor comprises at least one working electrode, which has an analyte detection agent that is sensitive to a particular analyte provided on a substrate, and at least one of a reference electrode or combined counter electrode and reference electrode. Generally, the reference electrode or the combined counter electrode and reference electrode comprises a composition of silver particles and silver chloride particles, which is commonly provided by using a continuous reel in order to enable a fast production and to avoid sedimentation of the solid particles.

[0008] WO 2022 / 112138 Al discloses a method for the preparation of an electrode and to an analyte sensor comprising the electrode as well as to the use of the analyte sensor for detecting at least one analyte in a sample. In particular, the invention relates to a method for the preparation of an electrode, the method comprising a partial reduction of Ag+ cations present in the electrode material.

[0009] US 2023 / 0093665 Al discloses analyte sensors and methods for fabricating analyte sensors in a roll-to-roll process. In an exemplary embodiment, a method includes providing a roll of a polyester substrate having a first side coated with a layer of platinum, wherein the platinum is in direct contact with the polyester substrate; patterning the layer of platinum to form electrodes; punching the polyester substrate to form ribbons, wherein each ribbon is connected to a remaining polyester substrate web by a tab, and wherein each sensor includes an electrode; after punching the polyester substrate to form ribbons, depositing an enzyme layer over the portions of the working electrodes and coating the working electrodes with a glucose limiting membrane; after depositing the enzyme layer over the portions of the working electrodes and coating the working electrodes with a glucose limiting membrane, singulating the individual sensors by completely separating each individual sensor from the polyester substrate.

[0010] US 11,512,384 B2 discloses analyte sensors and methods for fabricating analyte sensors. In an exemplary embodiment, a method for fabricating a planar flexible analyte sensor includes sputtering platinum onto a polyester base layer to form a layer of platinum. The method includes patterning the layer of platinum to form working electrodes and additional electrodes. Further, the method includes forming an insulating dielectric layer over the base layer, wherein the insulating dielectric layer is formed with openings exposing portions of the working electrodes and portions of the additional electrodes. Also, the method includes partially singulating individual sensors from the base layer, wherein each individual sensor is connected to the base layer by a tab. The method further includes depositing an enzyme layer over the exposed portions of the working electrodes and coating the working electrodes with a glucose limiting membrane.

[0011] CN 103884757 A discloses a continuous production method of enzyme electrode for glucose detection. The method is characterized in that a continuous roll-to-roll coating production mode is adopted to overcome the defects of low efficiency and uncontrollable quality in the traditional uni-wafer printing operation and implements continuous automatic high- efficiency production of the biosensor; and the thickness of the slurry coated on the substrate electrode is precisely controllable to the minimum of a single molecular layer.

[0012] However, the deposition of the silver particles and the silver chloride particles for forming a reference electrode or a combined counter electrode and reference electrode, such as in a two-electrode or three-electrode based continuous monitoring system, brings additional requirements with regard to morphology, homogeneity, and spatial extensions, especially due to a much higher amount of silver particles and silver chloride particles required and / or due to a biocompatibility in spite of high accessibility of ingredients. Prior art solutions exhibit a disadvantage in that commercially available compositions of silver particles and silver chloride particles for coating purposes, typically, employ semi-volatile solvents which are not compatible with reel-to-reel drying processes, especially due to particularly short dwell times.

[0013] Problem to be solved

[0014] It is, therefore, desirable to provide a method of continuously manufacturing a template for a reference electrode or a combined counter electrode and reference electrode, a plurality of reference electrodes or combined counter electrodes and reference electrodes, and a continuous monitoring system, which at least partially overcome the limitations of the prior art.

[0015] Specifically, it is desirable to provide a method of continuously manufacturing a template for a reference electrode or a combined counter electrode and reference electrode, which meets the additional requirements with regard to morphology, homogeneity, and spatial extensions by applying a particular deposition process for the composition of the silver particles and the silver chloride particles when forming the reference electrode or the combined counter electrode and reference electrode. Summary

[0016] This problem is addressed by a method of continuously manufacturing a template for a reference electrode or a combined counter electrode and reference electrode, a plurality of reference electrodes or combined counter electrodes and reference electrodes, and a continuous monitoring system having the features of the independent claims. Advantageous embodiments that can be implemented in an isolated fashion or in any arbitrary combination are listed in the dependent claims as well as throughout the specification.

[0017] In a first aspect of the present invention, a method of continuously manufacturing a template for a reference electrode or a combined counter electrode and reference electrode. In the following, the method may also be referred to as “manufacturing method”. The method comprises the following method steps: i. providing a continuous electrically conductive substrate; and ii. applying a paste composition comprising at least one binder material, silver particles and silver chloride particles to the substrate by using a continuous reel- to-reel coating process, whereby a continuous line having a lateral width of 1 mm to 8 mm and a mean thickness of 1 pm to 100 pm is formed.

[0018] The method steps may, as a preferred example, be performed in the given order. It shall be noted, however, that it is possible to perform one or more or even all of the method steps once or repeatedly. Further, it is possible to perform two or more of the method steps simultaneously or in a timely overlapping fashion. The method may comprise additional method steps, which are not listed.

[0019] The method is directed to a manufacturing process. The term “manufacturing” or any grammatical variation thereof as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a process of producing at least one product from one or more base products. Specifically, the manufacturing process may comprise processing and / or transforming one or more base products into the product. The product of the manufacturing method may comprise a template for a reference electrode or a combined counter electrode and reference electrode. The manufacturing of the template for the reference electrode or the combined counter electrode and reference electrode may comprise processing at least one element and / or component in such as manner as to retrieve the template for the reference electrode or the combined counter electrode and reference electrode. The method is performed as a continuous manufacturing process. The term “continuous” or any grammatical derivation hereof as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. On one hand, the term specifically may refer, without limitation, to a characteristic of a process of potentially being uninterrupted and / or perpetual, which may, however, be interrupted by an intent of the user of the method or an unpredictable event. On the other hand, the term specifically may refer, without limitation, to a characteristic of an object of potentially having an unlimited extension, especially in one dimension, wherein the object may be provided in consecutive portions during subsequent time intervals by using a continuous process. As described below in more detail, the continuous manufacturing of the template comprises using a continuous reel-to-reel coating process, whereby consecutive portions of the continuous substrate are provided during subsequent time intervals for applying the analyte detection agent to the substrate.

[0020] The method is directed to manufacturing a template for a reference electrode or a template for a combined counter electrode and reference electrode. As already indicated above, an electrochemical biosensor comprises at least one working electrode, which has an analyte detection agent that is sensitive to a particular analyte provided on a substrate, and at least one of a reference electrode or combined counter electrode and reference electrode. The term “reference electrode” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a further electrode of the electrochemical biosensor that is configured to provide an electrochemical reference potential which, at least widely, is independent of the presence or absence or concentration of the analyte. Further, the term “combined counter electrode and reference electrode” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a further electrode of the electrochemical biosensor that is configured to provide an electrochemical reference potential and to balance the current flow from the working electrode.

[0021] As outlined above, the present method is directed to continuously manufacturing a template for a reference electrode or a template for a combined counter electrode and reference electrode. The term “template” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an intermediate product being manufactured from simpler base products and intended for further processing of more complex products. Specifically, the template may be used for further processing to manufacture the plurality of the reference electrodes or the combined counter electrodes and reference electrodes. The intermediate product may at least partially form part of the manufactured plurality of the reference electrodes or the combined counter electrodes and reference electrodes. Alternatively, in other examples, the intermediate product may not be part of the manufactured plurality of the reference electrodes or the combined counter electrodes and reference electrodes but may be used in one or more processing steps to manufacture the plurality of the reference electrodes or the combined counter electrodes and reference electrodes.

[0022] The template for the reference electrode or the combined counter electrode and reference electrode as manufactured by using the present method is an intermediate product, which may, preferably, be configured for producing at least one reference electrode or combined counter electrode and reference electrode in a continuous monitoring system. The term “continuous monitoring system” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a system configured for performing a process of continuously surveilling a person by consecutively acquiring data and deriving desired information therefrom without user interaction. For this purpose, a plurality of measurement signals are generated and evaluated, wherefrom the desired information is determined. Herein, the plurality of measurement signals may be recorded within fixed or variable time intervals or, alternatively or in addition, at an occurrence of at least one prespecified event. In particular, the continuous monitoring system may be configured for monitoring one or more analytes, in particular of glucose, such as for managing, monitoring, and controlling a diabetes state.

[0023] As outlined above, step i. of the present method comprises providing a continuous electrically conductive substrate. The term “providing” or any grammatical variation thereof as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a process of supplying and / or making available. Specifically, the providing of the substrate in step i. may comprise making the substrate available for further processing during the manufacturing process. The providing of the substrate may comprise supplying the substrate to a manufacturing device and / or producing the substrate from one or more base products. The substrate as provided during step i. of the present method is a continuous substrate. As used herein, the term “substrate” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an arbitrary element designed to carry one or more other elements disposed thereon or therein. Specifically, the substrate may be flexible and / or deformable. Preferably, the substrate may be a planar substrate. As generally used, the term “planar” refers to a body comprising extensions in two dimensions, typically denoted as “surface” of the planar body, which exceed the extension in a third dimension, usually denoted as “thickness” of the planar body, by a factor of 2, at least a factor of 5, at least a factor of 10, or even at least a factor of 20 or more. As an example, the substrate may have a thickness of 50 pm to 1 mm, specifically of 80 pm to 500 pm, such as 110 pm to 250 pm. Using a planar substrate may, particularly, facilitate providing a flat electrode. As generally used, the term “flat electrode” refers to a particular type of electrode which comprises a planar substrate that provides a carrier for the further elements, preferably the analyte detection agent, of the electrode to be provided, preferably, in form of one or more layers, directly or indirectly, deposited on the substrate. For the term “continuous”, reference can be made to the definition provided above.

[0024] As outlined above, a continuous electrically conductive substrate is provided during step i. of the present method. The term “electrically conductive” or any grammatical variation thereof as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a property of a material, also denoted as “electrically conductive material”, which is designed for carrying an electrical current through the material. For this purpose, an electrically conductive material having a low electrical resistance is preferred, in particular to avoid a dissipation of electrical energy carried by the electrical current within the material.

[0025] The substrate may be selected from a carbon-coated polymer foil. The term “coating” or any grammatical variation thereof as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a process which comprises depositing a material onto a surface. Further, the term “polymer” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. Further, the term “foil” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an arbitrary film like material being designed as a carrier. Specifically, the foil may have a foil shape, wherein the foil in a first extension direction may be at least ten times smaller than an extension of the foil in another direction, extending orthogonally to the first direction. The foil specifically may be made of at least one flexible or deformable material, such as at least one flexible or deformable plastic foil. The foil, as an example, may have a thickness of 10 pm to 500 pm. The polymer foil, specifically, may comprise macromolecules having a plurality of repeated subunits in a manner that they constitute the foil.

[0026] The polymer foil may be coated on at least one side, preferably on both sides, by a carbon ink, wherein the carbon ink may, in particular, comprise a binder material. The term “carbon” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a formation of the chemical element carbon from the period table of chemical elements. The term “carbon ink” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a formation of carbon that comprises paracrystalline particles, also denoted as pigment “carbon black”, which can be obtained from incomplete combustion of a carbon-comprising material. In contrast to soot, carbon ink has a higher surface-area-to-volume ratio and a significantly lower, particularly a negligible and non-bioavailable, polycyclic aromatic hydrocarbon content. However, using, alternatively or in addition, a different kind of carbon, in particular graphite, may also be feasible.

[0027] The carbon ink may, preferably, be a suspension having a solid content of 20 wt.% to 70 wt.%, more preferred of 30 wt.% to 60 wt.%, in particular of 40 wt.%, of the binder material. The term “binder material” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a first material which is configured to maintain at least one further material in a composition ‘as is’, preferably by using adhesion and / or cohesion. The binder material may, preferably, be selected from an organic binder material, specifically from the group consisting of polyvinyl acetate (PVA), peroxyacetic acid (PAA), polyethylene glycol (PEG), polyvinylphenol (PVP), polyvinyl sulfonate, polyvinyl amine, and polyvinyl chloride (PVC). However, using a different kind of binder material may also be feasible. Alternatively, the substrate may be selected from the group consisting of a metal-coated polymer foil, or a metallic foil. For the terms “coating, “polymer and “foil”, reference can be made to the respective definitions provided above. Further, the term “metal” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to at least one respective chemical element from the period table of chemical elements or to a composition comprising at least two metals. The metal for the metal-coated polymer foil or for the metallic foil may, preferably, be selected from the group consisting of gold, platinum, palladium, or a and copper-gold alloy; however using a different kind of metal may also be feasible.

[0028] As outlined above, step ii. of the present method comprises applying a paste composition comprising at least one binder material, silver particles and silver chloride particles to the substrate. The term “applying” or any grammatical variation thereof as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a process of disposing or and / or placing at least one element on at least one further element. The applying may comprise forming a layer of one element on a surface of another element. Specifically, the applying in step ii. may comprise disposing a selected kind of paste composition on a portion of the surface of the substrate. The term “surface” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an anterior area of an object or element. Specifically, the surface of the substrate may be an area having the selected kind of paste composition disposed thereon. In other words, the surface of the substrate may be an area facing towards the selected kind of paste composition as disposed onto the substrate.

[0029] The paste composition which is applied to the substrate during step ii. of the present method comprises at least one binder material, silver particles and silver chloride particles. The term “silver” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a formation of the chemical element silver from the period table of chemical elements. Further, the term “silver chloride” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a composition comprising the chemical elements silver and chlorine from the period table of chemical elements.

[0030] The term “binder material” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a first material which is configured to maintain at least one further material in a composition ‘as is’, preferably by using adhesion and / or cohesion. The binder material may, preferably, be selected from an organic binder material, specifically from the group consisting of thermoplastic polyurethane, silicone, (meth)acrylate, polyurethane, cellulose or a derivative thereof, resins, and waxes, or from an inorganic binder material. However, using a different kind of binder material may also be feasible.

[0031] The paste composition may, preferably, comprise a solid content of 25 wt.% to 75 wt.%, more preferred of 30 wt.% to 60 wt.%, in particular of 50 wt.%. In particular, the paste composition may comprise silver particles and silver chloride particles and 1 wt.% to 20 wt.%, preferably 1 wt.% to 5 wt.%, in particular 5 wt.%, of a the binder material.

[0032] In particular, the paste composition may, further, comprise at least one first solvent and, preferably, at least one second solvent. The term “solvent” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a first substance which is designed for receiving a second substance, whereby at least one of a solution or a suspension but no chemical composition is obtained.

[0033] The at least one first solvent may exhibit a higher volatility compared to the second solvent. The at least one first solvent may be a highly volatile solvent. The term “highly volatile solvent” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a substance which is designed for readily leaving the solution after introduction into it, in particular by fast vaporization. The at least one first solvent may, preferably, be selected from the group consisting of tetrahydrofuran, dioxane, methyl tetrahydrofuran, and toluene, acetone, diethyl ether, butylacetate, ethanol, methyl isobutyl ketone, and hexane. Using a highly volatile solvent together with a polar solvent exhibits the advantage that fast drying times and high web speeds of at least 5 m / min become possible when applying the paste composition to the substrate during step ii. The at least one optional second solvent is a polar solvent. The term “polar solvent” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an organic solvent having a high dielectric constant suitable for being miscible with the aqueous solution as comprised by the hydrogel compound. A highly volatile solvent as the first solvent is combined here with a further polar solvent as the second solvent to achieve both, firstly, a fast drying allowing a high application speed without taking into account typical disadvantages known for highly volatile solvents, in particular an early evaporation, resulting in in a loss of solvent during handling and / or a blockage of the coating tool during the coating process. The at least one polar solvent may, preferably, be selected from the group consisting of ethanol, ethyl acetate, 1 -propanol, isopropyl alcohol, water, acetonitrile, methanol, pyridine, ethylene glycol, diethylene glycol, gamma-butyrolactone, dimethylformamide, ethylene carbonate, dimethyl carbonate, sulfolane, dimethyl sulfoxide, formic acid, n-butanol, nitromethane, and acetic acid.

[0034] The paste composition may, preferably, be selected for adjusting a shear-thinning behavior on the substrate. For this purpose, a viscosity of the paste composition may, preferably, be adjusted to 200 mPas to 4000 mPas, more preferred to 500 mPas to 2000 mPas. During handling and holding times, sedimentation can be reduced by a high viscosity, while the composition may exhibit a rather low viscosity within the tool during coating. The desired shear-thinning behavior can be achieved in the paste composition by using the binder, the highly volatile solvent, the polar solvent, the silver particles, and the silver chloride particles. The term "viscosity" as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a grade of resistance of a fluid, particularly of the paste composition, to a deformation at a particular rate, wherein the grade is indicated by a force applied to the fluid multiplied by a time and divided by an area application of the force to the fluid.

[0035] Alternatively or in addition, the paste composition may, preferably, be selected for adjusting a wettability of the paste composition on the substrate and a homogeneous topography of the paste composition compound after drying. The term "wettability" as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a grade of a solid surface to maintain contact with a liquid compound, especially resulting from an intermolecular interaction between the solid surface and the liquid compound. The term “after drying” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a period of time after which a content of a highly volatile solvent in a composition, particularly in the paste composition, may be below a predefined threshold, such as below 5 wt.%, preferably below 1 wt.%, more preferred below 0.1 wt.%. The paste composition may, after drying, preferably have a silver chloride content of 5 wt.% to 40 wt.%, more preferred of 10 wt.% to 30 wt.%, in the template for the combined counter electrode and reference electrode. Further, the paste composition may, after drying, preferably has a silver chloride content of 30 wt.% to 90 wt.%, more preferred of 50 wt.% to 80 wt.%, in the template for the combined counter electrode and reference electrode.

[0036] The paste composition comprising the at least one binder material, the silver particles and the silver chloride particles is applied during step ii. of the present method to the substrate in a manner that a continuous line is formed, especially on the surface of the electrically conductive substrate. For the term “continuous”, reference can be made to the definition provided above. The term “continuous line” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an extended body having a continuous extension in one dimension while the extension in the two dimensions perpendicular thereto are small compared to the planar extension of substrate. The term “forming” or any grammatical variation thereof as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a process of generating at least one element, especially by using the paste composition that is designed for this purpose.

[0037] The continuous line of at the paste composition is applied to the carbon-coated substrate in a manner that the continuous line has a lateral width of 1 mm to 8 mm. The term “lateral width” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a lateral extension of an element, specifically the continuous line, in a direction that is perpendicular to a direction of a longitudinal extension of the element but parallel to the surface whereto the element is applied, wherein the longitudinal extension surpasses both the lateral width and the thickness of the element as defined below. The continuous line of the paste composition is applied to the carbon-coated substrate in a further manner that the continuous line has a mean thickness of 1 pm to 100 pm. The term “thickness” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an elevational extension of an element, specifically the continuous line, in a direction which is perpendicular with respect to both the direction of the longitudinal extension of the element and the lateral width of the element, and which is further perpendicular with respect to the surface whereto the element is applied.

[0038] As further outlined above, step ii. of the present method is performed by using a reel-to-reel process. The term “reel-to-reel process” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a process involving at least two turning objects and / or rotating objects, such as at least two rotating wheels and / or rolls. The reel-to-reel process may, specifically, comprise transferring at least one element stored on a first roll, such as an element having a sheet form and / or tape form, onto a second element, wherein at least one processing step is performed during the transfer. Thus, as an example, the reel-to-reel process may refer to a process starting with a first roll of material, wherein the first roll comprises a layer of the paste composition, and depositing the material as provided by the roll to a further roll as provided during step i., wherein the further roll comprises the electrically conductive substrate. The reel-to-reel-process may also be referred to as roll-to-roll-process.

[0039] The continuous reel-to-reel coating process may, particularly, be selected from a slot die coating process.. Herein, the slot die coating process may, preferably, be selected for manufacturing the continuous line having the lateral width 3 mm to 8 mm. The term “slot die coating process” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a process of depositing a coating material dissolved or suspended in an ink, comprising a precursor solution or a slurry, by using a shim. For applying the slot die coating process according to the present invention, the shim may, preferably, have a width of 0.1 mm to 0.7 mm, more preferred of 0.25 mm to 0.5 mm. In particular, the width for the shim may be adjusted for reducing or avoiding clogging of the at least one paste composition. As an alternative, the continuous reel-to-reel coating process may, particularly, be selected from a cannula coating process. Herein, the cannula coating process may, preferably, be selected for manufacturing the continuous line having the lateral width of 1 mm to below 3 mm. The term “cannula” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a device configured for guiding a liquid sample along a predetermined path. In particular, upon entry into the cannula, the liquid sample, especially the paste composition, may flow through the cannula, thus being transported by the cannula along the predetermined path, such as to the surface of a substrate. The cannula may specifically be a tube, in particular a small tube, such as a tube having a limited height and / or a limited cross section or diameter. However, using a different type of cannula or performing the continuous reel-to-reel coating process without using a cannula may also be feasible.

[0040] At least a surface of the cannula that is configured for being in contact with the paste composition may, preferably, be coated with a hydrophobic material. The term “hydrophobic material” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a substance which is configured to repel a paste composition from its surface. In particular, the hydrophobic material may be selected for adjusting an interaction between the cannula and the paste composition in a manner that a pinning on a dimension of the cannula and / or a creeping of the paste composition along the cannula may, preferably, be avoided. The hydrophobic material as used for the cannula may, preferably, be selected from the group consisting of polytetrafluoroethylene (PTFE), polyethylene (PE), polypropylene (PP), and silicon; however, using a different kind of hydrophobic material may also be feasible.

[0041] The method may further comprise at least one further step: iii. applying at least one further continuous line of at least one additional substance to the substrate.

[0042] The at least one further continuous line of the at least one additional substance may, preferably, be applied laterally with respect to the continuous line on the same surface of the substrate. The at least one further continuous line of the at least one additional substance may, preferably, be selected from at least one of an insulating layer, a mechanical protective layer, a biocompatibility layer, or an interference detection layer. The term “insulating layer” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a layer which comprises an electrically non-conductive material. The electrically non-conductive material may, preferably be selected from thermoplastic polyurethane, polytetrafluoroethylene, polyethylene, polyvinylidene difluoride, silicone, (meth)acrylate, polyurethane, polyimide, phenolic resins, polyolefines, resins, or waxes.

[0043] The term “mechanical protective layer” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a layer which is configured for providing mechanical protection to the substrate and / or the continuous line. The material for the mechanical protective layer may, preferably be the same as for the non-conductive material which, however, exhibits appropriate elasticity properties in a range known by the person skilled in the art.

[0044] The term “biocompatibility layer” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a layer which is configured for increasing a biocompatibility by masking the substrate and / or the continuous line against the immune system of a user of the biochemical sensor. The material for the biocompatibility layer may, preferably be selected from polyurethane, polyvinyl alcohol, polyethylene oxide, polyvinyl pyridine, or polymethacrylate.

[0045] The term “interference detection layer” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a layer which is configured for determining measuring errors of unknown magnitude that may occur due to the additional current in a glucose sensor, especially due to an amount of one or more interferents within the body fluid. In general, additional redox active substances may be present in a body fluid and can, thus, influence a measurement. In particular, a kind of interferent may react with an intermediate product, such as hydrogen peroxide (H2O2) being present due to a glucose reaction, whereby a concentration of the intermediate product in the body fluid may decrease, thereby diminishing a sensitivity of the measurement device. The interference detection layer may, preferably comprise polymethacrylate, polyurethane or polyvinyl pyridine. The method may further comprise at least one further step: iv. cutting the substrate comprising the continuous line into pieces in manner that each piece comprises a portion of the template.

[0046] The term “cutting” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a process of separating at least one element from at least one further element. The cutting may comprise using at least one cutting device configured for cutting the at least one element in the cutting process completely or using a device configured for introducing perforation lines into the at least one element. The cutting device may, preferably, be selected from a cutting blade or a laser, particularly depending on the dimensions involved in the cutting process; however using a different kind of cutting device may also be feasible.

[0047] In principle, the optional steps iii. to vi. may be performed in any desired order, however, performing the optional steps iii. to vi. in the indicated order may be preferred, wherein any one of the optional steps iii. to vi. may be performed in a repeating manner.

[0048] In a further aspect of the present invention, a plurality of reference electrodes or combined counter electrodes and reference electrodes is disclosed, wherein each electrode is based on the template for the particular electrode which is produced by a method of continuously manufacturing a template for a reference electrodes or a combined counter electrode and reference electrode according to the present invention, such as according to any one of the embodiments disclosed above and / or according to any one of the embodiments disclosed in further detail below. Each electrode may, preferably, be configured for being inserted into a skin of a patient.

[0049] The plurality of the electrodes produced by the manufacturing method according to the present invention may be assembled in units of manufactured plurality of electrodes, particularly in roll ware units or sheet ware units of 10, 20, 50, or even 100 electrodes having perforation lines between adjacent electrodes. Additionally or alternatively, the plurality of electrodes produced by the manufacturing method according to the present invention may be identified at a cutting edge between two separations of the plurality of the electrodes, e.g. at a plain cutting edge for a batch manufacturing method or at an angled cutting edged for a continuous manufacturing method. In a further aspect of the present invention, a continuous monitoring system is disclosed, wherein the continuous monitoring system comprises at least one electrode from the plurality of the reference electrodes or the combined counter electrodes and reference electrodes.

[0050] The manufacturing method, the template for a reference electrode or a combined counter electrodes and reference electrodes, and the plurality of the reference electrodes or combined counter electrodes and reference electrodes according to the present invention may provide a larger number of advantages, specifically compared with known methods or devices. In particular, a sensor roll substrate can be used which allows applying the paste composition via a continuous coating technique, such as cannula or slot die coating. This approach enables processing all relevant materials as quickly as possible, reducing a stand time of the paste composition to a minimum. It is sufficient that the paste composition only comprises a polymeric binder, silver and silver chloride particles as ingredients such that sedimentation of the particles within the paste composition can be neglected, resulting in a more homogeneous structure of the continuous lines on the substrate. The use of a highly volatile solvent with a polar solvent enables fast drying times and high web speeds of at least 5 m / min during formation of the continuous line when applying the paste composition to the substrate. Further, applying the chosen formulation comprising the highly volatile solvent and the polar solvent by using a slot die coating process with a coating width of 3 mm to 8 mm. The use of a coating width of 3 mm to 8 mm enables slot die coating to achieve the desired homogeneity. Clogging problems can be avoided by using a shim having a width of 0.1 mm to 0.7 mm, preferably of 0.25 mm to 0.50 mm, instead of a usual shim having a width of 0.10 mm to 0.15 mm. In particular, experimental data have shown that a higher width may be beneficial to prevent clogging, however, using a higher width increases a risk for air entrainment. Thus, the shim width of 0.1 mm to 0.7 mm, preferably of 0.25 mm to 0.50 mm, can be considered as an advantageous trade-off depending on the formulation of the paste composition and the process conditions used during step ii. In addition, a further coating compound can be applied without air bubbles rising, which may occur in the resulting dry layer due to air contained in the initial layer. For forming a continuous line having a width of 1 mm to below 3 mm, a cannula coating process can, preferably, be used. By filling up defect areas in the continuous by using a wet-on-wet process in which the binder is applied by slot die coating, a homogeneous topography can also be achieved here.

[0051] As used in the herein, the terms “have”, “comprise” or “include” or any arbitrary grammatical variations thereof are used in a non-exclusive way. Thus, these terms may both refer to a situation in which, besides the feature introduced by these terms, no further features are present in the entity described in this context and to a situation in which one or more further features are present. As an example, the expressions “A has B”, “A comprises B” and “A includes B” may both refer to a situation in which, besides B, no other element is present in A (i.e. a situation in which A solely and exclusively consists of B) and to a situation in which, besides B, one or more further elements are present in entity A, such as element C, elements C and D or even further elements.

[0052] Further, it shall be noted that the terms “at least one”, “one or more” or similar expressions indicating that a feature or element may be present once or more than once typically will be used only once when introducing the respective feature or element. Herein, in most cases, when referring to the respective feature or element, the expressions “at least one” or “one or more” will not be repeated, non-withstanding the fact that the respective feature or element may be present once or more than once.

[0053] Further, as used herein, the terms "preferably", "more preferably", "particularly", "more particularly", "specifically", "more specifically" or similar terms are used in conjunction with optional features, without restricting alternative possibilities. Thus, features introduced by these terms are optional features and are not intended to restrict the scope of the claims in any way. The invention may, as the skilled person will recognize, be performed by using alternative features. Similarly, features introduced by "in an embodiment of the invention" or similar expressions are intended to be optional features, without any restriction regarding alternative embodiments of the invention, without any restrictions regarding the scope of the invention and without any restriction regarding the possibility of combining the features introduced in such way with other optional or non-optional features of the invention.

[0054] Summarizing and without excluding further possible embodiments, the following embodiments may be envisaged:

[0055] Embodiment 1. A method of continuously manufacturing a template for a reference electrode or a combined counter electrode and reference electrode, the method comprising: i. providing a continuous electrically conductive substrate; and ii. applying a paste composition comprising at least one binder material, silver particles and silver chloride particles to the substrate by using a continuous reel-to-reel coating process, whereby a continuous line having a lateral width of 1 mm to 8 mm and a mean thickness of 1 pm to 100 pm is formed.

[0056] Embodiment 2. The method according to the preceding embodiment, wherein the paste composition is applied to a surface of the substrate. Embodiment 3. The method according to any one of the preceding embodiments, wherein the paste composition comprises a solid content of 25 wt.% to 75 wt.%, preferably of 30 wt.% to 60 wt.%, in particular of 50 wt.%.

[0057] Embodiment 4. The method according to the preceding embodiments, wherein the paste composition comprises 1 wt.% to 20 wt.%, preferably 1 wt.% to 10 wt.%, in particular 5 wt.%, of the binder material.

[0058] Embodiment 5. The method according to the preceding embodiment, wherein the binder material is selected from the group consisting of thermoplastic polyurethane, silicone, (meth)acrylate, polyurethane, cellulose or a derivative thereof, resins, waxes, and inorganic binder material.

[0059] Embodiment 6. The method according to any one of the three preceding embodiments, wherein the paste composition further comprises at least one first solvent.

[0060] Embodiment 7. The method according to the preceding embodiment, wherein the at least one first solvent is a highly volatile solvent selected from the group consisting of tetrahydrofuran, dioxane, methyl tetrahydrofuran, toluene, acetone, diethyl ether, butylacetate, ethanol, methyl isobutyl ketone, and hexane.

[0061] Embodiment 8. The method according to any one of the two preceding embodiments, wherein the paste composition further comprises at least one second solvent.

[0062] Embodiment 9. The method according to the preceding embodiment, wherein the at least one first solvent exhibits a higher volatility compared to the second solvent.

[0063] Embodiment 10. The method according to any one of the two preceding embodiments, wherein the at least one second solvent is a polar solvent selected from the group consisting of ethanol, ethyl acetate, 1 -propanol, isopropyl alcohol, water, acetonitrile, methanol, pyridine, ethylene glycol, diethylene glycol, gamma-butyrolactone, dimethylformamide, ethylene carbonate, dimethyl carbonate, sulfolane, dimethyl sulfoxide, formic acid, n- butanol, nitromethane, and acetic acid. Embodiment 11. The method according to any one of the preceding embodiments, wherein the paste composition is selected for adjusting a shear-thinning behavior on the substrate.

[0064] Embodiment 12. The method according to the preceding embodiment, wherein a viscosity of the paste composition is adjusted to 200 mPas to 4000 mPas, preferably to 500 mPas to 2000 mPas.

[0065] Embodiment 13. The method according to any one of the preceding embodiments, wherein the paste composition is selected for adjusting a wettability of the paste composition on the substrate and a homogeneous topography of the paste composition compound after drying.

[0066] Embodiment 14. The method according to any one of the preceding embodiments, wherein the paste composition after drying has a silver chloride content of 5 wt.% to 40 wt.%, preferably of 10 wt.% to 30 wt.%, in the template for the combined counter electrode and reference electrode.

[0067] Embodiment 15. The method according to any one of the preceding embodiments, wherein the paste composition after drying has a silver chloride content of 30 wt.% to 90 wt.%, preferably of 50 wt.% to 80 wt.%, in the template for the combined counter electrode and reference electrode.

[0068] Embodiment 16. The method according to any one of the preceding embodiments, wherein the substrate is selected from the group consisting of a carbon-coated polymer foil or a metal- coated polymer foil, or a metallic foil.

[0069] Embodiment 17. The method according to any one of the preceding embodiments, wherein the metal for the metal-coated polymer foil or the metallic foil is selected from the group consisting of gold, platinum, palladium, and copper-gold alloy.

[0070] Embodiment 18. The method according to any one of the preceding embodiments, wherein the continuous reel-to-reel coating process is selected from a slot die coating process or a cannula coating process.

[0071] Embodiment 19. The method according to the preceding embodiment, wherein the slot die coating process is selected for manufacturing the continuous line having the lateral width 3 mm to 8 mm. Embodiment 20. The method according to the preceding embodiment, wherein applying the slot die coating process comprises using a shim having a width of 0.1 mm to 0.7 mm, preferably of 0.25 mm to 0.5 mm.

[0072] Embodiment 21. The method according to the preceding embodiment, wherein the width for the shim is adjusted for reducing or avoiding clogging of the at least one paste composition.

[0073] Embodiment 22. The method according to any one of the four preceding embodiments, wherein the cannula coating process is selected for manufacturing the continuous line having the lateral width of 1 mm to below 3 mm.

[0074] Embodiment 23. The method according to any one of the preceding embodiments, wherein the cannula coating process comprises using a cannula.

[0075] Embodiment 24. The method according to any one of the preceding embodiments, the method further comprising iii. applying at least one further continuous line of at least one additional substance to the substrate.

[0076] Embodiment 25. The method according to the preceding embodiment, wherein the at least one further continuous line of the at least one additional substance is applied laterally with respect to the continuous line on the same surface of the substrate.

[0077] Embodiment 26. The method according to any one of the two preceding embodiments, wherein the at least one further continuous line of the at least one additional substance is selected from at least one of an insulating layer, a mechanical protective layer, a biocompatibility layer, or an interference detection layer.

[0078] Embodiment 27. The method according to the preceding embodiment, wherein the at least one insulating layer is a hydrophobic cover layer or an additional protective layer.

[0079] Embodiment 28. The method according to the preceding embodiment, wherein the at least one additional protective layer is adjusted for reducing or avoiding a generation of bubbles or air pockets in the at least one paste composition. Embodiment 29. The method according to any one of the three preceding embodiments, wherein at least one of the insulating layer or the mechanical protective layer comprises a material selected from the group consisting of thermoplastic polyurethane, polytetrafluoroethylene, polyethylene, polyvinylidene difluoride, silicone, (meth)acrylate, polyurethane, resins, waxes, polyimides, phenolic resins, and polyolefines.

[0080] Embodiment 30. The method according to any one of the four preceding embodiments, wherein the biocompatibility layer comprises a material selected from the group consisting of polyurethane, polyvinyl alcohol, polyethylene oxide, polyvinyl pyridine, and polymethacrylate.

[0081] Embodiment 31. The method according to any one of the four preceding embodiments, wherein the interference detection layer comprises a material selected from the group consisting of polymethacrylate, polyurethane, and polyvinyl pyridine.

[0082] Embodiment 32. The method according to any one of the preceding embodiments, the method further comprising iv. cutting the substrate comprising the continuous line into pieces in manner that each piece comprises a portion of the template.

[0083] Embodiment 33. The method according to the preceding embodiment, wherein the cutting process is a continuous cutting process.

[0084] Embodiment 34. The method according to any one of the preceding embodiments, wherein the template is an intermediate product configured for producing the reference electrode or the combined counter electrode and reference electrode in a continuous monitoring system.

[0085] Embodiment 35. A plurality of reference electrodes or combined counter electrodes and reference electrodes, wherein each reference electrode or combined counter electrode and reference electrode is based on the template that is produced by a method according to any one of the preceding embodiments.

[0086] Embodiment 36. The plurality of the reference electrodes or the combined counter electrodes and reference electrodes according to the preceding embodiment, wherein each reference electrode or combined counter electrode and reference electrode is configured for being inserted into a skin of a patient.

[0087] Embodiment 37. A continuous monitoring system, wherein the continuous monitoring system comprises at least one reference electrode or combined counter electrode and reference electrode from the plurality of the reference electrodes or the combined counter electrodes and reference electrodes according to any one of the two preceding embodiments.

[0088] Short description of the Figures

[0089] Further optional features and embodiments are disclosed in more detail in the subsequent description of embodiments, preferably in conjunction with the dependent claims. Therein, the respective optional features may be implemented in an isolated fashion as well as in any arbitrary feasible combination, as the skilled person will realize. The scope of the invention is not restricted by the preferred embodiments. The embodiments are schematically depicted in the Figures. Therein, identical reference numbers in these Figures refer to identical or functionally comparable elements. In the Figures:

[0090] Figure 1 schematically illustrates an exemplary embodiment of an apparatus configured for performing a method of continuously manufacturing a template for a combined counter electrode and reference electrode in a side view;

[0091] Figures 2A to 2B schematically illustrate exemplary embodiments of templates in a top view after continuously manufactured by the method as illustrated in Figure 1 in a top view;

[0092] Figure 3 schematically illustrates an exemplary embodiment of a side of the combined counter electrode and reference electrode in a continuous monitoring sensor in a top view, the electrode being based on the template as illustrated in Figure 2B; and

[0093] Figure 4 schematically illustrates an exemplary embodiment of a topography of the combined counter electrode and reference electrode as illustrated in Figure 3 in a side view.

[0094] Detailed description of the embodiments

[0095] Figure 1 schematically illustrates an exemplary embodiment of an apparatus 110, which is configured for performing a method of continuously manufacturing a template 112 for an electrode 114 according to the present invention in a side view, wherein the electrode 114 is selected from a reference electrode or a combined counter electrode and reference electrode. In the following, the combined counter electrode and reference electrode is exemplarily used; however, the method steps as described herein are mutatis mutandis also applicable to a reference electrode (not depicted here).

[0096] As outlined above, the working electrode 114 is manufactured for a purpose of providing an electrochemical reference potential and balancing a current flow from a working electrode, which is designed for performing an electrochemical detection reaction for detecting a presence and / or a concentration of at one or more analytes in a sample of a bodily fluid. In the field of medical diagnostics, such in point of care applications and / or in laboratories, the sample of the bodily fluid may, particularly, be selected from saliva, blood, interstitial fluid, urine, salvia, sweat, or serum. Examples of analytes to be detected are antigenic proteins of viruses, such as antigenic proteins of the SARS-CoV-2 coronavirus, and other types of analytes, such as glucose, triglycerides, lactate, cholesterol or other types of analytes typically present in these bodily fluids. In the following, the analyte is represented by blood glucose as a particular example; however, the methods and apparatuses as described therein are also applicable to other kind of analytes and / or a further kind of samples comprising an analyte.

[0097] In accordance with step i. of the present method, a continuous electrically conductive 116 is provided in a continuous manner by using a first roll 118 as illustrated in Figure 1. As outlined above, the substrate 116 may, preferably, comprise a polymer foil or a metallic foil (not depicted here), wherein the polymer foil may be coated on at least one side, preferably on both sides, by a metal or by carbon ink. The metal for the metal-coated polymer foil or the metallic foil may, preferably, be selected from the group consisting of gold, platinum, palladium, and copper-gold alloy. The carbon ink may, preferably, be a suspension having a solid content of 20 wt.% to 70 wt.%, more preferred of 30 wt.% to 60 wt.%, in particular of 40 wt.%, of a binder material. The carbon ink may, preferably, be a formulation of at least one of carbon black, i.e. paracrystalline particles obtained from an incomplete combustion of a carbon-comprising material or graphite. The binder material is configured to maintain the carbon ink in a composition ‘as is’, preferably by using adhesion and / or cohesion. The binder material may, preferably, be selected from an organic binder material, specifically from the group consisting of polyvinyl acetate (PVA), peroxyacetic acid (PAA), polyethylene glycol (PEG), polyvinylphenol (PVP), polyvinyl sulfonate, polyvinyl amine, and polyvinyl chloride (PVC). However, using a different kind of binder material may also be feasible. In accordance with step ii. of the present method, a continuous line 120 is formed on the substrate 116 by applying a paste composition 122 by using the continuous reel-to-reel coating process. As illustrated in Figure 1, the continuous reel-to-reel coating process involves the first roll 118, which is configured for providing the continuous substrate 116 in a continuous manner, and a second roll 124, which is configured for transporting the template 112 for the electrode 114. The paste composition 122 is a mixture comprising at least one binder material, silver particles and silver chloride particles. As outlined above, the paste composition 122 may, preferably, comprise a solid content of 25 wt.% to 75 wt.%, preferably of 30 wt.% to 60 wt.%, in particular of 50 wt.%. The paste composition 122 further comprises one or more first solvents and, optionally, one or more second solvents, wherein the first solvent may exhibit a higher volatility compared to the second solvent. While the first solvent may be highly volatile solvent, preferably, be selected from the group consisting of tetrahydrofuran, dioxane, methyl tetrahydrofuran, toluene, acetone, diethyl ether, butylacetate, ethanol, methyl isobutyl ketone, and hexane, the second solvent may be a polar solvent, preferably, be selected from the group consisting of ethanol, ethyl acetate, 1 -propanol, isopropyl alcohol, water, acetonitrile, methanol, pyridine, ethylene glycol, diethylene glycol, gamma-butyrolactone, dimethylformamide, ethylene carbonate, dimethyl carbonate, sulfolane, dimethyl sulfoxide, formic acid, n-butanol, nitromethane, and acetic acid. However using, as different first solvent and / or second solvent may also be feasible. In particular, the first solvent and / or second solvent may be chosen to adjust a viscosity of the paste composition 122, preferably to 200 mPas to 4000 mPas, more preferred to 500 mPas to 2000 mPas.

[0098] During handling and holding times, sedimentation can be reduced by a high viscosity, while the composition may exhibit a rather low viscosity within the tool during coating. The desired shear-thinning behavior can be achieved in the paste composition 122 by using the binder, the highly volatile solvent, the polar solvent, the silver particles, and the silver chloride particles. Both the solid content in the paste composition 122 and the substrate 116 have been coordinated in such a manner that a robust coating becomes possible over a wide viscosity range of 200 mPas to 4000 mPas as demonstrated by the following Table, which indicates the dynamic viscosity in mPas for 11 samples having different compositions:

[0099]

[0100] As further illustrated in Figure 1, the paste composition 122 can be applied to the substrate 116 by using a cannula 126, which is configured for guiding the initial composition 123 along a predetermined path towards a surface 130 of the substrate 116. The illustrated cannula 126 is a small tube having a limited cross section or diameter; however, using a different type of the cannula 126 or performing the continuous reel-to-reel coating process without using the cannula 126 may also be feasible. Further, the illustrated cannula 126 has a hydrophobic coating 128 configured to repel the paste composition 122 from a surface of the cannula 126, particularly for adjusting an interaction between the cannula 126 and the paste composition 122 in a manner that a pinning on a dimension of the cannula 126 and / or a creeping of the paste composition 122 along the cannula 126 may, preferably, be avoided. As outlined above, the hydrophobic coating 128 may, preferably, comprise polytetrafluoroethylene (PTFE), polyethylene (PE), polypropylene (PP), or silicon; however, using a different kind of hydrophobic material may also be feasible.

[0101] The application of the paste composition 122 to the substrate 116 is performed in a manner that the continuous line 120, which is formed by application of the paste composition 122 on the surface 130 of the substrate, has a lateral width 132 of 1 mm to 8 mm and a mean thickness 134 of 1 pm to 100 pm. Herein, the lateral width 132 indicates a lateral extension of the continuous line 120 in a direction that is perpendicular to a direction 136 of transport of the substrate 116 by using the rolls 118, 124, while the mean thickness 134 indicates an elevational extension of the continuous line 120 in a direction that is perpendicular to both the direction 132 of transport of the substrate 116 and the lateral extension of the continuous line 120. Figure 4 schematically illustrates a manner of determining a value for the mean thickness 134 of the continuous line 120 on the substrate 116.

[0102] In accordance with optional step iii. of the present method, one or more further continuous lines 140, 140’ of at least one additional substance can be applied to the carbon-coated substrate. As schematically illustrated in Figure 2B, the further continuous lines 140, 140’ may, preferably, be applied laterally with respect to the continuous line 120 of the paste composition 122 on the same surface 130 of the substrate 116. As shown there, the further continuous lines 140, 140’ may, preferably, be insulating layers comprising at least one electrically non-conductive material. As an alternative (not depicted here), the one or more further continuous lines 140, 140’ may, preferably, be selected from a mechanical protective layer, a biocompatibility layer, or an interference detection layer.

[0103] In accordance with further optional step v. of the present method, the substrate 116 comprising the continuous line 120 of the paste composition 122 is cut into pieces 150 in manner that each piece 150 comprises a portion of the template 112 for the electrode 114. As further illustrated in Figure 1, a continuous cutting process may comprise consecutively using at least one cutting device 152, which may be configured for cutting the template 112 into the desired pieces 150 during the cutting process. Herein, the cutting device may, preferably, be selected from a cutting blade or a laser, particularly depending on the dimensions involved in the cutting process. As an alternative (not depicted here), a device for introducing perforation lines can be used, wherein the desired pieces 150 can be obtained later by breaking the perforation lines.

[0104] Figures 2A to 2B schematically illustrate exemplary embodiments of the templates 112 for the combined counter electrode and reference electrode 114 in a top view after continuously manufacturing the templates 112 by the method as illustrated in Figure 1 prior to an optional cutting process according to optional method step v.

[0105] The exemplary template 112 as shown in Figure 2A illustrates the templates 112 for the electrode 114 after performing method step ii. as indicated above. As shown in Figure 2A, the paste composition 122 has already been formed on the substrate 116 in a manner that the continuous line 120 has a lateral width 132 of 1 mm to 8 mm and a mean thickness 134 of 1 pm to 100 pm. The exemplary template 112 as further shown in Figure 2B illustrates the templates 112 for the electrode 114 after performing optional method step iii. as indicated above. As shown in Figure 2B, the further continuous lines 140, 140’ have already been formed laterally with respect to the continuous line 120 of the at least one paste composition 122 on the same surface 130 of the substrate 116.

[0106] Figure 3 schematically illustrates an exemplary embodiment of a side of the combined counter electrode and reference electrode 114 of a continuous monitoring sensor in a top view. The continuous monitoring sensor may, preferably, be configured for being inserted into a skin of a patient. As shown in Figure 3, the electrode 114 as illustrated here is based on the template 112 for the electrode 114 as depicted in Figure 2B having the continuous line 120 of the paste composition 122 and the further continuous lines 140, 140’ both formed during method step ii. along the whole piece 150 of the substrate 116 along the direction 136 of transport of the substrate 116.

[0107] In this manner, a plurality of the electrodes 114 can, preferably, be produced by the manufacturing method according to the present invention, wherein the plurality of the electrodes 114 may be assembled in units of manufactured plurality of the working electrodes 114, particularly in roll ware units or sheet ware units of 10, 20, 50, or even 100 electrodes 114 already being cut into the pieces 150 or having perforation lines between adjacent electrodes 114 configured for generating the pieces 150 later.

[0108] Figure 4 schematically illustrates an exemplary embodiment of a topography 154 of the combined counter electrode and reference electrode 114 as illustrated in Figure 3 in a side view. As depicted therein, the mean thickness 134 of the continuous line 120 on the substrate 116 can be determined by measuring a mean height over a plateau region formed by the lateral width 132 of the continuous line 120.

[0109] List of reference numbers apparatus template electrode, selected from a reference electrode or a combined counter electrode and reference electrode

[0110] (continuous electrically conductive) substrate first roll continuous line enzyme-wired hydrogel compound second roll cannula hydrophobic coating surface lateral width mean thickness direction of transport surface , 140’ further continuous line piece cutting device topography

Claims

Roche Diabetes Care GmbH September 30, 2025RD15692PC ST / GS / KVClaims1. A method of continuously manufacturing a template (112) for a reference electrode or a combined counter electrode and reference electrode (114), the method comprising: i. providing a continuous electrically conductive substrate (116); and ii. applying a paste composition (122) comprising at least one binder material, silver particles and silver chloride particles to the substrate (116) by using a continuous reel-to-reel coating process, whereby a continuous line (120) having a lateral width (132) of 1 mm to 8 mm and a mean thickness (134) of 1 pm to 100 pm is formed.

2. The method according to the preceding claim, wherein the paste composition (122) comprises a solid content of 25 wt.% to 75 wt.%.

3. The method according to any one of the preceding claims, wherein the paste composition (120) comprises 1 wt.% to 20 wt.% of the binder material.

4. The method according to any one of the preceding claims, wherein the paste composition further comprises at least one first solvent.

5. The method according to the preceding claim, wherein the at least one first solvent is a highly volatile solvent selected from the group consisting of tetrahydrofuran, dioxane, methyl tetrahydrofiiran, toluene, acetone, diethyl ether, butylacetate, ethanol, methyl isobutyl ketone, and hexane, and wherein the at least one second solvent is a polar solvent selected from the group consisting of ethanol, ethyl acetate, 1-propanol, isopropyl alcohol, water, acetonitrile, methanol, pyridine, ethylene glycol, diethylene glycol, gamma-butyrolactone, dimethylformamide, ethylene carbonate, dimethyl carbonate, sulfolane, dimethyl sulfoxide, formic acid, n-butanol, nitromethane, and acetic acid6. The method according to any one of the two the preceding claims, wherein the paste composition further comprises at least one second solvent, wherein the at least one first solvent exhibits a higher volatility compared to the second solvent.

7. The method according to any one of the preceding claims, wherein a viscosity of the paste composition (122) is adjusted to 200 mPas to 4000 mPas.

8. The method according to any one of the preceding claims, wherein the continuous reel- to-reel coating process is selected from a slot die coating process or a cannula coating process.

9. The method according to the preceding claim, wherein the slot die coating process is selected for manufacturing the continuous line (120) having the lateral width 3 mm to 8 mm, and wherein the cannula coating process is selected for manufacturing the continuous line (120) having the lateral width of 1 mm to below 3 mm.

10. The method according to any one the two preceding claims, wherein applying the slot die coating process comprises using a shim having a width of 0.1 mm to 0.7 mm.

11. The method according to any one of the preceding claims, the method further comprising iii. applying at least one further continuous line (140, 140’) of at least one additional substance to the substrate (116).

12. The method according to the preceding claim, wherein the at least one further continuous line (140, 140’) of the at least one additional substance is applied laterally with respect to the continuous line (120) on the same surface (130) of the substrate (116), wherein the at least one further continuous line (140, 140’) of the at least one additional substance is selected from at least one of an insulating layer, a mechanical protective layer, a biocompatibility layer, or an interference detection layer.

13. The method according to any one of the preceding claims, the method further comprising iv. cutting the substrate (116) comprising the continuous line (120) into pieces (150) in manner that each piece (150) comprises a portion of the template (112).

14. A plurality of reference electrodes or combined counter electrodes and reference electrodes (114), wherein each reference electrode or combined counter electrode andreference electrode (114) is based on the template (112) that is produced by a method according to any one of the preceding claims.

15. A continuous monitoring system, wherein the continuous monitoring system comprises at least one reference electrode or combined counter electrode and reference electrode (114) from the plurality of the reference electrodes or the combined counter electrodes and reference electrodes (114) according to the preceding claim.

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