Sensor assembly and monitoring method
Technical Field
The invention relates to a sensor assembly and a monitoring method. The sensor assembly and the monitoring method may be used for determining at least one of an analyte value in a body fluid of a subject or a risk of hypoglycemia of the subject. The sensor assembly may be applied in the field of continuous monitoring of the at least one analyte, specifically in the field of home care and in the field of professional care, such as in hospitals. However, other applications are feasible.
Background art
Determining at least one analyte value, such as a concentration of at least one metabolite, in a body fluid of a subject plays an important role in the prevention and treatment of various diseases. Such analytes can include by way of example, but not exclusively, glucose, lactate, cholesterol or other types of analytes and metabolites. Without restricting further possible applications, the following description is going to refer to glucose monitoring. However, additionally or alternatively, an application to other types of analytes id also feasible.
As described in the Review Article by Diouri O, Cigler M, Vettoretti M, Mader JK, Choudhary P, Renard E. Hypoglycaemia detection and prediction techniques: A systematic review on the latest developments. Diabetes Metab Res Rev. 2021; 37(7):e3449; doi:10.1002/dmrr.3449, in more detail, various clinical studies demonstrate a close relationship of cardiovascular morbidity and mortality from diabetes. It has been shown that hypoglycemia speeds heart rate and alters rate variability. Using a wearable medical patch, which measures heart rate and beat-to-beat variation, may support an early detection of hypoglycemia. Various sensors are available, which are configured to measure the heart rate or to record an electrocardiogram (ECG), wherein data obtained in this fashion can be used for hypoglycemia detection or prediction.
US 2009/0299155 Al is directed to a method for determining cardiac health using a sensor to continuously, continually, and/or intermittently detect a concentration of a cardiac marker in vivo. The sensor system can be partly inserted, e.g. in a subcutaneous, transdermal, or intervascular manner, into a circulatory system of the subject, or non-invasively positioned in an extracorporeal blood circulation device. The sensor may be an enzymatic sensor and may comprise a detection electrode and at least one reference electrode, as well as a third electrode configured for measuring at least one additional signal. For determining the at least one additional signal, the sensor is configured for continuously, continually, and/or intermittently measuring in vivo a second substance, such as glucose. A communication device is configured for receiving and processing the at least one additional signal from a secondary medical device, such as an ECG sensor.
WO 2022/104997 Al discloses an ECG sensor fusing BCG (cardiac cerebral glucose) signals by using a dual signal collection electrode patch, i.e. only on-skin electrodes, for collecting the electrical signals, wherein the patch comprises two BCG sensing electrodes and one ECG electrode in a flat layered structure.
US 2023/028745 Al discloses an optical physiological sensor comprising LEDs and a plurality of detectors integrated into a wearable device configured for measuring at least one physiological parameter of a subject, such as heart rate or glucose. The sensor may additionally comprise an ECG sensor having at least two electrodes positioned on a housing of the wearable device.
US 2023/078426 Al and US 8,718,742 B2 are directed to a sensor system having a plurality of on-skin electrodes configured for monitoring human generated voltages.
Problem to be solved
It is therefore desirable to provide a sensor assembly and a method for determining at least one analyte value in a body fluid of a subject, which at least partially address the above-mentioned technical challenges. Specifically, reducing a complexity of the sensor assembly in order to make the device simpler, cheaper and smaller is desirable.
Summary
This problem is addressed by a sensor assembly and a monitoring method having the features of the independent claims. Advantageous embodiments which might be implemented in an isolated fashion or in any arbitrary combination listed in the dependent claims as well as throughout the specification.
As used in the following, the terms “have”, “comprise” or “include” or any arbitrary grammatical variations thereof are used in a non-exclusive way. Thus, these terms may both refer to a situation in which, besides the feature introduced by these terms, no further features are present in the entity described in this context and to a situation in which one or more further features are present. As an example, the expressions “A has B”, “A comprises B” and “A includes B” may both refer to a situation in which, besides B, no other element is present in A (i.e. a situation in which A solely and exclusively consists of B) and to a situation in which, besides B, one or more further elements are present in entity A, such as element C, elements C and D or even further elements.
Further, it shall be noted that the terms “at least one”, “one or more” or similar expressions indicating that a feature or element may be present once or more than once typically will be used only once when introducing the respective feature or element. In the following, in most cases, when referring to the respective feature or element, the expressions “at least one” or “one or more” will not be repeated, non-withstanding the fact that the respective feature or element may be present once or more than once.
Further, as used in the following, the terms "preferably", "more preferably", "particularly", "more particularly", "specifically", "more specifically" or similar terms are used in conjunction with optional features, without restricting alternative possibilities. Thus, features introduced by these terms are optional features and are not intended to restrict the scope of the claims in any way. The invention may, as the skilled person will recognize, be performed by using alternative features. Similarly, features introduced by "in an embodiment of the invention" or similar expressions are intended to be optional features, without any restriction regarding alternative embodiments of the invention, without any restrictions regarding the scope of the invention and without any restriction regarding the possibility of combining the features introduced in such way with other optional or non-optional features of the invention.
The problem is solved by a sensor assembly and a monitoring method for hypoglycemic prediction, wherein an analyte sensor is combined with an electrocardiogram sensor, in particular, with at least one shared electrode.
In a first aspect, a sensor assembly comprising at least two sensors is disclosed.
The sensor assembly comprises at least one analyte sensor configured for detecting at least one analyte in a body fluid of a subject. The analyte sensor comprises at least two first electrodes. The at least two first electrodes may either be at least two electrodes selected from subcutaneous electrodes or minimally-invasive electrodes, or at least one on-skin electrode and at least one electrode selected from a subcutaneous electrode or a minimally-invasive electrode. The sensor assembly comprises at least one electrocardiogram sensor configured for detecting at least one cardiac parameter of the subject. The electrocardiogram sensor comprises at least two second electrodes. The at least two second electrodes may either be at least two on-skin electrode, or at least one on-skin and at least one electrode selected from a subcutaneous electrode or a minimally-invasive electrode.
The analyte sensor and the electrocardiogram sensor have at least one shared electrode. The shared electrode may be an on-skin electrode or an electrode selected from a subcutaneous electrode or a minimally-invasive electrode.
In addition, the sensor assembly may comprise at least one further type of sensor as disclosed below.
The term “sensor assembly” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a system comprising at least two individual sensors. The term “sensor” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an arbitrary element or device configured for detecting at least one condition or for measuring at least one measurement variable.
A sensor may comprise at least one electrode. The term “electrode” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an, generally arbitrary shaped, electrical conductor. The term specifically may refer, without limitation, to a conductor staying in contact with an ionic part of the circuit. The sensor assembly comprises at least one shared electrode. The term “shared” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to at least one electrode, which is used by two different sensors. Even though the sensors comprising the “sensor assembly” may share one or more electrodes, they can be considered as individual. The term “individual” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to at least two sensors, wherein any synergy between the sensors apart from using the at least one shared electrode is excluded.
The term “analyte sensor” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a sensor which is configured for qualitatively or quantitatively detecting at least one of a presence or a quantity or a concentration of the at least one analyte. The term “detecting” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a process of determining at least one value, particularly selected from a presence or a quantity or a concentration, of the at least one analyte. The detection may be or may comprise at least one of a qualitative detection or a quantitative detection, wherein the qualitative detection comprises determining the presence of the at least one analyte or the absence of the at least one analyte, and wherein the quantitative detection comprises determining at least one of the quantity or the concentration of the at least one analyte.
The term “analyte” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to at least one of a chemical substance or a biological substance, wherein the substance participates in a metabolism of the body of a subject. The analyte can be any electrochemically detectable species, including simple ions, such as potassium, but also much more complex structures, like creatinine. Exemplarily, the analyte may be a metabolite or a combination of at least two metabolites. By way of example, the analyte may be selected from the group consisting of: glucose, ascorbate, ketones, lactate, triglycerides, cholesterol. A preferred analyte is glucose, however, another analyte or a combination of at least two analytes may be detected
The term “subject” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically relates to a human being or an animal, independent from the fact that the human being or animal, respectively, may be in a healthy condition or may suffer from one or more diseases. The subject may be a patient. As an example, the subject may be a human being or an animal suffering from diabetes. The subject may be a user, e.g. a patient, intending to monitor an analyte value, such as a glucose value, in the user’s body tissue and/or to deliver medication, such as insulin, into the user’s body tissue. However, in an embodiment, the user of the sensor assembly may be different from the subject. Additionally or alternatively, the invention may be applied to other types of users or patients.
As further used herein, the term “bodily fluid”, generally, refers to a fluid, in particular a liquid, which is typically present in a body or a body tissue of the subject and/or may be produced by the body of the subject. The bodily fluid may be selected from the group consisting of blood and interstitial fluid. However, additionally or alternatively, at least one other type of bodily fluid may be used, wherein the other type of bodily fluid may, preferably, be selected from saliva, tear fluid, or urine.
The analyte sensor may be at least one of a subcutaneous analyte sensor or a minimally-invasive sensor. The term “subcutaneous” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an arrangement of the analyte sensor fully or at least partly below a skin tissue within a body tissue of a subject. The term “minimally-invasive” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an arrangement of the analyte sensor fully or at least partly within the skin tissue of a subject. The analyte sensor may be a fully or partially implantable analyte sensor. The analyte sensor may be an in-vivo sensor. The analyte sensor is adapted for performing the detection of the analyte in a bodily fluid of the subject in at least one of a subcutaneous tissue or a skin tissue of the subject.
The analyte sensor may comprise an insertable portion. The term “insertable portion” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a part or component of an element configured, in particular at least one detection electrode, to be insertable into an arbitrary body tissue. Other parts or components of the analyte sensor, in particular at least one of a counter electrode, a reference electrode or a combined counter/reference electrode, may remain outside of the body. The insertable portion may be fully or partially covered with at least one diffusion limiting membrane layer, such as at least one polymer membrane or a gel membrane, which, on one hand, limits diffusion of the analyte towards the detection electrode, on the other hand, may retain sensor substances, such as one or more test chemicals within the analyte sensor, thus preventing a migration thereof into the body tissue. The insertable portion may fully or partially comprise a biocompatible surface having as little detrimental effects on the user or the body tissue as possible. The insertable portion may be fully or partially covered with at least one biocompatibility membrane layer, such as at least one polymer membrane or a gel membrane, which, on one hand, may be permeable for the body fluid or at least for the analyte as comprised therein.
The analyte sensor may be inserted into at least one of the skin tissue or the body tissue of the subject by using at least one insertion device, also denoted as inserter. The sensor assembly may, additionally, comprise the insertion device. The sensor assembly may be configured for inserting the analyte sensor into the body tissue of the subject. The insertion may take place in a manner that the analyte sensor is fully or partially placed in or under the skin, respectively, after insertion. The insertion may take place in a manner that a part of the analyte sensor may protrude from the body tissue, through the skin, to be contacted on the outside of the body, such as electrically. A puncture site may be used for placing the respective electrode in at least one of the skin tissue or the body tissue of the subject. After insertion of the analyte sensor into at least one of the skin tissue or the body tissue, the sensor assembly may disassemble into a disposable handling component, e.g. including an inserter in a used state, and the analyte sensor having a body mount, wherein the body mount may be attached to the skin of the subject and wherein the analyte sensor may protrude into at least one of the skin tissue or the body tissue.
The analyte sensor is an electrochemical sensor. The term “electrochemical sensor” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an analyte sensor which is configured for a detection of an electrochemically detectable property of the analyte, such as an electrochemical detection reaction. By way of example, the electrochemical detection reaction may be detected by applying and comparing at least one electrode potential or current. Specifically, the analyte sensor is configured to generate the at least one analyte sensor signal which may, directly or indirectly, indicate at least one of a presence or an extent of the electrochemical detection reaction. The analyte sensor signal may be at least one of a qualitative or a quantitative signal. Still, other embodiments are feasible. As a result of the detection, the at least one analyte sensor signal may be generated, which characterizes an outcome of the detection. The at least one analyte sensor signal specifically may be or may comprise at least one electronic signal, especially as at least one of a voltage or a current. The at least one analyte sensor signal may be or may comprise at least one of an analogue signal or a digital signal.
The analyte sensor comprises at least two first electrodes. Embodiments are feasible, in which the analyte sensor may comprise three or more first electrodes. The terms “first”, “second” and “third” as used herein are broad terms and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The terms specifically are considered, without limitation, as a description without specifying an order and without excluding a possibility that other elements of that kind may be present. The at least one first electrode of the analyte sensor is a subcutaneous electrode or a minimally-invasive electrode. Using one or more on-skin electrodes comprising the analyte sensor may also be feasible. The term “on-skin” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an arrangement of an electrode attached to the body tissue from the outside of the body of a subject. In a preferred embodiment, the on-skin electrode may be an adhesive electrode to be attached to the body tissue by using at least one adhesive.
In particular, the analyte sensor may comprise at least one detection electrode, selected from a subcutaneous detection electrode or a minimally-invasive detection electrode, also denoted as “working electrode”, and at least one further electrode, wherein the further electrode may, preferably be selected from a counter electrode, a reference electrode, or a combined counter/reference electrode, which may be either subcutaneous as well or be an on-skin electrode. The term “detection electrode” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an electrode configured for performing at least one electrochemical detection reaction for detecting the at least one analyte. The detection electrode may have an analyte detection agent being sensitive to the analyte to be detected. The term “analyte detection agent” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an arbitrary material or a composition of materials adapted to change a detectable property in a presence of an analyte. This property may be an electrochemically detectable property. Specifically, the analyte detection agent may be a highly selective analyte detection agent, which only changes the property if the analyte is present in the body fluid, whereas no change occurs if the analyte is not present. A degree or a change of the property is dependent on the concentration of the analyte in the body fluid, in order to allow a quantitative detection of the analyte. By way of example, the analyte detection agent may comprise an enzyme, such as glucose oxidase and/ or glucose dehydrogenase. For potential analyte detection agents, reference may be made to WO 2007/ 071562 Al and the prior art documents disclosed therein. However, other embodiments are feasible. The term “counter electrode” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an electrode configured for performing at least one electrochemical counter reaction adapted for balancing a current flow required by the detection reaction at the detection electrode. The term “reference electrode” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an electrode adapted for providing a constant electrode potential as a reference potential, in particular at least within tolerances, such as by providing a redox system having a constant electrode potential. The counter electrode and the reference electrode may be two separate electrodes or a common electrode denoted herein by the term “combined counter/reference electrode”. For potential materials usable for the counter electrode and/or the reference electrode, reference may be made to WO 2007/071562 Al and the prior art documents disclosed therein. However, other embodiments are feasible. The detection electrode may be sensitive for the analyte of interest at a polarization voltage applied between the working and reference electrode and regulated by a potentiostat. A sensor signal may be provided as an electric current between the counter electrode and the detection electrode.
The analyte sensor may be configured for determining conductivity by using at least one of a DC measurement or an AC measurement, in particular at least one of a resistance measurement or an impedance measurement. Impedance may be a ratio of an AC voltage over the AC current caused by the AC voltage at different frequencies. The mentioned techniques for determining conductivity, the DC measurement and the AC measurement may, preferably, work independently. The at least two electrodes may be used for at least one of an amperometric measurement or a potentiometric measurement. The potentiometric measurement may comprise measuring a potential in a galvanostatic manner, wherein the current is maintained constant over a period of time, or in a galvanodynamic manner, wherein the current is intentionally altered over the period of time. The amperometric measurement may comprise measuring a current in a potentiostatic manner, wherein the potential is maintained constant over a period of time, or in a potentiodynamic manner, wherein the potential is intentionally altered over the period of time. An impedance measurement can be performed as potentiostatic method or as galvanostatic method. Alternatively or in addition, open circuit potentiometry (OCP) may be used, wherein no current flow may intentionally be induced by a measurement electronics. These types of measurements generally are known to the skilled person in the art of analyte detection, such as from WO 2007/071562 Al and the prior art documents disclosed therein. For potential setups of the electrodes, electrode materials or measurement setups, reference may be made thereto. Analyte sensors are generally known in the art and include continuous glucose sensor systems or for example continuous ketone measurement.
The term “electrocardiogram sensor” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a sensor which is configured for qualitatively or quantitatively detecting at least one cardiac parameter of the subj ect. In general, the electrocardiogram sensor is configured for detecting the at least one cardiac parameter by measuring an electrical activity of the heart of the subject. The term “detecting” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a process of determining the at least one of at least one cardiac parameter of the subject.
The term “cardiac parameter” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a quantitative value which is related to the heart of the subject. In a preferred embodiment, the cardiac parameter may be a heart rate of the subject; however, using a different quantitative value related to the heart of the subject may also be feasible. The term “heart rate” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an inverse of a period of time between consecutive heartbeats of the subject. The term may, alternatively or in addition, refer, without limitation, to at least one other parameter as detected by using the electrocardiogram sensor.
The electrocardiogram sensor comprises at least two second electrodes. Embodiments are feasible, in which the electrocardiogram sensor may comprise three or more second electrodes. As already indicated above, the terms “first”, “second” and “third” specifically are considered, without limitation, as a description without specifying an order and without excluding a possibility that other elements of that kind may be present. As already further indicated above, the term “electrode” may refer, without limitation, to an, generally arbitrary shaped, electrical conductor. A minimum distance between the second electrodes is used for generating a measurable voltage, particularly since the measurable voltage is proportional to the distance between the electrodes. Surprisingly, it has been found that when the voltage which is measured between a subcutaneous electrode and an on-skin electrode, a detectable level can be achieved at smaller distances compared to two on-skin electrodes. The at least two second electrodes of the electrocardiogram sensor may be, preferably, be on-skin electrodes, however using one or more on-skin electrodes, subcutaneous electrodes or minimally invasive electrodes may also be feasible. As already further indicated above, the term “on-skin” as used herein may refer, without limitation, to an arrangement of an electrode fully attached to the body tissue from the outside of the body of a subject. The electrocardiogram sensor is adapted for performing at least one measurement for detecting at least one cardiac parameter of the subject.
In particular, the at least two second electrodes of the electrocardiogram sensor may be configured for generating at least one electrocardiogram sensor signal. In a preferred embodiment, the at least one electrocardiogram sensor signal is generated by performing a at least one micro-voltage measurement. The term “micro-voltage measurement” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a kind of measurement in which a small amplitude voltage is measured by at least one particular electronic element having a high input impedance and being configured for amplifying a measurement signal, thereby rejecting noise, preferably in an efficient manner.
At least one of the first electrodes of the analyte sensor and at least one of the second electrodes of the electrocardiogram sensor constitute a shared electrode. The term “shared electrode” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a common electrode which is mutually used by at least two individual sensors for detecting at least one sensor signal. The shared electrode is configured for dual use, triple use, or multiple use, depending on the number of sensors comprised by the sensor assembly. The shared electrode may be or comprise an Ag/AgCl containing electrode, however, using a different electrode material may also be feasible. As already indicated above, the term “individual” as used herein may refer, without limitation, to at least two sensors, wherein any synergy between the sensors apart from using the at least one shared electrode is excluded. The term “constitute” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a resulting state of forming a particular kind of arrangement of elements in an assembly. The shared electrode may, preferably, be selected from a subcutaneous electrode, an on-skin electrode, or a minimally-invasive electrode. As already indicated above, the terms “subcutaneous”, “on-skin”, and “minimally-invasive”, as used herein may refer, without limitation, to an arrangement of the shared electrode fully or at least partly within at least one of the skin tissue or the body tissue of a subject, or fully attached to the body tissue from the outside of the body of a subject, respectively.
The shared electrode may be configured to be used simultaneously, i.e. can be simultaneously used by at least two individual sensors, wherein each of two or more individual sensors uses the shared electrode during a time interval for a particular purpose. In a preferred embodiment, the shared electrode may be used as at least one of the counter electrode, the reference electrode, or the combined counter/reference electrode by the analyte sensor for detecting the analyte sensor signal and, during the same time interval, as one of the second electrodes of the of the electrocardiogram sensor for detecting the electrocardiogram sensor signal. In this embodiment, the shared electrode may, preferably be an on-skin electrode. Alternatively or in addition, the shared electrode can be consecutively used by at least two individual sensors.
In a preferred embodiment, the shared electrode may be used as at least one of the detection electrode, the counter electrode, the reference electrode, or the combined counter/reference electrode by the analyte sensor for detecting the analyte sensor signal and, after the time interval during which the analyte sensor signal has been detected, as one of the second electrodes of the of the electrocardiogram sensor for detecting the electrocardiogram sensor signal. In this embodiment, the shared electrode may, preferably be a subcutaneous electrode. However, a combination of these embodiments as well as other embodiments may also be feasible.
The mutual use of a shared electrode for both the analyte sensor and the electrocardiogram sensor may reduce a complexity of the sensor assembly, especially due to the feature that the sensor assembly may use at least one electrode less compared to a prior art combination of an analyte sensor and an electrocardiogram sensor. By way of example, using an on-skin second electrode which is designed for the electrocardiogram sensor, concurrently, as a counter-reference electrode for the analyte sensor may result in simplifying the analyte sensor and, in addition, in improving its biocompatibility, especially due to the feature that one electrode less can be subcutaneously inserted into the skin of the subject. As a further example, using an on-skin first electrode which is designed for the analyte sensor, concurrently, as a further second electrode for the electrocardiogram sensor results in introducing an additional second electrode of the electrocardiogram sensor or, as an alternative, in reducing a number of leads for the second electrodes of the electrocardiogram sensor. In this manner, an overall size of the electrocardiogram sensor can be reduced without diminishing an amplitude of the electrocardiogram sensor signal. In a particularly preferred embodiment, the sensor assembly may further comprise at least one additional sensor. Preferably, the least one additional sensor may be selected from a temperature sensor configured for determining at least one temperature value of the subject; however, using a different type of sensor may also be feasible. The term “temperature sensor” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a sensor which comprises at least one electronic element configured for generating at least one temperature sensor signal. The temperature sensor signal may be selected from a voltage signal or a current signal, wherefrom a resistance value may be determined. The temperature sensor signal may be used for compensating at least one adverse temperature effect, especially by using a corresponding algorithm; however, further uses may also be conceivable.
The at least one additional sensor may comprise at least two third electrodes As already indicated above, the terms “first”, “second” and “third” specifically are considered, without limitation, as a description without specifying an order and without excluding a possibility that other elements of that kind may be present. The least two third electrodes may, preferably, be selected from a subcutaneous electrode, a minimally-invasive electrode, or an on-skin electrode. Preferably, the at least one temperature sensor signal as generated by the temperature sensor may be related to a temperature of the subject, particularly selected from a temperature at or inside the skin of the subject. The at least one temperature sensor signal may be generated by performing at least one of a voltage measurement across the at least two third electrodes or a current measurement through the at least two third electrodes. By way of example, the voltage across at least two third electrodes may be used for determining the at least one temperature value at or inside the skin of the subject.
In a preferred embodiment, the shared electrode may, in addition, be used as one of the third electrodes. The shared electrode may, simultaneously or consecutively, be used by the temperature sensor in addition to the analyte sensor and the electrocardiogram sensor as described elsewhere herein in more detail. By way of example, the shared electrode may be an on-skin electrode used as the counter electrode, the reference electrode, or the combined counter/reference electrode of the analyte sensor and, during the same time interval, used as one of the second electrodes of the of the electrocardiogram sensor, and, still during the same time interval, used as one of the third electrodes of the temperature sensor. As a further example, the shared electrode may be a subcutaneous electrode or a minimally-invasive electrode used as the detection electrode, the counter electrode, the reference electrode, or the combined counter/reference electrode of the analyte sensor and, thereafter, used as one of the second electrodes of the of the electrocardiogram sensor, and, thereafter, as one of the third electrodes of the temperature sensor. However, a combination of these embodiments as well as other embodiments may also be feasible.
In a preferred embodiment, the sensor assembly may comprise at least one electronics unit which is configured to be connected to the at least two sensors. Alternatively or in addition, a separate electronics unit that is not comprised by the sensor assembly may be configured to be connected to the at least two sensors. The at least two sensors as comprised by the sensor assembly may be operably connected to the electronics unit. The term “electronics unit” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an arbitrary unit, such as a unit which may be handled as a single piece, which is configured for performing at least one electronic function. For example, the electronics unit may have at least one interface for being connected to the at least two sensors. Each sensor may comprise one or more leads for electrically contacting the electrodes. The leads may at any point in time before use of the sensor assembly, such as during application or at a later point in time, be connected to one or more electronic components. For example, the leads may already be connected to the electronics unit before applying the sensor assembly to the subject. The electronics unit may provide at least one electronic function interacting with each sensor, such as at least one measurement function. By way of example, the electronics unit may be a single device comprising at least one analogue front-end, preferably two partly combined analogue front-ends, wherein the sensor signals may be digitized and processed by using an algorithm. The electronics unit may be configured for at least one of determining or controlling at least one sensor signal or transmitting the at least one sensor signal to another component. The electronics unit may comprise at least one microcontroller unit configured for controlling operation a sensor.
Specifically, the electronics unit may be configured for performing at least one measurement with the at least two sensors, particularly selected from at least one of a voltage measurement or a current measurement, recording at least one sensor signal, storing the at least one sensor signals, transmitting the at least one sensor signal to another component. The electronics unit specifically may comprise at least one of: a voltmeter, an ammeter, a potentiostat, a voltage source, a current source, a signal receiver, a signal transmitter, an analog-digital converter, an electronic filter, a data storage device, an energy storage. For example, the electronics unit may be embodied as a transmitter or may comprise at least one transmitter configured for transmitting data to a remote computer or to a remote device. The sensor assembly further may comprise at least one electronic remote device configured to communicate and/or control with the sensor assembly. The electronic remote device may be selected from a personal computer, a wearable, a smartphone, a proprietary remote control, a tablet, or a server.
For performing the at least one measurement with the at least two sensors, the electronics unit may be configured for measuring the corresponding sensor signals from the at least two sensors in at least one of a concurrent or a consecutive manner. The term “concurrent” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a manner of performing a process, wherein the sensor signals from the at least two sensors are simultaneously recorded during the same time interval. By way of example, the shared electrode can be used for providing a common electrical potential that may mutually be used by the at least two sensors. The term “consecutive” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an alternative manner of performing a process, wherein the sensor signals from the at least two sensors are subsequently recorded during successive time intervals. By way of example, the shared electrode can be used for providing different electrical potentials during the successive time intervals that may subsequently be used by the at least two sensors. In this manner, an interlacing between the sensor signals from the at least two sensors can be controlled. By way of example, at least one interference signal may be generated between the at least one analyte sensor signal and the at least one electrocardiogram sensor signal. As a further example, a DC voltage applied between a subcutaneous working electrode against, for instance, a combined counter/reference electrode may be adjusted during regulation of the polarization potential of the subcutaneous working electrode against the combined counter/reference electrode. When the combined counter/reference electrode is shared with one of the two ECG electrodes, this voltage transition may influence the ECG signal. The acquisition of the ECG signal may, preferably, be decoupled from the regulation of the polarization potential in terms of time.
The sensor assembly may comprise an electrical energy reservoir, such as at least one battery. The term “battery” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically relates to an arbitrary source of electric power comprising at least one electrochemical cell having at least one external connection for powering at least one electrical device. When a battery supplies power, its positive terminal may be referred to as cathode and its negative terminal may be referred to as anode. The battery may specifically be a primary battery. The primary battery may be configured for single-use or as a disposable battery. The sensor assembly may comprise at least one connector element configured for establishing an electrical contact between the electrical energy reservoir and electronic components of the sensor assembly.
The electronics unit may, preferably, be configured for determining at least one of an analyte value in the body fluid of the subject or a risk of hypoglycemia of the subject by combining the at least one analyte sensor signal and the at least one electrocardiogram sensor signal. In a particular embodiment, the at least one temperature sensor signal may further be used for this purpose. The term “combining” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a process of determining at least one value by considering at least two individual values that may be detected at the same point in time, during the same time interval or in consecutive time intervals. By way of example, using a concomitant observation of the at least one cardiac parameter, especially of the heart rate, of the subject on addition to the recording of the at least one analyte sensor signal may contribute to an early detection of hypoglycemia. For further details in this regard, reference can be made to the approaches as disclosed by Diouri O et al., see above.
The term “hypoglycemia” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to an observation of a value of blood sugar below a critical concentration, typically 70 mg/dL; however, using a different threshold may also be feasible. The term “risk” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a prediction of an expected observation, such as that of a value of blood sugar reaching the critical concentration that would result in hypoglycemia.
The sensor assembly specifically may be a unitary system which may be handled as one single piece before use. For example, elements of the sensor assembly, such as the at least two sensors, an insertion cannula, an electronics unit, a housing and connector elements, may form a preassembled single unit. The term “preassembled” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to the fact that an assembly process has already taken place. The components of the sensor assembly may be assembled, such as by being mechanically interconnected, thereby being mechanically ready for use, such as for being inserted into the body tissue of the subject for detection of the analyte. The pre-assembling may take place in a factory, thereby rendering the sensor assembly a factory- assembled functional module.
In a further aspect of the present invention, a monitoring method, which may, preferably, use the sensor assembly as described elsewhere herein, is disclosed. The monitoring method comprises continuously receiving at least two sensor signals from at least two associated individual sensors having a shared electrode, wherein the at least two sensor signals are correlated over time. With respect to definitions and embodiments of the monitoring method reference is made to the description of the sensor assembly as described elsewhere herein.
In particular, the monitoring method comprises the following steps: a) continuously receiving at least one analyte sensor signal from at least one analyte sensor, wherein the analyte sensor comprises at least two first electrodes configured for generating at least one analyte sensor signal; and b) continuously receiving at least one electrocardiogram sensor signal from at least one electrocardiogram sensor, wherein the electrocardiogram sensor comprises at least two second electrodes configured for generating at least one electrocardiogram sensor signal, wherein at least one of the first electrodes and at least one of second electrodes constitute a shared electrode, and wherein the at least one analyte sensor signal is correlated over time to the at least one electrocardiogram sensor signal.
The method steps may be performed in the given order. Further, one or more of the method steps may be performed in parallel and/or in a time overlapping fashion. Further, one or more of the method steps may be performed in a non-continuous manner or in an alternating manner. Further, one or more of the method steps may be performed repeatedly. Further, additional method steps may be present which are not mentioned herein.
The term “receiving” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a process of obtaining at least one measurement result, in particular at least one sensor signal from one of the at least two individual sensors. The term “continuously” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a repeated process of the same kind, particularly of consecutively receiving a plurality of sensor signals from the associated sensor. By consecutively receiving the plurality of sensor signals from each associated sensor, wherein the sensor signals from different sensors are correlated over time, preferably by using at least one time stamp, and by, subsequently, combining the temporally correlated sensor signals from the different sensors at least one of the following further steps can, preferably be performed: c) determining at least one analyte value in the body fluid of the subject; or d) determining a risk of hypoglycemia of the subject.
The term “correlated” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a fixed relationship between two individual items, wherein the relationship as used herein, particularly refers to a temporal relationship in a manner that sensor signals that originate from different sensors refer to a common temporal parameter. By way of example, the sensor signals may be generated by different sensors at the same point in time. As a further example, each sensor signal from a particular sensor may have a time stamp indicating a temporal value of its generation. In this manner, a time difference between the generation of the two sensor signals by two different sensors can be considered when combining the temporally correlated sensor signals from the different sensors. The term “time stamp” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a temporal value related to an item, whereby a pair of values can be provided. In particular, the time stamp can be a pair of values comprising, on one hand, a value of a particular sensor signal generated by a particular sensor and, on the other hand, a point in time which is associated with the particular sensor signal as generated by the particular sensor. However, using a different kind of correlation between a particular sensor signal and a particular sensor having generated the particular sensor signal may also be feasible.
In a particularly preferred embodiment, the monitoring method may comprise at least one further step. The at least one further step may, preferably, selected from
- continuously or intermittently receiving at least one additional value of the subject from at least one additional sensor;
- using the at least one additional value of the subject in any one of step c) or d).
In particular, the at least one additional sensor may be selected from at least one temperature sensor as described elsewhere herein in more detail. In this embodiment, the at least one further step may, preferably, selected from e) continuously or intermittently receiving at least one temperature value of the subject from at least one temperature sensor; f) using the at least one temperature value of the subject in any one of step c) or d).
As already indicated above, the term “continuously” as used herein may refer, without limitation, to a repeated process of the same kind, particularly of consecutively receiving a plurality of sensor signals from the associated sensor within successive time intervals. The term “intermittently” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a repeated process of the same kind, particularly of receiving a single sensor signal from the associated sensor, within successive time intervals. Intermittently receiving at least one temperature senor signal from the temperature sensor may, on one hand, save measuring time while, on the other hand, the temperature value of the subject as determined therefrom may remain constant over a considerably longer time interval compared to the analyte value in the body fluid of the subject.
The monitoring method may be computer-implemented. The term “computer implemented method” as used herein is a broad term and is to be given its ordinary and customary meaning to a person of ordinary skill in the art and is not to be limited to a special or customized meaning. The term specifically may refer, without limitation, to a method involving at least one computer and/or at least one computer network. The computer and/or computer network may comprise at least one processor which is configured for performing at least one of the method steps of the method according to the present invention. Specifically, each of the method steps may be performed by the computer and/or computer network. The method may be performed completely automatically, specifically without user interaction.
Further disclosed and proposed herein is a computer program including computer-executable instructions for performing the monitoring method as disclosed herein, when the instructions are executed on a computer or computer network. Specifically, the computer program may be stored on a computer-readable data carrier and/or on a computer-readable storage medium. As used herein, each of the terms “computer-readable data carrier” and “computer-readable storage medium” specifically may refer to a non-transitory data storage means, such as a hardware storage medium having stored thereon computer-executable instructions. The computer-readable data carrier or the storage medium specifically may be or may comprise a storage medium, such as at least one of a random-access memory (RAM) or a read-only memory (ROM). Thus, specifically, one, more than one or even all of method steps as disclosed herein may be performed by using a computer or a computer network, preferably by using a computer program.
Further disclosed and proposed herein is a computer program product having program code means, in order to perform the method as disclosed herein, when the program is executed on a computer or computer network. Specifically, the program code means may be stored on a computer-readable data carrier and/or on a computer-readable storage medium.
Further disclosed and proposed herein is a data carrier having a data structure stored thereon, which, after loading into a computer or computer network, such as into a working memory or main memory of the computer or computer network, may execute the method as disclosed herein.
Further disclosed and proposed herein is a non-transient computer-readable medium including instructions that, when executed by one or more processors, cause the one or more processors to perform the method as disclosed herein.
Further disclosed and proposed herein is a computer program product with program code means stored on a machine-readable carrier, in order to perform the method as disclosed herein, when the program is executed on a computer or computer network. As used herein, a computer program product refers to the program as a tradable product. The product may generally exist in an arbitrary format, such as in a paper format, or on a computer-readable data carrier and/or on a computer- readable storage medium. Specifically, the computer program product may be distributed over a data network.
Finally, disclosed and proposed herein is a modulated data signal which contains instructions readable by a computer system or computer network, for performing the method according to one or more of the embodiments disclosed herein.
Referring to the computer-implemented aspects of the invention, one or more of the method steps or even all of the method as disclosed herein may be performed by using a computer or computer network. Thus, generally, any of the method steps including provision and/or manipulation of data may be performed by using a computer or computer network. Generally, these method steps may include any of the method steps, typically except for method steps requiring manual work, such as providing the samples and/or certain aspects of performing the actual measurements. The sensor assembly and the monitoring method as disclosed herein may, preferably, be applied in the field of continuous monitoring of the at least one analyte, such as for continuous glucose monitoring (CGM), specifically in the field of home care and in the field of professional care, such as in hospitals. However, other applications are feasible.
Summarizing and without excluding further possible embodiments, the following embodiments may be envisaged:
Embodiment 1. A sensor assembly, comprising at least two sensors selected from:
- at least one analyte sensor configured for detecting at least one analyte in a body fluid of a subject, wherein the analyte sensor comprises at least two first electrodes; and
- at least one electrocardiogram sensor configured for detecting at least one cardiac parameter of the subject, wherein the electrocardiogram sensor comprises at least two second electrodes; wherein at least one of the first electrodes and at least one of second electrodes constitute a shared electrode.
Embodiment 2. The sensor assembly according to the preceding embodiment, wherein the shared electrode is configured to be used simultaneously by the at least one analyte sensor and the at least one electrocardiogram sensor.
Embodiment s. The sensor assembly according to the preceding embodiments, wherein the analyte sensor is at least one of a subcutaneous analyte sensor or a minimally-invasive sensor.
Embodiment 4. The sensor assembly according to any one of the preceding embodiments, wherein the shared electrode is selected from an on-skin electrode, a subcutaneous electrode, or a minimally-invasive electrode.
Embodiment s. The sensor assembly according to any one of the preceding embodiments, wherein one of the first electrodes of the analyte sensor is a detection electrode.
Embodiment 6. The sensor assembly according to the preceding embodiment, wherein the detection electrode is at least one of a subcutaneous electrode, or a minimally-invasive electrode. Embodiment 7. The sensor assembly according to any one the two preceding embodiments, wherein one other of the first electrodes of the analyte sensor is selected from a reference electrode, a counter electrode or a counter/reference electrode.
Embodiment 8. The sensor assembly according to the preceding embodiment, wherein at least one of the reference electrode, the counter electrode or the counter/reference electrode is an on- skin electrode.
Embodiment 9. The sensor assembly according to any one of the preceding embodiments, wherein the at least two first electrodes of the analyte sensor are configured for generating at least one analyte sensor signal.
Embodiment 10. The sensor assembly according to the preceding embodiment, wherein the at least one analyte sensor signal is generated by performing a potentiostatic measurement.
Embodiment 11. The sensor assembly according to any one of the preceding embodiments, wherein the at least two second electrodes of the electrocardiogram sensor are configured for generating at least one electrocardiogram sensor signal.
Embodiment 12. The sensor assembly according to the preceding embodiment, wherein at least one of the at least two second electrodes of the electrocardiogram sensor is an on-skin electrode.
Embodiment 13. The sensor assembly according to any one of the two preceding embodiments, wherein the at least one electrocardiogram sensor signal is generated by performing a microvoltage measurement.
Embodiment 14. The sensor assembly according to any one of the preceding embodiments, wherein the at least one cardiac parameter of the subject is a heart rate of the subject.
Embodiment 15. The sensor assembly according to any one of the preceding embodiments, further comprising at least one additional sensor, wherein the additional sensor comprises at least two third electrodes.
Embodiment 16. The sensor assembly according to the preceding embodiment, wherein the at least two third electrodes of the temperature sensor are configured for generating at least one additional sensor signal. Embodiment 17. The sensor assembly according to the preceding embodiment, wherein the shared electrode is used as one of the third electrodes.
Embodiment 18. The sensor assembly according to the three preceding embodiments, wherein the at least one additional sensor is:
- a temperature sensor configured for determining at least one temperature value of the subject.
Embodiment 19. The sensor assembly according to any one of the preceding embodiments, further comprising:
- at least one electronics unit configured to be connected to the at least two sensors.
Embodiment 20. The sensor assembly according to the preceding embodiment, wherein the electronics unit comprises at least one microcontroller unit configured for controlling an operation of the at least two sensors.
Embodiment 21. The sensor assembly according to any one of the two preceding embodiments, wherein the electronics unit is configured for determining at least one of
- an analyte value in the body fluid of the subject;
- a risk of hypoglycemia of the subj ect by combining the at least one analyte sensor signal and the at least one electrocardiogram sensor signal.
Embodiment 22. A monitoring method, comprising the following steps: a) continuously receiving at least one analyte sensor signal from at least one analyte sensor, wherein the analyte sensor comprises at least two first electrodes configured for generating at least one analyte sensor signal; and b) continuously receiving at least one electrocardiogram sensor signal from at least one electrocardiogram sensor, wherein the electrocardiogram sensor comprises at least two second electrodes configured for generating at least one electrocardiogram sensor signal, wherein at least one of the first electrodes and at least one of second electrodes constitute a shared electrode, and wherein the at least one analyte sensor signal is correlated over time to the at least one electrocardiogram sensor signal. Embodiment 23. The method according to the preceding embodiment, wherein the method is performed by using a sensor assembly according to any one of the preceding sensor assembly embodiments.
Embodiment 24. The method according to any one of the preceding method embodiments, wherein correlating over time comprises using at least one time stamp.
Embodiment 25. The method according to any one of the preceding method embodiments, wherein the at least one analyte sensor signal and the at least one electrocardiogram sensor signal have been recorded in at least one of a concurrent or a consecutive manner.
Embodiment 26. The method according to any one of the preceding method embodiments, further comprising at least one of the following further steps: c) determining at least one analyte value in the body fluid of the subject; d) determining a risk of hypoglycemia of the subj ect by combining the at least one analyte sensor signal and the at least one electrocardiogram sensor signal.
Embodiment 27. The method according to any one of the preceding method embodiments, further comprising at least one of the following further steps: e) continuously or intermittently receiving at least one temperature value of the subj ect from at least one temperature sensor; and f) using the at least one temperature value of the subject in any one of step c) or d).
Embodiment 28. A computer or computer network comprising at least one processor, wherein the processor is configured to perform the method according to any one of the preceding method embodiments.
Embodiment 29. A computer loadable data structure that is adapted to perform the method according to any one of the preceding method embodiments while the data structure is being executed on a computer.
Embodiment 30. A computer program, wherein the computer program is adapted to perform the method according to any one of the preceding method embodiments while the program is being executed on a computer. Embodiment 31. A computer program, comprising program means for performing the method according to any one of the preceding method embodiments, while the computer program is being executed on a computer or on a computer network.
Embodiment 32. A computer program, comprising program means for performing the method according to any one of the preceding method embodiments, wherein the program means are stored on a storage medium readable to a computer.
Embodiment 33. A storage medium, wherein a data structure is stored on the storage medium and wherein the data structure is adapted to perform the method according to any one of the preceding method embodiments, after having been loaded into at least one of a main storage or a working storage of a computer or of a computer network.
Embodiment 34. A computer program product having program code means, wherein the program code means can be stored or are stored on a storage medium, for performing the method according to any one of the preceding method embodiments, if the program code means are executed on a computer or on a computer network.
Short description of the Figures
Further optional features and embodiments are disclosed in more detail in the subsequent description of embodiments, preferably in conjunction with the dependent claims. Therein, the respective optional features may be implemented in an isolated fashion as well as in any arbitrary feasible combination, as the skilled person will realize. The scope of the invention is not restricted by the preferred embodiments. The embodiments are schematically depicted in the Figures. Therein, identical reference numbers in these Figures refer to identical or functionally comparable elements.
In the Figures:
Figure 1 schematically illustrates an exemplary embodiment of a sensor assembly; and
Figure 2 schematically illustrates an exemplary embodiment of a monitoring method.
Detailed description of the embodiments
Figure 1 schematically illustrates an exemplary embodiment of a sensor assembly 110, which may, preferably, be configured for performing a monitoring method 210 as shown in Figure 2 in more detail. The exemplary sensor assembly 110 as schematically depicted in Figure 1 comprises the following three sensors,
- a subcutaneous analyte sensor 112 configured for detecting at least one analyte in a body fluid of a subject;
- an electrocardiogram sensor 114 configured for detecting at least one cardiac parameter, in particular a heart rate, of the subject; and
- an optional temperature sensor 116 configured for determining at least one temperature value of the subject.
As an alternative, the analyte sensor may be a minimally-invasive analyte sensor. As a further alternative or in addition to the optional temperature sensor 116, the sensor assembly 110 may comprise one or more optional additional sensors (not depicted here).
As shown in Figure 1, the subcutaneous analyte sensor 112 comprises two first electrodes 118, 118’, wherein the first electrode 118 is a detection electrode 120, while the further first electrode 118’ is a counter/reference electrode 122. As an alternative or in addition to the counter/reference electrode 122, the subcutaneous analyte sensor 112 may comprise one or more optional additional electrodes selected from a reference electrode or a counter electrode (not depicted here). As further shown in Figure 1, the electrocardiogram sensor 114 comprises two second electrodes 124, 124’. As still further shown in Figure 1, the optional temperature sensor 116 comprises two optional third electrodes 126, 126’.
As schematically illustrated in Figure 1, the further first electrode 118’ embodied here as the counter/reference electrode 122, the second electrode 124’ and the optional third electrode 126’ constitute a shared electrode 128. As a consequence thereof, the exemplary sensor assembly 110 as depicted in Figure 1 uses only the three electrodes 118, 124, 128 for the subcutaneous analyte sensor 112 and the electrocardiogram sensor 114 and the four electrodes 118, 124, 126, 128 for the subcutaneous analyte sensor 112, the electrocardiogram sensor 114 and the optional temperature sensor 116.
The sensor assembly 110 can be attached to a skin 130 of the subject. In the exemplary sensor assembly 110 of Figure 1 each of the shared electrode 128, the second electrode 124 and the optional third electrode 126 is an on-skin electrode 132 being placed on a surface 134 of the skin 130 outside a body 136 of the subject, preferably by using an adhesive, while the first electrode 118 being embodied as the detection electrode 120 is a subcutaneous electrode 138 being placed under the surface 134 of the skin 130 outside the body 136 of the subject, preferably by using an inserter. In an alternative arrangement (not depicted here) of the sensor assembly 110 both first electrodes 118, 118’ of the subcutaneous analyte sensor 112 may be subcutaneous electrodes, whereas the two second electrodes 124, 124’ of the electrocardiogram sensor 114 may comprise an on-skin electrode and a subcutaneous electrode. In this example, the shared electrode 128 may be a subcutaneous electrode shared by both the subcutaneous analyte sensor 112 and the electrocardiogram sensor 114. However, various further alternative arrangements (not depicted here) are feasible, wherein the electrodes are embodied in a different manner as on the surface 134 of the skin 130 or subcutaneously. In this manner, the exemplary sensor assembly 110 as depicted in Figure 1 may exhibit an improved biocompatibility, especially due to the feature that one electrode less is subcutaneously inserted into the skin 130 of the subject compared to prior art sensor assemblies.
The two first electrodes 118, 118’ of the subcutaneous analyte sensor 112, wherein the further first electrode 118’ corresponds to the shared electrode 128, are configured for generating at least one analyte sensor signal. According to the exemplary arrangement of the sensor assembly 110 as depicted in Figure 1, the at least one analyte sensor signal may be generated by performing a potentiostat measurement using the two first electrodes 118, 118’, wherein the first electrode 118 is used here as the detection electrode 120, while the further first electrode 118 is used here as the counter/reference electrode 122.
In a similar manner, the two second electrodes 124, 124’ of the electrocardiogram sensor 114, wherein the further second electrode 124’ corresponds to the shared electrode 128, are configured for generating at least one electrocardiogram sensor signal. According to the exemplary arrangement of the sensor assembly 110 as depicted in Figure 1, the at least one electrocardiogram sensor signal may be generated by performing a micro-voltage measurement by using the two second electrodes 124, 124’.
Still in a similar manner, the two third electrodes 126, 126’ of the optional temperature sensor 116, wherein the further third electrode 126’ corresponds to the shared electrode 128, are configured for generating at least one temperature sensor signal. According to the exemplary arrangement of the sensor assembly 110 as depicted in Figure 1, the at least one temperature sensor signal may be generated by performing a voltage measurement and/or a current measurement by using the two third electrodes 126, 126’.
As further illustrated in Figure 1, leads 140, 140’, 140”, 140* are used for transmitting the various sensor signals, i.e. the at least one analyte sensor signal, the at least one electrocardiogram sensor signal and, optionally, the at least one temperature sensor signal to an electronics unit 142. The electronics unit 142 is configured to be connected to the various sensors, i.e. the subcutaneous analyte sensor 112, the electrocardiogram sensor 114 and the optional temperature sensor 116. The electronics unit 142 comprises at least one microcontroller unit (not depicted here) which is configured for controlling an operation of the various sensors. The electronics unit 142 may be comprised by the sensor assembly 110; alternatively or in addition, the electronics unit 142 may, as schematically depicted in Figure 1, be an external unit not comprised by the sensor assembly 110. The electronics unit 142 may provide at least one electronic function interacting with each sensor 112, 114 and, optionally 116, such as at least one measurement function.
The electronics unit 142 may be configured for determining and/or controlling at least one sensor signal and/or transmitting the at least one sensor signal. The electronics unit 142 may be configured for determining
- an analyte value in the body fluid of the subject; and/or a risk of hypoglycemia of the subj ect.
For this purpose, the electronics unit 142 may be configured for combining the at least one analyte sensor signal and the at least one electrocardiogram sensor signal and, optionally, the at least one temperature signal as described elsewhere herein in more detail.
Figure 2 schematically illustrates an exemplary embodiment of the monitoring method 210, which is, exemplarily, be performed here by using the sensor assembly 110 of Figure 1. As indicated above, the first electrode 118’, the second electrode 124’ and, optionally, the third electrode 126’ constitute the shared electrode 128. For further details concerning the monitoring method 210, reference can be made to the description of the exemplary embodiment of the sensor assembly 110 as depicted in Figure 1.
In a first receiving step 212 according to method step a), at least one analyte sensor signal is continuously received from the subcutaneous analyte sensor 112.
In a second receiving step 214 according to method step b), at least one electrocardiogram sensor signal is continuously received from the electrocardiogram sensor 114.
In an optional third receiving step 216 according to method step e), at least one temperature signal may, in addition, continuously or intermittently be received from the temperature sensor 116. As schematically indicated by the arrows 218, 218’, the at least one sensor signal from each associated sensor 112, 114 and optionally 116 are correlated over time, preferably by using a time stamp 220. The consecutively received sensor signals from each associated sensor 112, 114 and optionally 116, wherein the sensor signals from different sensors are correlated over time, preferably by using the time stamp 220, can, subsequently, be combined as follows during the further steps:
- In a first determining step 222 according to step c), at least one analyte value in the body fluid of the subject may be determined. - In a second determining step 224 according to step d), a risk of hypoglycemia of the subject may be determined.
Optionally, at least one temperature value of the subject as, additionally, determined from the at least one temperature signal received from the temperature sensor 116 can, further, be used according to step f) in the first determining step 222 and/or the second determining step 224.
List of reference numbers
110 sensor assembly
112 subcutaneous analyte sensor
114 electrocardiogram sensor
116 (optional) temperature sensor
118, 118’ first electrode
120 detection electrode
122 counter/reference electrode
124, 124’ second electrode
126, 126’ third electrode
128 shared electrode
130 skin
132 on-skin electrode
134 surface (of skin)
136 body (of subject)
138 subcutaneous electrode
140, 140’, 140”, 140* lead
142 electronics unit
210 monitoring method
212 first receiving step
214 second receiving step
216 (optional) third receiving step
218, 218’ Arrow
220 time stamp
222 first determining step
224 second determining step