Electrode for an analyte sensor and manufacturing method thereof

Abstract

The present invention relates in a first aspect to an electrode for an analyte sensor, comprising a layer, which comprises silver chloride (AgCl) and a thermoplastic polyurethane, wherein the thermoplastic polyurethane is obtained or obtainable from an aliphatic polyisocyanate and a polyether polyol. A second aspect of the invention relates to an analyte sensor comprising an electrode of the first aspect of the invention. In a third aspect, the invention is directed to a method for manufacturing an electrode of an analyte sensor. A fourth aspect of the invention is directed to an electrode of an analyte sensor, obtained or obtainable from the method of the second aspect of the invention. In a fifth aspect, the invention is related to a method for manufacturing an analyte sensor as of the second aspect. A sixth aspect of the invention is directed to an analyte sensor, obtained or obtainable from the method of the fifth aspect of the invention. A seventh aspect of the invention is directed to a use of an analyte sensor of the sixth aspect for detecting at least one analyte.

Description

[0001] ELECTRODE FOR AN ANALYTE SENSOR AND MANUFACTURING METHOD THEREOF

[0002] Technical Field

[0003] The present invention relates in a first aspect to an electrode for an analyte sensor, comprising a layer, which comprises silver chloride (AgCl) and a thermoplastic polyurethane, wherein the thermoplastic polyurethane is obtained or obtainable from an aliphatic polyisocyanate and a poly ether polyol.

[0004] A second aspect of the invention relates to an analyte sensor comprising an electrode of the first aspect of the invention. In a third aspect, the invention is directed to a method for manufacturing an electrode of an analyte sensor. A fourth aspect of the invention is directed to an electrode of an analyte sensor, obtained or obtainable from the method of the second aspect of the invention. In a fifth aspect, the invention is related to a method for manufacturing an analyte sensor as of the second aspect. A sixth aspect of the invention is directed to an analyte sensor, obtained or obtainable from the method of the fifth aspect of the invention. A seventh aspect of the invention is directed to a use of an analyte sensor of the sixth aspect for detecting at least one analyte.

[0005] Background art

[0006] WO 2022 / 112138 Al describes a method for manufacturing an electrode of an analyte sensor, and the respective analyte sensor itself. The analyte sensor comprises a layer of an AgCl-containing composition, the layer having an outer surface and an inner surface. At least a part of the AgCl on the outer surface of the layer of the AgCl containing composition is reduced, whereby elemental Ag on the outer surface is formed.

[0007] WO 2022 / 008394 Al discloses an analyte sensor comprising a substrate, at least one working electrode, at least one second electrode and a membrane, wherein the membrane is located on top of the at least one second electrode. Silver, in particular Ag / AgCl, is comprised in the at least one second electrode, which is why the membrane provides a selective barrier, which restricts transfer of silver cations and / or silver chloride through the membrane.

[0008] Commercial silver (Ag) / silver chloride (AgCl) formulations are commonly used for electrocardiography (ECG), biosensors, and iontophoresis (drug delivery). However, commercial pastes are not produced with the focus of obtaining extended in vivo runtime of biosensors. Therefore, as described in the prior art, a covering of the reference electrode (RE) is required to reduce the solubility of AgCl; see Anal. Chem. 1994, 66, 674-679. The consumption / solubility of the AgCl component in the RE in vivo is multifactorial and is described in the literature. The released amount of AgCl, especially of Ag+, leads to undesired immune reactions, which distort the measurement signal of an analyte sensor. Thus, polymer based formulations are described, which are intended to avoid AgCl release. However, existing formulations based on, for example, dipropylene glycol monomethyl ether and polyester is have the disadvantage of a greatly reduced in vivo sensitivity, at least initially if no protective layer is used. A protective layer is thus essential but any opening size to the Ag / AgCl electrode must be precisely controlled in vivo in order to avoid a negative effect in an in vivo measurement.

[0009] The problem underlying the present invention was thus the provision of formulation that ensures reduced accessibility through the appropriate choice of a polymeric material, thus also allowing the omit a protective layer.

[0010] Summary of the invention

[0011] This problem is addressed by an electrode for an analyte sensor, comprising a layer, which comprises silver chloride (AgCl) and a thermoplastic polyurethane, wherein the thermoplastic polyurethane is obtained or obtainable from an aliphatic polyisocyanate and a polyether polyol, by an analyte sensor, a method for manufacturing an electrode of an analyte sensor, an electrode of an analyte sensor, obtained or obtainable from the method, a method for manufacturing an analyte sensor, an analyte sensor, obtained or obtainable from said method and a use of a respective analyte sensor t for detecting at least one analyte with the features of the independent claims. Advantageous embodiments which might be realized in an isolated fashion or in any arbitrary combinations are listed in the dependent claims as well as throughout the specification.

[0012] As used in the following, 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. 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. In the following, in most cases, when referring to the respective feature or element, the expressions “at least one” or “one or more” will not be repeated, notwithstanding the fact that the respective feature or element may be present once or more than once.

[0013] Further, as used in the following, 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 a way with other optional or non-optional features of the invention.

[0014] 1staspect - electrode

[0015] This problem is addressed by an electrode for an analyte sensor, comprising a layer, which comprises silver chloride (AgCl) and a thermoplastic polyurethane, wherein the thermoplastic polyurethane is obtained or obtainable from an aliphatic polyisocyanate and a polyether polyol.

[0016] It was surprisingly found that using said specific thermoplastic polyurethane for the AgCl layer, compared to a layer with another polymer of the state of the art (polyester), showed a drastically reduced leaching of Ag+into an aqueous phase. This allows when implanted to avoid undesired immune reactions caused by Ag+leaching. Furthermore, for electrode and consequently also for the related analyte sensor, a simpler and thus cost optimized design becomes possible as additional protective layers can be omitted.

[0017] In some preferred embodiments of the electrode, the aliphatic polyisocyanate is an aliphatic diisocyanate, more preferably selected from the group consisting of isophorone diisocyanates (IPDI), hexamethylene diisocyanates (HDI), dicyclohexylmethane diisocyanates (HMDI), cyclohexyl diisocyanates (CHDI), tetramethylxylene diisocyanates (TMXDI), isomers of these aliphatic diisocyanates and mixtures of two or more thereof. In some preferred embodiments of the electrode, the polyether polyol is a polyether diol, preferably selected from the group consisting of polyethylene glycol) (PEG), polypropylene glycol) (PPG), poly(tetramethylene glycol) (PTMG), copolymers of two or more thereof and mixtures of two or more thereof, more preferably selected from the group consisting of polypropylene glycol) (PPG), poly(tetramethylene glycol) (PTMG), copolymers of these two and mixtures of these two, more preferably the polyether polyol comprises, more preferably is, PTGM.

[0018] In some preferred embodiments of the electrode, the aliphatic polyisocyanate comprises at least HMDI and the polyether polyol comprises at least PTMG.

[0019] In some preferred embodiments of the electrode, the thermoplastic polyurethane is obtained or obtainable from an aliphatic polyisocyanate, a polyether polyol and a diol (chain extender).

[0020] In some preferred embodiments of the electrode, the diol (chain extender)has a molecular weight of less than 500 g / mol and is preferably selected from the group consisting of 1,4-butanediol (1,4- BD), 1,2-propylene glycol, 1,3 -butanediol, dipropylene glycol, tripropylene glycol, propylene glycol and mixtures of two or more thereof, more preferably the diol comprises at least 1,4- butanediol.

[0021] In some preferred embodiments of the electrode, the thermoplastic polyurethane is obtained or obtainable from an aliphatic polyisocyanate, which comprises at least HMDI, a polyether polyol, which comprises at least PTMG and a diol, which comprises at least 1,4-BD.

[0022] In some preferred embodiments of the electrode, the thermoplastic polyurethane comprises a soft segment and a hard segment, wherein the soft segment / hard segment ratio (SS / HS) is in the range of from 4 to 15, preferably determined by 'H NMR spectroscopy.

[0023] The hard segment of the thermoplastic polyurethane is based on the remainder of the polyether polyol, whereas the soft segment is based on the remainder of the aliphatic polyisocyanate and the diol (chain extender). Preferably, when the thermoplastic polyurethane is obtained from at least HMDI, PTMG and 1,4-BD, the hard segment is based on the remainders of HMDI and 1,4-BD (chain extender), and the soft segment is based on the remainder of PTMG.

[0024] In some preferred embodiments of the electrode, the thermoplastic polyurethane is hydrophobic, wherein the thermoplastic polyurethane has a water uptake in the range from 0 to 5 % by weight, preferably a water uptake in the range from 0 to <2 % by weight, more preferably a water uptake in the range from 0.1 to <1.5 % by weight, based on the total weight of the thermoplastic polyurethane in dry state being 100 weight-%, determined according to ASTM-D 570 after 24 hours at 23°C. “Dry state” according to ASTM-D 570 means that the specimen to be determined is dried in an oven for a specified time and temperature and then placed in a desiccator to cool. Immediately upon cooling the specimen is weighed, this giving the dry weight, which corresponds to 100 weight-%. The specimen is then emerged in water at 23°C for 24 hours. Afterwards, the specimen is removed, patted dry with a lint free cloth, and weighed, this giving the wet weight. Water uptake is expressed as increase in weight percent according to: Percent water uptake = [(wet weight - dry weight) / dry weight] x 100. The hydrophobic character of the thermoplastic polyurethane is relevant for the reduction of the leaching and the reduced accessibility of the Ag / AgCl.

[0025] In some preferred embodiments of the electrode, the thermoplastic polyurethane has a shore D hardness in the range of from 20 to 40 and / or a shore A hardness in the range of from 70 to 90, determined according to ASTM D2240. The Shore hardness as an indicator for the crystallinity of the thermoplastic polyurethane influences the leaching and the accessibility of the Ag / AgCl.

[0026] In some preferred embodiments of the electrode, the thermoplastic polyurethane has an elongation at break in the range of from 400 to 600 %, determined according to ASTM D412.

[0027] In some preferred embodiments of the electrode, the thermoplastic polyurethane has a flexural modulus in the range of from 300 to 3500 PSI, determined according to ASTM D790. The specific flexural modulus of the thermoplastic polyurethane is relevant in order to ensure adhesion to the substrate in particular under bending.

[0028] In some preferred embodiments of the electrode, the thermoplastic polyurethane has a glass transition temperature Tg of at least 40°C, wherein Tg is preferably determined by modulated differential scanning calorimetry (MDSC).

[0029] In some preferred embodiments of the electrode, the thermoplastic polyurethane has a number average molecular weight Mn in the range of from 40 to 160 g / mol.

[0030] In some preferred embodiments of the electrode, the thermoplastic polyurethane has a weight average molecular weight Mw in the range of from 50 to 250 g / mol.

[0031] In some preferred embodiments of the electrode, the layer which comprises silver chloride (AgCl) and a thermoplastic polyurethane comprises the thermoplastic polyurethane in a range of from 1 to 50 weight-%, preferably in the range of from 5 to 40 weight-%, more preferably in the range of from 10 to 30 weight-%, more preferably in the range of from 12 to 20 weight-%, based on the total weight of the layer being 100 weight-%. In some preferred embodiments of the electrode, the layer which comprises silver chloride (AgCl) and a thermoplastic polyurethane has a thickness in the range of from 1 pm to 60 pm (dry state).

[0032] In some preferred embodiments of the electrode, the weight based ratio of AgCl to thermoplastic polyurethane in the layer which comprises silver chloride (AgCl) and a thermoplastic polyurethane is in the range of from 1 : 10 (w / w) to 10 : 1 (w / w).

[0033] In some preferred embodiments of the electrode, the layer which comprises silver chloride (AgCl) and a thermoplastic polyurethane further comprises elemental silver (Ag). Preferably, the weight based ratio of Ag to AgCl in the layer is in the range of from 1 : 0.1 (w / w) to 1 : 5 (w / w).

[0034] In some preferred embodiments of the electrode, the layer which comprises silver chloride (AgCl), a thermoplastic polyurethane and elemental silver (Ag), comprises Ag and / or AgCl as particles, wherein the particles within the layer are at least in partial contact with each other and / or wherein Ag and AgCl are evenly distributed throughout the layer. The layer which comprises silver chloride (AgCl), a thermoplastic polyurethane and elemental silver (Ag) has at least two surfaces, wherein one surface represents the outer surface when considering an analyte sensor and another surface represents the inner surface of the layer when considering an analyte sensor. As indicated above, the layer before implantation comprises Ag and AgCl evenly distributed. Further, it is understood that when in use, i.e. when implanted, AgCl contained in particles closer to the one surface (the outer surface), due to contact with Ag and with surrounding electrolyte, is reduced thus forming Ag, so that over time a gradient of the Ag and AgCl concertation respectively is established throughout the layer.

[0035] In some preferred embodiments, the electrode is a counter electrode or a reference electrode or a combined counter / reference electrode.

[0036] 2ndaspect - Analyte sensor

[0037] In a second aspect, the invention is directed to an analyte sensor comprising:

[0038] (i) a substrate with a first side and a second side, and at least one conductive material positioned on the first side of the substrate;

[0039] (ii) an electrode positioned on the at least one conductive material, wherein the electrode comprises a layer, which comprises silver chloride (AgCl) and a thermoplastic polyurethane, said layer having an outer surface and an inner surface, wherein the outer surface faces away from the conductive material and wherein the inner surface is in contact with the conductive material, wherein the thermoplastic polyurethane is obtained or obtainable from an aliphatic polyisocyanate and a poly ether polyol; and

[0040] (iii) a working electrode.

[0041] In some preferred embodiments of the analyte sensor the working electrode of (iii) comprises at least one conductive material positioned on the second side of the substrate and at least one enzyme.

[0042] In some preferred embodiments of the analyte sensor the electrode according to (ii) is a counter electrode, a reference electrode or a combined counter / reference electrode. Preferably, the enzyme is selected from the group consisting of a glucose oxidase (EC 1.1.3.4), ahexose oxidase (EC 1.1.3.5), an (S)-2 hydroxy acid oxidase (EC 1.1.3.15), a cholesterol oxidase (EC 1.1.3.6), a glucose dehydrogenase, a galactose oxidase (EC 1.1.3.9), an alcohol oxidase (EC 1.1.3.13), an L-glutamate oxidase (EC 1.4.3.11), an L-aspartate oxidase (EC 1.4.3.16) and mixtures of two or more thereof.

[0043] As indicated above, the working electrode comprises an enzyme, which can be precisely one enzyme or a mixture of two or more enzymes. Precisely one enzyme is preferred. Specifically, the enzyme is capable of catalyzing a chemical reaction converting the analyte. As indicated above, enzyme is selected from the group consisting of a glucose oxidase (EC 1.1.3.4), ahexose oxidase (EC 1.1.3.5), an (S)-2 hydroxy acid oxidase (EC 1.1.3.15), a cholesterol oxidase (EC 1.1.3.6), a glucose dehydrogenase, a galactose oxidase (EC 1.1.3.9), an alcohol oxidase (EC 1.1.3.13), an L- glutamate oxidase (EC 1.4.3.11), and an L-aspartate oxidase (EC 1.4.3.16). In particular, the enzyme is a glucose oxidase (GOx) and / or modifications thereof. The enzyme may be comprised in a sensing material. The sensing material which comprises the enzyme may be located at least partially on the electrically conductive material of the working electrode. In particular, the sensing material may cover at least a portion of the at least one conductive trace. The sensing material in conjunction with the conductive trace forms the at least one working electrode. In particular, the sensing material preferably forms a layer on the at least one electrically conductive material. The sensing material may be applied by any known method to the at least one electrically conductive material, for example by a wet-coating process. A suitable wet-coating process is for example selected from the group consisting of spin-coating, spray-coating, doctor-blading, printing, dispensing, slot-coating, dip coating and screen printing. After the wet-coating process, the layer of the sensing material may be further treated. Such treatments are for example drying treatment, curing treatments and / or laser ablation treatments. Such treatments are known as such. The term “sensing 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 material that may be or may comprise at least a polymeric material; specifically it may be or may comprise at least a polymeric material and at least a metal containing complex. The metal containing complex may be selected from the group of transition metal element complexes, specifically the metal containing complex may be selected from osmium-complexes, ruthenium-complexes, vanadium-complexes, cobalt- complexes, and iron-complexes, such as ferrocenes, such as 2-aminoethylferrocene. Even more specifically, the sensing material may be a polymeric transition metal complex as described for example in WO 01 / 36660 A2, the content of which is included by reference. In particular, the sensing material may comprise a modified poly(vinylpyridine) backbone loaded with poly(bi- imidizyl) Os complexes covalently coupled through abidentate linkage. A suitable sensing material is further described in Feldmann et al, Diabetes Technology & Therapeutics, 5 (5), 2003, 769-779, the content of which is included by reference. Suitable sensing materials further may include ferrocene-containing polyacrylamide -based viologen-modified redox polymer, pyrrole-2, 2'- azino- bis(3-ethylbenzthiazoline-6-sulfonic acid)(ABTS)-pyrene, Naphthoquinone-LPEI. The polymeric transition metal complex may represent a redox mediator incorporated into a crosslinked redox polymer network. This is advantageous as it may facilitate electron transfer between the at least one enzyme or analyte and the conductive trace. In order to avoid a sensor drift, the redox mediator and the enzyme may be covalently incorporated into a polymeric structure. In an embodiment the sensing material may comprise a polymeric material and MnCE-particles or any other material catalyzing hydrogen peroxide oxidation reaction as well as the at least one enzyme. Another material catalyzing hydrogen peroxide oxidation reaction is Pt (platinum). Moreover, the sensing material may additionally comprise at least one crosslinker; the crosslinker may for example be capable of crosslinking at least part of the sensing material. Specifically the sensing material may comprise at least one crosslinker selected from UV-curable crosslinkers and chemical crosslinkers; more specifically the sensing material comprises a chemical crosslinker. Alternatively, the sensing material may be free of any crosslinker. “Free of any crosslinker” 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 to a concentration of crosslinker in the range from 0 to 0.5 wt-% based on the dry weight of the sensing material. The term “dry weight” as used herein refers to the dry matter of the respective material, e.g. the material without the addition of any water or other solvent. Suitable chemical crosslinkers according to the present invention are preferably selected from the group consisting of epoxide based crosslinkers, such as diglycidyl ethers like poly(ethylene glycol) di-glycidyl ether (PEG-DGE) and polypropylene glycol) diglycidyl ether; trifunctional short chain epoxides; anhydrides; diglycidyl ethers such as resorcinol diglycidyl ether, bisphenol A diglycidyl ether, diglycidyl 1,2-cyclohexanedicarboxylate, polyethylene glycol diglycidyl ether, glycerol diglycidyl ether, 1,4-butanediol diglycidyl ether, polypropylene glycol diglycidyl ether, bisphenol diglycidyl ether, poly(dimethylsiloxane), diglycidyl ether, neopentyl glycol diglycidyl ether, 1,2, 7, 8-di epoxy octane, l,3-glycidoxypropyl-l,l,3,3-tetramethyldisioxane; triglycidyl ethers such as N,N-diglycidyl-4-glycidyloxyaniline, trimethylolpropane triglycidyl ether; and tetraglycidyl ethers such as tetrakisepoxy cyclosiloxane, pentaerythritol tetraglycidyl ether, tetraglycidyl-4,4'-methylenebisbenzenamine.

[0044] The term “chemical crosslinker” 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 crosslinker that is capable of initiating a chemical reaction generating a crosslinked molecular network and / or a cross-linked polymer when exposed to heat. “Exposed to heat” may refer to being exposed to a temperature above 15°C, specifically to a temperature above 20 °C; more specifically to a temperature in the range from 20 °C to 50 °C and even more specifically to a temperature in the range from 20 °C to 25 °C. More specifically, chemical crosslinkers may initiate crosslinking of the sensing material when exposed to heat. The term “UV-curable crosslinker” 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 the ability of a chemical substance of initiating a photochemical reaction generating a crosslinked molecular network and / or a crosslinked polymer when irradiated by light in the UV spectral range. More specifically, UV-curable crosslinkers may initiate crosslinking of the layer of the sensing material when irradiated by UV light. Suitable UV curable crosslinkers according to the present invention include: benzophenone, diazirine and azide. Particularly suitable UV-curable crosslinkers are for example selected from the group consisting of, benzophenone comprising cross-linkers, poly(di(2 -hydroxy 3 aminobenzophenonepropylene) glycol), dibenzophenone 1,2-cyclohexanedicarboxylate, bis[2-(4- azidosalicylamido)ethyl] disulfide, reaction products of the reaction of 4-aminobenzophenone with any one of the above for the chemical cross-linker described di-glycidyl cross-linkers, triglycidyl cross-linkers and tetraglycidyl cross-linkers, an example of such a reaction product is 2, 4, 6, 8- tetramethyl-2,4,6,8- tetrakis(2-hydroxy 3-aminpropylbenzophenone)-cyclotetrasiloxan, and reaction products of the reaction of 4-benzoylbenzoic acid N-succinimidyl ester with a diamin or a jeffamin.

[0045] In some preferred embodiments of the analyte sensor the substrate is selected from the group consisting of an epoxy resin, a polycarbonate, a polyester, a polyvinylchloride, a polyurethane, a polyethylene, a polypropylene, polystyrene, a polyether, a polyamide, a polyimide, polytetrafluoroethylene or a copolymer thereof, and alumina.

[0046] In some preferred embodiments of the analyte sensor the substrate comprises a polyester, preferably selected from the group consisting of polyethylene terephthalate (PET), glycol modified polyethylene terephthalate, polyethylene naphthalate and mixtures of two or more thereof.

[0047] Within the context of the present invention, the term "substrate" specifically may refer, without limitation, to any kind of material or combination of materials which is suitable to form a carrier layer to support the at least one working electrode and the at least one second electrode. In particular the substrate may comprise an electrically insulating material. Within the context of the present invention "electrically insulating material" is a broad term and given its ordinary and customary meaning to a person of ordinary skill in the art. The term "electrically insulating material" may also encompass a dielectric material. The term specifically may refer, without limitation, to a material or combination of materials which prevent the transfer of electrical charges and which do not sustain a significant electrical current.

[0048] In some preferred embodiments of the analyte sensor the conductive material of (ii) and / or of the working electrode is selected from the group consisting of metals, nonmetallic electrically conductive materials and mixtures of two or more thereof.

[0049] A ’’conductive material" within the context of the present invention refers to an electrically conductive material, i.e. a material being capable of sustaining an electrical current. Thus, the at least one conductive material may be selected from the group consisting of metals, and nonmetallic electrically conductive materials. Suitable metals are known as such and are, for example, selected from the group consisting of gold, nickel, platinum, and palladium, wherein gold is particularly preferred. Suitable nonmetallic electrically conductive materials are for example selected from the group consisting of carbon, carbon paste, gold paste or conductive polymers. Suitable conductive polymers are, for example polyaniline and / or poly-3 ,4-ethylenedioxythiophene (PEDOT). Carbon paste may comprise, for example, carbon and a solvent such as diethylene glycol butyl ether and at least one binder such as vinyl chloride co- and terpolymers. Carbon paste is known as such. Thus, the at least one electrically conductive material of the at least one working electrode preferably is selected from the group consisting of gold, nickel, platinum, palladium, carbon, carbon paste, polyaniline and poly-3 ,4-ethylenedioxythiophene (PEDOT), particularly preferred, the at least one electrically conductive material of the at least one working electrode is selected from the group consisting of gold, carbon, and carbon paste. More preferably, the at least one electrically conductive material consists essentially of gold and / or carbon and / or carbon paste. In an embodiment, the at least one electrically conductive material has a layered structure wherein a first layer consists of gold and a second layer consists of carbon and / or carbon paste. In this embodiment, preferably, gold is positioned on top of the first side of the substrate and on top of the gold, carbon and / or carbon paste is positioned. In particular, the at least one working electrode may comprise the at least one electrically conductive material in the form of at least one conductive trace. The term “conductive trace” within the context of the present invention refers, without limitations, to an electrically conductive strip, layer, wire or other type of electrical conductor. The conductive trace may have a thickness of at least 0.05 pm, preferably of at least 0.5 pm, more preferably of at least 5 pm, specifically of at least 7 pm, or at least 10 pm. In the case where the conductive trace comprises carbon or is carbon, the conductive trace may specifically have a thickness of at least 7 pm, more specifically of at least 10 pm. Specifically, in the case where the conductive trace is gold, the conductive trace may have a thickness of at least 50 nm, more specifically of at least 900 nm. The at least one electrically conductive material may be positioned on the first side of the substrate by any known method, for example via chemical vapor deposition (CVD), physical vapor deposition (PVD), or a wet-coating process. Wet-coating processes are known as such. A suitable wet-coating process is for example selected from the group consisting of spin-coating, spray coating, doctor-blading, printing, dispensing, slot-coating, dip coating and screen printing.

[0050] In some preferred embodiments, the analyte sensor does not comprise a protective layer at least partially covering the outer surface of the layer of the electrode of (ii).

[0051] In some preferred embodiments, the analyte sensor further comprising a protective layer at least partially covering the outer surface of the layer of the electrode of (ii).

[0052] The protective layer generally may selectively allow for one or more molecules and / or compounds to pass, whereas other molecules and / or compounds are stopped by the protective layer. Thus, the protective layer is permeable for the at least one analyte to be detected. Thus, as an example, the protective layer may be permeable for one or more of glucose, lactate, cholesterol or other types of analytes. The at least one protective layer may hence function as a diffusion barrier that controls diffusion of the analyte from the exterior, e.g. the body fluid surrounding the analyte sensor, to the sensing material, i.e. the enzyme molecules in the sensing material. Furthermore, the protective layer may function to reduce leaching of Ag+cations from the layer of the electrode of (ii) into its surroundings. In addition, the at least one protective layer may function as a biocompatibility membrane layer as mentioned elsewhere herein. The protective layer, as an example, may have a thickness sufficient for providing mechanical stability. The at least one protective layer specifically may have a thickness of about 1 pm to about 150 pm. For the at least one protective layer, as outlined herein, several materials may be used, standalone or in combination. Thus, as an example, the protective layer specifically may comprise one or more of a polymeric material, specifically a polyvinyl pyridine based copolymer, a polyurethane; a hydrogel; a polyacrylate; a methacrylate-acrylate copolymer or block-copolymer; among which polyvinyl pyridine based copolymers are particularly suitable. These types of polymeric layers are generally known in the art. Moreover, the protective layer may comprise a crosslinker, specifically a chemical crosslinker or a UV-curable crosslinker.

[0053] In some preferred embodiments of the analyte sensor, the protective layer comprise one or more hole(s), preferably penetrating through the thickness of the whole protective layer. The term “hole(s)” within the context of the present invention is given its ordinary and customary meaning to a person skilled in the art. In particular, it means any opening and / or perforation within the protective layer. The hole(s) allow passage of one or more molecules and / or compounds through the hole(s), i.e. thereby through the protective layer. Thus, the hole(s) provide a fluidic channel between the at least one second electrode and the body fluid. The holes may have any shape and any size. The holes may be positioned anywhere within the protective layer. For example, the holes may be positioned at an edge of the protective layer and / or essentially in the center of the protective layer. Especially when the analyte sensor is dimensioned by cutting from a larger three dimensional piece, the holes may at least partially, preferably completely, formed by the cutting surfaces.

[0054] In some preferred embodiments of the analyte sensor, the total area of the hole(s) comprised in the protective layer is at least 0.05 mm2, preferably at least 0.10 mm2, more preferably at least 0.15 mm2, more preferably > 0.15 mm2, more preferably at least 0.18 mm2.

[0055] In some preferred embodiments of the analyte sensor, the total area of the hole(s) comprised in the protective layer is in the range of from 0.05 to 5.00 mm2, preferably in the range of from 0.05 to 1.00 mm2, more preferably in the range of from 0.10 to 0.50 mm2, more preferably in the range of from 0.10 to 0.20 mm2, more preferably in the range of from 0.10 to 0.18 mm2.

[0056] Within the context on the present invention, “the total area of hole(s)” relates to the sum of the surface area of the hole(s). In a preferred embodiment of the present invention, the analyte sensor does not comprise a protective layer at least partially covering the outer surface of the layer of the electrode of (ii).

[0057] As indicated above, the electrode of according to (ii) of the analyte sensor comprises a layer, which comprises silver chloride (AgCl) and a thermoplastic polyurethane, wherein the thermoplastic polyurethane is obtained or obtainable from an aliphatic polyisocyanate and a polyether polyol. Preferably, the aliphatic polyisocyanate is an aliphatic diisocyanate, more more preferably selected from the group consisting of isophorone diisocyanates (IPDI), hexamethylene diisocyanates (HDI), dicyclohexylmethane diisocyanates (HMDI), cyclohexyl diisocyanates (CHDI), tetramethylxylene diisocyanates (TMXDI), isomers of these aliphatic diisocyanates and mixtures of two or more thereof. The polyether polyol is preferably a polyether diol, more preferably selected from the group consisting of poly(ethylene glycol) (PEG), polypropylene glycol) (PPG), poly(tetramethylene glycol) (PTMG), copolymers of two or more thereof and mixtures of two or more thereof, more preferably selected from the group consisting of polypropylene glycol) (PPG), poly(tetramethylene glycol) (PTMG), copolymers of these two and mixtures of these two, more preferably the polyether polyol comprises, more preferably is, PTGM. Preferably, the aliphatic polyisocyanate comprises at least HMDI and the polyether polyol comprises at least PTMG. Preferably, the thermoplastic polyurethane is obtained or obtainable from an aliphatic polyisocyanate, a polyether polyol and a diol (chain extender). Preferably, the diol (chain extender)has a molecular weight of less than 500 g / mol and is preferably selected from the group consisting of 1,4-butanediol (1,4-BD), 1,2-propylene glycol, 1,3 -butanediol, dipropylene glycol, tripropylene glycol, propylene glycol and mixtures of two or more thereof, more preferably the diol comprises at least 1,4-butanediol. Preferably, the thermoplastic polyurethane is obtained or obtainable from an aliphatic polyisocyanate, which comprises at least HMDI, a polyether polyol, which comprises at least PTMG and a diol, which comprises at least 1,4-BD. Preferably, the thermoplastic polyurethane comprises a soft segment and a hard segment, wherein the soft segment / hard segment ratio (SS / HS) is in the range of from 4 to 15, preferably determined by 'H NMR spectroscopy. The hard segment of the thermoplastic polyurethane is based on the remainder of the polyether polyol, whereas the soft segment is based on the remainder of the aliphatic polyisocyanate and the diol (chain extender). Preferably, when the thermoplastic polyurethane is obtained from at least HMDI, PTMG and 1,4-BD, the hard segment is based on the remainders of HMDI and 1,4-BD (chain extender), and the soft segment is based on the remainder of PTMG. Preferably, the thermoplastic polyurethane is hydrophobic, wherein the thermoplastic polyurethane more preferably has a water uptake in the range from 0 to 5 % by weight, preferably a water uptake in the range from 0 to <2 % by weight, more preferably a water uptake in the range from 0.1 to <1.5 % by weight, based on the total weight of the thermoplastic polyurethane in dry state being 100 weight-%, determined according to ASTM-D 570 after 24 hours at 23°C. Preferably, the thermoplastic polyurethane has a shore D hardness in the range of from 20 to 40 and / or a shore A hardness in the range of from 70 to 90, determined according to ASTM D2240. Preferably, the thermoplastic polyurethane has an elongation at break in the range of from 400 to 600 %, determined according to ASTM D412. Preferably, the thermoplastic polyurethane has a flexural modulus in the range of from 300 to 3500 PSI, determined according to ASTM D790. Preferably, the thermoplastic polyurethane has a glass transition temperature Tg of at least 40°C, wherein Tg is preferably determined by modulated differential scanning calorimetry (MDSC). Preferably, the thermoplastic polyurethane has a number average molecular weight Mn in the range of from 40 to 160 g / mol. Preferably, the thermoplastic polyurethane has a weight average molecular weight Mw in the range of from 50 to 250 g / mol. Preferably, the layer which comprises silver chloride (AgCl) and a thermoplastic polyurethane comprises the thermoplastic polyurethane in a range of from 1 to 50 weight-%, preferably in the range of from 5 to 40 weight-%, more preferably in the range of from 10 to 30 weight-%, more preferably in the range of from 12 to 20 weight-%, based on the total weight of the layer being 100 weight-%. Preferably, the layer which comprises silver chloride (AgCl) and a thermoplastic polyurethane has a thickness in the range of from 1 pm to 60 pm (dry state). Preferably, the weight based ratio of AgCl to thermoplastic polyurethane in the layer which comprises silver chloride (AgCl) and a thermoplastic polyurethane is in the range of from 1 : 10 (w / w) to 10 : 1 (w / w). Preferably, the layer which comprises silver chloride (AgCl) and a thermoplastic polyurethane further comprises elemental silver (Ag). Preferably, the weight based ratio of Ag to AgCl in the layer is in the range of from 1 : 0.1 (w / w) to 1 : 5 (w / w). Preferably, the layer which comprises silver chloride (AgCl), a thermoplastic polyurethane and elemental silver (Ag), comprises Ag and / or AgCl as particles, wherein the particles within the layer are at least in partial contact with each other and / or wherein Ag and AgCl are evenly distributed throughout the layer. The layer which comprises silver chloride (AgCl), a thermoplastic polyurethane and elemental silver (Ag) has at least two surfaces, wherein one surface represents the outer surface when considering an analyte sensor and another surface represents the inner surface of the layer when considering an analyte sensor. As indicated above, the layer before implantation comprises Ag and AgCl evenly distributed. Further, it is understood that when in use, i.e. when implanted, AgCl contained in particles closer to the one surface (the outer surface), due to contact with Ag and with surrounding electrolyte, is reduced thus forming Ag, so that over time a gradient of the Ag and AgCl concertation respectively is established throughout the layer.

[0058] The analyte sensor may be configured for at least partial implantation, specifically transcutaneous insertion, into a body tissue of a user; more specifically the analyte sensor may be configured for continuous monitoring of the analyte, even more specifically the analyte sensor may be configured for continuous glucose monitoring. In certain embodiments, the analyte sensor is sterilized and / or packaged after its manufacturing.

[0059] The terms "user" and "subject" are used interchangeably herein. The terms may in particular relate to a human being.

[0060] The term "analyte sensor" 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 or device configured for detecting or for measuring the concentration of the at least one analyte. The analyte sensor specifically may be an analyte sensor suitable for at least partial implantation, specifically transcutaneous or subcutaneous insertion, into a body tissue of a user, more specifically an analyte sensor for continuous monitoring of the analyte.

[0061] Particularly, the analyte sensor according to the present invention may be fully or a partially implantable and may, thus, be adapted for performing the detection of the analyte in the body fluid in a subcutaneous tissue, in particular, in an interstitial fluid. Other parts or components may remain outside of the body tissue. For example, as used herein, the terms "implantable", “transcutaneous” or "subcutaneous" refer to be fully or at least partly arranged within the body tissue of the user. For this purpose, the analyte sensor may comprise an insertable portion, wherein the term "insertable portion" may generally refer to a part or component of an element configured to be insertable into an arbitrary body tissue. The insertable portion comprises the working electrode and at least the electrode as defined above, e.g. as a counter, reference and / or counter / reference electrode. In certain embodiments, the working electrode is positioned on the second side of the substrate, the electrode as defined above is positioned on the first side of the substrate and all electrodes are positioned on the insertable portion, i.e. the inteneded intracorporal part. The part of the sensor, which is not intended to be inserted, i.e. the intended extracorporal part, is the part of the sensor, which comprises the contacts to connect the sensor electronically to an electronics unit.

[0062] 3rdaspect - Method for manufacturing an electrode

[0063] In a third aspect, the invention is directed to a method for manufacturing an electrode of an analyte sensor, the method comprising the steps: a) providing a substrate comprising a first side and a second side, and at least one conductive material positioned on the first side of the substrate, b) applying a layer onto the conductive material wherein the layer comprises silver chloride (AgCl) and a thermoplastic polyurethane, said layer having an outer surface and an inner surface, wherein the outer surface faces away from the conductive material and wherein the inner surface is in contact with the conductive material, wherein the thermoplastic polyurethane is obtained or obtainable from an aliphatic polyisocyanate and a polyether polyol, thus obtaining an electrode comprising a substrate having at least one conductive material positioned on the first side of the substrate and having a layer comprising silver chloride (AgCl) and a thermoplastic polyurethane on the conductive material.

[0064] In some preferred embodiments of the method, the thermoplastic polyurethane is obtained or obtainable from an aliphatic polyisocyanate and a polyether polyol.

[0065] In some preferred embodiments of the method, the aliphatic polyisocyanate is an aliphatic diisocyanate, preferably selected from the group consisting of isophorone diisocyanates (IPDI), hexamethylene diisocyanates (HDI), dicyclohexylmethane diisocyanates (HMDI), cyclohexyl diisocyanates (CHDI), tetramethylxylene diisocyanates (TMXDI), isomers of these aliphatic diisocyanates and mixtures of two or more thereof. In some preferred embodiments of the method, the polyether polyol is a polyether diol, preferably selected from the group consisting of polyethylene glycol) (PEG), polypropylene glycol) (PPG), poly(tetramethylene glycol) (PTMG), copolymers of two or more thereof and mixtures of two or more thereof, more preferably selected from the group consisting of polypropylene glycol) (PPG), poly(tetramethylene glycol) (PTMG), copolymers of these two and mixtures of these two, more preferably the polyether polyol comprises, more preferably is, PTGM.

[0066] In some preferred embodiments of the method, the aliphatic polyisocyanate comprises at least HMDI and the polyether polyol comprises at least PTMG.

[0067] In some preferred embodiments of the method, the thermoplastic polyurethane is obtained or obtainable from an aliphatic polyisocyanate, a polyether polyol and a diol (chain extender).

[0068] In some preferred embodiments of the method, the diol has a molecular weight of less than 500 g / mol and is preferably selected from the group consisting of 1,4-butanediol (1,4-BD), 1,2- propylene glycol, 1,3 -butanediol, dipropylene glycol, tripropylene glycol, propylene glycol and mixtures of two or more thereof, more preferably the diol comprises at least 1,4-butanediol.

[0069] In some preferred embodiments of the method, the thermoplastic polyurethane is obtained or obtainable from an aliphatic polyisocyanate, which comprises at least HMDI, a polyether polyol, which comprises at least PTMG and a diol, which comprises at least 1,4-BD. In some preferred embodiments of the method, the thermoplastic polyurethane comprises a soft segment and a hard segment, wherein the soft segment / hard segment ratio (SS / HS) is in the range of from 4 to 15, preferably determined by1H NMR spectroscopy. As indicated herein above, the hard segment of the thermoplastic polyurethane is based on the remainder of the polyether polyol, whereas the soft segment is based on the remainder of the aliphatic polyisocyanate and the diol (chain extender). Preferably, when the thermoplastic polyurethane is obtained from at least HMDI, PTMG and 1,4- BD, the hard segment is based on the remainders of HMDI and 1,4-BD (chain extender), and the soft segment is based on the remainder of PTMG.

[0070] In some preferred embodiments of the method, the thermoplastic polyurethane is hydrophobic, wherein the thermoplastic polyurethane has a water uptake in the range from 0 to 5 % by weight, preferably a water uptake in the range from 0 to <2 % by weight, more preferably a water uptake in the range from 0.1 to <1.5 % by weight, based on the total weight of the thermoplastic polyurethane in dry state being 100 weight-%, determined according to ASTM-D 570 after 24 hours at 23°C. In some preferred embodiments of the method, the thermoplastic polyurethane has a shore D hardness in the range of from 20 to 40 and / or a shore A hardness in the range of from 70 to 90, determined according to ASTM D2240.

[0071] In some preferred embodiments of the method, the thermoplastic polyurethane has an elongation at break in the range of from 400 to 600 %, determined according to ASTM D412.

[0072] In some preferred embodiments of the method, the thermoplastic polyurethane has a flexural modulus in the range of from 300 to 3500 PSI, determined according to ASTM D790.

[0073] In some preferred embodiments of the method, the thermoplastic polyurethane has a glass transition temperature Tg of at least 40°C, wherein Tg is preferably determined by modulated differential scanning calorimetry (MDSC).

[0074] In some preferred embodiments of the method, the thermoplastic polyurethane has a number average molecular weight Mn in the range of from 40 to 160 g / mol.

[0075] In some preferred embodiments of the method, the thermoplastic polyurethane has a weight average molecular weight Mw in the range of from 50 to 250 g / mol.

[0076] In some preferred embodiments of the method, the layer which comprises silver chloride (AgCl) and a thermoplastic polyurethane comprises the thermoplastic polyurethane in a range of from 1 to 50 weight-%, preferably in the range of from 5 to 40 weight-%, more preferably in the range of from 10 to 30 weight-%, more preferably in the range of from 12 to 20 weight-%, based on the total weight of the layer being 100 weight-%.

[0077] In some preferred embodiments of the method, the layer which comprises silver chloride (AgCl) and a thermoplastic polyurethane has a thickness in the range of from 1 pm to 60 pm (dry state).

[0078] In some preferred embodiments of the method, the weight based ratio of AgCl to thermoplastic polyurethane in the layer which comprises silver chloride (AgCl) and a thermoplastic polyurethane is in the range of from 1 : 10 (w / w) to 10 : 1 (w / w).

[0079] In some preferred embodiments of the method, the layer which comprises silver chloride (AgCl) and a thermoplastic polyurethane further comprises elemental silver (Ag).

[0080] In some preferred embodiments of the method, the weight based ratio of Ag to AgCl in the layer is in the range of from 1 : 0.1 (w / w) to 1 : 5 (w / w). In some preferred embodiments of the method, the layer which comprises silver chloride (AgCl), a thermoplastic polyurethane and elemental silver (Ag) comprises Ag and / or AgCl particles, wherein the particles within the layer are at least in partial contact with each other and / or wherein Ag and AgCl are evenly distributed throughout the layer.

[0081] In some preferred embodiments of the method, b) comprises b. l) applying silver chloride (AgCl) and optionally elemental (Ag) onto the conductive material, preferably by a method selected from the group consisting of slot-die-coating, screen printing, stencil-printing, dosing and mixed forms of two or more of these methods, thus obtaining a AgCl and optionally Ag containing layer on the conductive material; b.2) applying a layer comprising thermoplastic polyurethane onto the AgCl and optionally Ag containing layer obtained in b.1), thus obtaining an electrode comprising a substrate having at least one conductive material positioned on the first side of the substrate and having a layer comprising silver chloride (AgCl) and a thermoplastic polyurethane on the conductive material.

[0082] In some preferred embodiments, the method further comprises c) applying a protective layer at least partially onto the layer comprising silver chloride (AgCl) and a thermoplastic polyurethane, thus obtaining an electrode comprising a substrate having at least one conductive material positioned on the first side of the substrate and having a layer comprising silver chloride (AgCl) and a thermoplastic polyurethane on the conductive material and having a protective layer at least partially on of the layer comprising silver chloride (AgCl) and a thermoplastic polyurethane.

[0083] In some preferred embodiments, the method further comprises d) cutting one or more pieces from the electrode obtained according to (b), (b.2) or (c), wherein if the cutting is done based on the electrode obtained according to (c), at least the cutting surfaces are free of protective layer.

[0084] 4thaspect - Electrode - product-bv-process

[0085] A fourth aspect of the invention is related to an electrode of an analyte sensor, obtained or obtainable from the method of the third aspect of the invention, preferably from step (d) of method of the third aspect of the invention.

[0086] 5thaspect - Method for manufacturing an analyte sensor In a fifth aspect, the invention is directed to method for manufacturing an analyte sensor comprising a) providing a substrate comprising

[0087] - a first side and a second side, and

[0088] - at least one conductive material positioned on the first side of the substrate, b) applying a layer onto the conductive material wherein the layer comprises silver chloride (AgCl) and optionally elemental silver (Ag) and a thermoplastic polyurethane, said layer having an outer surface and an inner surface, wherein the outer surface faces away from the conductive material and wherein the inner surface is in contact with the conductive material, wherein the thermoplastic polyurethane is obtained or obtainable from an aliphatic polyisocyanate and a poly ether polyol; c) applying a sensing material to the second side of the substrate, in particular onto at least one second conductive material positioned on second side of the substrate, wherein the sensing material comprises at least one enzyme, and optionally at least one cross-linker and / or optionally at least one polymeric metal complex, thereby obtaining a working electrode of the analyte sensor on the second side of the substrate.

[0089] In some preferred embodiments of the method for manufacturing an analyte sensor, the enzyme is a glucose dehydrogenase (GOD) or a glucose oxidase (GOx).

[0090] In some preferred embodiments of the method for manufacturing an analyte sensor, the thermoplastic polyurethane is obtained or obtainable from an aliphatic polyisocyanate and a poly ether polyol.

[0091] In some preferred embodiments of the method for manufacturing an analyte sensor, the aliphatic polyisocyanate is an aliphatic diisocyanate, preferably selected from the group consisting of isophorone diisocyanates (IPDI), hexamethylene diisocyanates (HDI), dicyclohexylmethane diisocyanates (HMDI), cyclohexyl diisocyanates (CHDI), tetramethylxylene diisocyanates (TMXDI), isomers of these aliphatic diisocyanates and mixtures of two or more thereof.

[0092] In some preferred embodiments of the method for manufacturing an analyte sensor, the polyether polyol is a polyether diol, preferably selected from the group consisting of polyethylene glycol) (PEG), polypropylene glycol) (PPG), poly(tetramethylene glycol) (PTMG), copolymers of two or more thereof and mixtures of two or more thereof, more preferably selected from the group consisting of polypropylene glycol) (PPG), poly(tetramethylene glycol) (PTMG), copolymers of these two and mixtures of these two, more preferably the polyether polyol comprises, more preferably is, PTGM.

[0093] In some preferred embodiments of the method for manufacturing an analyte sensor, the aliphatic polyisocyanate comprises at least HMDI and the polyether polyol comprises at least PTMG.

[0094] In some preferred embodiments of the method for manufacturing an analyte sensor, the thermoplastic polyurethane is obtained or obtainable from an aliphatic polyisocyanate, a polyether polyol and a diol (chain extender).

[0095] In some preferred embodiments of the method for manufacturing an analyte sensor, the diol has a molecular weight of less than 500 g / mol and is preferably selected from the group consisting of 1,4-butanediol (1,4-BD), 1,2-propylene glycol, 1,3 -butanediol, dipropylene glycol, tripropylene glycol, propylene glycol and mixtures of two or more thereof, more preferably the diol comprises at least 1,4-butanediol.

[0096] In some preferred embodiments of the method for manufacturing an analyte sensor, the thermoplastic polyurethane is obtained or obtainable from an aliphatic polyisocyanate, which comprises at least HMDI, a polyether polyol, which comprises at least PTMG and a diol, which comprises at least 1,4-BD.

[0097] In some preferred embodiments of the method for manufacturing an analyte sensor, the thermoplastic polyurethane comprises a soft segment and a hard segment, wherein the soft segment / hard segment ratio (SS / HS) is in the range of from 4 to 15, preferably determined by 'H NMR spectroscopy. As indicated herein above, the hard segment of the thermoplastic polyurethane is based on the remainder of the polyether polyol, whereas the soft segment is based on the remainder of the aliphatic polyisocyanate and the diol (chain extender). Preferably, when the thermoplastic polyurethane is obtained from at least HMDI, PTMG and 1,4-BD, the hard segment is based on the remainders of HMDI and 1,4-BD (chain extender), and the soft segment is based on the remainder of PTMG.

[0098] In some preferred embodiments of the method for manufacturing an analyte sensor, the thermoplastic polyurethane is hydrophobic, wherein the thermoplastic polyurethane has a water uptake in the range fromO to 5 % by weight, preferably a water uptake in the range from 0 to <2 % by weight, more preferably a water uptake in the range from 0.1 to <1.5 % by weight, based on the total weight of the thermoplastic polyurethane in dry state being 100 weight-%, determined according to ASTM-D 570 after 24 hours at 23°C. In some preferred embodiments of the method for manufacturing an analyte sensor, the thermoplastic polyurethane has a shore D hardness in the range of from 20 to 40 and / or a shore A hardness in the range of from 70 to 90, determined according to ASTM D2240.

[0099] In some preferred embodiments of the method for manufacturing an analyte sensor, the thermoplastic polyurethane has an elongation at break in the range of from 400 to 600 %, determined according to ASTM D412.

[0100] In some preferred embodiments of the method for manufacturing an analyte sensor, the thermoplastic polyurethane has a flexural modulus in the range of from 300 to 3500 PSI, determined according to ASTM D790.

[0101] In some preferred embodiments of the method for manufacturing an analyte sensor, the thermoplastic polyurethane has a glass transition temperature Tg of at least 40°C, wherein Tg is preferably determined by modulated differential scanning calorimetry (MDSC).

[0102] In some preferred embodiments of the method for manufacturing an analyte sensor, the thermoplastic polyurethane has a number average molecular weight Mn in the range of from 40 to 160 g / mol.

[0103] In some preferred embodiments of the method for manufacturing an analyte sensor, the thermoplastic polyurethane has a weight average molecular weight Mw in the range of from 50 to 250 g / mol.

[0104] In some preferred embodiments of the method for manufacturing an analyte sensor, the layer which comprises silver chloride (AgCl) and a thermoplastic polyurethane comprises the thermoplastic polyurethane in a range of from 1 to 50 weight-%, preferably in the range of from 5 to 40 weight- %, more preferably in the range of from 10 to 30 weight-%, more preferably in the range of from 12 to 20 weight-%, based on the total weight of the layer being 100 weight-%.

[0105] In some preferred embodiments of the method for manufacturing an analyte sensor, the layer which comprises silver chloride (AgCl) and a thermoplastic polyurethane has a thickness in the range of from 1 pm to 60 pm (dry state).

[0106] In some preferred embodiments of the method for manufacturing an analyte sensor, the weight based ratio of AgCl to thermoplastic polyurethane in the layer which comprises silver chloride (AgCl) and a thermoplastic polyurethane is in the range of from 1 : 10 (w / w) to 10 : 1 (w / w). In some preferred embodiments of the method for manufacturing an analyte sensor, the layer which comprises silver chloride (AgCl) and a thermoplastic polyurethane further comprises elemental silver (Ag).

[0107] In some preferred embodiments of the method for manufacturing an analyte sensor, the weight based ratio of Ag to AgCl in the layer is in the range of from 1 : 0.1 (w / w) to 1 : 5 (w / w).

[0108] In some preferred embodiments of the method for manufacturing an analyte sensor, the layer which comprises silver chloride (AgCl), a thermoplastic polyurethane and elemental silver (Ag) comprises Ag and / or AgCl particles, wherein the particles within the layer are at least in partial contact with each other and / or wherein Ag and AgCl are evenly distributed throughout the layer.

[0109] In some preferred embodiments of the method for manufacturing an analyte sensor, b) comprises b. l) applying silver chloride (AgCl) and optionally elemental (Ag) onto the conductive material, preferably by a method selected from the group consisting of slot-die-coating, screen printing, stencil-printing, dosing and mixed forms of two or more of these methods, thus obtaining a AgCl and optionally Ag containing layer on the conductive material; b.2) applying a layer comprising thermoplastic polyurethane onto the AgCl and optionally Ag containing layer obtained in b.1), thus obtaining an electrode comprising a substrate having at least one conductive material positioned on the first side of the substrate and having a layer comprising silver chloride (AgCl) and a thermoplastic polyurethane on the conductive material.

[0110] In some preferred embodiments of the method for manufacturing an analyte sensor, the method further comprises c) applying a protective layer at least partially onto the layer comprising silver chloride (AgCl) and a thermoplastic polyurethane, thus obtaining an electrode comprising a substrate having at least one conductive material positioned on the first side of the substrate and having a layer comprising silver chloride (AgCl) and a thermoplastic polyurethane on the conductive material and having a protective layer at least partially on of the layer comprising silver chloride (AgCl) and a thermoplastic polyurethane.

[0111] In some preferred embodiments of the method for manufacturing an analyte sensor, the method further comprises d) cutting one or more pieces from the electrode obtained according to (b), (b.2) or (c), wherein if the cutting is done based on the electrode obtained according to (c), at least the cutting surfaces are free of protective layer. 6thaspect - Analyte sensor - product-by-i

[0112] A sixth aspect of the invention is directed to an analyte sensor, obtained or obtainable from the method of the fifth aspect of the invention, preferably from step d) of the method of the fifth aspect of the invention.

[0113] 7thaspect - Use

[0114] In a seventh aspect, the invention relates to a use of an analyte sensor of the second aspect of the invention or of the sixth aspect of the invention for detecting at least one analyte. Preferably, the analyte is selected from the group consisting of glucose, cholesterol, triglycerides, lactate, creatinine, potassium cation, calcium cation, sodium cation, chloride anion and mixtures of two or more thereof.

[0115] The invention according to the seventh aspect is also related to a method for determining at least one analyte in a sample using the analyte sensor of the second aspect of the invention or of the sixth aspect of the invention. Preferably, the analyte is selected from the group consisting of glucose, cholesterol, triglycerides, lactate, creatinine, potassium cation, calcium cation, sodium cation, chloride anion.

[0116] Summarizing and without excluding further possible embodiments, the following embodiments may be envisaged:

[0117] Embodiment (1): An electrode for an analyte sensor, comprising a layer, which comprises silver chloride (AgCl) and a thermoplastic polyurethane, wherein the thermoplastic polyurethane is obtained or obtainable from an aliphatic polyisocyanate and a polyether polyol.

[0118] Embodiment (2): The electrode of embodiment (1), wherein the aliphatic polyisocyanate is an aliphatic diisocyanate, preferably selected from the group consisting of isophorone diisocyanates (IPDI), hexamethylene diisocyanates (HDI), dicyclohexylmethane diisocyanates (HMDI), cyclohexyl diisocyanates (CHDI), tetramethylxylene diisocyanates (TMXDI), isomers of these aliphatic diisocyanates and mixtures of two or more thereof.

[0119] Embodiment (3): The electrode of embodiment (1) or (2), wherein the polyether polyol is a polyether diol, preferably selected from the group consisting of poly(ethylene glycol) (PEG), polypropylene glycol) (PPG), poly(tetramethylene glycol) (PTMG), copolymers of two or more thereof and mixtures of two or more thereof, more preferably selected from the group consisting of polypropylene glycol) (PPG), poly(tetramethylene glycol) (PTMG), copolymers of these two and mixtures of these two, more preferably the poly ether polyol comprises, more preferably is, PTGM.

[0120] Embodiment (4): The electrode of any one of embodiments (1) to (3), wherein the aliphatic polyisocyanate comprises at least HMDI and the polyether polyol comprises at least PTMG.

[0121] Embodiment (5): The electrode of any one of embodiments (1) to (4), wherein the thermoplastic polyurethane is obtained or obtainable from an aliphatic polyisocyanate, a polyether polyol and a diol (chain extender).

[0122] Embodiment (6): The electrode of embodiment (5), wherein the diol (chain extender) has a molecular weight of less than 500 g / mol and is preferably selected from the group consisting of

[0123] 1.4-butanediol (1,4-BD), 1,2-propylene glycol, 1,3 -butanediol, dipropylene glycol, tripropylene glycol, propylene glycol and mixtures of two or more thereof, more preferably the diol comprises at least 1,4-butanediol.

[0124] Embodiment (7): The electrode of any one of embodiments (1) to (6), wherein the thermoplastic polyurethane is obtained or obtainable from an aliphatic polyisocyanate, which comprises at least HMDI, a polyether polyol, which comprises at least PTMG and a diol, which comprises at least

[0125] 1.4-BD.

[0126] Embodiment (8): The electrode of any one of embodiments (1) to (7), wherein the thermoplastic polyurethane comprises a soft segment and a hard segment, wherein the soft segment / hard segment ratio (SS / HS) is in the range of from 4 to 15, preferably determined by 'H NMR spectroscopy.

[0127] Embodiment (9): The electrode of any one of embodiments (1) to (8), wherein the thermoplastic polyurethane is hydrophobic, wherein the thermoplastic polyurethane has a water uptake in the range from 0 to 5 % by weight, preferably a water uptake in the range from 0 to <2 % by weight, more preferably a water uptake in the range from 0.1 to <1.5 % by weight, based on the total weight of the thermoplastic polyurethane in dry state being 100 weight-%, determined according to ASTM-D 570 after 24 hours at 23°C.

[0128] Embodiment (10): The electrode of any one of embodiments (1) to (9), wherein the thermoplastic polyurethane has a shore D hardness in the range of from 20 to 40 and / or a shore A hardness in the range of from 70 to 90, determined according to ASTM D2240. Embodiment (11): The electrode of any one of embodiments (1) to (10), wherein the thermoplastic polyurethane has an elongation at break in the range of from 400 to 600 %, determined according to ASTM D412.

[0129] Embodiment (12): The electrode of any one of embodiments (1) to (11), wherein the thermoplastic polyurethane has a flexural modulus in the range of from 300 to 3500 PSI, determined according to ASTM D790.

[0130] Embodiment (13): The electrode of any one of embodiments (1) to (12), wherein the thermoplastic polyurethane has a glass transition temperature Tg of at least 40°C, wherein Tg is preferably determined by modulated differential scanning calorimetry (MDSC).

[0131] Embodiment (14): The electrode of any one of embodiments (1) to (13), wherein the thermoplastic polyurethane has a number average molecular weight Mn in the range of from 40 to 160 g / mol.

[0132] Embodiment (15): The electrode of any one of embodiments (1) to (14), wherein the thermoplastic polyurethane has a weight average molecular weight Mw in the range of from 50 to 250 g / mol.

[0133] Embodiment (16): The electrode of any one of embodiments (1) to (15), wherein the layer which comprises silver chloride (AgCl) and a thermoplastic polyurethane comprises the thermoplastic polyurethane in a range of from 1 to 50 weight-%, preferably in the range of from 5 to 40 weight- %, more preferably in the range of from 10 to 30 weight-%, more preferably in the range of from 12 to 20 weight-%, based on the total weight of the layer being 100 weight-%.

[0134] Embodiment (17): The electrode of any one of embodiments (1) to (16), wherein the layer which comprises silver chloride (AgCl) and a thermoplastic polyurethane has a thickness in the range of from 1 pm to 60 pm (dry state).

[0135] Embodiment (18): The electrode of any one of embodiments (1) to (17), wherein the weight based ratio of AgCl to thermoplastic polyurethane in the layer which comprises silver chloride (AgCl) and a thermoplastic polyurethane is in the range of from 1 : 10 (w / w) to 10 : 1 (w / w).

[0136] Embodiment (19): The electrode of any one of embodiments (1) to (18), wherein the layer which comprises silver chloride (AgCl) and a thermoplastic polyurethane further comprises elemental silver (Ag).

[0137] Embodiment (20): The electrode of embodiment (19), wherein the weight based ratio of Ag to AgCl in the layer is in the range of from 1 : 0.1 (w / w) to 1 : 5 (w / w). Embodiment (21): The electrode of embodiment (16) or (17), wherein the layer which comprises silver chloride (AgCl), a thermoplastic polyurethane and elemental silver (Ag), comprises Ag and / or AgCl as particles, wherein the particles within the layer are at least in partial contact with each other and / or wherein Ag and AgCl are evenly distributed throughout the layer.

[0138] Embodiment (22): The electrode of any one of embodiments (1) to (21), being a counter electrode or a reference electrode or a combined counter / reference electrode.

[0139] Embodiment (23): An analyte sensor comprising:

[0140] (i) a substrate with a first side and a second side, and at least one conductive material positioned on the first side of the substrate;

[0141] (ii) an electrode positioned on the at least one conductive material, wherein the electrode comprises a layer, which comprises silver chloride (AgCl) and a thermoplastic polyurethane, said layer having an outer surface and an inner surface, wherein the outer surface faces away from the conductive material and wherein the inner surface is in contact with the conductive material, wherein the thermoplastic polyurethane is obtained or obtainable from an aliphatic polyisocyanate and a poly ether polyol; and

[0142] (iii) a working electrode.

[0143] Embodiment (24): The analyte sensor of Embodiment (23), wherein the working electrode of (iii) comprises at least one conductive material positioned on the second side of the substrate and at least one enzyme.

[0144] Embodiment (25): The analyte sensor of Embodiment (23) or (24), wherein the electrode according to (ii) is a counter electrode, a reference electrode or a combined counter / reference electrode.

[0145] Embodiment (26): The analyte sensor of any one of embodiments (23) to (25), wherein the enzyme is selected from the group consisting of a glucose oxidase (EC 1.1.3.4), ahexose oxidase (EC 1.1.3.5), an (S)-2 hydroxy acid oxidase (EC 1.1.3.15), a cholesterol oxidase (EC 1.1.3.6), a glucose dehydrogenase, a galactose oxidase (EC 1.1.3.9), an alcohol oxidase (EC 1.1.3.13), an L-glutamate oxidase (EC 1.4.3.11), an L-aspartate oxidase (EC 1.4.3.16) and mixtures of two or more thereof.

[0146] Embodiment (27): The analyte sensor of any one of embodiments (23) to (25), wherein the substrate is selected from the group consisting of an epoxy resin, a polycarbonate, a polyester, a polyvinylchloride, a polyurethane, a polyethylene, a polypropylene, polystyrene, a polyether, a polyamide, a polyimide, polytetrafluoroethylene or a copolymer thereof, and alumina.

[0147] Embodiment (28): The analyte sensor of embodiment (27), wherein the substrate comprises a polyester, preferably selected from the group consisting of polyethylene terephthalate (PET), glycol modified polyethylene terephthalate, polyethylene naphthalate and mixtures of two or more thereof.

[0148] Embodiment (29): The analyte sensor of any one of embodiments (23) to (28), wherein the conductive material of (ii) and / or of the working electrode is selected from the group consisting of metals, nonmetallic electrically conductive materials and mixtures of two or more thereof.

[0149] Embodiment (30): The analyte sensor of any one of embodiments (23) to (29) which does not comprise a protective layer at least partially covering the outer surface of the layer of the electrode of (ii).

[0150] Embodiment (31): The analyte sensor of any one of embodiments (23) to (29) further comprising a protective layer at least partially covering the outer surface of the layer of the electrode of (ii).

[0151] Embodiment (32): The analyte sensor of embodiment (31), wherein the protective layer comprise one or more hole(s), preferably penetrating through the thickness of the whole protective layer.

[0152] Embodiment (33): The analyte sensor of embodiment (32), wherein the total area of the hole(s) comprised in the protective layer is at least 0.05 mm2, preferably at least 0.10 mm2, more preferably at least 0.15 mm2, more preferably > 0.15 mm2, more preferably at least 0.18 mm2.

[0153] Embodiment (34): The analyte sensor of embodiment (32) or (33), wherein the total area of the hole(s) comprised in the protective layer is in the range of from 0.05 to 5.00 mm2, preferably in the range of from 0.05 to 1.00 mm2, more preferably in the range of from 0.10 to 0.50 mm2, more preferably in the range of from 0.10 to 0.20 mm2, more preferably in the range of from 0.10 to 0.18 mm2.

[0154] Embodiment (35): A method for manufacturing an electrode of an analyte sensor, the method comprising the steps: a) providing a substrate comprising a first side and a second side, and at least one conductive material positioned on the first side of the substrate, b) applying a layer onto the conductive material wherein the layer comprises silver chloride (AgCl) and a thermoplastic polyurethane, said layer having an outer surface and an inner surface, wherein the outer surface faces away from the conductive material and wherein the inner surface is in contact with the conductive material, wherein the thermoplastic polyurethane is obtained or obtainable from an aliphatic polyisocyanate and a polyether polyol, thus obtaining an electrode comprising a substrate having at least one conductive material positioned on the first side of the substrate and having a layer comprising silver chloride (AgCl) and a thermoplastic polyurethane on the conductive material.

[0155] Embodiment (36): The method of embodiment (35), wherein the thermoplastic polyurethane is obtained or obtainable from an aliphatic polyisocyanate and a polyether polyol.

[0156] Embodiment (37): The method of embodiment (35) or (36), wherein the aliphatic polyisocyanate is an aliphatic diisocyanate, preferably selected from the group consisting of isophorone diisocyanates (IPDI), hexamethylene diisocyanates (HDI), dicyclohexylmethane diisocyanates (HMDI), cyclohexyl diisocyanates (CHDI), tetramethylxylene diisocyanates (TMXDI), isomers of these aliphatic diisocyanates and mixtures of two or more thereof.

[0157] Embodiment (38): The method of any one of embodiments (35) to (37), wherein the polyether polyol is a polyether diol, preferably selected from the group consisting of polyethylene glycol) (PEG), polypropylene glycol) (PPG), poly(tetramethylene glycol) (PTMG), copolymers of two or more thereof and mixtures of two or more thereof, more preferably selected from the group consisting of polypropylene glycol) (PPG), poly(tetramethylene glycol) (PTMG), copolymers of these two and mixtures of these two, more preferably the polyether polyol comprises, more preferably is, PTGM.

[0158] Embodiment (39): The method of any one of embodiments (35) to (38), wherein the aliphatic polyisocyanate comprises at least HMDI and the polyether polyol comprises at least PTMG.

[0159] Embodiment (40): The method of any one of embodiments (35) to (39), wherein the thermoplastic polyurethane is obtained or obtainable from an aliphatic polyisocyanate, a polyether polyol and a diol (chain extender).

[0160] Embodiment (41): The method of any one of embodiments (35) to (40), wherein the diol has a molecular weight of less than 500 g / mol and is preferably selected from the group consisting of 1,4-butanediol (1,4-BD), 1,2-propylene glycol, 1,3 -butanediol, dipropylene glycol, tripropylene glycol, propylene glycol and mixtures of two or more thereof, more preferably the diol comprises at least 1,4-butanediol.

[0161] Embodiment (42): The method of any one of embodiments (35) to (41), wherein the thermoplastic polyurethane is obtained or obtainable from an aliphatic polyisocyanate, which comprises at least HMDI, a polyether polyol, which comprises at least PTMG and a diol, which comprises at least 1,4-BD.

[0162] Embodiment (43): The method of any one of embodiments (35) to (42), wherein the thermoplastic polyurethane comprises a soft segment and a hard segment, wherein the soft segment / hard segment ratio (SS / HS) is in the range of from 4 to 15, preferably determined byJH NMR spectroscopy.

[0163] Embodiment (44): The method of any one of embodiments (35) to (43), wherein the thermoplastic polyurethane is hydrophobic, wherein the thermoplastic polyurethane has a water uptake in the range from 0 to 5 % by weight, preferably a water uptake in the range from 0 to <2 % by weight, more preferably a water uptake in the range from 0.1 to <1.5 % by weight, based on the total weight of the thermoplastic polyurethane in dry state being 100 weight-%, determined according to ASTM-D 570 after 24 hours at 23°C.

[0164] Embodiment (45): The method of any one of embodiments (35) to (44), wherein the thermoplastic polyurethane has a shore D hardness in the range of from 20 to 40 and / or a shore A hardness in the range of from 70 to 90, determined according to ASTM D2240.

[0165] Embodiment (46): The method of any one of embodiments (35) to (45), wherein the thermoplastic polyurethane has an elongation at break in the range of from 400 to 600 %, determined according to ASTM D412.

[0166] Embodiment (47): The method of any one of embodiments (35) to (46), wherein the thermoplastic polyurethane has a flexural modulus in the range of from 300 to 3500 PSI, determined according to ASTM D790.

[0167] Embodiment (48): The method of any one of embodiments (35) to (47), wherein the thermoplastic polyurethane has a glass transition temperature Tg of at least 40°C, wherein Tg is preferably determined by modulated differential scanning calorimetry (MDSC).

[0168] Embodiment (49): The method of any one of embodiments (35) to (48), wherein the thermoplastic polyurethane has a number average molecular weight Mn in the range of from 40 to 160 g / mol. Embodiment (50): The method of any one of embodiments (35) to (49), wherein the thermoplastic polyurethane has a weight average molecular weight Mw in the range of from 50 to 250 g / mol.

[0169] Embodiment (51): The method of any one of embodiments (35) to (50), wherein the layer which comprises silver chloride (AgCl) and a thermoplastic polyurethane comprises the thermoplastic polyurethane in a range of from 1 to 50 weight-%, preferably in the range of from 5 to 40 weight- %, more preferably in the range of from 10 to 30 weight-%, more preferably in the range of from 12 to 20 weight-%, based on the total weight of the layer being 100 weight-%.

[0170] Embodiment (52): The method of any one of embodiments (35) to (51), wherein the layer which comprises silver chloride (AgCl) and a thermoplastic polyurethane has a thickness in the range of from 1 pm to 60 pm (dry state).

[0171] Embodiment (53): The method of any one of embodiments (35) to (52), wherein the weight based ratio of AgCl to thermoplastic polyurethane in the layer which comprises silver chloride (AgCl) and a thermoplastic polyurethane is in the range of from 1 : 10 (w / w) to 10 : 1 (w / w).

[0172] Embodiment (54): The method of any one of embodiments (35) to (53), wherein the layer which comprises silver chloride (AgCl) and a thermoplastic polyurethane further comprises elemental silver (Ag).

[0173] Embodiment (55): The method of any one of embodiments (35) to (54), wherein the weight based ratio of Ag to AgCl in the layer is in the range of from 1 : 0.1 (w / w) to 1 : 5 (w / w).

[0174] Embodiment (56): The method of any one of embodiments (35) to (55), wherein the layer which comprises silver chloride (AgCl), a thermoplastic polyurethane and elemental silver (Ag) comprises Ag and / or AgCl particles, wherein the particles within the layer are at least in partial contact with each other and / or wherein Ag and AgCl are evenly distributed throughout the layer.

[0175] Embodiment (57): The method of any one of embodiments (35) to (56), wherein b) comprises b. l) applying silver chloride (AgCl) and optionally elemental (Ag) onto the conductive material, preferably by a method selected from the group consisting of slot-die-coating, screen printing, stencil-printing, dosing and mixed forms of two or more of these methods, thus obtaining a AgCl and optionally Ag containing layer on the conductive material; b.2) applying a layer comprising thermoplastic polyurethane onto the AgCl and optionally Ag containing layer obtained in b.1), thus obtaining an electrode comprising a substrate having at least one conductive material positioned on the first side of the substrate and having a layer comprising silver chloride (AgCl) and a thermoplastic polyurethane on the conductive material.

[0176] Embodiment (58): The method of any one of embodiments (35) to (57) further comprising c) applying a protective layer at least partially onto the layer comprising silver chloride (AgCl) and a thermoplastic polyurethane, thus obtaining an electrode comprising a substrate having at least one conductive material positioned on the first side of the substrate and having a layer comprising silver chloride (AgCl) and a thermoplastic polyurethane on the conductive material and having a protective layer at least partially on of the layer comprising silver chloride (AgCl) and a thermoplastic polyurethane.

[0177] Embodiment (59): The method of any one of embodiments (35) to (58) further comprising d) cutting one or more pieces from the electrode obtained according to (b), (b.2) or (c), wherein if the cutting is done based on the electrode obtained according to (c), at least the cutting surfaces are free of protective layer.

[0178] Embodiment (60): An electrode of an analyte sensor, obtained or obtainable from the method of any one of embodiments (35) to (59), preferably from step (d) of embodiment (U59).

[0179] Embodiment (61): A method for manufacturing an analyte sensor comprising a) providing a substrate comprising

[0180] - a first side and a second side, and

[0181] - at least one conductive material positioned on the first side of the substrate, b) applying a layer onto the conductive material wherein the layer comprises silver chloride (AgCl) and optionally elemental silver (Ag) and a thermoplastic polyurethane, said layer having an outer surface and an inner surface, wherein the outer surface faces away from the conductive material and wherein the inner surface is in contact with the conductive material, wherein the thermoplastic polyurethane is obtained or obtainable from an aliphatic polyisocyanate and a poly ether polyol; c) applying a sensing material to the second side of the substrate, in particular onto at least one second conductive material positioned on second side of the substrate, wherein the sensing material comprises at least one enzyme, and optionally at least one cross-linker and / or optionally at least one polymeric metal complex, thereby obtaining a working electrode of the analyte sensor on the second side of the substrate. Embodiment (62): The method of embodiment (61), wherein the enzyme is a glucose dehydrogenase (GOD) or a glucose oxidase (GOx).

[0182] Embodiment (63): The method of embodiment (61) or (62), wherein the thermoplastic polyurethane is obtained or obtainable from an aliphatic polyisocyanate and a polyether polyol.

[0183] Embodiment (64): The method of any one of embodiments (61) to (63), wherein the aliphatic polyisocyanate is an aliphatic diisocyanate, preferably selected from the group consisting of isophorone diisocyanates (IPDI), hexamethylene diisocyanates (HDI), dicyclohexylmethane diisocyanates (HMDI), cyclohexyl diisocyanates (CHDI), tetramethylxylene diisocyanates (TMXDI), isomers of these aliphatic diisocyanates and mixtures of two or more thereof.

[0184] Embodiment (65): The method of any one of embodiments (61) to (64), wherein the poly ether polyol is a polyether diol, preferably selected from the group consisting of polyethylene glycol) (PEG), polypropylene glycol) (PPG), poly(tetramethylene glycol) (PTMG), copolymers of two or more thereof and mixtures of two or more thereof, more preferably selected from the group consisting of polypropylene glycol) (PPG), poly(tetramethylene glycol) (PTMG), copolymers of these two and mixtures of these two, more preferably the polyether polyol comprises, more preferably is, PTGM.

[0185] Embodiment (66): The method of any one of embodiments (1) to (65), wherein the aliphatic polyisocyanate comprises at least HMDI and the polyether polyol comprises at least PTMG.

[0186] Embodiment (67): The method of any one of embodiments (61) to (66), wherein the thermoplastic polyurethane is obtained or obtainable from an aliphatic polyisocyanate, a polyether polyol and a diol (chain extender).

[0187] Embodiment (68): The method of any one of embodiments (61) to (67), wherein the diol has a molecular weight of less than 500 g / mol and is preferably selected from the group consisting of

[0188] 1.4-butanediol (1,4-BD), 1,2-propylene glycol, 1,3 -butanediol, dipropylene glycol, tripropylene glycol, propylene glycol and mixtures of two or more thereof, more preferably the diol comprises at least 1,4-butanediol.

[0189] Embodiment (69): The method of any one of embodiments (61) to (68), wherein the thermoplastic polyurethane is obtained or obtainable from an aliphatic polyisocyanate, which comprises at least HMDI, a polyether polyol, which comprises at least PTMG and a diol, which comprises at least

[0190] 1.4-BD. Embodiment (70): The method of any one of embodiments (61) to (69), wherein the thermoplastic polyurethane comprises a soft segment and a hard segment, wherein the soft segment / hard segment ratio (SS / HS) is in the range of from 4 to 15, preferably determined by H NMR spectroscopy.

[0191] Embodiment (71): The method of any one of embodiments (61) to (70), wherein the thermoplastic polyurethane is hydrophobic, wherein the thermoplastic polyurethane has a water uptake in the range fromO to 5 % by weight, preferably a water uptake in the range from 0 to <2 % by weight, more preferably a water uptake in the range from 0.1 to <1.5 % by weight, based on the total weight of the thermoplastic polyurethane in dry state being 100 weight-%, determined according to ASTM-D 570 after 24 hours at 23°C.

[0192] Embodiment (72): The method of any one of embodiments (61) to (71), wherein the thermoplastic polyurethane has a shore D hardness in the range of from 20 to 40 and / or a shore A hardness in the range of from 70 to 90, determined according to ASTM D2240.

[0193] Embodiment (73): The method of any one of embodiments (61) to (72), wherein the thermoplastic polyurethane has an elongation at break in the range of from 400 to 600 %, determined according to ASTM D412.

[0194] Embodiment (74): The method of any one of embodiments (61) to (73), wherein the thermoplastic polyurethane has a flexural modulus in the range of from 300 to 3500 PSI, determined according to ASTM D790.

[0195] Embodiment (75): The method of any one of embodiments (61) to (74), wherein the thermoplastic polyurethane has a glass transition temperature Tg of at least 40°C, wherein Tg is preferably determined by modulated differential scanning calorimetry (MDSC).

[0196] Embodiment (76): The method of any one of embodiments (61) to (75), wherein the thermoplastic polyurethane has a number average molecular weight Mn in the range of from 40 to 160 g / mol.

[0197] Embodiment (77): The method of any one of embodiments (61) to (76), wherein the thermoplastic polyurethane has a weight average molecular weight Mw in the range of from 50 to 250 g / mol.

[0198] Embodiment (78): The method of any one of embodiments (61) to (77), wherein the layer which comprises silver chloride (AgCl) and a thermoplastic polyurethane comprises the thermoplastic polyurethane in a range of from 1 to 50 weight-%, preferably in the range of from 5 to 40 weight- %, more preferably in the range of from 10 to 30 weight-%, more preferably in the range of from 12 to 20 weight-%, based on the total weight of the layer being 100 weight-%. Embodiment (79): The method of any one of embodiments (61) to (78), wherein the layer which comprises silver chloride (AgCl) and a thermoplastic polyurethane has a thickness in the range of from 1 pm to 60 pm (dry state).

[0199] Embodiment (80): The method of any one of embodiments (61) to (79), wherein the weight based ratio of AgCl to thermoplastic polyurethane in the layer which comprises silver chloride (AgCl) and a thermoplastic polyurethane is in the range of from 1 : 10 (w / w) to 10 : 1 (w / w).

[0200] Embodiment (81): The method of any one of embodiments (61) to (80), wherein the layer which comprises silver chloride (AgCl) and a thermoplastic polyurethane further comprises elemental silver (Ag).

[0201] Embodiment (82): The method of any one of embodiments (61) to (81), wherein the weight based ratio of Ag to AgCl in the layer is in the range of from 1 : 0.1 (w / w) to 1 : 5 (w / w).

[0202] Embodiment (83): The method of any one of embodiments (61) to (82), wherein the layer which comprises silver chloride (AgCl), a thermoplastic polyurethane and elemental silver (Ag) comprises Ag and / or AgCl particles, wherein the particles within the layer are at least in partial contact with each other and / or wherein Ag and AgCl are evenly distributed throughout the layer.

[0203] Embodiment (84): The method of any one of embodiments (61) to (83), wherein b) comprises b. l) applying silver chloride (AgCl) and optionally elemental (Ag) onto the conductive material, preferably by a method selected from the group consisting of slot-die-coating, screen printing, stencil-printing, dosing and mixed forms of two or more of these methods, thus obtaining a AgCl and optionally Ag containing layer on the conductive material; b.2) applying a layer comprising thermoplastic polyurethane onto the AgCl and optionally Ag containing layer obtained in b.1), thus obtaining an electrode comprising a substrate having at least one conductive material positioned on the first side of the substrate and having a layer comprising silver chloride (AgCl) and a thermoplastic polyurethane on the conductive material.

[0204] Embodiment (85): The method of any one of embodiments (61) to (84) further comprising c) applying a protective layer at least partially onto the layer comprising silver chloride (AgCl) and a thermoplastic polyurethane, thus obtaining an electrode comprising a substrate having at least one conductive material positioned on the first side of the substrate and having a layer comprising silver chloride (AgCl) and a thermoplastic polyurethane on the conductive material and having a protective layer at least partially on of the layer comprising silver chloride (AgCl) and a thermoplastic polyurethane.

[0205] Embodiment (86): The method of any one of embodiments (61) to (85) further comprising d) cutting one or more pieces from the electrode obtained according to (b), (b.2) or (c), wherein if the cutting is done based on the electrode obtained according to (c), at least the cutting surfaces are free of protective layer.

[0206] Embodiment (87): An analyte sensor, obtained or obtainable from the method of any one of embodiments (61) to (86), preferably from step d) of embodiment (86).

[0207] Embodiment (88): Use of an analyte sensor of any one of embodiments (23) to (34) or of embodiment (87) for detecting at least one analyte.

[0208] Embodiment (89): Use of the analyte sensor according to embodiment (88), wherein the analyte is selected from the group consisting of glucose, cholesterol, triglycerides, lactate, creatinine, potassium cation, calcium cation, sodium cation, chloride anion and mixtures of two or more thereof.

[0209] Embodiment (90): A method for determining at least one analyte in a sample using the analyte sensor of embodiment (87).

[0210] Embodiment (92): The method for determining an analyte in a sample, wherein the analyte is selected from the group consisting of glucose, cholesterol, triglycerides, lactate, creatinine, potassium cation, calcium cation, sodium cation, chloride anion.

[0211] The following examples serve to illustrate the invention. They must not be interpreted as limiting with regard to the scope of protection.

[0212] Examples

[0213] Reference Example 1: Preparation of analyte sensors

[0214] Analyte sensors were prepared comprising a substrate (PET, thickness of 130 pm), a first (working) electrode, wherein the electrically conductive material was a layer of gold (100 nm thickness), with a layer of carbon paste on top of said layer, an enzyme (glucose oxidase comprised in sensing chemistry (Os-complex modified polymer), a second electrode: combined counter / reference electrode, wherein the electrically conductive material was a layer of gold (100 nm thickness) and a silver / silver chloride containing paste (Ag / AgCl paste) was applied to provide a layer which comprises silver chloride (AgCl) and a polymer.

[0215] A protective layer comprising a hydrophobic polymer (hydrophobic thermoplastic polyurethane) was located on top of the second electrode. The analyte sensors were laser cut. Holes were formed in the protective layer of the analyte sensor depending on the laser cutting conditions of the cutting.

[0216] Example 1: Preparation of an analyte sensor with silver / silver chloride containing paste based on specific thermoplastic polyurethane

[0217] An analyte sensor was prepared according to Reference example 1, wherein the Ag / AgCl paste comprised silver / silver chloride (Ag: 20 weight-%, AgCl: 70 weight-%) and an aliphatic polyether TPU based on HMDI, PTMG and 1,4-butanediol (10 weight-%). Analyte sensors of Examples la to Id were prepared with layers comprising silver / silver chloride and aliphatic polyether TPU differing in the weight based amount of the aliphatic polyether TPU layer based on a total weight of the layer being 100 weight-%, as indicated in the following Table 1 :

[0218] Table 1

[0219] Comparative Example 1: Preparation of analyte sensor with silver / silver chloride containing paste based on dipropylene glycol monomethyl ether and polyester

[0220] An analyte sensor was prepared according to Reference example 1, wherein the Ag / AgCl paste comprised silver / silver chloride (Ag: 26 weight-%, AgCl: 59 weight-%) and 15 weight-% polyester, based on the total weight of the paste being 100 weight-%.

[0221] Example 2: Leaching test The analyte sensors of Example la to Id, each having a surface area of Ag / AgCl of approximately 0,08 mm2(calculated value) were tested for leaching. The sensors with different Ag / AgCl compositions and different polymer binders were transferred into vials with 1 ml water (pH 7) and were maintained therein for 24 hours at 25°C.

[0222] After these 24 hours, the aqueous phase was analysed to determine the silver cations (Ag+) leached into the water by inductively coupled plasma mass spectrometry (ICP-MS). The results are shown in Table 2 as well as in Figure 1.

[0223] Table 2

[0224] Formulations and leaching data

[0225] In addition, a comparative testing was made based on an analyte sensor according to Example lb and a comparative sensor (Comparative Example 1) with the same conditions as described above for the leaching test of the analyte sensors of Examples la to Id. The results are shown in Table 3 as well as in Figure 2.

[0226] Table 3

[0227] The analyte sensor of Comparative Example 1 showed by far the most leaching in that almost 40 ng of Ag+could be detected in the aqueous phase, whereas all analyte sensors of Examples la to Id showed a leaching of less than 30 ng Ag+.

Claims

1. Claims1. An electrode for an analyte sensor, comprising a layer, which comprises silver chloride (AgCl) and a thermoplastic polyurethane, wherein the thermoplastic polyurethane is obtained or obtainable from an aliphatic polyisocyanate and a polyether polyol, wherein the thermoplastic polyurethane is hydrophobic and has a water uptake in the range from 0 to 5 % by weight.

2. The electrode of claim 1, wherein the aliphatic polyisocyanate is an aliphatic diisocyanate, preferably selected from the group consisting of isophorone diisocyanates (IPDI), hexamethylene diisocyanates (HDI), dicyclohexylmethane diisocyanates (HMDI), cyclohexyl diisocyanates (CHDI), tetramethylxylene diisocyanates (TMXDI), isomers of these aliphatic diisocyanates and mixtures of two or more thereof; and / or, preferably and, wherein the polyether polyol is a polyether diol, preferably selected from the group consisting of poly(ethylene glycol) (PEG), polypropylene glycol) (PPG), poly(tetramethylene glycol) (PTMG), , copolymers of two or more thereof and mixtures of two or more thereof, more preferably selected from the group consisting of polypropylene glycol) (PPG), poly(tetramethylene glycol) (PTMG), copolymers of these two and mixtures of these two, more preferably the polyether polyol comprises, more preferably is, PTGM.

3. The electrode of claim 1 or 2, wherein the thermoplastic polyurethane is obtained or obtainable from an aliphatic polyisocyanate, a polyether polyol and a diol, wherein the diol preferably has a molecular weight of less than 500 g / mol and is preferably selected from the group consisting of 1,4-butanediol (1,4-BD), 1,2-propylene glycol, 1,3 -butanediol, dipropylene glycol, tripropylene glycol, propylene glycol and mixtures of two or more thereof, more preferably the diol comprises at least 1,4-butanediol.

4. The electrode of any one of claims 1 to 3, wherein the thermoplastic polyurethane has a water uptake in the range from 0 to <2 % by weight, more preferably a water uptake in the range from 0.1 to <1.5 % by weight, based on the total weight of the thermoplastic polyurethane in dry state being 100 weight-%, wherein the water uptake is determined according to ASTM-D 570 after 24 hours at 23°C.

5. The electrode of any one of claims 1 to 4, wherein the weight based ratio of AgCl to thermoplastic polyurethane in the layer which comprises silver chloride (AgCl) and a thermoplastic polyurethane is in the range of from 1 : 10 (w / w) to 10 : 1 (w / w).

6. The electrode of any one of claims 1 to 5, wherein the layer which comprises silver chloride (AgCl) and a thermoplastic polyurethane further comprises elemental silver (Ag), wherein the weight based ratio of Ag to AgCl in the layer is preferably in the range of from 1 : 0.1 (w / w) to 1 : 5 (w / w).

7. The electrode of any one of claims 1 to 6, being a counter electrode or a reference electrode or a combined counter / reference electrode.

8. An analyte sensor comprising:(i) a substrate with a first side and a second side, and at least one conductive material positioned on the first side of the substrate;(ii) an electrode positioned on the at least one conductive material, wherein the electrode comprises a layer, which comprises silver chloride (AgCl) and a thermoplastic polyurethane, said layer having an outer surface and an inner surface, wherein the outer surface faces away from the conductive material and wherein the inner surface is in contact with the conductive material, wherein the thermoplastic polyurethane is obtained or obtainable from an aliphatic polyisocyanate and a polyether polyol, wherein the thermoplastic polyurethane is hydrophobic and has a water uptake in the range from 0 to 5 % by weight; and(iii) a working electrode, which preferably comprises at least one conductive material positioned on the second side of the substrate and at least one enzyme.

9. The analyte sensor of claim 8, which does not comprise a protective layer at least partially covering the outer surface of the layer of the electrode of (ii).

10. The analyte sensor of any claim 8, further comprising a protective layer at least partially covering the outer surface of the layer of the electrode of (ii), wherein the protective layer preferably comprise one or more hole(s), more preferably penetrating through the thickness of the whole protective layer.

11. A method for manufacturing an electrode of an analyte sensor, the method comprising the steps: a) providing a substrate comprising- a first side and a second side, and- at least one conductive material positioned on the first side of the substrate, b) applying a layer onto the conductive material wherein the layer comprises silver chloride (AgCl) and a thermoplastic polyurethane, said layer having an outer surfaceand an inner surface, wherein the outer surface faces away from the conductive material and wherein the inner surface is in contact with the conductive material, wherein the thermoplastic polyurethane is obtained or obtainable from an aliphatic polyisocyanate and a polyether polyol, wherein the thermoplastic polyurethane is hydrophobic and has a water uptake in the range from 0 to 5 % by weight; thus obtaining an electrode comprising a substrate having at least one conductive material positioned on the first side of the substrate and having a layer comprising silver chloride (AgCl) and a thermoplastic polyurethane on the conductive material; c) optionally applying a protective layer at least partially onto the layer comprising silver chloride (AgCl) and a thermoplastic polyurethane, thus obtaining an electrode comprising a substrate having at least one conductive material positioned on the first side of the substrate and having a layer comprising silver chloride (AgCl) and a thermoplastic polyurethane on the conductive material and having a protective layer at least partially on of the layer comprising silver chloride (AgCl) and a thermoplastic polyurethane; and d) optionally cutting one or more pieces from the electrode obtained according to (b) or (c), wherein if the cutting is done based on the electrode obtained according to (c), at least the cutting surfaces are free of protective layer.

12. An electrode of an analyte sensor, obtained or obtainable from the method of claims 11, preferably from step (d) of claim 11.

13. A method for manufacturing an analyte sensor comprising a) providing a substrate comprising- a first side and a second side, and- at least one conductive material positioned on the first side of the substrate, b) applying a layer onto the conductive material wherein the layer comprises silver chloride (AgCl) and optionally elemental silver (Ag) and a thermoplastic polyurethane, said layer having an outer surface and an inner surface, wherein the outer surface faces away from the conductive material and wherein the inner surface is in contact with the conductive material, wherein the thermoplastic polyurethane is obtained or obtainable from an aliphatic polyisocyanate and a polyether polyol, wherein the thermoplastic polyurethane is hydrophobic and has a water uptake in the range from 0 to 5 % by weight; c) applying a sensing material to the second side of the substrate, in particular onto at least one second conductive material positioned on second side of the substrate, wherein the sensing material comprises at least one enzyme, and optionally at leastone cross-linker and / or optionally at least one polymeric metal complex, thereby obtaining a working electrode of the analyte sensor on the second side of the substrate; c) optionally applying a protective layer at least partially onto the layer comprising silver chloride (AgCl) and a thermoplastic polyurethane, thus obtaining an electrode comprising a substrate having at least one conductive material positioned on the first side of the substrate and having a layer comprising silver chloride (AgCl) and a thermoplastic polyurethane on the conductive material and having a protective layer at least partially on of the layer comprising silver chloride (AgCl) and a thermoplastic polyurethane; d) optionally cutting one or more pieces from the electrode obtained according to (b) or(c), wherein if the cutting is done based on the electrode obtained according to (c), at least the cutting surfaces are free of protective layer.

14. An analyte sensor, obtained or obtainable from the method of claim 11, preferably from step d) of claim 13.

15. Use of an analyte sensor of any claim 14 for detecting at least one analyte.

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