Method for manufacturing an analyte sensor and an analyte sensor obtained by the above method

Abstract

The present invention proposes a method for manufacturing at least one analyte sensor (110) for measuring at least one analyte in a body fluid. The method is as follows: A) providing at least one substrate (112) including a first surface (114) and a second surface (116); B) providing at least one first conductive layer (122) that at least partially covers the first surface (114) of the substrate (112); C) providing at least one second conductive layer (124) that partially covers at least one of the first surface (114) and the second surface (116); D) providing at least one working electrode (128) on the first surface (114) by providing at least one working electrode material (132) that at least partially covers the first conductive layer (122); E) A step of providing at least one additional electrode (142) on at least one of the first surface (114) and the second surface (116) by providing: - At least one AgCl-containing composition (146) that at least partially covers the second conductive layer (124); and - At least one protective layer (148) covering an AgCl-containing composition (146) arranged spaced apart from at least one interaction area (150) accessible to body fluids; F) Includes the step of exposing the AgCl-containing composition (146) to at least partial ultraviolet light.

Description

Technology Field

[0001] The present invention relates to a method for manufacturing at least one analyte sensor for measuring at least one analyte, an analyte sensor obtained by the method, and a system configured to carry out the method. The analyte sensor may be used primarily to measure the concentration of at least one analyte in body fluids, in particular blood glucose levels. However, additional applications may also be possible. Background Technology

[0002] Measuring the concentration of one or more analytes in body fluids, particularly blood glucose levels, plays an important role in the prevention and treatment of various diseases. Without limiting additional possible applications, the present invention is described below with respect to glucose in interstitial fluid. However, the present invention may be applied to other types of analytes.

[0003] In a subcutaneous glucose biosensor, an Ag / AgCl-based electrode can be used as a reference electrode (RE) that provides a known reference potential, or as a coupled counter electrode / reference electrode (CERE) that provides a reference potential and acts as an electron acceptor to function as a counter electrode.

[0004] Ag / AgCl-based electrodes are typically fabricated by coating a substrate with a paste or ink containing AgCl powder, a binder, elemental Ag powder, and optionally additional components. Subcutaneous glucose biosensors operating in a two-electrode configuration rely on the solubility of AgCl in the glucose concentration measurement process. In particular, the amount of AgCl constituting the CERE must be at least equivalent to the amount of glucose oxidized during the sensor's operating time. Depending on sensor sensitivity, for example, considering an operating time of about 10 to 14 days, an amount of AgCl in the range of tens of micrograms will generally be required.

[0005] Generally, AgCl is a sparingly soluble salt, but interstitial fluid can be composed of different substances that can form soluble forms of silver, for example, coordination complexes. Then, the complexed Ag + Ions can diffuse out of the analyte sensor and trigger bodily reactions, which can degrade the sensor's performance or induce an immune response. Therefore, while a sufficient amount of AgCl is required for the analyte sensor to function properly for its expected duration, AgCl can, on the other hand, reduce the sensor's biocompatibility.

[0006] PCT / EP2021 / 068429 describes an analyte sensor for performing analyte measurements in a user's body fluid. The analyte sensor comprises a substrate, at least one working electrode, at least one second electrode, and a membrane, wherein the membrane is positioned on top of at least one second electrode.

[0007] PCT / EP2021 / 082392 discloses an analyte sensor and a method for manufacturing the analyte sensor. The analyte sensor comprises an electrode comprising a layer of an AgCl-containing composition. The AgCl on the outer surface of the layer of the AgCl-containing composition is at least partially reduced to reduce the amount of exposed AgCl.

[0008] WO2023012138A1 describes an analyte sensor comprising a substrate, at least one first electrode, at least one second electrode, and at least one protective layer covering at least one second electrode. The analyte sensor can be used primarily to perform analyte measurements in a user's body fluids.

[0009] Despite significant advancements in the field of analyte sensors and their manufacturing, several challenges remain. In particular, there is still a need for stable and cost-effective manufacturing methods for analyte sensors that ensure biocompatibility while simultaneously providing a sufficient amount of AgCl to the sensor. The problem to be solved

[0010] Accordingly, the present invention preferably provides a method for manufacturing an analyte sensor for measuring at least one analyte in body fluid and an analyte sensor obtained by said method, which at least partially avoids the disadvantages of known methods and analyte sensors and at least partially solves the aforementioned problem. In particular, it is preferable to provide an analyte sensor that combines increased biocompatibility with a high level of sensitivity to the analyte and a long duration, and the method for manufacturing said analyte sensor should be simple and rapid.

[0011] This problem is solved by a method for manufacturing at least one analyte sensor for measuring at least one analyte in body fluids and by an analyte sensor obtained by the method having the features of the independent claims. Advantageous embodiments that can be realized independently or in any combination are listed in the dependent claims and throughout the specification.

[0012] As used below, the terms "have," "possess," or "include," or any grammatical variations thereof, are used non-exclusively. Accordingly, these terms may refer to both situations in which no additional features exist in the content described in this context, other than those introduced by these terms, and situations in which one or more additional features exist. For example, the expressions "A has B," "A has B," and "A includes B" may refer to both situations in which no other elements other than element B exist in A (i.e., situations in which A constitutes B alone and exclusively) and situations in which one or more additional elements other than element B, such as elements C, elements C and D, or even other additional elements, exist in element A.

[0013] Additionally, it should be noted that expressions such as "at least one," "one or more," or similar expressions indicating that a feature or element may exist one or more times are generally used only once when introducing each feature or element. In the following, in most cases, when referring to each feature or element, the expressions "at least one" or "one or more" will not be repeated, despite the fact that each feature or element may exist more than once.

[0014] Additionally, as used below, terms "preferably," "more preferably," "particularly," "more particularly," "specifically," "more specifically," or similar terms are used with optional features without limiting alternative possibilities. Accordingly, features introduced by these terms are optional features and are not intended to limit the scope of the claims in any way. As will be recognized by those skilled in the art, the present invention may be performed using alternative features. Similarly, features introduced by "in embodiments of the present invention" or similar expressions are intended to refer to optional features without any limitation regarding alternative embodiments of the present invention, without any limitation regarding the scope of the present invention, and without any limitation regarding the possibility of combining features introduced in this manner with other optional or non-optional features of the present invention.

[0015] In a first aspect of the present invention, a method for manufacturing at least one analyte sensor for measuring at least one analyte in a body fluid is disclosed. The method comprises the following method steps, which may be performed specifically in a given order. However, a different order may also be possible. The method may further comprise additional method steps not listed. Additionally, one or more or all of the method steps may be performed only once or repeatedly. The method steps may be performed such that, in particular, two or more steps may overlap completely or at least partially in time. The method comprises the following steps:

[0016] A) providing at least one substrate including a first surface and a second surface;

[0017] B) a step of providing at least one first conductive layer that at least partially covers a first surface of a substrate, specifically a step of applying;

[0018] C) a step of providing at least one second conductive layer that partially covers at least one of the first surface and the second surface, specifically a step of applying;

[0019] D) providing at least one working electrode on a first surface by providing at least one working electrode material that at least partially covers the first conductive layer;

[0020] E) A step of providing at least one additional electrode on at least one of the first surface and the second surface by providing:

[0021] - At least one AgCl-containing composition covering at least partially a second conductive layer; and

[0022] - At least one protective layer covering the AgCl-containing composition, excluding at least one interaction area accessible to body fluids;

[0023] F) Includes the step of exposing the AgCl-containing composition to at least partial ultraviolet light.

[0024] As used herein, the term “analyte sensor” is a broad term and should be given the ordinary and customary meaning to those skilled in the art, and should not be limited to a special or customized meaning. Specifically, this term may refer to, but is not limited to, a sensor configured to detect at least one analyte quantitatively and / or qualitatively. An analyte sensor may be a device configured to perform the detection of an analyte by generating and / or acquiring at least one measurement signal, particularly by the presence, absence, or concentration of the analyte and / or related thereto. An analyte sensor may be or include at least one electrochemical sensor. Depending on the analyte, the measurement signal generated and / or acquired by the analyte sensor may be, in particular, an electrical signal, e.g., at least one current signal or at least one voltage signal.

[0025] The analyte sensor may be composed of an in vivo analyte sensor configured to measure at least one analyte in body fluid while the body fluid is still contained within the user's body. Accordingly, the analyte sensor may be specifically implantable at least partially within the user's body tissue. Specifically, the analyte sensor may be a subcutaneously implantable analyte sensor or a transdermal implantable analyte sensor. Accordingly, generally, the analyte sensor may include at least one implantable portion, and the analyte sensor may be in at least partial contact with the user's body fluid, for example, by the implantable portion. For example, the implantable portion may be fully or partially flexible or deformable. Specifically, the implantable portion may have a length not exceeding 20 mm, e.g., a length not exceeding 10 mm, e.g., a length between 5 mm and 7 mm. The implantable portion may have a width not exceeding 3 mm, e.g., a width not exceeding 1 mm, e.g., a width between 0.5 mm and 0.7 mm. The implantable portion may have a thickness not exceeding 2 mm, for example, not exceeding 0.5 mm, for example, a thickness of 0.1 mm to 0.3 mm. The implantable portion may be in particular rod shape. The implantable portion may have a diameter not exceeding 2 mm, for example, not exceeding 1 mm, for example, a diameter of 0.2 mm to 0.5 mm. In addition to the implantable portion, the analyte sensor may include at least one additional portion or component that may optionally remain outside the body tissue, for example, a contact portion having one or more electrical contact pads electrically connected to an operating electrode and an additional electrode, respectively. The implantable portion placed within the body tissue and the additional portion or component placed outside the body tissue may be electrically connected and / or capable of being connected.

[0026] The analyte sensor may include one or more additional components, such as one or more electronic units that are electrically connected to or capable of being electrically connected to the electrode.

[0027] As used herein, the term “analyte” is a broad term that should be given to those skilled in the art its ordinary and customary meaning and should not be limited to a special or customized meaning. Specifically, this term may refer to, but is not limited to, any element such as a chemical substance, a component or compound and / or other parameters being detected and / or measured. For example, at least one analyte may be a compound involved in the metabolism of one or more of glucose, cholesterol, or triglycerides. However, additionally or alternatively, other types of analytes may be used and / or any combination of analytes may be measured. The determination of at least one analyte may, in particular, be analyte-specific detection. Without limiting further possible applications, the present invention is described in particular with respect to the detection and / or monitoring of glucose in interstitial fluid. The analyte sensor may, specifically, be a subcutaneous glucose biosensor.

[0028] As used herein, the term “at least one analyte” is a broad term that should be given a common and customary meaning to those skilled in the art and should not be limited to a special or customized meaning. Specifically, this term may refer to, but is not limited to, a process for detecting at least one analyte in a qualitative and / or quantitative manner. A process for detecting at least one analyte may include, in particular, a step of generating and / or acquiring at least one measurement signal depending on the analyte to be measured. In particular, at least one attribute, such as the presence, absence, and / or concentration of the analyte in a body fluid, may be inferred and / or deduced from the measurement signal.

[0029] The term "body fluid" as used herein is a broad term and will have its ordinary and customary meaning to a person skilled in the art and is not limited to a special or customized meaning. Specifically, this term may refer to, but is not limited to, fluids produced and / or present in the body of a person or animal. For example, body fluid may be present in the body tissues of a user. For example, body fluid may be one or more of blood, interstitial fluid, urine, saliva, tears, etc., or may contain one or more of these. Other body fluids may also be possible.

[0030] As used herein, the term “providing” is a broad term and should be given a common and ordinary meaning to those skilled in the art and should not be limited to a special or customized meaning. Specifically, the term may refer to, but is not limited to, a process that provides and / or enables a target to be used for further processing or use in one or more subsequent steps. Specifically, providing may include one or more of using, manufacturing, adding, coating, or dispensing at least one target or component. Thus, for example, instead of applying at least one first conductive layer to a first surface or at least one second conductive layer to a second surface, the substrate provided for the process may already have the first conductive layer and / or the second conductive layer applied thereon. However, applying one or both of these first and second conductive layers may be part of the process itself.

[0031] The term “coating” as used herein is a broad term and should be given a common and ordinary meaning to those skilled in the art and should not be limited to a special or customized meaning. Specifically, the term may refer to, but is not limited to, a process of depositing, printing, dispensing, diffusing, or arranging at least one first object, such as at least one material or composition, onto a second object. In said process, the second object may be, for example, completely or partially covered by the first object.

[0032] The term “covered” as used herein is a broad term and should be given a common and ordinary meaning to those skilled in the art and should not be limited to a special or customized meaning. Specifically, the term refers to, but is not limited to, at least one first object, such as at least one material or composition, being placed or disposed upon a second object, e.g., the surface of the second object. Consequently, the second object may be at least partially surrounded and / or coated by the first object, which may act as a layer that completely or partially covers at least one surface of the second object. In particular, the first object “at least partially covering” the second object may cover the second object completely or only partially, and certain areas and / or sections of the second object may be left empty or without the first object.

[0033] As used herein, the term “substrate” is a broad term and should be given to those skilled in the art its ordinary and customary meaning and should not be limited to a special or customized meaning. Specifically, this term may refer to, but is not limited to, any element configured to carry one or more other elements disposed and / or arranged thereon. For example, the substrate may carry one or more electrodes, which may be disposed, for example, on different sides of the substrate. The substrate may include at least one electrical insulating material to prevent electrical contact between electrodes disposed, for example, on different sides of the substrate. For example, the electrical insulating material may be selected from polyethylene terephthalate (PET), polycarbonate (PC), or polyimide (PI). Other electrical insulating materials may also be possible. The substrate may be a flat substrate. The substrate may have an elongated shape, particularly such as a strip shape, a bar shape, or a rod shape. However, other types of shapes may also be possible.

[0034] The substrate has at least one first surface and at least one second surface. The first surface of the substrate and the second surface of the substrate may be opposite surfaces of the substrate facing in opposite directions. In particular, the first surface and the second surface may be oriented essentially parallel. In particular, the first surface and the second surface may each include at least one surface of the substrate.

[0035] As part of step B) of the method, at least one first conductive layer is applied to at least partially cover a first surface of a substrate. As part of step C) of the method, at least one second conductive layer is applied to at least partially cover one of the first surface and the second surface of the substrate. In particular, in step C), the second conductive layer may be applied to the second surface of the substrate such that the second surface of the substrate is at least partially covered. The first conductive layer and the second conductive layer may each comprise at least one electrically conductive or semiconductor material. In particular, the first conductive layer and the second conductive layer may both comprise the same conductive material or be formed by the same conductive material. The conductive material may comprise at least one inorganic electrically conductive material such as at least one metal selected from the group of electrically conductive carbon and metals, particularly gold; silver; platinum; copper, for example, gold-plated copper. Additionally or alternatively, at least one organic electrically conductive or semiconductor material, for example, at least one electrically conductive polymer such as PEDOT, where PEDOT represents poly-3,4-ethylenedioxythiophene, may be used. Other conductive materials may also be possible. Examples of additional electrically conductive materials may include ITO and FTO, where ITO represents indium tin oxide and FTO represents fluorine-doped tin oxide, and thus, both the first conductive layer and the second conductive layer may be electrically conductive.

[0036] The first conductive layer may be electrically in contact with a working electrode material that covers at least partially the first conductive layer. The first conductive layer may facilitate electron transport from the working electrode material. The second conductive layer may be electrically in contact with an AgCl-containing composition provided on the second conductive layer. The second conductive layer may facilitate electron transport to and / or into the AgCl-containing composition. The first conductive layer and the second conductive layer may be separated from each other by a substrate, and the first conductive layer and the second conductive layer may be electrically insulated from each other.

[0037] For example, the terms 'first' and 'second' used in connection with the terms 'surface' and 'layer,' or any other ordinal numbers used herein, do not imply any order or sequence regarding the provision or application of objects, or any different difference in the importance of the objects. Instead, 'first' and 'second' or other ordinal terms are used to clearly distinguish the numbered objects.

[0038] The term “electrode” as used herein is a broad term and should be given to those skilled in the art its ordinary and customary meaning and should not be limited to a special or customized meaning. Specifically, the term may refer to any electrically conductive or semiconductor element to which voltage or current may be applied, but is not limited thereto. The electrode may comprise at least one electrically conductive material, such as in the form of an electrically conductive layer, for example. For example, voltage may be applied between the electrode and at least one additional electrically conductive element by at least one potentiometer and / or at least one current measuring unit. The potentiometer and / or at least one current measuring unit may optionally form part of an analysis sensor and / or an analysis system comprising the analysis sensor and at least one potentiometer and / or current measuring unit.

[0039] As used herein, the term “working electrode” is a broad term and should be given to those skilled in the art its ordinary and common meaning and should not be limited to a special or customized meaning. Specifically, this term may refer to, but is not limited to, an electrode sensitive to the analyte to be measured.

[0040] Accordingly, the term “working electrode material” as used herein is a broad term and should be given a common and ordinary meaning to those skilled in the art and should not be limited to a special or customized meaning. Specifically, this term may refer to, but is not limited to, a material, compound, or chemical composition configured to produce, at least one electrochemical reaction detectable in the presence of an analyte or an analyte, more specifically, an electrochemical reaction electrically detectable by one or more of potentiostatic and amperometric methods.

[0041] Consequently, the working electrode comprises at least one first electrically conductive layer or a portion of the first electrically conductive layer covered by at least one working electrode material, and, for example in a layered structure, at least one working electrode material. The portion of the first electrically conductive layer not covered by at least one working electrode material may form at least one electrical lead for electrically contacting the working electrode. The electrical lead may also include at least one electrical contact pad on the substrate.

[0042] Accordingly, specifically, the working electrode may be configured to change the electrochemical potential in the presence of the analyte and induce current flow at an appropriate polarization. Specifically, the working electrode material may include at least one material or compound configured to react selectively with the analyte, such as at least one enzyme. For example, if the analyte is glucose or contains glucose, the enzyme may include one or more of glucose oxidase and glucose dehydrogenase. Additionally, the working electrode material may include one or more additional components, such as a mediator compound configured for electron transfer, etc. Refer to "based amperometric biosensors" by Paolo Bollella and Lo Gorton.

[0043] Accordingly, the working electrode may generally be configured to interact with the analyte, particularly through redox reactions. For example, the interaction may involve at least one exchange of electrons, such as the transfer of electrons from the analyte to the working electrode in at least one electrochemical detection reaction. The electrochemical detection reaction at the working electrode may be one of two half reactions, and the greater of the two half reactions may occur at one or more additional electrodes, such as the counter electrode or CERE. As a result of the potential applied between the working electrode and at least one additional electrode and the electrochemical detection reaction, a current may flow between the working electrode and the additional electrode through at least one electrolyte, particularly body fluid. At least one measurement signal may be generated depending on the presence, absence, and / or concentration of the analyte. The measurement signal may be an electrical signal comprising at least one current signal or at least one voltage signal.

[0044] Step D) includes the step of providing at least one working electrode on the first surface by providing at least one working electrode material that at least partially covers the first conductive layer. The working electrode material may include at least one reagent layer for detecting an analyte. Accordingly, Step D) may particularly include the step of applying at least one reagent layer to the first conductive layer. The reagent layer may at least partially cover the first conductive layer. In the region where the reagent layer covers the first conductive layer, the first conductive layer and the reagent layer may form a working electrode. The reagent layer may particularly include at least one biometric component, particularly an enzyme, which is tuned to interact with the analyte. The reagent layer may include one specific biometric component or a mixture of two or more biometric components. The biometric component, particularly an enzyme, may catalyze at least one chemical reaction that alters the analyte, for example, a chemical reaction in which the analyte is oxidized and / or reduced. Specifically, the biometric component, particularly an enzyme, may be tuned to oxidize or reduce the analyte. In particular, the biometric component, in particular the enzyme, may be at least one of glucose oxidase (GOx) and glucose dehydrogenase (GDH).

[0045] Step E) comprises providing at least one additional electrode on at least one of the first and second surfaces by providing at least one AgCl-containing composition that at least partially covers the second conductive layer; and at least one protective layer that covers the AgCl-containing composition, excluding at least one interaction region accessible to body fluids. In particular, in step C) of the method, the second conductive layer is applied so that the second conductive layer at least partially covers the second surface of the substrate, and in step E), the additional electrode may be provided on the second surface of the substrate. For better readability, this embodiment will be referred to below. Those skilled in the art will be able to easily translate the description of an embodiment in which both the working electrode and the additional electrode are provided on the first surface.

[0046] Consequently, at least one additional electrode on the second surface of the substrate comprises at least one second electrically conductive layer or at least a portion of the second electrically conductive layer covered by at least one AgCl-containing composition, and, for example, in a layer configuration, at least one AgCl-containing composition. Additionally, at least one protective layer covering the AgCl-containing composition, excluding at least one interaction region accessible to body fluids, may optionally form a portion of at least one additional electrode. At least one portion of the second conductive layer may remain uncovered by the AgCl-containing composition. This at least one portion may, for example, form at least one conductive lead for electrically contacting at least one additional electrode, or may include at least one conductive lead. For example, at least one conductive lead may also form one or more electrical contact pads for electrically contacting at least one additional electrode.

[0047] At least one additional electrode and a working electrode may form part of an electrochemical circuit. Both the working electrode and the additional electrode may be part of an implantable portion of the analyte sensor and may be placed within body tissue. In particular, thus, the analyte sensor may be used for one or more measurements of potential difference or current. For example, different potentials of electric voltage or electric potential may be measured between the working electrode and at least one additional electrode. Additionally, or alternatively, a voltage may be applied between the working electrode and the additional electrode, and a current may be measured by allowing a current to flow between the working electrode and the additional electrode through at least one electrolyte, such as body fluid, for example. Thus, the measurement signal of the analyte sensor may include one or more of a voltage measurement signal and a current measurement signal. The measurement signal may be used for the measurement of the analyte, such as the detection of the analyte concentration.

[0048] The additional electrode may include at least one electrode among a counter electrode, a reference electrode, and a combined counter / reference electrode. The electrode type of the at least one additional electrode is generally determined by the measurement configuration in which the at least one additional electrode is used. Thus, for example, in a kinetic potential measurement, a voltage may be measured between the working electrode and the additional electrode. In such a configuration, typically, at least one additional electrode may be referred to as a reference electrode or may at least partially function as a reference electrode, and the fact that the electrode potential of the additional electrode, which typically comprises an Ag / AgCl composition, may not be extensively affected by the concentration of an analyte such as the concentration of glucose may be utilized. Meanwhile, in an amperometric measurement, a current may be measured between the working electrode and at least one additional electrode or at least a part thereof by applying a known voltage, or alternatively, a voltage between the working electrode and at least one additional electrode or at least a part thereof required to achieve a predetermined current may be measured. In this configuration, for example, at least one additional electrode may be referred to as a counter electrode.

[0049] Accordingly, the term "counter electrode" as used herein is a broad term and should be given a common and ordinary meaning to those skilled in the art, and should not be limited to a special or customized meaning. Specifically, the electrochemical detection reaction occurring at the working electrode is one of two half-reactions, and an additional half-reaction of the two half-reactions may occur at the counter electrode in the form of a counter reaction. In particular, the half-reaction occurring at the working electrode may involve the oxidation of the analyte, in particular glucose, and the half-reaction occurring at the counter electrode may involve reduction, in particular reduction at the counter electrode, e.g., element Ag +It may include the reduction of element Ag. The counter electrode may be configured to balance the current flow resulting from the electrochemical detection reaction at the working electrode in particular.

[0050] As used herein, the term “reference electrode” is a broad term and should be given to those skilled in the art its ordinary and common meaning and should not be limited to a special or customized meaning. Specifically, this term may refer to, but is not limited to, an electrode configured to provide at least one electrical reference potential. The electrochemical reference potential of the reference electrode may be at least broadly independent of the presence, absence, or concentration of the analyte. The reference electrode may be configured to serve as a reference for measuring and / or controlling the potential of the working electrode. The reference electrode may have a stable and well-known electrode potential.

[0051] In particular, the additional electrode can combine multiple functions. Specifically, the additional electrode may combine or include a counter / reference electrode, also known as CERE. Thus, the additional electrode can provide a reference potential and balance the current flow from the working electrode.

[0052] The term “containing composition” as used herein is a broad term and should be given a common and ordinary meaning to those skilled in the art and should not be limited to a special or customized meaning. Specifically, this term may refer to materials such as solid, liquid, or paste-type materials containing AgCl, which may also be referred to as silver chloride, but is not limited thereto. The AgCl-containing composition may comprise AgCl in the form of particles with a particle size in the range of 0.5 μm to 80 μm, particularly in the range of 1 μm to 50 μm, more specifically in the range of 2 μm to 20 μm. The AgCl-containing composition covering at least partially an analyte sensor, particularly an additional electrode, particularly a second conductive layer, may comprise a total amount of AgCl in the range of 10 μg to 100 μg, specifically 20 μg to 50 μg, more specifically 25 μg to 35 μg. The AgCl-containing composition, in particular, at least one coating process, particularly, for example, doctor blading; dispensing; slot-dye coating; The AgCl-containing composition may be provided by applying it to the second conductive layer in the form of a paste or ink using a wet coating process selected from the group consisting of cannula coating; printing, e.g., screen printing, particularly rotary screen printing. Thus, the AgCl-containing composition may be provided in step E) as an AgCl-containing layer having a thickness in the range of 1 μm to 100 μm, particularly 5 μm to 60 μm, more specifically 15 μm to 25 μm.

[0053] The AgCl-containing composition may include at least one additional component, particularly a plurality of additional components. Specifically, the AgCl-containing composition may include elemental Ag and at least one of at least one binder, such as an organic binder. The weight ratio (also referred to as w / w) of elemental Ag to AgCl in the AgCl-containing composition may be in the range of 10:1 to 1:20, for example, in the range of 10:1 to 1:10. The terms elemental Ag and elemental silver may be used interchangeably throughout this document. The binder may specifically include non-conductive polymers, in particular PVC-based polymers and / or polyurethane-based polymers, in particular TPU-based polymers. The expression TPU-based polymer may refer to thermoplastic polyurethane. The AgCl-containing composition may include both elemental Ag and at least one binder, in particular in a ratio in the range of 1:100 to 100:1, specifically in the range of 1:50 to 50:1, and more specifically in the range of 1:10 to 10:1.

[0054] The term “protective layer” as used herein is a broad term and should be given a common and ordinary meaning to those skilled in the art and should not be limited to a special or customized meaning. Specifically, the term may refer, but is not limited to, a material forming a sheet and / or film extending over an object so as to completely or partially cover at least one surface of the object. Thus, the protective layer may shield the object by covering or partially covering it. In particular, the protective layer may be a physical barrier or function as a physical barrier capable of completely or partially preventing or hindering physical contact between the covered object and its environment. In particular, a protective layer covering an AgCl-containing composition may prevent physical contact between the covered portion of the AgCl-containing composition and the body fluid and / or body tissue into which the analyte sensor is inserted, for example, while such contact occurs in at least one interaction area not covered by the protective layer. The protective layer may be particularly impermeable to body fluids. The protective layer can prevent interactions, e.g., chemical, biochemical allergies, and / or electrochemical interactions, between a portion of the AgCl-containing composition covered by the protective layer and body fluids and / or body tissues surrounding the AgCl-containing composition. The protective layer prevents Ag from entering body fluids from a portion of the AgCl-containing composition covered by the protective layer. + It can prevent leaching. The protective layer may comprise at least one polymer, for example, at least one of a TPU-based polymer, a PVC-based polymer, a polyester-based polymer, or a polystyrene-based polymer. The term "PVC-based polymer" may refer to a polyvinyl chloride-based polymer. Additional materials for the protective layer are possible. For example, the protective layer may comprise a hydrophobic polymer, an industrial photoresist, or an insulating varnish. For example, a material that can be applied as a thin layer and is impermeable to water may be further used.

[0055] The term “interaction area” as used herein is a broad term and should be given a common and ordinary meaning to those skilled in the art and should not be limited to a special or customized meaning. Specifically, this term may refer to, but is not limited to, a section, segment, and / or part of an object where an interaction may occur between the object and its surrounding environment. Specifically, the interaction area of ​​an AgCl-containing composition may comprise at least one surface section of an AgCl-containing composition without a protective layer. Thus, the surface section may come into physical contact with body fluids, particularly when an analyte sensor is implanted in body tissue, and an interaction may occur between the AgCl-containing composition and the body fluids. For example, the interaction may be chemical, particularly electrochemical, interaction. The interaction area may further allow for interaction between the surface section of the AgCl-containing composition formed by the interaction area and incident electromagnetic radiation, for example, ultraviolet radiation, when the analyte sensor is not implanted, such as photochemical interaction.

[0056] At least one interaction region is provided as part of step E). Specifically, the at least one interaction region may be located on a second surface of the substrate and / or at least one edge of a layered structure comprising the substrate, a second conductive layer, at least one AgCl-containing composition, and at least one protective layer. Accordingly, specifically, at least one edge of the additional electrode may not be covered by the protective layer, and the uncovered edge may form at least one interaction region where the AgCl-containing composition can come into contact with body fluids.

[0057] At least one interaction region may be formed specifically by cutting a layered structure comprising a substrate, an operating electrode, and at least one additional electrode. For example, by cutting, at least one edge portion within the layered structure may be created, and the edge portion may include an interaction region. The cutting process may specifically include one or more of mechanical cutting and laser cutting, as described in more detail below. In particular, a plurality of interaction regions may be provided as part of step E), for example, two or more interaction regions may be provided. Specifically, step E) may include the step of providing at least one additional electrode comprising exactly two interaction regions. The two interaction regions may face opposite directions. The interaction region is 0.01 mm 2 to 1 mm 2 , specifically 0.1 mm 2 up to 0.5 mm 2 , more specifically 0.2 mm 2 up to 0.4 mm 2 It can have a surface of a range.

[0058] Alternatively or additionally to form an interaction region by cutting a layered structure comprising a substrate, an operating electrode, and at least one additional electrode, the interaction region may be formed by creating at least one opening, for example, a single opening or multiple openings, in the protective layer. The opening may also be described as the entire protective layer, and the AgCl-containing composition may be absent from the protective layer at at least one opening. A laser may be applied to create at least one opening. Specifically, the AgCl-containing composition may be applied in the form of a dot or a rod and covered by the protective layer so that the AgCl-containing composition is not cut and thus not exposed during subsequent sensor cutting. A laser may be applied to create a single or multiple openings in the protective layer to create an interaction region. Reference may be made to WO2023012138A1. For example, the interaction region in the form of at least one opening in the protective layer may allow for mass transport.

[0059] The term “accessible to body fluids” as used herein is a broad term and should be given a common and ordinary meaning to those skilled in the art and should not be limited to a special or customized meaning. Specifically, this term may refer without limitation to the properties of an object that can come into direct physical contact with body fluids. Thus, unlike parts of an AgCl-containing composition covered by a protective layer, the interaction area may come into contact with body fluids, specifically immersed in body fluids, for example, when an implantable part of an analyte sensor is placed within a tissue.

[0060] As used herein, the term “exposed to ultraviolet light” is a broad term and should be given a common and ordinary meaning to those skilled in the art and should not be limited to a special or customized meaning. Specifically, this term may refer to, but is not limited to, a process of illuminating an object with ultraviolet light and / or exposing the object to ultraviolet light. Step F) includes the step of exposing an AgCl-containing composition to ultraviolet light at least partially. Thus, the AgCl-containing composition may be fully exposed to ultraviolet light, for example, the entire AgCl-containing composition, particularly the entire surface of the AgCl-containing composition, may be exposed to ultraviolet light. Alternatively, the AgCl-containing composition may be partially exposed to ultraviolet light, for example, only a specific part, section, or region of the AgCl-containing composition, particularly a specific surface area, is exposed to ultraviolet light, and other parts, sections, or regions of the AgCl-containing composition, particularly other surface areas, are not illuminated by ultraviolet light. In particular, Step F) may include the step of exposing an interaction area to ultraviolet light at least partially. In particular, Step F) of the method may be performed after the interaction area is provided.

[0061] The term “ultraviolet” as used herein is a broad term and should be given a common and ordinary meaning to those skilled in the art and should not be limited to a special or customized meaning. Specifically, this term may refer to, but is not limited to, a division of electromagnetic radiation having wavelengths in the range of 10 nm to 400 nm, particularly in the range of 100 nm to 380 nm. In particular, in step F), an artificial ultraviolet light source, particularly an artificial ultraviolet light source having a peak wavelength in the range of 200 nm to 400 nm, may be used. For example, an ultraviolet light-emitting diode array (also called a UV LED array) having a peak wavelength of 365 nm may be used. In particular, the ultraviolet used in step F) may have an intensity in the range of 1 mW / cm² to 200 mW / cm², particularly 10 mW / cm² to 100 mW / cm², more specifically 50 mW / cm² to 75 mW / cm². For example, the intensity may be 65 mW / cm². In particular, the analyte sensor, in particular the AgCl-containing composition, may be at least partially exposed to ultraviolet light as part of step F) by positioning it at a certain distance from an ultraviolet light source. For example, other irradiation conditions related to the ultraviolet light source, intensity, and duration of irradiation may be possible. In particular, the irradiation conditions may cause the AgCl-containing composition exposed to ultraviolet light to receive a predetermined amount of radiation, in particular the total energy per area.

[0062] Step F) includes the step of exposing the AgCl-containing composition to ultraviolet light, at least partially. As part of Step F), AgCl may be at least partially photochemically transformed into elemental Ag, unless one wishes to be bound by this theory. Specifically, in Step F), elemental Ag may be formed by reducing the AgCl in the interaction region, particularly the AgCl on the surface of the interaction region, at least partially by ultraviolet light. Thus, in Step F), an amount of AgCl, for example, a portion of the AgCl in the AgCl-containing composition, may be reduced to elemental Ag. Electrochemical measurements indicate a 1% to 5% reduction in electrochemically accessible AgCl depending on the treatment conditions, which can be explained by the photochemical reduction of the amount of AgCl. In particular, in Step F), the concentration of AgCl may decrease in the interaction region, particularly on the surface of the interaction region. Thus, at least partial decomposition and / or reduction of AgCl near the surface of the interaction region may be a result of photochemical treatment using ultraviolet light in Step F). This AgCl would otherwise be Ag + It can be a source of ions. AgCl located further away from the surface of the interaction region is Ag + It may contribute less to the leaching of ions. Therefore, direct contact between body fluids and AgCl and Ag into body fluids + The biocompatibility of the analyte sensor can be increased by reducing leaching and in vivo side effects. Additionally, exposing the AgCl-containing composition to ultraviolet light, at least partially as performed in step F) of the method, can be a particularly dry process, which can enable simple and rapid fabrication of the analyte sensor.

[0063] For example, in step F), an amount ranging from 0.1 μg to 2 μg of a total of 30 μg of AgCl may be reduced to elemental Ag. Other amounts are also possible. In particular, the given values ​​may be specific to different designs, shapes, and / or examples of the analyte sensor, particularly different designs, shapes, and / or examples of the AgCl-containing composition, and may differ for different designs, shapes, and / or examples.

[0064] Step F) may include a step of exposing the AgCl-containing composition to ultraviolet light at least partially in a stepwise manner, each exposure step may include a step of exposing the AgCl-containing composition to ultraviolet light at least partially for an exposure time ranging from 3 seconds to 2 minutes, specifically from 15 seconds to 1 minute, more specifically from 30 seconds. Each exposure step may be followed by at least one dissipation step comprising radiation blocking for a range of 1 second to 30 seconds, specifically from 3 seconds to 10 seconds, more specifically from 5 seconds. In the dissipation step, the AgCl-containing composition, particularly the interaction region, may not be exposed to ultraviolet light. Instead, ultraviolet light may be stopped. Since heat dissipation from the AgCl-containing composition may occur during the dissipation step, thermal stress caused by exposure to ultraviolet light may be reduced. In Step F), the AgCl-containing composition, particularly the interaction region, may be at least partially exposed to ultraviolet light for a total exposure time ranging from 10 seconds to 1 hour, specifically from 30 seconds to 30 minutes, more specifically from 1 minute to 20 minutes. In particular, step F) may include multiple exposure steps, and a burn-out step follows each exposure step, and the total amount of exposure time may correspond to the sum of the exposure times of each exposure step.

[0065] A method for manufacturing at least one analyte sensor may specifically include the step of cutting a layered structure, for example, a sheet-type template, comprising a substrate, a first conductive layer, a second conductive layer, an operating electrode material, an AgCl-containing composition, and a protective layer, to form at least one analyte sensor, particularly by laser cutting. In particular, an interaction region may be formed in the laser cutting process, particularly, by the cutting edge of the layered structure, for example, the sheet-type template. In particular, a plurality of analyte sensors may be manufactured by continuously laser cutting each of the plurality of analyte sensors from a layered structure, for example, a sheet-type template. In the laser cutting process, for example, at least one laser among a carbon dioxide laser and an ultrashort pulse laser may be used.

[0066] In a further aspect of the present invention, an analyte sensor for measuring at least one analyte in body fluids is proposed. The analyte sensor is obtained by a method for manufacturing at least one analyte sensor for measuring at least one analyte in body fluids as described above and / or as further described below. Accordingly, regarding details of the analyte sensor and terms and definitions, one may refer to the method for manufacturing at least one analyte sensor described above and / or the description further described below.

[0067] The analyte sensor is:

[0068] a) at least one substrate, wherein the substrate comprises a first surface and a second surface;

[0069] b) at least one first conductive layer, wherein the first conductive layer at least partially covers a first surface of the substrate;

[0070] c) at least one second conductive layer, wherein the second conductive layer partially covers at least one of the first surface and the second surface;

[0071] d) As at least one working electrode, the working electrode is:

[0072] - At least one part of the first conductive layer; and

[0073] - Includes at least one working electrode material that partially covers at least one portion of the first conductive layer;

[0074] e) at least one additional electrode, wherein the additional electrode is:

[0075] - At least one part of the second conductive layer;

[0076] - An AgCl-containing composition that partially covers at least one portion of the second conductive layer; and

[0077] - Includes a protective layer covering the AgCl-containing composition, except for at least one interaction area accessible to body fluids.

[0078] In a further aspect of the present invention, a system for manufacturing at least one analyte sensor for measuring at least one analyte in body fluids is proposed. The system is configured to perform the method as described above and / or as described in more detail below. Accordingly, regarding details, terms, and definitions of the system for manufacturing at least one analyte sensor, reference may be made to the description of the method for manufacturing at least one analyte sensor described above and / or as described in more detail below. The system is:

[0079] i. At least one first coating device for applying at least one first conductive layer that at least partially covers a first surface of a substrate;

[0080] ii. A coating device for applying a second conductive layer that partially covers at least one of the first surface and the second surface;

[0081] iii. At least one device for providing at least one working electrode material that at least partially covers the first conductive layer;

[0082] iv. At least one apparatus for providing at least one AgCl-containing composition that at least partially covers the second conductive layer;

[0083] v. At least one device for providing at least one protective layer covering an AgCl-containing composition, excluding at least one interaction region accessible to body fluids; and

[0084] vi. Includes at least one exposure device for exposing the AgCl-containing composition to at least partially ultraviolet light.

[0085] A method for manufacturing at least one analyte sensor and the analyte sensor obtained by said method provide many advantages over methods and analyte sensors known to those skilled in the art. Accordingly, as part of the method, additional photochemical treatment of CERE protected by TPU may be proposed to convert AgCl into elemental silver in an open Ag / AgCl region, e.g., at least one interaction region. The photochemical treatment may include irradiation of CERE with ultraviolet light. The irradiation spectrum may be selected from a broad range, and a preferred range may be UV B and / or UV C, e.g., 365 nm. The irradiation duration may vary depending on the spectrum and flux. For example, the duration is 65 mWatt / cm² 2 The duration is 15 minutes, and the spectrum can have a peak wavelength of 365 nm and a FWHM of 6 nm. The abbreviation FWHM can represent the expression "Full Width at Half." Additionally, different intensities, spectra, and durations may be applied and may vary depending on the CERE composition and / or design. Furthermore, irradiation can occur at different intensities and durations rather than in a single irradiation session. This can be useful for reducing the thermal load on the substrate.

[0086] In particular, an analyte sensor obtained by a method for manufacturing at least one analyte sensor may exhibit increased biocompatibility compared to sensors known in the art. In particular, if an AgCl-containing composition is exposed at least partially to ultraviolet light, AgCl may be reduced in the interaction region. Therefore, contact between body fluids and AgCl and Ag into body fluids + The leaching of silver can be reduced. This can increase the biocompatibility of the analyte sensor by reducing adverse effects in the body. Additionally, adverse effects may occur due to soluble forms of silver ions diffusing into body fluids. These adverse bodily reactions can degrade the performance of the analyte sensor. Therefore, by reducing these reactions, the analyte sensor may exhibit increased sensitivity and / or reliability compared to analyte sensors known to those skilled in the art, particularly during the time immediately following sensor insertion.

[0087] In addition, the analyte sensor obtained by the method can also exhibit improved sensor performance compared to analyte sensors known in the art, particularly improved CERE performance after sensor insertion, for example, during sensor run-in for a period of several minutes after insertion.

[0088] In addition, the method for manufacturing the analyte sensor may be more cost-effective than methods known to those skilled in the art. In particular, step F) of the method may be performed as a dry method step. In particular, a wet method step may be avoided in step F) of the method. Therefore, the method may be performed in a faster and simpler manner than methods known to those skilled in the art.

[0089] To summarize without excluding other possible embodiments, the following embodiments may be expected:

[0090] Example 1: A method for manufacturing at least one analyte sensor for measuring at least one analyte in a body fluid, wherein the method comprises:

[0091] A) providing at least one substrate including a first surface and a second surface;

[0092] B) a step of providing at least one first conductive layer that at least partially covers a first surface of a substrate, specifically a step of applying;

[0093] C) a step of providing at least one second conductive layer that partially covers at least one of the first surface and the second surface, specifically a step of applying;

[0094] D) providing at least one working electrode on a first surface by providing at least one working electrode material that at least partially covers the first conductive layer;

[0095] E) A step of providing at least one additional electrode on at least one of the first surface and the second surface by providing:

[0096] - At least one AgCl-containing composition covering at least partially a second conductive layer; and

[0097] - At least one protective layer covering the AgCl-containing composition, excluding at least one interaction area accessible to body fluids;

[0098] F) A method comprising the step of exposing an AgCl-containing composition to at least partially ultraviolet light.

[0099] Example 2: A method in which, in step C) the second conductive layer covers at least partially the second surface of the substrate, and in step E) an additional electrode may be provided on the second surface of the substrate.

[0100] Example 3: A method in which, in any one of the prior examples, AgCl is photochemically converted to elemental Ag in step F).

[0101] Example 4: A method in which, in any one of the prior examples, the interaction area in step F) is at least partially exposed to ultraviolet light.

[0102] Example 5: A method in which, in any one of the prior examples, an artificial ultraviolet light source, in particular an artificial ultraviolet light source having a peak wavelength in the range of 200 nm to 400 nm, is used in step F).

[0103] Example 6: A method in which, in any one of the prior examples, the AgCl-containing composition, particularly the interaction region, in step F) is exposed to ultraviolet light with a total intensity of 1 mW / cm² to 200 mW / cm², particularly 10 mW / cm² to 100 mW / cm², more specifically 50 mW / cm² to 75 mW / cm² in the spectral range of 200 nm to 400 nm.

[0104] Example 7: A method in which, in any one of the prior examples, the interaction region comprises at least one surface section of an AgCl-containing composition.

[0105] Example 8: In any one of the prior examples, the interaction area is 0.01 mm 2 to 1 mm 2 A method having a surface of a range.

[0106] Example 9: A method in which, in any one of the prior examples, the element Ag in step F) is formed by reducing at least partially the AgCl in the interaction region, particularly the AgCl on the surface of the interaction region, by ultraviolet light.

[0107] Example 10: A method in which, in any one of the prior examples, at step F), an amount ranging from 0.1 μg to 2 μg of a total of 30 μg of AgCl is reduced to elemental Ag.

[0108] Example 11: A method in which, in any one of the prior examples, in step F), the AgCl of the AgCl-containing composition is at least partially decomposed, particularly on the surface of the interaction region.

[0109] Example 12: A method in which, in any one of the prior examples, the additional electrode comprises at least two interaction regions, particularly exactly two interaction regions facing opposite directions.

[0110] Example 13: A method in which, in any one of the prior examples, at least one interaction region is formed by at least one cutting of mechanical cutting and laser cutting.

[0111] Example 14: In any one of the prior examples, the method comprises the step of cutting a layered structure, in particular a sheet-type template, comprising a substrate, an operating electrode and an additional electrode, to form at least one analyte sensor.

[0112] Example 15: A method in which, in a prior example, the interaction region is formed in a cutting process, particularly as a cutting edge of a layered structure.

[0113] Example 16: A method of manufacturing a plurality of analyte sensors by continuously cutting each of the plurality of analyte sensors from a layered structure in any one of the prior examples.

[0114] Example 17: A method in which, in any one of the prior examples, at least one laser among a carbon dioxide laser and an ultrashort pulse laser is used in a laser cutting process.

[0115] Example 18: In any one of the prior examples, step F) of the method is performed after the interaction area is provided.

[0116] Example 19: A method in which, in any one of the prior examples, step F) comprises stepwise partially exposing an AgCl-containing composition to ultraviolet light, wherein each exposure step comprises exposing the AgCl-containing composition to ultraviolet light for at least one exposure time in the range of 3 seconds to 2 minutes, specifically 15 seconds to 1 minute, more specifically 30 seconds.

[0117] Example 20: A method in which, in the prior example, at least one dissipation step follows each exposure step, and each dissipation step includes radiation shielding in the range of 1 second to 30 seconds, specifically 3 seconds to 10 seconds, more specifically 5 seconds.

[0118] Example 21: A method in which, in step F) of any one of the prior examples, the AgCl-containing composition, particularly the interacting region, is at least partially exposed to ultraviolet light for a total exposure time ranging from 10 seconds to 1 hour, specifically from 30 seconds to 30 minutes, more specifically from 1 minute to 20 minutes.

[0119] Example 22: A method in which, in any one of the prior examples, the working electrode material comprises at least one reagent layer for detecting an analyte.

[0120] Example 23: A method in which, in a prior example, the reagent layer comprises at least one biometric component, in particular an enzyme, adjusted to interact with an analyte.

[0121] Example 24: A method in which, in the prior example, a biometric component, in particular an enzyme, is adjusted to oxidize an analyte.

[0122] Example 25: A method in which, in any one of the prior examples, the biometric component, in particular the enzyme, is at least one of glucose oxidase (GOx) and glucose dehydrogenase (GDH).

[0123] Example 26: A method in which, in any one of the prior examples, the analyte measurable by the analyte sensor is glucose.

[0124] Example 27: A method in which, in any one of the prior examples, the additional electrode comprises at least one electrode among a counter electrode, a reference electrode, and a combined counter / reference electrode.

[0125] Example 28: In the prior example, the additional electrode is a single combined counter / reference electrode or a method comprising the same.

[0126] Example 29: In the prior example, the AgCl-containing composition is provided in step E as an AgCl-containing layer having a thickness in the range of 1 μm to 100 μm, specifically 5 μm to 60 μm, more specifically 15 μm to 25 μm.

[0127] Example 30: A method in which, in any one of the prior examples, the AgCl-containing composition comprises AgCl in the form of particles with a particle size ranging from 0.5 μm to 80 μm, specifically from 1 μm to 50 μm, more specifically from 2 μm to 20 μm.

[0128] Example 31: A method in which, in any one of the prior examples, the AgCl-containing composition comprises a total amount of AgCl in the range of 10 μg to 100 μg, specifically 20 μg to 50 μg, more specifically 25 μg to 35 μg.

[0129] Example 32: A method in which, in any one of the prior examples, the AgCl-containing composition further comprises at least one of element Ag and at least one binder.

[0130] Example 33: A method in which, in the prior example, the weight ratio of element Ag to AgCl in the AgCl-containing composition may be in the range of 10:1 to 1:20, for example, in the range of 10:1 to 1:10.

[0131] Example 34: A method in which, in any one of the prior examples, the binder comprises a non-conductive polymer, in particular a PVC-based polymer and / or a polyurethane-based polymer, in particular a TPU-based polymer.

[0132] Example 35: A method in which, in any one of the prior examples, the AgCl-containing composition comprises AgCl and at least one binder in a ratio of 1:100 to 100:1, particularly in a ratio of 1:50 to 50:1, more specifically in a ratio of 1:10 to 10:1.

[0133] Example 36: A method in which, in any one of the prior examples, the first conductive layer and the second conductive layer are both formed by the same conductive material.

[0134] Example 37: A method in which the conductive material comprises at least one material selected from carbon, gold, silver, platinum, and copper, e.g., gold-plated copper.

[0135] Example 38: A method in which, in any one of the prior examples, the substrate comprises at least one electrical insulating material.

[0136] Example 39: A method in which, in any one of the prior examples, the first surface of the substrate and the second surface of the substrate face in opposite directions.

[0137] Example 40: An analyte sensor for measuring at least one analyte in a body fluid, wherein the analyte sensor is obtained by a method according to any one of the prior examples.

[0138] Example 41: In the prior example, the analyte sensor is:

[0139] a) at least one substrate, wherein the substrate comprises a first surface and a second surface;

[0140] b) at least one first conductive layer, wherein the first conductive layer at least partially covers a first surface of the substrate;

[0141] c) at least one second conductive layer, wherein the second conductive layer partially covers at least one of the first surface and the second surface;

[0142] d) As at least one working electrode, the working electrode is:

[0143] - At least one part of the first conductive layer; and

[0144] - Includes at least one working electrode material that partially covers at least one portion of the first conductive layer;

[0145] e) at least one additional electrode, wherein the additional electrode is:

[0146] - At least one part of the second conductive layer;

[0147] - An AgCl-containing composition that partially covers at least one portion of the second conductive layer; and

[0148] - An analyte sensor comprising a protective layer covering an AgCl-containing composition, excluding at least one interaction region accessible to body fluids.

[0149] Example 42: A system for manufacturing at least one analyte sensor for measuring at least one analyte in a body fluid, wherein the system is configured to perform a method according to any one of the prior embodiments in relation to the method, and the system:

[0150] i. At least one first coating device for applying at least one first conductive layer that at least partially covers a first surface of a substrate;

[0151] ii. A coating device for applying a second conductive layer that partially covers at least one of the first surface and the second surface;

[0152] iii. At least one device for providing at least one working electrode material that at least partially covers the first conductive layer;

[0153] iv. At least one apparatus for providing at least one AgCl-containing composition that at least partially covers the second conductive layer;

[0154] v. At least one device for providing at least one protective layer covering an AgCl-containing composition, excluding at least one interaction region accessible to body fluids; and

[0155] vi. A system comprising at least one exposure device for exposing an AgCl-containing composition to ultraviolet light, at least partially. Brief explanation of the drawing

[0156] Additional optional features and embodiments will preferably be disclosed in more detail in the subsequent description of the embodiments with respect to the dependent claims. Therein, each optional feature may be realized in any feasible combination as well as in a separate manner, as recognized by those skilled in the art. The scope of the invention is not limited by the preferred embodiments. Embodiments are schematically illustrated in the drawings. In this specification, the same reference numerals in these drawings indicate the same or functionally comparable elements. In drawings and tables: FIG. 1 is a perspective view of an analyte sensor for measuring at least one analyte in body fluid; FIG. 2 is a flowchart illustrating a method for manufacturing at least one analyte sensor for measuring at least one analyte in body fluids; FIG. 3 is a diagram of a voltage measurement experiment including an additional electrode of an analyte sensor; Fig. 4 is a diagram with a representative potential difference curve; FIG. 5 is experimental data illustrating the electrochemical capacity of an additional electrode as a function of the duration of exposure to ultraviolet light; and Figure 6 illustrates experimental data illustrating leached silver as a function of the duration of exposure to ultraviolet rays. Table 1 shows Ag from the additional electrode + Experimental data regarding the leaching effect of is shown. Specific details for implementing the invention

[0157] FIG. 1 illustrates a perspective view of an analyte sensor (110) obtained by a method for manufacturing at least one analyte sensor (110) for measuring at least one analyte in a body fluid as described above or as further described herein. The analyte sensor (110) comprises at least one substrate (112), and the substrate (112) comprises a first surface (114) and a second surface (116). The substrate (112) may particularly comprise at least one insulating material (118), such as polyethylene terephthalate (PET) or polycarbonate (PC). Other electrical insulating materials (118) may also be possible. Specifically, the substrate (112) may be a planar substrate (112). As illustrated in FIG. 1, the substrate (112) may have an elongated shape, such as a bar shape or a strip shape (120), having a first surface (114) and a second surface (116), where the second surface is the opposite surface of the strip-shaped substrate (112) facing in the opposite direction. Other shapes of the substrate (112), for example, a bar shape (not shown in the drawing), may also be possible.

[0158] The analyte sensor (110) further comprises at least one first conductive layer (122), the first conductive layer (122) at least partially covers the first surface (114) of the substrate (112). An embodiment schematically illustrated in FIG. 1 shows the first conductive layer (122) completely covering the first surface (114) of the substrate (112). However, other embodiments are possible in which the first conductive layer (122) may cover only a portion of the first surface (114), such as at least one area of ​​the first surface (114) (not illustrated). The analyte sensor (110) also further comprises at least one second conductive layer (124), the second conductive layer at least partially covers at least one of the first surface (114) and the second surface (116) of the substrate (112). In the embodiment schematically illustrated in FIG. 1, the second conductive layer (124) completely covers the second surface (116) of the substrate (112). Alternatively, the second conductive layer (124) may cover only a portion of the second surface (116), for example, only at least one area of ​​the second surface (116) (not illustrated). In a further embodiment, the second conductive layer (124) may cover a portion of the first surface (114), and both the first conductive layer (122) and the second conductive layer (124) may be placed on the first surface (114). In this case, the working electrode (128) and the additional electrode (142) may both be placed and / or positioned on the first surface (114) of the substrate (112). As an example, at least one conductor may be disposed on the substrate (112) of each of the working electrode (128) and the additional electrode (142), and the conductor may be individually led to the working electrode (128) and the additional electrode (142) (not shown). In the above embodiment, the working electrode (128) may be covered and / or masked in step F) so that the electrode (128) can be protected from exposure to ultraviolet light while the AgCl-containing composition (146) is exposed to ultraviolet light. As an example, at least one covering device, e.g., a general covering device that protects from ultraviolet light, may be used.FIG. 1 illustrates an embodiment of an analyte sensor (110), wherein a second conductive layer (124) covers at least partially a second surface (116) of a substrate (112), and an additional electrode (142) is provided on the second surface (116) of the substrate (112).

[0159] The first conductive layer (122) and the second conductive layer (124) may each include at least one electrically conductive or semiconductor material (126), for example, at least one material selected from conductive carbon, gold, silver, platinum and copper, for example, gold-plated copper. In particular, the first conductive layer (122) and the second conductive layer (124) may both be composed of the same conductive material (126) or formed by the same conductive material.

[0160] As illustrated in FIG. 1, the analyte sensor (110) further comprises at least one working electrode (128). The working electrode (128) comprises at least one portion (130) of the first conductive layer (122) and at least one working electrode material (132) that at least partially covers the at least one portion of the first conductive layer (122). Accordingly, the working electrode (128) may comprise a layered structure, particularly as illustrated in FIG. 1. Specifically, the portion of the first electrically conductive layer (122) not covered by the at least one working electrode material (132) may form at least one electrical lead (134) for electrically contacting the working electrode (128). The electrical lead (134) may also include at least one electrical contact pad on the substrate (112) (not illustrated).

[0161] The working electrode material (132) may be configured to undergo a chemical reaction detectable in the presence of an analyte or an analyte, more specifically at least one electrochemical reaction, which may be electrically detected by one or more measurements of a potential measurement and an electric current measurement. The working electrode material (132) may include, for example, at least one enzyme (136) capable of catalyzing at least one chemical reaction that alters the analyte, for example, a chemical reaction in which the analyte is oxidized and / or reduced. For example, if the analyte is glucose or contains glucose, the enzyme (136) may include one or more of a glucose oxidase and a glucose dehydrogenase. Additionally, the working electrode material (132) may further include one or more additional components, such as a mediating compound configured for electron transfer, etc. The working electrode material (132) may include at least one reagent layer (138) comprising at least one biometric component (140), particularly the enzyme (136), which is adjusted to interact with the analyte. As illustrated in FIG. 1, in the region where the reagent layer (138) covers the first conductive layer (122), the first conductive layer (122) and the reagent layer (138) can form an operating electrode (128).

[0162] As illustrated in FIG. 1, the analyte sensor (110) further comprises at least one additional electrode (142). The additional electrode (142) comprises at least one portion (144) of the second conductive layer (124) and at least one AgCl-containing composition (146) that at least partially covers the at least one portion (144) of the second conductive layer (124). The additional electrode (142) further comprises at least one protective layer (148) that covers the AgCl-containing composition (146), except for at least one interaction region (150) accessible to body fluids. Thus, as illustrated in FIG. 1, the at least one additional electrode (142) may comprise a layered structure comprising the second conductive layer (124), at least one AgCl-containing composition (146), and at least one protective layer (148). Accordingly, specifically, at least one edge (151) of the additional electrode (142) may not be covered by the protective layer (148), and the uncovered edge (151) may form at least one interaction area (150) where the AgCl-containing composition (146) can come into contact with body fluids. The interaction area (150), particularly the uncovered edge (151), may be created, for example, by cutting a layered structure comprising a substrate (112), an operating electrode (128), and at least one additional electrode (142), such as by at least one cutting of mechanical cutting and laser cutting. The additional electrode (142) may specifically include two interaction areas (150). As illustrated in FIG. 1, the two interaction areas (150) may be particularly parallel and may face in opposite directions. For example, the interaction area (150) is 0.01 mm 2 to 1 mm 2 , more specifically 0.1 mm 2 up to 0.5 mm 2 , more specifically, 0.2 mm 2 up to 0.4 mm 2 It can have a surface of a range.

[0163] As illustrated in FIG. 1, at least one portion of the second conductive layer (124) may remain uncovered by the AgCl-containing composition (146). This at least one portion may form or include at least one conductive lead (134) for electrically contacting, for example, at least one additional electrode (142). In particular, the at least one conductive lead (134) may also form one or more electrical contact pads for electrically contacting at least one additional electrode (142) (not shown).

[0164] The additional electrode (142) may include at least one electrode among a counter electrode, a reference electrode, and a combined counter / reference electrode (152). As illustrated in FIG. 1, the additional electrode (142) may be or may include the combined counter / reference electrode (152), and thus may combine multiple functions. At least one additional electrode (142) and the working electrode (128) may form part of an electrochemical circuit, and the additional electrode (152) in the form of the combined counter / reference electrode (152) may provide a reference potential and balance the current flow from the working electrode (128). In particular, the electrochemical detection reaction at the working electrode (128) may be one of two half reactions, and the other of the two half reactions may occur at the additional electrode (142), particularly at the combined counter / reference electrode (152). For example, the half reaction occurring at the working electrode (128) may include the oxidation of an analyte, particularly glucose, and the half reaction occurring at the combined counter / reference electrode (152) may include reduction, particularly Ag +It may include reducing to the element Ag. The analyte sensor (110) may be used for one or more measurements, particularly of a potential difference or positive potential measurement and a current measurement. Accordingly, the measurement signal of the analyte sensor (110) may include one or more of a voltage measurement signal and a current measurement signal. The measurement signal may be used for measuring the analyte, such as detecting the concentration of the analyte.

[0165] In particular, the analyte sensor (110) may be configured as an in vivo analyte sensor configured to measure at least one analyte in the body fluid while the body fluid is present in the user's body. Accordingly, the analyte sensor (110) may include at least one implantable part (154) as illustrated in FIG. 1, and the analyte sensor (110) may come into at least partial contact with the user's body fluid, for example, through the implantable part (154). In addition to the implantable part (154), the analyte sensor (110) may optionally include at least one additional part or component that may remain outside the body tissue, for example, a contact part having one or more electrical contact pads electrically connected to the working electrode (128) and the additional electrode (142), respectively (not illustrated). The implantable part (154) placed within the body tissue and the additional part or component placed outside the body tissue may be electrically connected and / or connectable.

[0166] Although not illustrated in FIG. 1, in the implantable portion (154) of the analyte sensor (110) outside the working electrode (128) and outside the additional electrode (142), the first and / or second conductive layers (122, 124) may be wholly or partially covered with one or more electrical insulating materials, such as one or more electrical insulating resins, to avoid direct contact between the first and / or second conductive layers (122, 124) and body fluids. Outside the implantable portion (154), the electrical insulating material may be wholly or partially removed to provide a contact portion for electrical contact with the working electrode (128) and the additional electrode (142). In addition to one or more electrical insulating materials or covers, one or more biocompatible materials may be present.

[0167] An analyte sensor (110) for measuring at least one analyte in a body fluid is obtained by a method for manufacturing at least one analyte sensor (110) for measuring at least one analyte in a body fluid as described above and / or further described below. This method is described in the flowchart illustrated in FIG. 2. This method comprises the following method steps, which may be performed specifically in a given order. However, a different order may also be possible. This method may further include additional method steps not listed. Additionally, one or more or all of the method steps may be performed only once or repeatedly. The method steps may be performed such that, in particular, two or more steps may overlap completely or at least partially in time. As illustrated in FIG. 2, the method comprises the following steps:

[0168] A) providing at least one substrate (112) including a first surface (114) and a second surface (116);

[0169] B) a step of providing at least one first conductive layer (122) that at least partially covers the first surface (114) of the substrate (112), particularly a step of applying;

[0170] C) a step of providing at least one second conductive layer (124) that partially covers at least one of the first surface (114) and the second surface (116), particularly a step of applying;

[0171] D) providing at least one working electrode (128) on the first surface (114) by providing at least one working electrode material (132) that at least partially covers the first conductive layer (122);

[0172] E) A step of providing at least one additional electrode (142) on at least one of the first surface (114) and the second surface (116) by providing:

[0173] - At least one AgCl-containing composition (146) that at least partially covers the second conductive layer (124); and

[0174] - At least one protective layer (148) covering the AgCl-containing composition (146), excluding at least one interaction area (150) accessible to body fluids;

[0175] F) Includes the step of exposing the AgCl-containing composition (146) to at least partial ultraviolet light.

[0176] In the flowchart of FIG. 2, method step A is indicated by reference number 156, method step B by reference number 158, method step C by reference number 160, method step D by reference number 162, method step E by reference number 164, and method step F by reference number 166.

[0177] As part of step F), the AgCl-containing composition (146) is exposed to ultraviolet light at least partially. Specifically, the interaction area (150) formed by the AgCl-containing composition (146) may be exposed to ultraviolet light at least partially. For example, in step F), an artificial ultraviolet light source having a peak wavelength in the range of 200 nm to 400 nm may be used. The ultraviolet light used in step F) may specifically have an intensity in the range of 1 mW / cm² to 200 mW / cm², specifically 10 mW / cm² to 100 mW / cm², and more specifically 50 mW / cm² to 75 mW / cm². Other irradiation conditions may also be possible. In particular, the irradiation conditions may be configured so that the AgCl-containing composition (146) exposed to ultraviolet light accommodates a predefined radiation dose, particularly the total energy per area.

[0178] Step F) may include stepwise at least partial exposure of the AgCl-containing composition (146) to ultraviolet light, and each exposure step may include step of at least partially exposing the AgCl-containing composition (146) to ultraviolet light for an exposure time ranging from 3 seconds to 2 minutes, specifically from 15 seconds to 1 minute, more specifically from 30 seconds. Each exposure step may be followed by at least one dissipation step including radiation blocking for a range of 1 second to 30 seconds, specifically from 3 seconds to 10 seconds, more specifically from 5 seconds. Thus, the AgCl-containing composition (146) may be at least partially exposed to ultraviolet light for a total exposure time ranging from 10 seconds to 1 hour, specifically from 30 seconds to 30 minutes, more specifically from 1 minute to 20 minutes.

[0179] As part of step F), AgCl can be at least partially photochemically transformed into elemental Ag, unless one wishes to be bound by this theory. Specifically, in step F), elemental Ag can be formed by reducing at least partially the AgCl in the interaction region (150), particularly the AgCl on the surface of the interaction region (150), by ultraviolet light. In particular, the AgCl in the AgCl-containing composition (146) can be decomposed at least partially, particularly on the surface of the interaction region (150). Thus, as a result of step F), the AgCl formed by the AgCl-containing composition (146) can be at least partially covered by elemental Ag. In particular, AgCl can be completely or partially shielded and / or separated from the body fluid by the elemental Ag generated in the photochemical reaction of step F). Thus, direct contact between the body fluid and AgCl and the leaching of Ag+ into the body fluid can be reduced.

[0180] Table 1 shows experimental data obtained using three analyte sensors (110) obtained by a method for manufacturing at least one analyte sensor (110). The three analyte sensors (110) are exposed to ultraviolet light from a UV LED array having a peak wavelength h of 365 nm and a FWHM of 6 nm. The UV LEDs are coupled to a homogeneous floodlight source. The intensity, in particular the incident irradiation power, is 65 mW / cm² 2The three analyte sensors (110) are exposed to ultraviolet light at a distance of 175 mm from the UV LED array. The three analyte sensors (110) are exposed to ultraviolet light in stages, followed by a 5-second radiation block for heat dissipation after 30 seconds of irradiation. The three analyte sensors (110), particularly the AgCl-containing composition (146), are exposed to ultraviolet light for a total of 1 minute, 4 minutes, and 16 minutes by repeating the aforementioned 30-second irradiation stage and consecutive radiation blocking time 2, 8, and 32 times, respectively. Additionally, in this experiment, an analyte sensor different from the three analyte sensors (110) is used only in that it is not exposed to ultraviolet light. The three analyte sensors (110) and the additional analyte sensor are each immersed in 1 ml of ultrapure water at 37°C for 24 hours. After 24 hours, remove the analyte sensor (110) and additional analyte sensor, and use mass spectrometry to examine the soluble form of Ag contained in 1 ml of eluent, particularly Ag + Measure the amount of. To measure Ag in the eluent, the eluent is diluted in 2% HNO3 at a ratio of 1:10. In the process of measuring the amount of Ag in soluble form, standards of 5 μg Ag / L, 10 μg Ag / L, and 20 μg Ag / L, and an internal standard of 10 μg rhodium / L are used.

[0181]

[0182] Table 1 shows the mass (ng) of Ag measured in four different eluents corresponding to three analyte sensors (110) exposed to UV light for 1 minute, 4 minutes, and 16 minutes, respectively, and an analyte sensor not exposed to UV light. Each value is the average value determined from three measurements. The three measurements were generated by measuring three specimens for each type of analyte sensor. As can be seen from the data shown in Table 1, for the analyte sensor (110) exposed to UV light, the amount of soluble form of Ag leached into the ultrapure water surrounding the analyte sensor is significantly reduced compared to the analyte sensor not exposed to UV light. Furthermore, the data in Table 1 indicates that the strongest effect in reducing the leaching of soluble form of Ag into the surrounding ultrapure water is when the total exposure time is 16 minutes. The experimental data shows that step F) of the method for manufacturing at least one analyte sensor (110) [leaks] Ag into body fluids + This supports the idea that reducing the leaching of Ag in soluble forms such as ions can increase the biocompatibility and reliability of the analyte sensor (110), particularly during the time period when adverse bodily reactions to soluble silver may occur after sensor insertion.

[0183] FIG. 3 illustrates a voltagram (182). In a corresponding experiment, when the current is measured, the voltage between the combined counter / reference electrode (152) and the working electrode (128) is varied. This experiment can particularly show how much the potential of the additional electrode (142), in particular CERE 152, shifts under a load of a specific current. In this specification, a low shift may be desirable, as it may correspond to a more stable reference potential of CERE 152, which can contribute to improving the sensor performance of the analyte sensor (110). The x-axis of the voltagram (182) is denoted by reference numeral 170 and displays the voltage in volts. The y-axis of the voltagram (182) is denoted by reference numeral 172 and displays the current in nanoamperes (nA). The curve illustrated in FIG. 3 corresponds to experimental data obtained for an analyte sensor (110) obtained by a method of manufacturing an analyte sensor (110) in which an AgCl-containing composition (146) is exposed to ultraviolet light for 1 minute, 4 minutes, and 16 minutes, respectively, and experimental data obtained for an analyte sensor that is different from said analyte sensor only in that the AgCl-containing composition (146) of the analyte sensor (110) is not exposed to ultraviolet light. In particular, data corresponding to an analyte sensor (110) with a total exposure time of 1 minute is indicated by reference numeral 174, data corresponding to an analyte sensor (110) with a total exposure time of 4 minutes is indicated by reference numeral 176, data corresponding to an analyte sensor (110) with a total exposure time of 16 minutes is indicated by reference numeral 178, and data corresponding to an analyte sensor in which the AgCl-containing composition (146) is not exposed to ultraviolet light is indicated by reference numeral 180. As can be seen in FIG. 3, under load, the reference potential shift of the analyte sensor (110) in which the AgCl-containing composition (146) is exposed to ultraviolet light for 16 minutes is smaller than the reference potential shift of the analyte sensor in which the AgCl-containing composition (146) is not exposed to ultraviolet light.For example, at a current of 20 nA, the potential shift of CERE 152 not exposed to UV light reaches about 25 mV compared to the theoretical 0 indicated by the dotted line. On the other hand, the corresponding potential shift of CERE 152 exposed to UV light for 16 minutes is less than 10 mV. The two potential shifts are indicated by the double arrows in Fig. 4. Although I do not want to be bound by this theory, the above remarkable effect is because the result of exposure to UV light is the generation of elemental silver nanoparticles that act as catalytic centers, which can improve the electrochemical performance of the additional electrode (142), particularly CERE 152.

[0184] FIG. 4 is a diagram illustrating representative potential difference curves (184) of three analyte sensors (110) exposed to ultraviolet light for 1 minute, 4 minutes, and 16 minutes, respectively, as well as an analyte sensor not exposed to ultraviolet light. In particular, data corresponding to the analyte sensor (110) with a total exposure time of 1 minute is indicated by reference numeral 174, data corresponding to the analyte sensor (110) with a total exposure time of 4 minutes is indicated by reference numeral 176, data corresponding to the analyte sensor (110) with a total exposure time of 16 minutes is indicated by reference numeral 178, and data corresponding to the analyte sensor in which the AgCl-containing composition (146) is not exposed to ultraviolet light is indicated by reference numeral 180. The x-axis of the diagram (183) is indicated by reference numeral 170 and displays time in hours (h). The y-axis of the diagram (183) is indicated by reference numeral 172 and displays potential in millivolts (mV). For the experiment, each CERE 142 is loaded with a 5-fold average nominal cathodic current in an appropriate electrolyte. The potential is measured relative to an external Ag / AgCl 100 mM Cl reference electrode. A potential shift of more than 40 mV is considered the depletion state of the corresponding CERE 142, and the duration of galvanostatic stripping represents the electrochemical CERE capacity. Figure 4 shows that as the UV treatment time increases, the duration of operation corresponding to the decrease in electrochemical CERE capacity becomes progressively shorter. This supports the hypothesis of AgCl decomposition by UV irradiation. As can be seen from the data shown in Figure 4, irradiation for 16 minutes results in a decrease in electrochemical CERE capacity of approximately 9%. At the same time, for at least the first 24 hours, the longer the UV treatment, the smaller the potential shift under load becomes. This may be a positive effect: the smaller the potential shift of the nonpolar CERE 142, the better the electrochemical performance of the CERE 142.

[0185] FIG. 5 illustrates a diagram (183) containing experimental data (185) illustrating CERE electrochemical capacity as a function of the duration of UV exposure. Correspondingly, the x-axis (170) of the diagram (183) represents the duration of exposure of the analyte sensor (110) to UV light in minutes (min). The y-axis (172) of the diagram (183) in FIG. 5 represents the duration of operation of the analyte sensor (110) in hours (h). The diagram (183) further illustrates an exponential reduction fitting (186). Considering the fitting (186), for example, exposure to UV light for 10 or 12 minutes may result in the same amount of decomposed AgCl as exposure for 16 minutes. Even after treatment for 10 minutes under given conditions, the amount of decomposed AgCl does not appear to change significantly. This can be explained by the decomposition of all AgCl on the outer surface of the interaction region (150) and the shadowing effect caused by the newly formed elemental silver, which covers the AgCl deeper and therefore further away from the interaction region (150). Therefore, no further AgCl in the AgCl-containing composition (146) can be accessed by ultraviolet irradiation, and thus no further AgCl can be decomposed.

[0186] FIG. 6 shows a diagram (183) containing experimental data (185) illustrating leached silver as a function of the duration of ultraviolet exposure. Correspondingly, the x-axis (170) of the diagram (183) in FIG. 6 represents the duration of exposure of the analyte sensor (110), in particular the AgCl-containing composition (146), to ultraviolet light. The duration is indicated in minutes (min). The y-axis (172) of the diagram (183) represents Ag in nanograms (ng). +The leaching of is illustrated. Diagram (183) further illustrates the exponential reduction fitting (186). Unlike the CERE electrochemical capacity exemplified in FIG. 5, it appears that the peak reached at the time point t = 16 min was not reached, but further extrapolation with UV treatment of a higher duration yields a Y0 value of approximately 110 ng, which is very close to the value at the time point t = 16 min. Here, the Y0-value may refer to the Ag leaching value corresponding to the expected plateau of the fitted curve (186). Thus, the Y0-value may correspond to the expected minimum amount of Ag leaching. After treatment with UV light for 16 minutes, the amount of leached silver is shown to be reduced by nearly half compared to the analyte sensor not exposed to UV light, while the amount of decomposed AgCl is about 9% as described by the data shown in FIG. 4. This may again indicate that while the AgCl placed on the surface of the interaction region (150) may be the primary source of silver ions, additional AgCl particles may be densely surrounded by a binder and / or polymer matrix initially composed of an AgCl-containing composition (146), particularly CERE. Explanation of the symbols

[0187] 110 analyte sensor 112 substrate 114 Page 1 116 Page 2 118 Insulating materials 120 Strip shape 122 First layer of conduction 124 Second layer of conduction 126 electrically conductive or semiconductor materials 128 working electrode 130 Part of the first conductive layer 132 Working electrode material 134 electric lead 136 enzyme 138 Reagent layer 140 Biometric components 142 Additional electrode 144 Part of the second conductive layer 146 AgCl-containing composition 148 protective layer 150 Interaction area 151 Edge 152 Combined counter / reference electrode 154 Transplantable parts 156 Method Step A 158 Method Step B 160 Method Step C 162 Method Step D 164 Method Step E 166 Method Step F 170 x-axis 172 y-axis 174 Exposure time 1 minute 176 Exposure time 4 minutes 178 Exposure time 16 minutes 180 Not exposed to ultraviolet rays 182 Voltamogram 183 diagram 184 Potential difference curve 185 Experimental data 186 Exponential reduction fitting

Claims

Claim 1 A method for manufacturing at least one analyte sensor (110) for measuring at least one analyte in a body fluid, the method comprising: A) providing at least one substrate (112) comprising a first surface (114) and a second surface (116); B) providing at least one first conductive layer (122) that at least partially covers the first surface (114) of the substrate (112); C) providing at least one second conductive layer (124) that at least partially covers at least one surface among the first surface (114) and the second surface (116); D) providing at least one working electrode (128) on the first surface (114) by providing at least one working electrode material (132) that at least partially covers the first conductive layer (122); E) providing at least one additional electrode (142) on at least one surface among the first surface (114) and the second surface (116) by providing - At least one AgCl-containing composition (146) that at least partially covers the second conductive layer (124); and - At least one protective layer (148) covering an AgCl-containing composition (146) arranged spaced apart from at least one interaction area (150) accessible to body fluids; F) a step of exposing the AgCl-containing composition (146) at least partially to ultraviolet light, comprising a method. Claim 2 In the preceding paragraph, a method in which AgCl is photochemically converted to elemental Ag in step F). Claim 3 A method in which, in any one of the preceding claims, an artificial ultraviolet light source, in particular an artificial ultraviolet light source having a peak wavelength in the range of 200 nm to 400 nm, is used in step F). Claim 4 A method in which, in any one of the preceding claims, the AgCl-containing composition (146), particularly the interaction region (150), is exposed to ultraviolet light with a total intensity of 1 mW / cm² to 200 mW / cm², particularly 10 mW / cm² to 100 mW / cm², more specifically 50 mW / cm² to 75 mW / cm² in the spectral range of 200 nm to 400 nm. Claim 5 A method in which, in any one of the preceding paragraphs, in step F), the AgCl of the AgCl-containing composition (146) is at least partially decomposed, particularly on the surface of the interaction area (150). Claim 6 In any one of the preceding paragraphs, in step F), the interaction area (150) is at least partially exposed to ultraviolet light. Claim 7 In any one of the preceding claims, the method comprises the step of cutting a layered structure comprising a substrate (112), an operating electrode (128), and an additional electrode (142) to form at least one analyte sensor (110). Claim 8 In the preceding paragraph, the interaction region (150) is formed in the cutting process, particularly as a cutting edge of the layer structure, in the method. Claim 9 A method wherein, in any one of the preceding claims, step F) comprises stepwise partially exposing the AgCl-containing composition (146) to ultraviolet light, and each exposure step comprises exposing the AgCl-containing composition (146) to ultraviolet light for at least one exposure time, specifically for an exposure time ranging from 3 seconds to 2 minutes, more specifically from 15 seconds to 1 minute, more specifically for an exposure time of 30 seconds. Claim 10 A method wherein, in the preceding paragraph, at least one dissipation step follows each exposure step, and each dissipation step includes radiation shielding in the range of 1 second to 30 seconds, specifically 3 seconds to 10 seconds, more specifically 5 seconds. Claim 11 A method wherein, in any one of the preceding claims, the working electrode material (132) comprises at least one reagent layer (138) for detecting an analyte, and said reagent layer (138) comprises at least one biometric component (140), in particular an enzyme (136), configured to interact with the analyte. Claim 12 In any one of the preceding paragraphs, the additional electrode (142) comprises at least one electrode among a counter electrode, a reference electrode, and a combined counter / reference electrode (152). Claim 13 An analyte sensor (110) for measuring at least one analyte in a body fluid, wherein the analyte sensor (110) is obtained by a method according to any one of the preceding claims. Claim 14 In the preceding paragraph, the analyte sensor (110) comprises: a) at least one substrate (112), wherein the substrate (112) includes a first surface (114) and a second surface (116); b) at least one first conductive layer (122), wherein the first conductive layer (122) at least partially covers the first surface (114) of the substrate (112); c) at least one second conductive layer (124), wherein the second conductive layer (124) at least partially covers at least one of the first surface (114) and the second surface (116); and d) As at least one working electrode (128), the working electrode (128) is: - At least one part of the first conductive layer (122); and - Includes at least one working electrode material (132) that partially covers at least one portion of the first conductive layer; e) As at least one additional electrode (142), the additional electrode (142) is: - At least one part of the second conductive layer (124); - An AgCl-containing composition (146) that partially covers at least one portion of the second conductive layer (124); and; - An analyte sensor (110) comprising a protective layer (148) covering an AgCl-containing composition (146) arranged spaced apart from at least one interaction area (150) accessible to body fluids. Claim 15 A system for manufacturing at least one analyte sensor (110) for measuring at least one analyte in a body fluid, wherein the system is configured to perform a method according to any one of the preceding claims with respect to the method, the system comprising: i. at least one first coating device for coating at least one first conductive layer covering at least partially a first surface (114) of a substrate (112); ii. a coating device for coating a second conductive layer (124) covering at least partially a surface of the first surface (114) and at least one second surface (116); iii. at least one device for providing at least one working electrode material (132) covering at least partially a first conductive layer; iv. at least one device for providing at least one AgCl-containing composition (146) covering at least partially a second conductive layer (124); v. at least one protective layer (148) covering the AgCl-containing composition (146), except for at least one interaction area (150) accessible to the body fluid; and vi. A system comprising at least one exposure device for at least partially exposing an AgCl-containing composition (146) to ultraviolet light.

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