Method for detecting at least one analyte and analyte sensor system

Abstract

The present invention relates to a method (200) for continuously detecting at least one analyte in a body fluid in vivo over a time span, an analyte sensor system (100) for continuously detecting at least one analyte in a body fluid in vivo over a measurement time span, a computer program and a computer readable storage medium. The method (200) utilizes at least one analyte sensor (102) comprising at least one working electrode (104) configured for performing at least one electrochemical detection reaction with the analyte, and at least one further electrode (106) comprising at least one redox material composition, the present invention relates to a method (200) for detecting an analyte sensor (102) comprising a redox material composition comprising silver and silver chloride, the method (200) comprising the steps of monitoring at least one standard sensor signal (132) obtained by using the analyte sensor (102) in a standard mode of operation, comparing the standard sensor signal (132) to at least one threshold value, it is thereby determined whether an operating mode of the analyte sensor (102) needs to be changed from the standard operating mode to an economical operating mode.

Description

Technical Field

[0001] The present invention relates to a method for detecting at least one analyte in a body fluid continuously in vivo over a time span. The present invention further relates to an analyte sensor system for detecting at least one analyte in a body fluid continuously in vivo over a measurement time span. The present invention further relates to a computer program and a computer readable storage medium. As an example, the method and device of the present invention can be used for diagnostic purposes, such as in clinical or laboratory analysis, or for home monitoring purposes. The method and device of the present invention can be used in particular for detecting at least one analyte in a body fluid or other liquid. Background Art

[0002] A variety of analyte sensors for detecting at least one analyte in at least one fluid sample, in particular in a bodily fluid, have been described. Analyte sensors configured to reliably detect chemical and / or biological substances in a qualitative and / or quantitative manner can be used for various purposes, such as, but not limited to, diagnostic purposes, environmental contamination monitoring, food safety assessment, quality control, or manufacturing processes.

[0003] An analyte sensor for detecting at least one analyte may be fully or partially implanted or inserted into body tissue. At least one analyte may be detected in an electrochemical detection reaction occurring between electrodes. To drive such a reaction, typically at least one of the electrodes may comprise a redox material composition comprising a silver compound, specifically silver or silver chloride. An example of such a redox material is molecular oxygen dissolved in interstitial fluid, which may be reduced to an ionic species. The use of such a counter electrode and / or auxiliary electrode may be typical for the Libre system, and may require the use of an additional reference electrode.

[0004] However, when implanted in body tissue, silver chloride may induce an immune response in the human body that may cause temporary or permanent failure of at least one analyte sensor. Therefore, it is generally desirable to keep the amount of silver chloride in the electrode, especially the amount of silver chloride in contact with body tissue, as low as possible in order to minimize these negative effects.

[0005] However, the amount of silver chloride cannot usually be reduced arbitrarily. On the contrary, other boundary conditions must be considered. In this sense, it must be taken into account that during the operation of the analyte sensor, silver chloride is usually consumed in a second electrochemical half reaction that may occur at the counter electrode or the reference-counter electrode of the combination. The consumption of silver chloride usually depends directly on the current between the electrodes, and this current usually depends on the amount of the analyte detected. Therefore, the consumption of silver chloride usually depends directly on the amount of the analyte detected. Therefore, in general, the higher the amount of analyte to be detected, the higher the consumption of silver chloride. Therefore, during the hyperglycemic period when the user or patient has a dangerously high blood sugar level, the consumption is usually particularly high. The minimum amount of silver chloride contained in the electrode must usually be calculated for the worst case scenario, in which it may be necessary to assume that a large amount of analyte is present in multiple hyperglycemic periods. Only in this way can the analyte sensor be used by any patient for a sufficiently long time span. Therefore, the electrode must contain a minimum amount of silver chloride.

[0006] In the prior art, different methods are known for designing and operating analyte sensors having reduced amounts of silver chloride in the redox material composition.

[0007] Richard D. Beach, Robert W. Conlan, Markham C. Godwin, and Francis Moussy, Towards a Miniature Implantable In Vivo Telemetry Monitoring System Dynamically Configurable as a Potentiostat or Galvanostat for Two- and Three-Electrode Biosensors, IEEE TRANSACTIONS ON INSTRUMENTATION AND MEASUREMENT, Volume 54, Issue 1, February 2005, Pages 61–72 describe a miniature implantable and dynamically configurable potentiostat and galvanostat for two- and three-electrode biosensors, wherein a telemetry electronics package is developed to provide remote monitoring of implantable amperometric and voltammetric biosensors such as for glucose. The package includes circuitry for sensor biasing, a transimpedance amplifier for generating a sensor ratiometric output signal, and a transceiver (transmitter and receiver) that receives both set parameter values ​​and transmits biosensor concentration data to a corresponding remote transceiver and computer for monitoring. Remotely configurable features included in the in vivo implant unit include: sensor excitation changes; filter frequency cutoffs, amplifier gain; and transmission intervals for end-to-end remote data monitoring using 303.825-MHz UHF RF telemetry. The developed mP / Gstat printed circuit board is approximately 51221 mm thick and is suitable for benchtop or packaged use.

[0008] US2021 / 0030338 A1 discloses a biosensor for measuring a physiological signal representing a physiological parameter associated with an analyte. The biosensor includes a working electrode and a counter electrode. The counter electrode includes silver and an initial amount of silver halide, wherein the initial amount is determined by the following steps: defining a required consumption range of silver halide during at least one measurement period in the measurement period performed by the biosensor; and determining the initial amount based on the sum of the upper limit of the required consumption range and the buffer amount, so that the required replenishment range of silver halide during the replenishment period is controlled to be sufficient to maintain the amount of silver halide within a safe storage range.

[0009] Despite these advantages achieved by known methods and devices as described above, several technical challenges remain. In particular, in many cases, the consumption of silver chloride remains a limiting factor for the duration of in vivo sensor use.

[0010] Issues to be resolved

[0011] Therefore, an object of the present invention is to provide a method and an apparatus that at least partially solve the above technical challenges. Specifically, a method and an analyte sensor system for continuously detecting at least one analyte in a body fluid in vivo over a measurement time span will be proposed, which solves the problem of limiting the sensor life due to the consumption of the redox material composition. It is generally desirable to further reduce the amount of the redox material composition without sacrificing the operating life of the sensor system. Summary of the invention

[0012] This problem is solved by a method for continuously detecting at least one analyte in a body fluid in vivo over a time span and by an analyte sensor system for continuously detecting at least one analyte in a body fluid in vivo over a measurement time span, the method and the analyte sensor system having the features of the independent claims. This problem is further solved by a computer program and a computer-readable storage medium. In the dependent claims and throughout the description, advantageous embodiments are listed which can be realized individually or in any combination.

[0013] As used below, the terms "having", "comprising" or "including" or any grammatical variations thereof are used in a non-exclusive manner. Thus, these terms may refer to the absence of other features in the entity described in this context in addition to the features introduced by these terms, or the presence of one or more other features. As an example, the expressions "A has B", "A includes B" and "A contains B" may refer to the absence of other elements in A in addition to B (i.e., the presence of A solely and exclusively consisting of B); or to the presence of one or more other elements in entity A in addition to B (such as element C, element C and element D, or even other elements).

[0014] Further, it should be noted that the terms "at least one", "one or more" or similar expressions indicating that a feature or element may be present once or more than once are usually used only once when introducing the corresponding feature or element. In the following, in most cases, when referring to the corresponding feature or element, the expression "at least one" or "one or more" is not repeated even though the corresponding feature or element may be present only once or more than once.

[0015] Further, as used hereinafter, the terms "preferably", "more preferably", "particularly", "more particularly", "specifically", "more specifically" or similar terms are used in conjunction with optional features without limiting the possibilities of alternatives. Therefore, the features introduced by these terms are optional features and are not intended to limit the scope of the claims in any way. As the skilled person will recognize, the present invention may be carried out using alternative features. Similarly, the features introduced by "in one embodiment of the present invention" or similar expressions are intended to be optional features without any limitation on alternative embodiments of the present invention, without any limitation on the scope of the present invention, and without any limitation on the possibility of combining the features introduced in this manner with other optional or non-optional features of the present invention.

[0016] In a first aspect of the invention, a method for continuously detecting at least one analyte in a body fluid in vivo over a time span is disclosed. The method uses at least one analyte sensor, the at least one analyte sensor comprising at least one working electrode configured to perform at least one electrochemical detection reaction with the analyte, and at least one additional electrode, the additional electrode comprising at least one redox material composition, the redox material composition comprising silver and silver chloride.

[0017] The method comprises the following steps, which can be performed in a given order. However, different orders are also feasible. Further, two or more steps in the method steps can be performed simultaneously or in a time-overlapping manner. Further, the method steps can be performed once or repeatedly. Therefore, one or more or even all of the method steps can be performed once or repeatedly. The method may include other method steps not listed herein.

[0018] The method comprises the following steps:

[0019] i. monitoring at least one standard sensor signal obtained by using the analyte sensor in a standard operating mode,

[0020] wherein, in a standard operating mode, a potentiostatic measurement is performed for detecting at least one analyte with the analyte sensor, wherein the potential of the working electrode relative to the further electrode is set to at least one predetermined standard operating potential, and wherein a current through the working electrode and the further electrode is determined, in particular wherein the predetermined standard operating potential is kept constant during the determination of the current; and

[0021] ii. comparing the standard sensor signal to at least one threshold, specifically for determining whether the standard sensor signal exceeds the threshold, thereby determining whether it is necessary to change the operating mode of the analyte sensor from the standard operating mode to the economic operating mode.

[0022] The term "analyte" as used herein is a broad term and is given a common and customary meaning to those of ordinary skill in the art, and is not limited to a special or customary meaning. The term may specifically refer to, but is not limited to, any chemical or biological substance or species, such as an ion, an atom, a molecule, or a chemical compound. An analyte may specifically be an analyte that may be present in a body fluid or body tissue. The term analyte may specifically encompass atoms, ions, molecules, and macromolecules, particularly biomacromolecules, such as nucleic acids, peptides and proteins, lipids, sugars (such as glucose), and metabolites. Additional examples of potential analytes to be detected will be given in more detail below.

[0023] As used herein, the term "analyte sensor" is a broad term and is given a common and customary meaning to a person of ordinary skill in the art, and is not limited to a special or customary meaning. The term may specifically refer to, but is not limited to, any device configured to detect at least one analyte by acquiring at least one sensor signal (specifically a standard sensor signal or an economic sensor signal). Alternatively or in addition, the sensor signal may be read from an electronic unit. Particularly preferably, the analyte sensor may be configured as a fully implantable analyte sensor or a partially implantable analyte sensor, which may be particularly suitable for detecting an analyte in a user's body fluid in subcutaneous tissue.

[0024] As used herein, the term "at least partially implantable analyte sensor" is a broad term and will be given a common and customary meaning for a person of ordinary skill in the art, and is not limited to a special or custom meaning. The term may specifically refer to, but is not limited to, an analyte sensor introduced into a user's body tissue in the following manner: a first portion of the implantable analyte sensor can be received by the body tissue, while another portion may or may not be received by the body tissue. For this purpose, the analyte sensor may include an insertable portion. As used herein, the term "insertable portion" is a broad term and is given a common and customary meaning for a person of ordinary skill in the art, and is not limited to a special or custom meaning. The term may specifically refer to, but is not limited to, a component or assembly of an analyte sensor configured to be insertable into any body tissue. Other components or assemblies of the analyte sensor, particularly the contact pad, may remain outside the body tissue. Specifically, the analyte sensor may be a percutaneously insertable analyte sensor that can be inserted into the body tissue in whole or in part through the skin. During use, the analyte sensor may be completely located in the body tissue beneath the skin, or may partially pass through the skin and protrude from the body tissue. In particular, a portion of the analyte sensor and / or one or more cables may protrude from body tissue through the skin, for example, for electrical contact purposes.

[0025] The terms "user" and "patient" as used herein are broad terms and are to be given the ordinary and customary meaning to those of ordinary skill in the art and are not limited to special or customized meanings. The terms may specifically refer to, but are not limited to, a human or an animal, regardless of the fact that the human or animal may be in a healthy state or may suffer from one or more diseases, respectively. As an example, a user or patient may be a human or animal suffering from diabetes. However, additionally or alternatively, the present invention may be applied to other types of users, patients or diseases.

[0026] The term "in vivo" as used herein is a broad term and will be given the ordinary and customary meaning to those of ordinary skill in the art and is not limited to a special or customized meaning. The term may specifically refer to, but is not limited to, at least one analyte sensor configured to be at least partially implanted in a user's body tissue. The analyte sensor may specifically be a subcutaneous analyte sensor or a transcutaneous analyte sensor. The analyte sensor may be configured to continuously monitor an analyte.

[0027] As further used herein, the term "body fluid" generally refers to a fluid, in particular a liquid, which is generally present in the body or body tissue of a user or patient and / or can be produced by the body of a user or patient. Preferably, the body fluid can be selected from the group consisting of blood and interstitial fluid. However, in addition or alternatively, one or more other types of body fluids, such as saliva, tears, urine or other body fluids, can be used. During the detection of at least one analyte, the body fluid can be present in the body or body tissue. Therefore, the analyte sensor can be specifically configured to detect at least one analyte in body tissue. Other examples of potential body fluids will be given in more detail below.

[0028] In particular, the analyte sensor can be an electrochemical analyte sensor. As used herein, the term "electrochemical sensor" is a broad term and will be given a common and customary meaning for a person of ordinary skill in the art, and is not limited to a special or custom meaning. The term may specifically refer to, but is not limited to, an analyte sensor suitable for detecting an electrochemically detectable characteristic of an analyte (such as an electrochemical detection reaction). Thus, for example, an electrochemical detection reaction may be detected by applying and / or comparing one or more electrode potentials and / or by applying one or more electrode currents and detecting one or more electrode potentials or voltages. An electrochemical detection reaction may mean that one or more redox reactions occur at one or more electrodes of an analyte sensor by electrical means. In particular, an electrochemical analyte sensor may be suitable for generating and / or affecting at least one sensor signal, specifically a standard sensor signal generated by an analyte sensor, or an economic sensor signal generated by an electronic unit of an analyte sensor system affected by an analyte sensor. The sensor signal may directly or indirectly indicate the presence and / or extent of an electrochemical detection reaction, such as at least one current signal in a standard operating mode in particular, and / or at least one voltage signal in an economic operating mode in particular. Alternatively or in addition, the sensor signal may be read out from the electronics unit. The measurements may be qualitative and / or quantitative measurements. Furthermore, other embodiments are possible.

[0029] The term "working electrode" as used herein is a broad term and will be given the ordinary and customary meaning to those of ordinary skill in the art and is not limited to a special or customized meaning. The term may specifically refer to, but is not limited to, an electrode of an analyte sensor that is configured to measure a signal, such as a voltage, current, charge, or electrical / electrochemical potential, that depends on the extent of an electrochemical detection reaction occurring at the working electrode for detecting at least one analyte. The working electrode may comprise at least one specific chemical component for enhancing the electrochemical process for a specific analyte. Alternatively or in addition, the working electrode may comprise at least one enzyme for catalyzing at least one reaction, in particular at least one oxidation reaction and / or at least one reduction reaction, of the analyte to be detected. Examples of enzymes suitable for glucose monitoring are given in the following document, J. et al.: "The Technology behind Glucose Meters: Test Strips", Diabetes Technology & Therapeutics, Vol. 10, Supplement 1, 2008, S-10 to S-26. However, other options, for example depending on the target analyte to be detected, are feasible and generally known to those skilled in the art of electrochemical analyte detection. As an example, the working electrode may include at least one enzyme for catalyzing at least one reaction, wherein the working electrode can oxidize and / or reduce at least one product of the reaction. Such products can be additional chemical components or at least one electron. The at least one analyte to be detected can be further specified by using at least one specific coating, in particular a membrane that allows penetration specifically for the at least one analyte to be detected.

[0030] The term "additional electrode" as used herein is a broad term and will be given the ordinary and customary meaning to those of ordinary skill in the art, and is not limited to a special or customary meaning. The term may specifically refer to, but is not limited to, an electrode that may contain at least one redox material composition, specifically silver and / or silver chloride. The additional electrode may be fully or partially covered with at least one redox material composition. As an example, the additional electrode may include at least one conductive electrode pad, such as an electrode pad made entirely or partially of at least one metal (such as gold or platinum), wherein the at least one electrode pad may be fully or partially covered with at least one layer of redox material composition as a component of the additional electrode.

[0031] The at least one other electrode may specifically include at least one counter electrode and / or at least one reference electrode. As used herein, the term "counter electrode" is a broad term and will be given a common and customary meaning for those of ordinary skill in the art, and is not limited to a special or custom meaning. The term specifically may refer to, but is not limited to, an electrode suitable for carrying out at least one electrochemical reverse reaction and / or configured to balance the current generated by the detection reaction at the working electrode. As used herein, the term "reference electrode" is a broad term and will be given a common and customary meaning for those of ordinary skill in the art, and is not limited to a special or custom meaning. The term specifically may refer to, but is not limited to, an electrode configured to provide an analyte sensor for an electrochemical reference potential, which reference potential is at least broadly independent of the presence or absence or concentration of the analyte. The reference electrode may be configured to be used as a reference for measuring and / or controlling the potential of the working electrode.

[0032] Therefore, the analyte sensor may be partially or completely implanted in body tissue, such as percutaneous implantation. Specifically, at least one working electrode and at least one other electrode may be located in body tissue, thereby preferably in contact with at least one body fluid of the user. As used herein, the term "implantation" or any grammatical variation thereof is a broad term and will be given a common and customary meaning for a person of ordinary skill in the art, and is not limited to a special or custom meaning. The term may specifically refer to, but is not limited to, inserting an artificial material or object completely or at least partially into the human body to retain at least a long period of time in the human body, specifically maintaining a process of at least a time span. Implantation may include an insertion process, which may include percutaneous insertion as an example, such as by inserting using a cannula. Specifically, implantation may include or may be percutaneous insertion through the skin of the user into body tissue, such as insertion into the interstitial tissue of the user. Thus, the implantation process may only mean a small incision in the skin without being implanted in the user's blood vessels.

[0033] Thus, the implantation process can be performed without substantial physical intervention into the body, which requires specialized medical expertise to perform and can result in substantial health risks even when performed with the required specialized care and expertise. As an example, the implantation may comprise only a small incision in the skin, e.g., an incision having a lateral extension of less than 5 mm, e.g., less than 3 mm. Further, the implantation may comprise insertion of the analyte sensor into body tissue to a depth of no more than 30 mm, e.g., no more than 20 mm.

[0034] Additionally or alternatively, the method may not include the step of implanting or inserting the analyte sensor into body tissue at all. Thus, as an example, the method may be a method of operating the analyte sensor only. Thus, the method may not provide any functional interaction with the effects of the analyte sensor on the body.

[0035] As used herein, the term "continuously detect" is a broad term and will be given a common and customary meaning for those of ordinary skill in the art, and is not limited to a special or custom meaning. The term may specifically refer to, but is not limited to, a process of detecting a series of measured values ​​over time of at least one measured variable. Specifically, continuous detection may include collecting and / or recording a series of measured values ​​at different time points (e.g., after a constant time interval) with a constant measurement frequency or after an irregular time interval. Continuous detection may include continuous, permanent and / or frequent measurements. Thus, at least one possible analyte may be qualitatively and / or quantitatively evaluated. The measurement may be quantitative, so that the concentration value of the analyte may be evaluated over a period of time (also referred to as the time span of the measurement). The measurement may be performed using an analyte sensor. For this purpose, a sensor signal may be generated, particularly by an analyte sensor and / or an electronic unit. Alternatively or in addition thereto, the sensor signal may be read from an electronic unit. As used herein, the term "over a time span" is a broad term and will be given a common and customary meaning for those of ordinary skill in the art, and is not limited to a special or custom meaning. The term may specifically refer to, but is not limited to, the detection of at least one analyte over a period of time, such as for hours or even days or weeks (eg, 7 days to 4 weeks).

[0036] According to the first aspect, the method comprises step i. According to step i., as described above, the method comprises monitoring at least one standard sensor signal obtained by using the analyte sensor in a standard operating mode. In the standard operating mode, a constant potential measurement is performed to detect at least one analyte using the analyte sensor, wherein the potential of the working electrode relative to the further electrode is set to at least one predetermined standard operating potential, and wherein the current through the working electrode and the further electrode is determined, in particular wherein the predetermined standard operating potential remains constant during the determination of the current. The current may be an electrical current. The potential may be an electrical potential.

[0037] As used herein, the term "monitoring" is a broad term and is given a common and customary meaning to a person of ordinary skill in the art and is not limited to a special or custom meaning. The term may specifically refer to, but is not limited to, a process of continuously collecting data and deriving desired information therefrom without user interaction. For this purpose, at least one standard sensor signal and / or at least one economic sensor signal, specifically a plurality of sensor signals, may be generated and evaluated, from which the desired information is determined, specifically for determining a desired change in the operating mode of at least one analyte sensor, in particular a change from a standard operating mode to an economic operating mode, and vice versa.

[0038] As used herein, the term "standard operating mode" is a broad term and will be given a common and customary meaning to a person of ordinary skill in the art, and is not limited to a special or customized meaning. The term may specifically refer to, but is not limited to, a specific operating mode of at least one analyte sensor. The standard operating mode may be an operating mode used as a default, for example, unless at least one abnormal condition is met, as described below. In the standard mode, at least one analyte may be detected continuously. Therefore, a standard sensor signal may be generated. In addition, a qualitative and / or quantitative assessment of at least one analyte may be performed. In the standard operating mode, a constant potential measurement may be performed.

[0039] The term "potentiostatic measurement" as used herein is a broad term and will be given a common and customary meaning for those of ordinary skill in the art, and is not limited to a special or custom meaning. The term may specifically refer to, but is not limited to, a measurement in which the standard operating potential between a working electrode and another electrode is predefined, particularly during detection of at least one analyte from a plurality of sensor signals (particularly a standard sensor signal). The standard operating potential may be constant at a predefined value of typically 30mV to 60mV or 50mV, particularly for media based on Os complex modified polymers. Thus, the analyte sensor may be operated in a diffusion controlled current mode, wherein the sensor signal (particularly the standard sensor signal) may depend only on the analyte concentration. The standard operating potential may be generated by an electronic unit.

[0040] The term "standard sensor signal" as used herein is a broad term and will be given a common and customary meaning for a person of ordinary skill in the art, and is not limited to a special or custom meaning. The term may specifically refer to, but is not limited to, a sensor signal, for example, an original signal and / or a pre-processed or processed sensor signal generated by the analyte sensor when the analyte sensor is operated in a standard operating mode. Specifically, the standard sensor signal may be an original sensor signal or a pre-processed or processed sensor signal obtained by detecting the current flowing between the working electrode and another electrode, specifically in a standard operating mode. The current may depend on the amount of at least one analyte, in particular the concentration of at least one analyte in a body fluid. Additionally or alternatively, the standard sensor signal may be obtained by the current, in particular by taking into account a calibration value and / or a calibration function. Thus, the standard sensor signal may be a glucose level, in particular a blood glucose level.

[0041] The term "determine" as used herein is a broad term and shall be given the ordinary and customary meaning to those of ordinary skill in the art and shall not be limited to a special or customary meaning. The term may specifically refer to, but is not limited to, a process of measuring and / or generating at least one representative result, particularly by evaluating at least one sensor signal such as acquired by an analyte sensor and / or an electronic unit, particularly for obtaining information about at least one sensor signal associated with at least one analyte for qualitative and / or quantitative detection of the at least one analyte.

[0042] According to the first aspect, the method comprises step ii., also as described above. According to step ii., the method comprises comparing the standard sensor signal with at least one threshold value, specifically for determining whether the standard sensor signal exceeds the threshold value, thereby determining whether it is necessary to change the operating mode of the analyte sensor from the standard operating mode to the economic operating mode.

[0043] The term "comparison" as used herein is a broad term and will be given a common and customary meaning for a person of ordinary skill in the art, and is not limited to a special or custom meaning. The term may specifically refer to, but is not limited to, finding a relationship between a corresponding sensor signal and a threshold value. Thus, when a quantifiable item A is compared to B, the result of the comparison may include at least one of the following items: A is greater than B, A is equal to B, and A is less than B. The term "threshold" as used herein is a broad term and will be given a common and customary meaning for a person of ordinary skill in the art, and is not limited to a special or custom meaning. The term may specifically refer to, but is not limited to, at least one predetermined or determinable comparison value, with which at least one other item or value is compared. As an example, in the case of an electrical signal, the threshold may include at least one threshold voltage and / or at least one threshold current, with which at least one voltage signal or at least one current signal may be compared. In the present case, the threshold may include at least one threshold current in a standard operating mode. The threshold current may be calculated by considering at least one of the following items: sensor sensitivity; or a threshold glucose level, specifically a threshold blood sugar level. For example, for an analyte sensor having a sensor sensitivity of 0.05 nA / mg / dl and a threshold glucose level (specifically a threshold blood glucose level) that can be considered as 250 mg / dl, the threshold current can reach 12.5 nA. Alternatively or in addition, the threshold current can correspond to a threshold glucose level, specifically a threshold blood glucose level. The threshold glucose level (specifically the threshold blood glucose level) can typically be 200 mg / dl or 300 mg / dl. Therefore, the threshold value can be determined empirically, for example in a laboratory environment, by determining the current occurring at a predetermined threshold glucose level (specifically a predetermined threshold blood glucose level, for example, a threshold blood glucose level selected within the range of 200 mg / dl to 300 mg / dl). A glucose level (specifically a threshold blood glucose level) above the threshold glucose level (specifically a blood glucose level) can be determined to be within the hyperglycemic range.

[0044] The term "determining whether the economy sensor signal exceeds the economy threshold" as used herein is a broad term and is to be given the ordinary and customary meaning to a person of ordinary skill in the art and is not limited to a special or customized meaning. The term may specifically refer to, but is not limited to, determining whether a standard sensor signal (particularly when the standard sensor signal is a current) exceeds a threshold current, particularly in a standard operating mode. Alternatively or in addition, particularly in a standard operating mode, determining whether a standard sensor signal (particularly when the standard sensor signal is a glucose level, particularly a blood sugar level) exceeds a threshold glucose level (particularly a threshold blood sugar level).

[0045] The term "change of operating mode" as used herein is a broad term and will be given the ordinary and customary meaning to those of ordinary skill in the art, and is not limited to a special or customized meaning. The term may specifically refer to, but is not limited to, a change or switch in the functionality of the analyte sensor, in particular causing a change or switch in the consumption of the redox material composition (specifically silver chloride). The operating mode of the analyte sensor may be at least a standard operating mode and an economic operating mode. Additional operating modes may exist. Specifically, the selection and / or change of the operating mode may be performed automatically, for example, by a computer implementation, such as by a processor of the analyte sensor system.

[0046] The term "economic mode" as used herein is a broad term and will be given a common and customary meaning for a person of ordinary skill in the art, and is not limited to a special or custom meaning. The term may specifically refer to, but is not limited to, a specific operating mode of at least one analyte sensor. The term may specifically refer to, but is not limited to, an abnormal operating mode of at least one analyte sensor, which is selected or activated when at least one specific condition is met, such as at least one condition selected from the group consisting of the following items: a standard sensor signal is above a threshold; a standard sensor signal is below a threshold; a standard sensor signal is above or equal to a threshold; a standard sensor signal is below or equal to a threshold. In the economic mode, at least one analyte may be further detected. Therefore, qualitative and / or quantitative detection and / or evaluation of at least one analyte may be performed in the economic mode. Additionally or alternatively, a constant current measurement may be performed in the economic mode. This will be described in more detail below.

[0047] Compared to the standard operating mode, in the economic operating mode, the sensitivity of the analyte sensor for detecting at least one analyte (particularly the concentration value of the analyte in the body fluid) may be lower. As used herein, the term "sensitivity" is a broad term and should be given its ordinary and customary meaning for ordinary technicians in the field, and should not be limited to a special or customized meaning. The term specifically may refer to, but is not limited to, the change in the sensor signal of the analyte sensor for each change in the analyte concentration value. In the standard operating mode, the current flowing through the working electrode and the other electrode may depend on the analyte concentration, where the sensitivity can generally be given in nA / mg / dl. In the economic mode, the analyte concentration can be calculated by considering the operating potential of the working electrode relative to the other electrode, where the sensitivity can generally be given in mV / mg / dl.

[0048] The standard sensor signal may include information about at least one analyte, specifically a concentration value, in particular wherein the standard sensor signal may be specifically analyzed specifically for detecting at least one analyte in a standard operating mode. The term "information including at least one analyte" as used herein is a broad term and will be given a common and customary meaning for a person of ordinary skill in the art, and is not limited to a special or custom meaning. The term may specifically refer to, but is not limited to, quantitatively and / or qualitatively evaluating and / or detecting at least one analyte based on a sensor signal (specifically based on a standard sensor signal or an economic sensor signal). The standard sensor signal may be related to the concentration value of the analyte in the body fluid. Additionally or alternatively, the standard sensor signal may be proportional to the concentration value of the analyte in the body fluid. Additionally or alternatively, the concentration value of the analyte in the body fluid may be proportional to the current through the working electrode and another electrode determined in the standard operating mode.

[0049] The analyte may in particular be selected from the group consisting of: glucose; lactate; or glutamate. The body fluid may in particular be selected from the group consisting of: interstitial fluid, blood, plasma, urine and saliva. Thus, as an example, the analyte may be glucose and the body fluid may be blood or may be interstitial fluid. However, other embodiments are also possible.

[0050] In particular, under the condition that the standard sensor signal is equal to the threshold value, the consumption of silver chloride of the redox material composition in the economic operation mode may be lower than or equal to the consumption of silver chloride of the redox material composition in the standard operation mode. As used herein, the term "consumption" is a broad term and will be given the common and customary meaning to those of ordinary skill in the art, and is not limited to a special or customized meaning. The term may specifically refer to, but is not limited to, a portion of a substance used, specifically a portion of silver chloride, where the amount is reduced due to the use. The amount of silver chloride may be consumed in a redox reaction occurring between at least one analyte and the silver chloride.

[0051] In the standard operating mode, the detected glucose value may be indicated to the patient. In the economic operating mode, the glucose level may be indicated to the patient that it is too high. As used herein, the term "indication" is a broad term and will be given the ordinary and customary meaning to a person of ordinary skill in the art, and is not limited to a special or customized meaning. The term may specifically refer to, but is not limited to, detailed data or information that is forwarded, particularly to the patient. The information and / or detailed data may be selected from at least one of the following: the detected glucose value; or a blood sugar level that is too high. The information and / or detailed data may be forwarded visually, particularly by displaying on a screen; and / or forwarded audibly; particularly by playing with a loudspeaker.

[0052] The method may further include step iii. According to step iii., if, preferably in step ii, it is determined that the operating mode of the analyte sensor needs to be changed from the standard operating mode to the economic operating mode, specifically if the standard sensor signal exceeds a threshold value, the method may include switching from the standard operating mode to the economic operating mode, wherein at least one economic sensor signal may be generated in the economic operating mode. As used herein, the term "switch" is a broad term and will be given a common and customary meaning to a person of ordinary skill in the art, and is not limited to a special or customized meaning. The term may specifically refer to, but is not limited to, a change in the operating mode of the analyte sensor, particularly a change from standard operation to economic operation.

[0053] As an example, the economic operation mode may be carried out for a predetermined economic time span or until at least one condition for switching back from the economic operation mode to the standard operation mode is met. To check the at least one condition, any measured economic sensor signal may be compared with at least one economic threshold condition. Alternatively or in addition, the average of at least two measured economic sensor signals may be compared with at least one economic threshold condition. The term "economic time span" as used herein is a broad term and will be given a common and customary meaning to a person of ordinary skill in the art, and is not limited to a special or customized meaning. The term may specifically refer to, but is not limited to, a time interval, in particular a time interval of at least 1 min; 2 min; 3 min; 4 min or 5 min. The term "condition for switching back" as used herein is a broad term and will be given a common and customary meaning to a person of ordinary skill in the art, and is not limited to a special or customized meaning. The condition for switching back to the standard operation mode may be that the economic sensor signal exceeds a threshold potential, in particular in the economic operation mode. The threshold potential may correspond to a threshold glucose level. Alternatively or in addition, the condition for switching back to the standard operation mode may be that the assessed glucose level falls below a threshold glucose level, in particular in the economic operation mode. The threshold glucose level may also typically be 200 mg / dl or 300 mg / dl.

[0054] In the economical operating mode, at least one economical sensor signal can be generated by performing a constant current measurement for detecting at least one analyte using an analyte sensor, wherein the current through the working electrode and the further electrode can be set to at least one predetermined economical current value, wherein the operating potential of the working electrode relative to the further electrode can be determined, and in particular wherein the predetermined economical current value can be kept constant during the determination of the operating potential.

[0055] The term "constant current measurement value" as used herein is a broad term and will be given the ordinary and customary meaning for ordinary technicians in the field, and is not limited to a special or customized meaning. The term can specifically refer to, but is not limited to, a measurement value in which the current through an electrode, specifically through a working electrode and an additional electrode, remains substantially constant, for example, with a variation of less than 1%, less than 0.75% or even less than 0.5% tolerance, particularly during monitoring of multiple sensor signals, particularly during monitoring of multiple economic sensor signals. During the generation of the multiple sensor signals, the current can be constantly maintained at a predefined value. The predefined value may depend on the sensor sensitivity. For example, for a threshold glucose level of 250 mg / dl and a sensor sensitivity of 0.1 nA / mg / dl, the predefined value may be 25 nA. For a threshold glucose level of 250 mg / dl and a sensor sensitivity of 0.05 nA / mg / dl, the predefined value may be 12.5 nA. Thus, the analyte sensor can be operated in a kinetic control region, wherein the economic sensor signal, in particular the operating potential of the working electrode relative to the further electrode, can depend in particular on the kinetics of the charge transfer. In the economic mode, the operating potential can be adjusted by the electronics unit, in particular to generate a predefined current value between the working electrode and the further electrode.

[0056] The term "economic sensor signal" as used herein is a broad term and will be given the ordinary and customary meaning to a person of ordinary skill in the art, and is not limited to a special or customized meaning. The term may specifically refer to, but is not limited to, an operating potential between a working electrode and a further electrode, particularly for regulating the current between the working electrode and the further electrode. The potential may depend on the amount of at least one analyte, particularly the concentration value of at least one analyte in a body fluid. Additionally or alternatively, the economic sensor signal may be obtained based on the operating potential, particularly by taking into account a calibration value and / or a calibration function. Thus, the economic sensor signal may be a glucose level.

[0057] The predetermined economic current value may be selected to not exceed the electrical threshold current through the working electrode and the additional electrode that occurs when the standard sensor signal is equal to the threshold value. The term "not exceeding" as used herein is a broad term and will be given a common and customary meaning to a person of ordinary skill in the art and is not limited to a special or customized meaning. The term may specifically refer to, but is not limited to, at least one of the following: the predetermined economic current value is lower than the electrical threshold current; or the predetermined economic current value is equal to the electrical threshold current.

[0058] The economic sensor signal may include information about at least one analyte, in particular, wherein the economic sensor signal may be specifically analyzed for detecting at least one analyte in the economic operation mode. The economic sensor signal may be related to a concentration value of the analyte in the body fluid. Additionally or alternatively, the economic sensor signal may be a function of the concentration value of the analyte in the body fluid. Additionally or alternatively, the concentration value of the analyte in the body fluid may be a function of the operating potential of the working electrode relative to the further electrode in the economic operation mode.

[0059] The method may further include a step iv. According to step iv., the method may include monitoring the economy sensor signal when the analyte sensor is used in the economy operation mode. The method may further include a step v. According to step v., the method may include comparing the economy sensor signal with at least one economy threshold, specifically determining whether the economy sensor signal drops below the economy threshold or exceeds the economy threshold, thereby determining whether it is necessary to change the operation mode of the analyte sensor from the economy operation mode to the standard operation mode.

[0060] The term "determining whether the economy sensor signal drops below an economy threshold or exceeds an economy threshold" as used herein is a broad term and is to be given the ordinary and customary meaning to one of ordinary skill in the art and is not limited to a special or customized meaning. The term may specifically refer to, but is not limited to, determining whether the economy sensor signal (particularly when the economy sensor signal is an operating potential) exceeds a threshold potential, particularly in an economy operating mode. Alternatively or in addition, determining whether the economy sensor signal (particularly when the economy sensor signal is a glucose level) drops below a threshold glucose level, particularly in an economy operating mode.

[0061] The method may further comprise a step vi. According to step vi., the method may comprise switching from the economy operating mode back to the standard operating mode if, preferably in step v., it is determined that the operating mode of the analyte sensor needs to be changed from the economy operating mode back to the standard operating mode, in particular if the economy sensor signal decreases below an economy threshold or exceeds an economy threshold.

[0062] The standard sensor signal and / or the economic sensor signal can each be selected from the group consisting of the following items: an electrical signal generated by an analyte sensor, specifically at least one of the current signals; an electrical signal generated for adjusting the analyte sensor, specifically a voltage signal; a secondary signal obtained from an electrical signal generated by an analyte sensor or generated for adjusting the analyte sensor, specifically a concentration value of an analyte in a body fluid determined by using an electrical signal generated by an analyte sensor or an electrical signal generated for adjusting the analyte sensor. The voltage signal can be generated by using an electronic unit. As used herein, the term "concentration value" is a broad term and will be given a common and customary meaning for a person of ordinary skill in the art, and is not limited to a special or customized meaning. The term can specifically refer to, but is not limited to, an information item that qualitatively or quantitatively indicates the concentration of at least one compound in at least one medium, such as a concentration by weight and / or by volume, such as an analyte in a body fluid, specifically the abundance of at least one analyte divided by the total volume of the body fluid. The concentration value can refer to at least one of the following items: mass concentration; molar concentration; number concentration; or volume concentration.

[0063] The method may further include obtaining at least one concentration value of the analyte in the body fluid by using the standard sensor signal or the economic sensor signal, respectively, according to the current operating mode of the analyte sensor. As used herein, the term "obtaining" is a broad term and will be given a common and customary meaning to a person of ordinary skill in the art, and is not limited to a special or customized meaning. The term may specifically refer to, but is not limited to, determining at least one concentration value by evaluating the corresponding sensor signal, in particular by further considering a calibration value and / or a calibration function or a transformation algorithm. Thus, at least one analyte can be detected.

[0064] The method may further include indicating to a user whether the analyte sensor is currently operating in a standard operating mode or an economy operating mode. As used herein, the term "indication" is a broad term and is to be given a common and customary meaning to one of ordinary skill in the art and is not limited to a special or customary meaning. The term may specifically refer to, but is not limited to, giving information to a user, specifically information about an operating mode. The operating mode may be indicated by displaying to the user an indication of the corresponding operating mode of operating the analyte sensor.

[0065] The method may include continuously detecting the analyte over a time span of at least one day, specifically over a time span of at least seven days. As used herein, the term "time span" is a broad term and is given a common and customary meaning to a person of ordinary skill in the art, and is not limited to a special or customized meaning. The term may specifically refer to, but is not limited to, a time interval for operating an analyte sensor. During this time interval or time span, the analyte sensor may continuously and / or reliably detect at least one analyte, specifically with a sensitivity higher than a predetermined sensitivity, and in particular without interruption to perform a maintenance procedure. Once this time span has passed, the analyte sensor may require a maintenance procedure or may need to be replaced.

[0066] The method may include continuously detecting an analyte by at least one of the following: permanently evaluating a sensor signal of an analyte sensor and repeatedly evaluating a sensor signal of an analyte sensor, specifically repeatedly evaluating a sensor signal collected at regular or irregular time intervals. As used herein, the term "permanently evaluating" is a broad term and should be given its common and customary meaning for a person of ordinary skill in the art, and should not be limited to a special or custom meaning. The term may specifically refer to, but is not limited to, a continuous or repeated, specifically uninterrupted evaluation of a sensor signal, specifically for detecting at least one analyte. As used herein, the term "repeatedly evaluating" is a broad term and should be given its common and customary meaning for a person of ordinary skill in the art, and should not be limited to a special or custom meaning. The term may specifically refer to, but is not limited to, a repeated and / or repeated and / or continuous evaluation of a sensor signal, specifically for detecting at least one analyte.

[0067] As described above, the method may basically refer to a method of operating an analyte sensor, such as an analyte sensor having sensor-related features according to any of the above-described embodiments and / or according to any of the embodiments described in further detail below. In other words, the method as proposed herein may be a method of operating an analyte sensor and / or an analyte sensor system as described in further detail below for continuously detecting at least one analyte in a body fluid in vivo over a time span, the method using at least one analyte sensor comprising at least one working electrode configured for performing at least one electrochemical detection reaction with the analyte, and at least one further electrode comprising at least one redox material composition comprising silver and silver chloride, the method comprising the method steps as disclosed above, i.e. at least step i. and step ii., and optionally also comprising one or more of the further method steps as described above.

[0068] A method for continuously detecting at least one analyte in a body fluid in vivo over a time span, specifically a method for operating an analyte sensor, can be at least partially implemented by a computer, specifically step i. and step ii., and optionally also including one or more or all of steps iii. to step vi. The term "implemented by a computer" as used herein is a broad term and will be given a common and customary meaning to a person of ordinary skill in the art, and is not limited to a special or customized meaning. The term can specifically refer to, but is not limited to, a method performed by at least one device, specifically an analyte sensor system including a processor. The computer-implemented method can be implemented as at least one computer program that can be provided on a memory of an analyte sensor system.

[0069] In a second aspect of the present invention, an analyte sensor system for continuously detecting at least one analyte in a body fluid in vivo over a measurement time span is disclosed. The analyte sensor system comprises:

[0070] a. at least one analyte sensor comprising at least one working electrode, and at least one additional electrode, the working electrode being configured to perform at least one electrochemical detection reaction with an analyte, the additional electrode comprising at least one redox material composition comprising silver and silver chloride;

[0071] b. A processor and a memory storing instructions which, when executed, cause the processor to perform at least the following steps:

[0072] i. monitoring at least one standard sensor signal obtained by using the analyte sensor in a standard operating mode,

[0073] wherein, in a standard operating mode, a potentiostatic measurement is performed for detecting at least one analyte with the analyte sensor, wherein the potential of the working electrode relative to the further electrode is set to at least one predetermined standard operating potential, and wherein a current through the working electrode and the further electrode is determined, in particular wherein the predetermined standard operating potential is kept constant during the determination of the current; and

[0074] ii. comparing the standard sensor signal to at least one threshold, specifically determining whether the standard sensor signal exceeds the threshold, thereby determining whether it is necessary to change the operating mode of the analyte sensor from the standard operating mode to the economy operating mode.

[0075] As used herein, the term "processor" is a broad term and is given a common and customary meaning to a person of ordinary skill in the art, and is not limited to a special or custom meaning. The term may specifically refer to, but is not limited to, any logic circuit system configured to perform basic operations of a computer or system; and / or, in general, a device configured to perform calculations or logical operations. In particular, a processor may be configured to process basic instructions that drive a computer or system. As an example, a processor may include at least one arithmetic logic unit (ALU), at least one floating point unit (FPU) (such as a math coprocessor or a numerical coprocessor), a plurality of registers (specifically registers configured to provide operands to the ALU and store operation results), and memory (such as L1 and L2 cache memories). In particular, the processor may be a multi-core processor. In particular, the processor may be or may include a central processing unit (CPU). Additionally or alternatively, the processor may be or may include a microprocessor, so that, in particular, the elements of the processor may be contained in a single integrated circuit (IC) chip. Additionally or alternatively, the processor may be or may include one or more application specific integrated circuits (ASICs) and / or one or more field programmable gate arrays (FPGAs) and / or one or more tensor processing units (TPUs) and / or one or more chips, such as dedicated machine learning optimization chips, etc. Additionally or alternatively, the processor may be or may include a microcontroller unit (MCU). The microcontroller unit may be coupled to an analog front end (AFE) or a digital constant potentiostat. The processor may be specifically configured (such as by software programming) to perform one or more evaluation operations. As used herein, the term "memory" is a broad term and is given a common and customary meaning to a person of ordinary skill in the art, and is not limited to a special or custom meaning. The term may specifically refer to, but is not limited to, a unit for storing computer-readable information, specifically for providing the stored information to a processor.

[0076] In the economical operating mode, at least one economical sensor signal can be generated for detecting at least one analyte using the analyte sensor by performing a constant current measurement, wherein the current through the working electrode and the further electrode is set to at least one predetermined economical current value, wherein the operating potential of the working electrode relative to the further electrode is determined, in particular wherein the predetermined economical current value remains constant during the determination of the operating potential.

[0077] The analyte sensor system may include an evaluation unit configured to analyze a standard sensor signal, and optionally analyze an economic sensor signal, for detecting at least one analyte, particularly for determining at least one concentration value of an analyte in a body fluid. As used herein, the term "evaluation unit" is a broad term and will be given a common and customary meaning for a person of ordinary skill in the art, and is not limited to a special or custom meaning. The term may specifically refer to, but is not limited to, any functional element configured to analyze and / or process data. The evaluation unit may specifically analyze and / or process measurement data, such as a measurement result generated by an impedance measurement unit. The evaluation unit may particularly include at least one processor. The processor may be specifically configured (such as by software programming) for performing one or more evaluation operations on the measurement result. As described above, the evaluation unit (specifically the processor of the evaluation unit) may be a part of the processor of feature b, such as by being fully or partially integrated into the processor. However, alternatively, the evaluation unit may also be independent of the processor of feature b.

[0078] The analyte sensor system can be configured (e.g. by software programming, such as by corresponding instructions in a memory) for performing a method according to any of the preceding claims relating to a method. Any definitions of terms given in the context of aspects and embodiments related to the method apply accordingly to aspects and embodiments related to the analyte sensor system.

[0079] The other electrode may include at least one layer, specifically at least one layer of redox material composition deposited on at least one substrate. The layer may be, for example, a non-continuous layer formed by a plurality of points. The term "layer" as used herein is a broad term and will be given a common and customary meaning to a person of ordinary skill in the art, and is not limited to a special or custom meaning. The term may specifically refer to, but is not limited to, any aliquot of material forming a sheet or film, or as an independent film or as a film deposited on a substrate. The layer may be specifically arranged as at least one bundle of multiple layers, such as arranged as a stack and / or multilayer element, wherein at least one layer may be placed and / or laid on or below at least one other layer.

[0080] The further electrode may comprise at least one layer comprising a redox material composition, in particular a concentration of 80% to 100% by weight, in particular 90% by weight of the redox material composition. The redox material composition may comprise silver in a concentration of 5% to 20% by weight. The layer may further comprise a polymer binder, in particular a concentration of 5% to 20% by weight, in particular 10% by weight. The layer may be a non-continuous layer, for example formed by a plurality of dots.

[0081] The additional electrode may be selected from the group consisting of: a counter electrode; a reference electrode; and a combined counter electrode / reference electrode. The term "combined counter electrode / reference electrode" as used herein is a broad term and will be given the ordinary and customary meaning to those of ordinary skill in the art and is not limited to a special or customized meaning. The term may specifically refer to, but is not limited to, an electrode intended to be used as a counter electrode and a reference electrode, specifically providing the functions of a counter electrode and a reference electrode.

[0082] The other electrodes may be at least partially coated with an insulating material. The term "insulating material" as used herein is a broad term and will be given a common and customary meaning to a person of ordinary skill in the art, and is not limited to a special or customary meaning. The term may specifically refer to, but is not limited to, at least one electrically insulating material, specifically to avoid unwanted currents between conductive elements. For example, the electrically insulating material may be selected from the group consisting of polyethylene terephthalate (PET) and polycarbonate (PC). However, other types of electrically insulating materials may also be feasible.

[0083] The insulating material may leave at least one window open through which the analyte can reach the other electrode. The term "window" as used herein is a broad term and will be given the common and customary meaning to those of ordinary skill in the art, and is not limited to a special or customized meaning. The term may specifically refer to, but is not limited to, at least one area of ​​insulating material that leaves an opening so that the other electrode, in particular at least one layer comprising a redox material composition, is not covered by the insulating material, specifically so that the other electrode, in particular at least one layer comprising a redox material composition, is in contact with the body fluid in a manner that a redox reaction can occur between at least one analyte and the other electrode.

[0084] In particular, the window may have an open area of ​​0.1% to 0.5% of the total electrode area of ​​the further electrode. The area of ​​the at least one window may be smaller than the area of ​​the layer comprising the redox material composition, in particular smaller than the area of ​​the layer covered by the insulating material. The insulating material may cover, in particular partially or completely, the layer comprising the redox material composition, so that the analyte can only reach the part of the layer comprising the redox material composition that remains open through the window. The entire area constructed by the at least one window may be filled with the layer comprising the redox material composition. The total area may be less than 0.1 mm 2 ; 0.09mm 2 ; 0.08mm 2 ; or 0.07mm 2 .

[0085] The electrochemical analyte sensor may specifically include at least one substrate, wherein the working electrode and the further electrode are deposited on the substrate. The term "substrate" as used herein is a broad term and is given a common and customary meaning to a person of ordinary skill in the art, and is not limited to a special or custom meaning. The term may specifically refer to, but is not limited to, any element designed to carry one or more other elements disposed thereon and / or therein in whole or in part. In particular, the substrate may be a planar substrate. The substrate may specifically have an elongated shape, such as a strip or a rod; however, other types of shapes are also possible. The working electrode and the further electrode may be deposited on opposite sides of the substrate. The substrate may include a flexible substrate, specifically having a strip shape or a rod shape.

[0086] The electrochemical analyte sensor may be specifically configured for at least partially percutaneous insertion into body tissue. The term "percutaneous" as used herein is a broad term and is to be given the ordinary and customary meaning to one of ordinary skill in the art and is not limited to a special or customized meaning. The term may specifically refer to, but is not limited to, penetrating and / or entering and / or passing through the skin of a user or patient.

[0087] The analyte sensor may specifically include at least one implantable portion and at least one contact portion for percutaneous insertion into body tissue, the contact portion including at least one electrode pad for electrically contacting a working electrode and at least one contact pad for electrically contacting another electrode. The term "implantable portion" as used herein is a broad term and will be given a common and customary meaning for a person of ordinary skill in the art, and is not limited to a special or custom meaning. The term may specifically refer to, but is not limited to, a component or assembly configured to be insertable into any body tissue, specifically a working electrode. Other components or assemblies of the analyte sensor may be retained outside the body tissue, such as a counter electrode and / or a reference electrode or a combined relative / reference electrode may be retained outside the body tissue. Preferably, the insertable portion may completely or partially contain a biocompatible surface, which has as little harmful effect as possible on the user or body tissue at least during a typical duration of use. For this purpose, the insertable portion may be completely or partially covered with at least one biocompatible film layer, such as at least one polymer film layer, such as a gel film.

[0088] The working electrode may comprise at least one detection material, wherein the detection material comprises at least one enzyme configured to perform an analyte-specific reaction with an analyte to be detected.

[0089] In particular, the enzyme may be selected from the group consisting of: glucose oxidase, glucose dehydrogenase, lactate oxidase, lactate dehydrogenase, glutamate oxidase and glutamate dehydrogenase. However, other enzymes are also feasible, for example, as described above.

[0090] Specifically, the electrochemical analyte sensor may include at least one membrane that is permeable to the analyte to be detected, specifically, the membrane is impermeable to the material of the working electrode and the additional electrode, and the membrane at least partially surrounds the working electrode and the additional electrode. The term "permeable to the analyte to be detected" as used herein is a broad term and will be given the common and customary meaning for those of ordinary skill in the art, and is not limited to a special or customized meaning. The term may specifically refer to, but is not limited to, a membrane that allows certain molecules or ions to pass through the membrane by diffusion, specifically allowing the analyte to be detected to pass through the membrane. The membrane may limit the diffusion of the analyte to the layer containing the redox material composition. The term "impermeable to the material of the working electrode and the additional electrode" as used herein is a broad term and will be given the common and customary meaning for those of ordinary skill in the art, and is not limited to a special or customized meaning. The term may specifically refer to, but is not limited to, a membrane that does not allow certain molecules or ions to pass through it by diffusion, specifically not allowing the products of the redox reaction occurring at the corresponding electrode to pass through it.

[0091] In a third aspect of the present invention, a computer program comprising instructions is disclosed, when the program is executed by a processor of an analyte sensor system according to any of the preceding claims relating to an analyte sensor system, the instructions cause the analyte sensor system to perform a method according to any of the preceding claims relating to a method, specifically at least method step i. and method step ii., and optionally also including one or more of step iii., step iv, step v and step vi. The term "computer program" as used herein is a broad term and will be given the ordinary and customary meaning for ordinary technicians in the field, and is not limited to a special or customized meaning. The term may specifically refer to but is not limited to at least one executable instruction for at least one programmable device (specifically a computer), preferably a sequence of executable instructions, for processing and / or solving at least one function and / or solving at least one task and / or at least one problem by using the at least one programmable device (specifically a computer), preferably for performing some or all steps of any one of the methods in any aspect or embodiment described in the present invention.

[0092] The computer program may further be used to evaluate the data for the detection of the at least one analyte, which evaluation may depend on the operating mode of the analyte sensor, in particular by evaluating the current or potential between the working electrode and the further electrode.

[0093] In a fourth aspect of the present invention, a computer-readable storage medium comprising instructions is disclosed, which, when executed by a processor of an analyte sensor system according to any one of the aforementioned aspects or embodiments (specifically relating to methods and / or relating to analyte sensor systems), causes the analyte sensor system to perform a method according to any one of the aforementioned claims relating to methods, specifically at least method steps i. and method steps ii., and optionally also including one or more of steps iii., step iv, step v, and step vi. As used herein, the term "computer-readable storage medium" may specifically refer to a non-transitory data storage device, such as a hardware storage medium on which computer executable instructions are stored. A computer-readable data carrier or storage medium may specifically be or may include a storage medium such as a random access memory (RAM) and / or a read-only memory (ROM).

[0094] Therefore, in particular, as described above, one, more than one or even all of method steps i. to method step vi., more particularly step i. and step ii., and optionally also one or more or all of steps iii. to step vi., can be performed by using a computer or a computer network, preferably by using a computer program.

[0095] This article further discloses and proposes a computer program product with program code means, so that when the program is executed on a computer or computer network, the method according to the present invention is performed in one or more embodiments attached hereto. Specifically, the program code means can be stored on a computer-readable data carrier and / or on a computer-readable storage medium.

[0096] The present invention further discloses and proposes a data carrier having a data structure stored thereon, which, after being loaded into a computer or a computer network, such as after being loaded into a working memory or a main memory of the computer or the computer network, can execute a method according to one or more embodiments disclosed herein.

[0097] The present invention further discloses and proposes a non-transitory computer-readable medium comprising instructions, which, when executed by one or more processors, causes the one or more processors to perform a method for continuously detecting at least one analyte in body fluids in vivo over a time span (as described in this aspect and embodiment), specifically at least method step i. and method step ii., and optionally also includes one or more of step iii., step iv, step v and step vi.

[0098] This article further discloses and proposes a computer program product having a program code tool stored on a machine-readable carrier so that when the program is executed on a computer or computer network, a method according to one or more embodiments disclosed herein is performed. As used herein, a computer program product refers to a program that is a tradable product. The product can generally exist in any format (such as in paper format) or on a computer-readable data carrier and / or on a computer-readable storage medium. Specifically, the computer program product can be distributed on a data network.

[0099] Further disclosed and proposed herein is a modulated data signal containing instructions readable by a computer system or a computer network for performing a method according to one or more embodiments disclosed herein.

[0100] With reference to the computer-implemented aspects of the present invention, one or more method steps or even all method steps of the method according to one or more embodiments disclosed herein can be performed using a computer or a computer network. Therefore, generally speaking, any method step including providing and / or manipulating data can be performed using a computer or a computer network. Generally speaking, these method steps can include any method step other than the method step that usually requires manual operation (such as providing samples and / or performing certain aspects of actual measurement).

[0101] Specifically, this article further discloses the following:

[0102] - a computer or a computer network comprising at least one processor, wherein the processor is adapted to perform the method according to one of the embodiments described in this specification, in particular at least method step i. and method step ii., and optionally also one or more of step iii., step iv, step v and step vi.,

[0103] - a computer loadable data structure, which is suitable for performing a method according to one of the embodiments described in this specification, in particular at least method step i. and method step ii., and optionally also one or more of step iii., step iv., step v and step vi., when the data structure is executed on a computer,

[0104] - a computer program, wherein the computer program is adapted to perform the method according to one of the embodiments described in the present specification, in particular at least method step i. and method step ii., and optionally also one or more of step iii., step iv., step v and step vi., when the program is executed on a computer,

[0105] - A computer program comprising program means for carrying out the method according to one of the embodiments described in this specification, in particular at least method step i. and method step ii., and optionally also step iii., step iv., step v and step vi., when the computer program is executed on a computer or a computer network.

[0106] One or more of

[0107] - a computer program comprising a program tool according to the preceding embodiment, the program tool being stored on a computer-readable storage medium, in particular at least method step i. and method step ii., and optionally further comprising one or more of step iii., step iv., step v and step vi.,

[0108] - a storage medium, on which a data structure is stored, and wherein the data structure is suitable for carrying out a method according to one of the embodiments described in the present specification after having been loaded into a main memory and / or a working memory of a computer or a computer network, in particular at least method step i. and method step ii., and optionally also one or more of step iii., step iv, step v and step vi., and

[0109] - A computer program product having program code means, wherein the program code means can be stored or stored on a storage medium, for performing a method according to one of the embodiments described in the present specification when the program code means is executed on a computer or a computer network, specifically at least method step i. and method step ii., and optionally also including one or more of step iii., step iv, step v and step vi.

[0110] In the context of this paragraph, embodiments may refer to aspects and / or preferred embodiments of the method as described above.

[0111] A method for continuously detecting at least one analyte in a body fluid in vivo over a time span, an analyte sensor system for continuously detecting at least one analyte in a body fluid in vivo over a measurement time span, a computer program and a computer readable storage medium present several advantages over the prior art.

[0112] By changing the operating mode, in particular between a standard operating mode and an economical operating mode (or vice versa), the consumption of the redox material composition can be reduced, in particular when compared to a conventional drive scheme of the analyte detector operated without changing the operating mode. Thereby, in particular, the consumption of silver chloride can be reduced, since the current through the further electrode and the working electrode can be reduced. This can prevent overuse, in particular during periods of time when the actual blood glucose level is particularly high, such as during periods of hyperglycemia.

[0113] In situations where the glucose level may be particularly high, the exact value of the glucose level may not be particularly important. Therefore, some clinically relevant maximum glucose value may be defined, or specifically a threshold glucose level may be defined. In an economical operating mode that can be used to operate the analyte sensor in situations where the determined glucose level is above the threshold glucose level, the current can be regulated in such a way that it remains constant at a defined value. Thereby, the maximum consumption of silver chloride can be limited. Therefore, the maximum consumption of silver chloride can be well defined, in particular for the worst case scenario. This can make it easy to calculate a reliable silver chloride content of the analyte sensor.

[0114] Thus, the analyte sensor may require only a reduced amount of silver chloride compared to an analyte sensor having a conventional drive mode and which may not be operated in an economical mode of operation. Thus, the biocompatibility of the analyte sensor may be enhanced, as the immune response caused by the silver chloride may be reduced, in particular due to the reduced amount of silver chloride in the analyte sensor. The efficiency or sensitivity of the analyte sensor may be further improved, as the reduced immune response may interfere less with the generated sensor signal. Additionally or alternatively, reducing the amount of redox material comprising silver may minimize the sensor size.

[0115] By coating at least a portion of the layer comprising the redox material composition with an insulating material, a portion of the silver chloride can be hidden. Thus, the immune response is further reduced. The use of a film can have the same effect.

[0116] To summarize and without excluding other possible embodiments, the following embodiments may be envisaged:

[0117] Embodiment 1: A method for continuously detecting at least one analyte in a body fluid in vivo over a time span, the method using at least one analyte sensor, the analyte sensor comprising at least one working electrode configured to perform at least one electrochemical detection reaction with the analyte, and at least one additional electrode, the additional electrode comprising at least one redox material composition, the redox material composition comprising silver and silver chloride, the method comprising the following steps:

[0118] i. monitoring at least one standard sensor signal obtained by using the analyte sensor in a standard operating mode,

[0119] wherein, in a standard operating mode, a potentiostatic measurement is performed for detecting at least one analyte with the analyte sensor, wherein the potential of the working electrode relative to the further electrode is set to at least one predetermined standard operating potential, and wherein a current through the working electrode and the further electrode is determined, in particular wherein the predetermined standard operating potential is kept constant during the determination of the current; and

[0120] ii. comparing the standard sensor signal to at least one threshold, specifically for determining whether the standard sensor signal exceeds the threshold, thereby determining whether it is necessary to change the operating mode of the analyte sensor from the standard operating mode to the economic operating mode.

[0121] Embodiment 2: The method according to the preceding embodiment, wherein the standard sensor signal comprises information about at least one analyte, in particular, wherein the standard sensor signal is specifically analyzed exclusively for detecting the at least one analyte in a standard operating mode.

[0122] Embodiment 3: A method according to any one of the preceding embodiments, wherein the standard sensor signal is related to the concentration value of the analyte in the body fluid, in particular wherein the standard sensor signal is proportional to the concentration value of the analyte in the body fluid, more particularly wherein the concentration value of the analyte in the body fluid is proportional to the current through the working electrode and the further electrode determined in a standard operating mode.

[0123] Embodiment 4: The method according to any one of the preceding embodiments, wherein the analyte is selected from at least one of the following:

[0124] -glucose;

[0125] - lactate; or

[0126] -Glutamate.

[0127] Embodiment 5: The method according to any one of the preceding embodiments, wherein the body fluid is selected from the group consisting of interstitial fluid, blood, plasma, urine and saliva.

[0128] Embodiment 6: A method according to any of the preceding embodiments, wherein, in the economic operation mode, the consumption of silver chloride of the redox material composition is lower than or equal to the consumption of silver chloride of the redox material composition in the standard operation mode, in particular under the condition that the standard sensor signal is equal to a threshold value.

[0129] Embodiment 7: According to the method of any one of the preceding embodiments, the method further comprises:

[0130] iii. If in step ii, it is determined that the operating mode of the analyte sensor needs to be changed from the standard operating mode to the economic operating mode, specifically if the standard sensor signal exceeds the threshold, switch from the standard operating mode to the economic operating mode, wherein at least one economic sensor signal can be generated in the economic operating mode.

[0131] Embodiment 8: The method according to the preceding embodiment, wherein the economy operation mode is performed for a predetermined economy time span or until at least one condition for switching back from the economy operation mode to the standard operation mode is met.

[0132] Embodiment 9: A method according to any one of the preceding embodiments, wherein, in an economical operating mode, at least one economical sensor signal is generated by performing a constant current measurement for detecting at least one analyte using an analyte sensor, wherein the current through the working electrode and the further electrode is set to at least one predetermined economical current value, wherein the operating potential of the working electrode relative to the further electrode is determined, in particular wherein the predetermined economical current value remains constant during determination of the operating potential.

[0133] Embodiment 10: The method according to the preceding embodiment, wherein the predetermined economical current value is selected not to exceed an electrical threshold current through the working electrode and the further electrode that occurs when the standard sensor signal is equal to the threshold value.

[0134] Embodiment 11: The method according to any of the four preceding embodiments, wherein the economy sensor signal comprises information about at least one analyte, in particular, wherein the economy sensor signal is specifically analyzed exclusively to detect the at least one analyte in the economy operating mode.

[0135] Embodiment 12: A method according to any one of the five preceding embodiments, wherein the economic sensor signal is related to the concentration value of the analyte in the body fluid, in particular, wherein the economic sensor signal is a function of the concentration value of the analyte in the body fluid, more particularly, wherein the concentration value of the analyte in the body fluid is a function of the operating potential of the working electrode relative to the other electrode in the economic operating mode.

[0136] Embodiment 13: The method according to any one of the six embodiments above, further comprising:

[0137] iv. monitoring the economy sensor signal when the analyte sensor is used in the economy mode of operation;

[0138] as well as

[0139] v. Comparing the economy sensor signal to at least one economy threshold, thereby determining whether it is necessary to change the operating mode of the analyte sensor from the economy operating mode back to the standard operating mode.

[0140] Embodiment 14: The method according to the above embodiment further comprises:

[0141] vi. If in step v., it is determined that the operating mode of the analyte sensor needs to be changed from the economy operating mode back to the standard operating mode, then switch from the economy operating mode back to the standard operating mode.

[0142] Embodiment 15: A method according to any one of the preceding embodiments, wherein the standard sensor signal and the economic sensor signal are each selected from the group consisting of: an electrical signal generated by an analyte sensor, specifically at least one of the current signals; an electrical signal generated for adjusting the analyte sensor, specifically at least one voltage signal; a secondary signal obtained from the electrical signal generated by the analyte sensor or generated for adjusting the analyte sensor, specifically a concentration value of the analyte in the body fluid determined by using the electrical signal generated by the analyte sensor or generated for adjusting the analyte sensor.

[0143] Embodiment 16: The method according to any one of the preceding embodiments, wherein the method further comprises obtaining at least one concentration value of the analyte in the body fluid by using a standard sensor signal or an economical sensor signal, respectively, according to a current operation mode of the analyte sensor.

[0144] Embodiment 17: The method of any preceding embodiment, wherein the method further comprises indicating to a user whether the analyte sensor is currently operating in the standard operating mode or the economy operating mode.

[0145] Embodiment 18: The method according to any one of the preceding embodiments, wherein the method comprises continuously detecting the analyte over a time span of at least one day, in particular over a time span of at least seven days.

[0146] Embodiment 19: A method according to any of the preceding embodiments, wherein the method comprises continuously detecting the analyte by at least one of: permanently evaluating a sensor signal of the analyte sensor and repeatedly evaluating a sensor signal of the analyte sensor, specifically repeatedly evaluating a sensor signal acquired at regular or irregular time intervals.

[0147] Embodiment 20: A method according to any one of the preceding embodiments, wherein the method is at least partially implemented by a computer, specifically step i. and step ii., and optionally also includes one or more or all of steps iii. to and step vi.

[0148] Embodiment 21: An analyte sensor system for continuously detecting at least one analyte in a body fluid in vivo over a measurement time span, the analyte sensor system comprising:

[0149] a. at least one analyte sensor comprising at least one working electrode, and at least one additional electrode, the working electrode being configured to perform at least one electrochemical detection reaction with an analyte, the additional electrode comprising at least one redox material composition comprising silver and silver chloride;

[0150] b. A processor and a memory storing instructions which, when executed, cause the processor to perform at least the following steps:

[0151] i. monitoring at least one standard sensor signal obtained by using the analyte sensor in a standard operating mode,

[0152] wherein, in a standard operating mode, a potentiostatic measurement is performed for detecting at least one analyte with the analyte sensor, wherein the potential of the working electrode relative to the further electrode is set to at least one predetermined standard operating potential, and wherein a current through the working electrode and the further electrode is determined, in particular wherein the predetermined standard operating potential is kept constant during the determination of the current; and

[0153] ii. comparing the standard sensor signal to at least one threshold, specifically determining whether the standard sensor signal exceeds the threshold, thereby determining whether it is necessary to change the operating mode of the analyte sensor from the standard operating mode to the economy operating mode.

[0154] Embodiment 22: An analyte sensor system according to the preceding embodiments, wherein, in an economical operating mode, at least one economical sensor signal is generated by performing a constant current measurement for detecting at least one analyte using the analyte sensor, wherein the current through the working electrode and the further electrode is set to at least one predetermined economical current value, wherein the operating potential of the working electrode relative to the further electrode is determined, in particular wherein the predetermined economical current value remains constant during determination of the operating potential.

[0155] Embodiment 23: An analyte sensor system according to any of the aforementioned embodiments relating to an analyte sensor system, wherein the analyte sensor system comprises an evaluation unit configured to analyze a standard sensor signal and optionally analyze an economic sensor signal for detecting at least one analyte, in particular for determining at least one concentration value of the analyte in a body fluid.

[0156] Embodiment 24: The analyte sensor system according to any of the preceding embodiments relating to analyte sensor systems, wherein the analyte sensor system is configured to perform a method according to any of the preceding embodiments relating to methods.

[0157] Embodiment 25: The analyte sensor system according to any of the preceding embodiments relating to analyte sensor systems, wherein the further electrode comprises a redox material composition in the form of at least one layer, in particular deposited on at least one substrate.

[0158] Embodiment 26: The analyte sensor system according to any of the preceding embodiments relating to analyte sensor systems, wherein the additional electrode is selected from the group consisting of: a counter electrode; a reference electrode; and a combined counter electrode / reference electrode.

[0159] Embodiment 27: The analyte sensor system according to any of the preceding embodiments relating to analyte sensor systems, wherein the further electrode comprises at least one layer comprising a redox material composition.

[0160] Embodiment 28: The analyte sensor system according to any of the preceding embodiments relating to analyte sensor systems, wherein the redox material composition comprises silver at a concentration of 5 wt % to 20 wt %.

[0161] Embodiment 29: The analyte sensor system according to any of the preceding embodiments relating to analyte sensor systems, wherein the further electrode is at least partially coated by an insulating material.

[0162] Embodiment 30: The analyte sensor system of the preceding embodiment, wherein the insulating material leaves open at least one window through which the analyte can reach the further electrode.

[0163] Embodiment 31: The analyte sensor system of the preceding embodiment, wherein the window has an open area of ​​0.1% to 0.5% of the total electrode area of ​​the further electrode.

[0164] Embodiment 32: The analyte sensor system according to any of the preceding embodiments relating to analyte sensor systems, wherein the electrochemical analyte sensor comprises at least one substrate, wherein the working electrode and the further electrode are deposited on the substrate.

[0165] Embodiment 33: The analyte sensor system according to the preceding embodiment, wherein the working electrode and the further electrode are deposited on opposite sides of the substrate.

[0166] Embodiment 34: The analyte sensor system according to any of the two preceding embodiments, wherein the substrate comprises a flexible substrate, in particular having a strip-like shape or a rod-like shape.

[0167] Embodiment 35: The analyte sensor system of any preceding embodiment, wherein the electrochemical analyte sensor is configured for at least partially percutaneous insertion into body tissue.

[0168] Embodiment 36: According to the analyte sensor system described in the previous embodiment, the analyte sensor specifically includes at least one implantable part for percutaneous insertion into body tissue and at least one contact part, which contact part includes at least one electrode pad for electrically contacting a working electrode and at least one contact pad for electrically contacting another electrode.

[0169] Embodiment 37: An analyte sensor system according to any of the aforementioned embodiments relating to analyte sensor systems, wherein the working electrode comprises at least one detection material, wherein the detection material comprises at least one enzyme, and the at least one enzyme is configured to perform an analyte-specific reaction with the analyte to be detected.

[0170] Embodiment 38: The analyte sensor system of the preceding embodiment, wherein the enzyme is selected from the group consisting of glucose oxidase, glucose dehydrogenase, lactate oxidase, lactate dehydrogenase, glutamate oxidase, and glutamate dehydrogenase.

[0171] Embodiment 39: An analyte sensor system according to any one of the aforementioned embodiments relating to an analyte sensor system, wherein the electrochemical analyte sensor may include at least one membrane that is permeable to the analyte to be detected, specifically, the membrane is impermeable to the material of the working electrode and the further electrode, and the membrane at least partially surrounds the working electrode and the further electrode.

[0172] Embodiment 40: A computer program comprising instructions which, when executed by a processor of an analyte sensor system according to any one of the preceding embodiments relating to analyte sensor systems, cause the analyte sensor system to perform a method according to any one of the preceding embodiments relating to methods.

[0173] Embodiment 41: A computer-readable storage medium comprising instructions which, when executed by a processor of an analyte sensor system according to any one of the aforementioned embodiments involving analyte sensor systems, cause the analyte sensor system to perform a method according to any one of the aforementioned embodiments involving methods. BRIEF DESCRIPTION OF THE DRAWINGS

[0174] Other optional features and embodiments will be disclosed in more detail in the subsequent description of embodiments, preferably in conjunction with the dependent claims. Wherein, as will be appreciated by those skilled in the art, each optional feature can be implemented in a separate manner and in any arbitrarily feasible combination. The scope of the present invention is not limited to the described embodiments. Embodiments are schematically depicted in the accompanying drawings. Wherein, the same reference numerals in these drawings refer to the same or functionally equivalent elements.

[0175] In the attached picture:

[0176] Figure 1 An exemplary embodiment of an analyte sensor system is shown;

[0177] Figure 2 An exemplary embodiment of a method for continuously detecting at least one analyte in a bodily fluid in vivo over a time span is shown;

[0178] Figure 3 shows the current-voltage characteristics of an exemplary embodiment of an analyte sensor; and

[0179] and

[0180] Figure 4 An error grid analysis indicating the required sensitivity of the analyte sensor system depending on the reference blood glucose level is shown.

[0181] exist Figure 1 In the figure, an exemplary embodiment of an analyte sensor system 100 is schematically depicted. The analyte sensor system 100 is designated for continuously detecting at least one analyte in a body fluid in vivo over a measurement time span. The analyte may specifically be selected from the group consisting of: glucose; lactate; and glutamate. Additionally or alternatively, one or more other analytes may be selected. The body fluid may be interstitial fluid, blood, plasma, urine and / or saliva. There may be other options for body fluids.

[0182] The analyte sensor system 100 includes at least one electrochemical analyte sensor 102, which includes at least one working electrode 104 and at least one additional electrode 106, the working electrode being configured to perform at least one electrochemical detection reaction with an analyte. The additional electrode 106 comprises at least one redox material composition, and the redox material composition comprises silver and silver chloride.

[0183] The analyte sensor system 100 further includes a processor 108 and a memory 110. A computer program comprising instructions that, when executed by the processor 108 of the analyte sensor system 100, can cause the analyte sensor system 100 to perform a method 200 of continuously detecting at least one analyte in a bodily fluid in vivo over a time span. The instructions can be stored in the memory 110. Figure 2 The method 200 is described in more detail. Alternatively, a computer-readable storage medium containing instructions may be provided that, when executed by the processor 108 of the analyte sensor system 100, causes the analyte sensor system 100 to perform the method 200. To perform the method 200, the processor 108 controls and / or regulates the electronics unit 128, which controls and / or regulates the analyte sensor 102, in particular, regulates the voltage between the working electrode 104 and the further electrode 106.

[0184] The analyte sensor system 100 may further comprise: an evaluation unit 112 configured for analyzing a sensor signal 130 of the analyte sensor 102; and / or an electronic unit 128 for detecting at least one analyte, in particular for determining at least one concentration value of the analyte in the body fluid. The sensor signal 130 may be a current between the working electrode 104 and the further electrode 106 and / or a voltage between the working electrode 104 and the further electrode 106. The sensor signal 130 may further be a glucose level derived from the current and / or voltage, in particular by using a correction value and / or a function, in particular by using the evaluation unit 112.

[0185] The electrochemical analyte sensor 102 is configured for at least partially percutaneous insertion into body tissue. The analyte sensor 102 may include at least one implantable portion for percutaneous insertion into body tissue and at least one contact portion including at least one electrode pad 122 for electrically contacting the additional electrode 106 and at least one contact pad 124 for electrically contacting the working electrode 104.

[0186] The electrochemical analyte sensor 102 may include at least one substrate 116, wherein the working electrode 104 and the further electrode 106 may be deposited on the substrate 116, in particular on opposite sides of the substrate 116. The contact pad 124 may be arranged between the working electrode 104 and the substrate 116. The electrode pad 122 may be arranged between the further electrode 106 and the substrate 116. As an example, the substrate 116 may be strip-shaped. Alternatively, as an example, the substrate 116 may have a rod-like shape. The substrate 116 may be a flexible substrate 116.

[0187] The electrochemical analyte sensor 102 may further include at least one membrane 126. The membrane 126 may be permeable to the analyte to be detected. In particular, the membrane 126 may be impermeable to the material of the working electrode 104 and the further electrode 106, in particular to the material produced in the redox reaction at the respective electrodes. The membrane 126 may at least partially surround the working electrode 104 and the further electrode 106. Alternatively, the membrane 126 may at least partially surround the working electrode 104 or the further electrode 106.

[0188] The further electrode 106 comprises at least one layer 114, in particular a redox material composition in the form of at least one layer 114 deposited on at least one substrate 116. Thus, the further electrode 106 may comprise at least one layer 114 comprising a redox material composition. In particular, the redox material composition may comprise silver in a concentration of 5 wt.-% to 20 wt.-%.

[0189] The further electrode 106 may be at least partially coated by an insulating material 118. The insulating material 118 may leave open at least one window 120 through which the analyte can reach the further electrode 106. In particular, the at least one window 120 may have an open area of ​​0.1% to 0.5% of the total electrode area of ​​the further electrode 106. In particular, the further electrode 106 may be selected from the group consisting of: a counter electrode; a reference electrode; and a combined counter electrode / reference electrode.

[0190] The working electrode 104 may include at least one detection material, wherein the detection material may include at least one enzyme configured to perform an analyte-specific reaction with the analyte to be detected. Specifically, the enzyme may be selected from the group consisting of: glucose oxidase, glucose dehydrogenase, lactate oxidase, lactate dehydrogenase, glutamate oxidase and glutamate dehydrogenase.

[0191] exist Figure 2 , a flow chart of an embodiment of a method 200 for continuously detecting at least one analyte in a bodily fluid in vivo over a time span is depicted. Figure 2 In an exemplary embodiment of the present invention, all steps of method 200 can be implemented by a computer. Alternatively, the method can be partially implemented by a computer. Therefore, specifically, step i. and step ii. can be implemented by a computer, and in addition, one or more or all of steps iii. to step vi. can also be implemented by a computer.

[0192] The method 200 utilizes the analyte sensor 102 as described above. Thus, the method 200 can be a method for operating the analyte sensor 102 and / or for operating the analyte sensor system 100. As described above, the analyte sensor 102 includes at least one working electrode 104 configured to perform at least one electrochemical detection reaction with an analyte, and at least one additional electrode 106.

[0193] The method 200 comprises the following steps:

[0194] i. a monitoring step 202, wherein at least one standard sensor signal 132 obtained by using the analyte sensor 102 in a standard operating mode is monitored,

[0195] wherein, in a standard operating mode, a potentiostatic measurement is performed for detecting at least one analyte with the analyte sensor 102, wherein the potential of the working electrode 104 relative to the further electrode 106 is set to at least one predetermined standard operating potential, and wherein a current through the working electrode 104 and the further electrode 106 is determined, in particular wherein the predetermined standard operating potential is kept constant during the determination of the current; and

[0196] ii. Comparison step 204, wherein the standard sensor signal 132 is compared with at least one threshold, specifically for determining whether the standard sensor signal 132 exceeds the threshold, thereby determining whether the operating mode of the analyte sensor 102 needs to be changed from the standard operating mode to the economic operating mode.

[0197] The standard sensor signal 132 may include information about at least one analyte, in particular, wherein the standard sensor signal 132 may be specifically analyzed for detecting at least one analyte in the standard operating mode. The standard sensor signal 132 is related to a concentration value of the analyte in the body fluid, in particular wherein the standard sensor signal 132 is proportional to the concentration value of the analyte in the body fluid, more particularly wherein the concentration value of the analyte in the body fluid is proportional to the current through the working electrode 104 and the further electrode 106 determined in the standard operating mode.

[0198] In the economical operation mode, the consumption of silver chloride of the redox material composition may be lower than or equal to the consumption of silver chloride of the redox material composition in the standard operation mode, particularly under the condition that the standard sensor signal 132 is equal to the threshold value.

[0199] The method 200 may further include:

[0200] iii. Switching step 206, wherein if in comparison step 204, it is determined that the operating mode of analyte sensor 102 needs to be changed from the standard operating mode to the economic operating mode, specifically if the standard sensor signal 132 exceeds a threshold, switching from the standard operating mode to the economic operating mode.

[0201] The economy mode of operation may be performed for a predetermined economy time span or until at least one condition for switching from the economy mode of operation back to the standard mode of operation is met.

[0202] In the economical operating mode, at least one economical sensor signal 134 may be generated for detecting at least one analyte using the analyte sensor 102 by performing a constant current measurement, wherein the current through the working electrode 104 and the further electrode 106 may be set to at least one predetermined economical current value, wherein the operating potential of the working electrode 104 relative to the further electrode 106 is determined, in particular wherein the predetermined economical current value may be kept constant during the determination of the operating potential. The predetermined economical current value may be selected not to exceed an electrical threshold current through the working electrode 104 and the further electrode 106 that occurs when the standard sensor signal 132 is equal to the threshold.

[0203] The economic sensor signal 134 may include information about at least one analyte, in particular, wherein the economic sensor signal 134 may be specifically analyzed for detecting at least one analyte in the economic operation mode. The economic sensor signal 134 may be related to a concentration value of the analyte in the body fluid, in particular, wherein the economic sensor signal 134 may be a function of the analyte concentration value in the body fluid, more particularly, wherein the analyte concentration value in the body fluid may be a function of the operating potential of the working electrode 104 relative to the further electrode 106 in the economic operation mode.

[0204] The method 200 may further include:

[0205] iv. an additional monitoring step 208, wherein the economy sensor signal 134 is monitored when the analyte sensor 102 is used in the economy mode of operation; and

[0206] v. A further comparison step 210, wherein the economy sensor signal 134 is compared to at least one economy threshold value, thereby determining whether it is necessary to change the operating mode of the analyte sensor 102 from the economy operating mode back to the standard operating mode.

[0207] The method 200 may further include:

[0208] vi. a further switching step 212, wherein if in the further comparison step 210 it is determined that the operating mode of the analyte sensor 102 needs to be changed from the economic operating mode back to the standard operating mode, switching from the economic operating mode back to the standard operating mode is performed.

[0209] The standard sensor signal 132 and the economic sensor signal 134 can each be selected from the group consisting of: an electrical signal generated by the analyte sensor 102, specifically at least one of the current signals; an electrical signal generated to adjust the analyte sensor 102, specifically a voltage signal; a secondary signal obtained based on the electrical signal generated by the analyte sensor 102, specifically a concentration value of the analyte in the body fluid determined by using the electrical signal generated by the analyte sensor 102.

[0210] The method 200 may further include obtaining at least one concentration value of the analyte in the body fluid by using the standard sensor signal 132 or the economy sensor signal 134, respectively, according to the current operation mode of the analyte sensor 102. The method 200 may further include indicating to the user whether the analyte sensor 102 is currently operating in the standard operation mode or in the economy operation mode.

[0211] The method 200 may include continuously detecting the analyte over a time span of at least one day, in particular over a time span of at least seven days. The method 200 may include continuously detecting the analyte by at least one of: permanently evaluating the sensor signal 130 of the analyte sensor 102; and repeatedly evaluating the sensor signal 130 of the analyte sensor 102, in particular repeatedly evaluating the sensor signal 130 acquired at regular or irregular time intervals.

[0212] exist Figure 3 , depicts the current-voltage characteristics of an exemplary embodiment of the analyte sensor 102. On the horizontal axis 300, the potential between the working electrode 104 and the additional electrode 106 is depicted. On the vertical axis 302, the current between the working electrode 104 and the additional electrode 106 is depicted. Further, depicted is a scheme I in which the analyte sensor 102 operates in the kinetic control region and a scheme II in which the analyte sensor 102 operates in the diffusion control region. Curve 306 represents the current characteristics for low glucose values, while curve 304 represents the current characteristics for high glucose values. When the exemplary analyte sensor 102 can be operated in a standard operating mode at a constant voltage of 50mV, the glucose level is proportional to the current. Changes in the potential within scheme II may not affect the current. In the economic operating mode, the current may be fixed at a predetermined value, as indicated by line 308. Then the analyte sensor 102 can operate in the kinetic control region and changes in the potential may affect the current.

[0213] Figure 4 The error grid analysis published in the following article is shown: William L. Clarke et al., Evaluating Clinical Accuracy of Systems for Self-Monitoring of Blood Glucose, Diabetes Care, Vol. 10, No. 5, September to October 1987. The reference blood glucose level is displayed on the x-axis 400. The corresponding values ​​of the reference glucose level generated by the monitoring system are depicted on the y-axis 402. The diagonal line 304 represents the complete agreement between the reference blood glucose level and the value generated by the monitoring system. The data points located in the area above and below the diagonal line 404 represent the overestimation and underestimation of the reference blood glucose level, respectively.

[0214] Based on several assumptions discussed further in the above reference, the grid is divided into five zones with different degrees of accuracy and inaccuracy of the monitored glucose estimates. Zone A represents glucose values ​​that deviate from the reference value by no more than 20%, or represent glucose values ​​that are within the hypoglycemic range (<70 mg / dl) when the reference value is also <70 mg / dl. Values ​​within this range are clinically accurate because they will lead to clinically correct treatment decisions. The upper and lower B zones represent values ​​that deviate from the reference value by >20% but will result in appropriate treatment or no treatment. Zone C values ​​will result in overcorrected acceptable blood glucose levels; such treatment may cause the actual blood glucose to drop below 70 mg / dl or rise above 180 mg / dl. Zone D represents a "test failure and treatment risk" error. The actual blood glucose value is outside the target range, but the patient-generated blood glucose value is within the target range. Zone E is the "wrong treatment" zone. The patient-generated values ​​in this zone are opposite to the reference values, and therefore the corresponding treatment decisions are opposite to what is required. In summary, values ​​in zones A and B are clinically acceptable, whereas values ​​in zones C, D, and E are potentially dangerous and therefore clinically significant errors.

[0215] In particular, zone A shows that as blood glucose levels increase, the increased deviation between the value generated by the monitoring system (such as analyte sensor system 100) and the reference blood glucose level is acceptable, while still making clinically acceptable decisions. When considering other zones, particularly zones C, D, and E, this explanation is further confirmed. This explanation is particularly applicable to any reference blood glucose level higher than 200 mg / dl and further to a reference blood glucose level higher than 300 mg / dl. Any reference blood glucose level higher than these levels can be regarded as a blood glucose level of hyperglycemia. Therefore, the sensitivity of analyte sensor 102 may decrease with the increase of reference blood glucose level, but clinically acceptable decisions will still be made. The present invention can utilize this effect by sacrificing sensitivity sensor system 100 in an economic operation mode, specifically for a reference blood glucose level higher than 200 mg / dl and / or for a reference blood glucose level higher than 300 mg / dl.

[0216] An exemplary CGM curve for a patient is given in the document "Monitoring Technologies-Continuous Glucose Monitoring, Mobile Technology, Biomarkers of Glycemic Control" by Nihaal Reddy (BS), Neha Verma (MD) and Kathleen Dungan (MD, MPH) in Feingold KR, Anawalt B, Boyce A et al., updated on August 16, 2020 in Endotext [Internet]. The patient showed glucose levels that were typically less than 150 mg / dl. The patient further showed episodes of hyperglycemia with a duration of about 4 hours. During these hyperglycemic episodes, the patient reached blood glucose levels above 400 mg / dl. Therefore, setting the blood glucose threshold to a blood glucose level of 200 mg / dl can allow for a 50% reduction in silver chloride consumption during these hyperglycemic episodes. Considering hyperglycemic episodes lasting 4 hours per day, the consumption of silver chloride can be reduced by more than 8%. The lower the blood glucose threshold and the longer and / or higher the analyte excursion, the more silver chloride can be saved.

[0217] This can be confirmed by considering the following formula:

[0218] (C is -C t )*S*t rel .

[0219] Among them C is is the glucose concentration during the hyperglycemic period, C t is the threshold of glucose concentration, S is the sensor sensitivity, and trel is the relative duration of the hyperglycemic period.

[0220] Reference numerals list

[0221] 100 Analyte Sensor System

[0222] 102 Analyte Sensor

[0223] 104 Working electrode

[0224] 106 Additional Electrodes

[0225] 108 Processors

[0226] 110 Memory

[0227] 112 evaluation units

[0228] 114th floor

[0229] 116 substrate

[0230] 118 Insulation Materials

[0231] 120 Window

[0232] 122 electrode pads

[0233] 124 Contact pads

[0234] 126 Membrane

[0235] 128 Electronic Units

[0236] 130 Sensor signal

[0237] 132 Standard sensor signals

[0238] 134 Economic sensor signal

[0239] 200 Methods

[0240] 202 Monitoring Steps (Step i.)

[0241] 204 Comparison step (step ii.)

[0242] 206 Switching step (step iii.)

[0243] 208 Additional monitoring steps (step iv.)

[0244] 210 Additional comparison step (step v.)

[0245] 212 Additional switching steps (step vi.)

[0246] 300 Horizontal axis

[0247] 302 Vertical axis

[0248] 304 Curve

[0249] 306 Curve

[0250] 308 lines

[0251] 400 Horizontal axis

[0252] 402 Vertical Axis

[0253] 404 Diagonal

Claims

1. A method (200) for continuously detecting at least one analyte in a body fluid in vivo over a time span, the method (200) using at least one analyte sensor (102), the at least one analyte sensor comprising at least one working electrode (104) configured to perform at least one electrochemical detection reaction with the analyte, and at least one further electrode (106), the further electrode (106) comprising at least one redox material composition, the redox material composition comprising silver and silver chloride, the method (200) comprising the following steps: i. monitoring at least one standard sensor signal (132) obtained by using the analyte sensor (102) in a standard operating mode, wherein, in the standard operating mode, a potentiostatic measurement is performed to detect the at least one analyte with the analyte sensor (102), wherein the potential of the working electrode (104) relative to the further electrode (106) is set to at least one predetermined standard operating potential, and wherein a current through the working electrode (104) and the further electrode (106) is determined; and ii. comparing the standard sensor signal (132) to at least one threshold value, thereby determining whether it is necessary to change the operating mode of the analyte sensor (102) from the standard operating mode to the economy operating mode.

2. The method (200) according to the preceding claim, wherein the analyte is selected from the group consisting of: -glucose; - lactate; or -Glutamate.

3. The method (200) according to any one of the preceding claims, further comprising: iii. If in step ii., it is determined that the operating mode of the analyte sensor (102) needs to be changed from the standard operating mode to the economic operating mode, switching from the standard operating mode to the economic operating mode, wherein an economic sensor signal is generated in the economic operating mode.

4. The method (200) according to the preceding claim, wherein the economy operating mode is carried out for a predetermined economy time span or until at least one condition for switching back from the economy operating mode to the standard operating mode is met.

5. A method (200) according to any of the preceding claims, wherein in the economical operating mode, at least one economical sensor signal (134) is generated by performing a constant current measurement to detect at least one analyte using the analyte sensor (102), wherein the current through the working electrode (104) and the additional electrode (106) is set to at least one predetermined economical current value, and wherein the operating potential of the working electrode (104) relative to the additional electrode (106) is determined.

6. A method (200) according to the preceding claim, wherein the predetermined economical current value is selected to not exceed the electrical threshold current through the working electrode (104) and the additional electrode (106) that occurs when the standard sensor signal (132) is equal to the threshold.

7. The method (200) according to any one of the four preceding claims, further comprising: iv. when using the analyte sensor (102) in the economy mode of operation, monitoring the economy sensor signal (134); as well as v. comparing the economy sensor signal (134) to at least one economy threshold value, thereby determining whether it is necessary to change the operating mode of the analyte sensor (102) from the economy operating mode back to the standard operating mode, vi. If in step v., it is determined that the operating mode of the analyte sensor (102) needs to be changed from the economic operating mode back to the standard operating mode, switching from the economic operating mode back to the standard operating mode.

8. A method (200) according to any one of the preceding five claims, wherein the standard sensor signal (132) and the economic sensor signal (134) are each selected from a group consisting of: an electrical signal generated by the analyte sensor (102); an electrical signal generated to adjust the analyte sensor (102); a secondary signal obtained from an electrical signal generated by the analyte sensor (102) or generated to adjust the analyte sensor (102).

9. An analyte sensor system (100) for continuously detecting at least one analyte in a body fluid in vivo over a measurement time span, the analyte sensor system (100) comprising: a. at least one electrochemical analyte sensor (102) comprising at least one working electrode (104) configured to perform at least one electrochemical detection reaction with the analyte, and at least one further electrode (106), the further electrode (106) comprising at least one redox material composition comprising silver and silver chloride; b. A processor (108) and a memory (110) storing instructions which, when executed, cause the processor (108) to perform at least the following steps: i. monitoring at least one standard sensor signal (132) obtained by using the analyte sensor (102) in a standard operating mode, wherein, in the standard operating mode, a potentiostatic measurement is performed to detect the at least one analyte with the analyte sensor (102), wherein the potential of the working electrode (104) relative to the further electrode (106) is set to at least one predetermined standard operating potential, and wherein a current through the working electrode (104) and the further electrode (106) is determined; and ii. comparing the standard sensor signal (132) to at least one threshold value, thereby determining whether it is necessary to change the operating mode of the analyte sensor (102) from the standard operating mode to the economy operating mode.

10. The analyte sensor system (100) according to the preceding claim, wherein the further electrode (106) comprises at least one layer (114) comprising the redox material composition.

11. The analyte sensor system (100) according to any of the preceding claims relating to an analyte sensor system (100), wherein the further electrode (106) is at least partially coated by an insulating material (118).

12. The analyte sensor system (100) according to the preceding claim, wherein the insulating material (118) leaves open at least one window (120) through which the analyte can reach the further electrode (106).

13. An analyte sensor system (100) according to any of the preceding claims relating to an analyte sensor system (100), wherein the electrochemical analyte sensor (102) comprises at least one membrane (126) which is permeable to the analyte to be detected, the membrane (126) at least partially surrounding the working electrode (104) and the further electrode (106).

14. A computer program comprising instructions which, when executed by a processor (108) of an analyte sensor system (100) according to any one of the preceding claims relating to an analyte sensor system (100), cause the analyte sensor system (100) to perform a method (200) according to any one of the preceding claims relating to a method (200).

15. A computer-readable storage medium comprising instructions, which, when executed by a processor (108) of an analyte sensor system (100) according to any of the preceding claims relating to an analyte sensor system (100), cause the analyte sensor system (100) to perform a method (200) according to any of the preceding claims relating to a method (200).

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