CN118680554A - Method and system for obtaining background signal in monitoring signal based on temperature - Google Patents

Abstract

The present disclosure describes a method and system for obtaining a background signal in a monitoring signal based on temperature, the method comprising: obtaining a monitoring temperature corresponding to the monitoring signal, the monitoring signal being obtained by monitoring an analyte and comprising a target signal and a background signal related to the concentration of the analyte, the monitoring temperature being related to the temperature of the environment in which the analyte is located; and determining the background signal based on the monitoring temperature. According to the present disclosure, the background signal can be obtained conveniently and more accurately based on the relationship between the background signal and the monitoring temperature.

Description

Method and system for obtaining background signal in monitoring signal based on temperature

Technical Field

The present disclosure generally relates to the field of medical devices, and more particularly to a method and system for acquiring a background signal in a monitoring signal based on temperature.

Background Art

Diabetes is a disease of a series of metabolic disorders such as sugar, protein, fat, water and electrolytes. If it is not well controlled, it may cause some complications, such as ketoacidosis, lactic acidosis, chronic renal failure and retinopathy. For diabetic patients, if the concentration of glucose can be monitored in real time and continuously, the occurrence of complications such as glucose and hyperglycemia can be predicted first.

Studies have shown that when the glucose concentration in the blood begins to decrease, the glucose concentration in the tissue fluid decreases before the glucose concentration in the blood. Therefore, the decrease in the glucose concentration in the tissue fluid can predict the upcoming low glucose. Generally, the glucose sensor of the glucose monitoring system used to sense the glucose concentration generally includes an electrode portion implanted in the body. The electrode portion can be placed subcutaneously to monitor the current generated by the glucose reaction in the subcutaneous tissue fluid, and the glucose monitoring system can monitor the change in the glucose concentration in the tissue fluid based on the current.

However, due to the complex environment and composition of the tissue fluid of the human body, the current monitored by the implanted part includes not only the current generated by the glucose reaction, but also the background current. The background current includes the current generated by other electrochemical reactions in the tissue fluid. The prior art generally presets the background current to a fixed value so that it can better handle the monitoring current obtained by the glucose sensor. However, under the changes in the state and environment of the human body, the electrochemical properties in the body fluid environment will also change, which will cause the background current to change, resulting in the background current based on the fixed value being difficult to accurately reflect the actual background current in the monitoring current of the implanted part. Therefore, how to improve the accuracy of measuring the background current remains to be studied.

Summary of the invention

The present disclosure is proposed in view of the above-mentioned prior art conditions, and its purpose is to provide a method and system for obtaining background signals in monitoring signals based on temperature, which can conveniently and accurately obtain background signals in monitoring signals.

To this end, the first aspect of the present disclosure provides a method for obtaining a background signal in a monitoring signal based on temperature, comprising: obtaining a monitoring temperature corresponding to the monitoring signal, wherein the monitoring signal is obtained by monitoring an analyte and includes a background signal and a target signal related to the concentration of the analyte, and the monitoring temperature is related to the temperature of the environment in which the analyte is located; and determining the background signal based on the monitoring temperature.

In the first aspect of the present disclosure, a background signal in a monitoring signal can be obtained based on a monitoring temperature. In this case, it is possible to obtain a corresponding background signal as the monitoring temperature changes, thereby being able to obtain the background signal more accurately. In addition, the present disclosure can obtain the background signal based on the temperature, thereby being able to make the process of obtaining the background signal more convenient.

In addition, in the method involved in the first aspect of the present disclosure, optionally, the background signal is determined based on the monitored temperature, the reference data, and a preset relationship between the background signal change and the monitored temperature change, and the reference data includes a reference temperature and a reference background signal corresponding to the reference temperature. In this case, the background signal corresponding to the monitored temperature can be obtained according to the preset relationship, so that the process of obtaining the background signal can be relatively simple.

In addition, in the method involved in the first aspect of the present disclosure, optionally, the preset relationship is a linear relationship. In this case, a mathematical formula with low complexity can be used to reflect the corresponding relationship between the background signal and the monitored temperature, so that the relationship between the background signal and the monitored temperature can be more intuitive.

In addition, in the method involved in the first aspect of the present disclosure, optionally, the preset relationship is obtained through experiments. Thus, the preset relationship can be determined through experiments.

In addition, in the method involved in the first aspect of the present disclosure, optionally, the monitoring signal is obtained by an analyte sensor, wherein the analyte sensor obtains the monitoring signal by participating in a chemical reaction related to the analyte in the environment. Thus, the background signal in the monitoring signal obtained by the analyte sensor participating in the chemical reaction can be easily and accurately identified.

In addition, in the method involved in the first aspect of the present disclosure, optionally, the monitoring signal is a current signal, and the environment is a solution environment. Thus, the background signal in the monitoring signal can be easily and accurately identified when the analyte sensor monitors the analyte in the liquid environment.

In addition, in the method involved in the first aspect of the present disclosure, optionally, the analyte is glucose, and the environment is a subcutaneous body fluid environment of a human body. Thus, the background signal in the monitoring signal can be easily and accurately identified when monitoring glucose in human body fluid.

In addition, in the method involved in the first aspect of the present disclosure, optionally, the analyte sensor can be implanted subcutaneously, and the monitored temperature is the body surface temperature or the temperature at the location of the analyte sensor. In this case, the correlation between the monitored temperature and the subcutaneous temperature can be made stronger, and then when the background signal is determined based on the monitored temperature, the obtained background signal can be made closer to the non-target signal of the environment where the analyte is located. In addition, when the monitored temperature is the body surface temperature, it can be relatively easy to obtain the monitored temperature in a non-invasive manner, thereby further improving the convenience of obtaining the background signal.

In addition, in the method involved in the first aspect of the present disclosure, optionally, if there is a delay in the temperature change between the measurement position of the monitored temperature and the environment, the temperature data is filtered to correct the delay, and then the monitored temperature corresponding to the monitoring signal is obtained, and the temperature data includes the monitored temperature before the monitoring time of the monitoring signal. In this way, the monitored temperature corresponding to the monitoring signal can be obtained in a more accurate manner.

The second aspect of the present disclosure also provides a system for acquiring a background signal in a monitoring signal based on temperature, comprising: a monitoring signal acquisition module, a temperature measurement module and a background signal acquisition module; the monitoring signal acquisition module is used to acquire a monitoring signal, the monitoring signal is obtained by monitoring an analyte and includes a background signal and a target signal related to the concentration of the analyte; the temperature measurement module is used to acquire a monitoring temperature, the monitoring temperature is related to the temperature of the environment where the analyte is located; the background signal acquisition module determines the background signal based on the monitoring temperature corresponding to the monitoring signal.

In the second aspect of the present disclosure, a background signal in the monitoring signal can be obtained based on the monitoring temperature. In this case, it is possible to obtain the corresponding background signal as the monitoring temperature changes, so that the background signal can be obtained more accurately. In addition, the present disclosure can obtain the background signal based on the temperature, so that the process of obtaining the background signal can be more convenient.

The third aspect of the present disclosure also provides a method for obtaining a target signal in a monitoring signal, comprising: obtaining a monitoring signal; obtaining a background signal from the monitoring signal using the method for obtaining a background signal in a monitoring signal based on temperature as described in the first aspect of the present disclosure; and obtaining the target signal based on the monitoring signal and the background signal, wherein the target signal is used to obtain the concentration of the analyte. In this case, a more accurate background signal can be obtained by monitoring the temperature, and the monitoring signal can be processed with the background signal, which can improve the accuracy of obtaining the target signal, thereby obtaining a more accurate analyte concentration.

The fourth aspect of the present disclosure also provides an analyte monitoring system, comprising: an implantable part that can be placed subcutaneously and includes a probe, an application part that can be placed on the body surface and has a temperature sensor, and a processing module; the probe is used to obtain a monitoring signal, the temperature sensor is used to obtain a monitoring temperature, and the processing module is used to receive the monitoring signal and the monitoring temperature and use the method involved in the first aspect of the present disclosure to obtain a background signal to obtain the concentration of the analyte. In this case, a more accurate background signal can be obtained using the monitoring temperature, and the monitoring signal can be processed with the background signal, so that a more accurate analyte concentration can be obtained.

In addition, in the analyte monitoring system involved in the fourth aspect of the present disclosure, optionally, the analyte is glucose, and the probe is a glucose sensor, thereby enabling the continuous glucose monitoring system to conveniently and accurately obtain background signals, and thus obtain a more accurate glucose concentration.

According to the present disclosure, a method and system for obtaining a background signal in a monitoring signal based on temperature are provided, which can conveniently and accurately obtain a background signal in the monitoring signal.

BRIEF DESCRIPTION OF THE DRAWINGS

The present disclosure will now be explained in further detail by way of example only with reference to the accompanying drawings, in which:

FIG. 1 is a schematic flow chart showing a method for acquiring a background signal according to an example of the present disclosure.

FIG. 2 is a schematic block diagram showing an acquisition system involved in an example of the present disclosure.

FIG. 3 is a schematic diagram showing a wearing state of the analyte monitoring system according to an example of the present disclosure.

FIG. 4 is a schematic diagram showing the structure of an implantable portion of an analyte monitoring system according to an example of the present disclosure.

FIG. 5 is a schematic diagram showing the structure of a working electrode of an implantable portion of an analyte monitoring system according to an example of the present disclosure.

FIG. 6 is a schematic diagram showing the electrochemical reaction of the analyte enzyme sensing layer of the analyte monitoring system according to an example of the present disclosure.

FIG. 7 is a schematic flow chart showing the acquisition of glucose concentration by the analyte monitoring system according to an example of the present disclosure.

FIG. 8 is a flow chart showing the process of obtaining background current by a processing module according to an example of the present disclosure.

FIG. 9 is an example diagram showing the correlation between background current changes and monitored temperature changes in an environment of tissue fluid of a human body involved in examples of the present disclosure.

Description of reference numerals:

Analyte monitoring system···1, implant part···2, working electrode···21, base layer···110, nanoparticle layer···120, analyte enzyme sensing layer···130, semipermeable membrane···140, biocompatible membrane···150, reference electrode···22, counter electrode···23, substrate···S, contact···24, application part···3, shell···31, temperature sensor···32, processing module···33.

DETAILED DESCRIPTION

Hereinafter, with reference to the accompanying drawings, the preferred embodiments of the present disclosure will be described in detail. In the following description, the same symbols are assigned to the same components, and repeated descriptions are omitted. In addition, the accompanying drawings are only schematic diagrams, and the ratio of the dimensions of the components or the shapes of the components may be different from the actual ones.

It should be noted that the terms "including" and "having" and any variations thereof in the present disclosure, such as a process, method, system, product or device that includes or has a series of steps or units, are not necessarily limited to those steps or units clearly listed, but may include or have other steps or units that are not clearly listed or inherent to these processes, methods, products or devices.

The inventor has found through research that background signal fluctuations are correlated with temperature fluctuations. To this end, the present disclosure provides a method and system for obtaining background signals in monitoring signals based on temperature. The method for obtaining background signals in monitoring signals based on temperature involved in the examples of the present disclosure can also be referred to as an identification method or an analysis method.

The scheme involved in the present disclosure is applicable to application scenarios in which, in addition to the target signal corresponding to the analyte, there are background signals corresponding to other substances in the monitoring signal when monitoring the concentration of various analytes (also referred to as analyte concentration). It is particularly applicable to scenarios where the target signal is smaller than the background signal. For example, when monitoring blood ketones, the current generated by the blood ketone reaction will actually be smaller than the background current, which is beneficial to improve the accuracy of the blood ketone concentration obtained in the monitoring of blood ketones.

In addition, the background signal can be a signal that is unrelated to the target signal. In addition, the target signal can be a signal related to the concentration of the analyte. In some examples, the background signal can also be referred to as noise or noise signal.

In addition, the signal detected by the monitoring device (such as an analyte sensor or an analyte monitoring system) in the monitored environment can be a monitoring signal, and the monitoring signal can include a target signal and a background signal. In some examples, the target signal can be obtained by identifying the background signal in the monitoring signal.

In some examples, the monitoring signal may be a voltage signal (which may be referred to as a monitoring voltage), in which case the background signal corresponding to the monitoring signal is also a voltage signal (which may be referred to as a background voltage). In other examples, the monitoring signal is a current signal (which may be referred to as a monitoring current), in which case the background signal corresponding to the monitoring signal is also a current signal (which may be referred to as a background current).

In some examples, the monitoring signal may be a current signal, and the environment monitored by the monitoring device may be a solution environment, thereby being able to conveniently and accurately identify the background signal in the monitoring signal when the analyte sensor monitors the analyte in the liquid environment.

In some examples, the analyte may be glucose, and the environment in which the analyte is located is a subcutaneous body fluid environment of a human body. Thus, the background signal in the monitoring signal when monitoring glucose in human body fluid can be easily and accurately identified.

Taking glucose as the analyte, the environment of the analyte is the tissue fluid of the human body, and the monitoring signal and the background signal can be current signals. Since the environment and composition of the tissue fluid of the human body are relatively complex, the monitoring current includes not only the current generated by the glucose reaction, but also the background current generated by the reaction of other substances (for example, impurities) besides glucose.

FIG. 1 is a schematic flow chart showing a method for acquiring a background signal according to an example of the present disclosure.

As shown in FIG. 1 , the method for obtaining a background signal may include obtaining a monitoring signal (step S110 ), obtaining a monitoring temperature corresponding to the monitoring signal (step S120 ), and determining a background signal in the monitoring signal based on the monitoring temperature (step S130 ).

In some examples, in step S110, the monitoring signal may be obtained by the analyte sensor, and the analyte sensor may obtain the monitoring signal by participating in a chemical reaction related to the analyte. Thus, the background signal in the monitoring signal obtained by the analyte sensor participating in the chemical reaction can be easily and accurately identified.

In some examples, the monitoring signal can be continuously obtained by the analyte sensor. In this case, it is beneficial to continuously identify the background signal and calibrate the target signal according to the identified background signal to obtain the concentration of the analyte.

In some examples, in step S120, the monitoring temperature can be obtained by a temperature monitoring device. For example, the temperature monitoring device can include at least one of a temperature sensor and a thermometer. In this case, the temperature of the environment where the analyte is located can be monitored in a variety of ways, so the temperature can be obtained in a variety of ways, and the monitoring temperature can be obtained more flexibly.

In some examples, the monitored temperature corresponding to the monitoring signal may be related to the measurement location of the monitored temperature. In some examples, the monitored temperature corresponding to the monitoring signal (hereinafter referred to as the target temperature) may represent the temperature of the measurement location of the analyte (ie, the environment where the analyte is located).

In some examples, when the measurement position of the monitoring temperature coincides with the measurement position of the analyte, the target temperature may be the monitoring temperature acquired simultaneously with the monitoring signal. In some examples, when the measurement position of the monitoring temperature does not coincide with the measurement position of the analyte, the target temperature may be the monitoring temperature acquired before or after the monitoring time (i.e., the monitoring moment) of the monitoring signal. That is, there is a time difference (e.g., delay or advance) in the temperature change between the two measurement positions.

In some examples, the measurement location for monitoring temperature (ie, the location where the temperature monitoring device is located) may be the location where the analyte sensor is located. In other examples, the measurement location for monitoring temperature may be a location adjacent to the location where the analyte sensor is located.

In some examples, the analyte sensor may be implanted subcutaneously, and the monitored temperature may be the body surface temperature or the temperature at the location of the analyte sensor. In this case, the monitored temperature is highly correlated with the subcutaneous temperature, and the background signal is determined based on the monitored temperature, so that the obtained background signal is closer to the non-target signal of the environment where the analyte is located. In addition, when the monitored temperature is the body surface temperature, it is relatively easy to obtain the monitored temperature in a non-invasive manner, thereby further improving the convenience of obtaining the background signal.

In some examples, in step S120, if the temperature change between the measurement location of the monitored temperature and the environment where the analyte is located is synchronized, the monitored temperature monitored at the monitoring time of the monitoring signal can be used as the target temperature.

In some examples, in step S120, if there is a delay in the temperature change between the measurement location of the monitored temperature and the environment where the analyte is located (that is, when the current external environment temperature changes, the temperature of the measurement location of the monitored temperature changes first, and the temperature of the environment where the analyte is located changes later), the temperature data can be filtered to correct the delay, thereby obtaining the target temperature. In addition, in the case of a delay, the temperature data can include the monitored temperature before the monitoring time of the monitoring signal. Thus, the monitoring temperature corresponding to the monitoring signal can be obtained in a more accurate manner.

In some examples, the temperature data may include monitored temperatures that vary over time. For example, the temperature data may be obtained by continuous monitoring by a temperature monitoring device. In some examples, for temperature data that varies continuously over time, filtering may be performed by shifting the temperature data in time.

In some examples, for temperature data that does not change continuously over time (e.g., there are breakpoints or discontinuities), filtering may be smoothing the temperature data and translating the smoothed temperature data in time. In some examples, smoothing may be interpolating the breakpoints or discontinuities of the temperature data. In this case, the interference to the temperature data caused by instability or sudden changes in the monitored temperature can be reduced.

It should be noted that the translation direction of the above translation can be forward or backward, which is specifically related to the time difference between the temperature change of the measurement position of the monitored temperature and the environment where the analyte is located.

In some examples, in step S130, the background signal can be determined based on the target temperature, the reference data, and the preset relationship between the background signal change and the monitoring temperature change. In some examples, the reference data may include a reference temperature (also referred to as a reference temperature) and a reference background signal corresponding to the reference temperature. In this case, the background signal corresponding to the monitoring temperature can be obtained according to the preset relationship, so that the process of obtaining the background signal can be relatively simple.

In some examples, the reference data may refer to initial data for determining the background signal. In addition, the reference data may be known before determining the background signal. That is, the reference data may be pre-acquired. Similarly, the reference temperature and the reference background signal may be pre-acquired.

In some examples, the reference temperature may be preset, and the reference background signal may be obtained according to the preset reference temperature.

In some examples, the reference temperature may include multiple temperature values. For example, the reference temperature includes 34°C, 35°C, 36°C, 36.5°C, 37°C, 37.5°C, 38°C, 39°C, 40°C, and 41°C. In some examples, the reference temperature may be selected from one of the multiple temperature values. For example, the reference temperature may be 34°C, 35°C, 36°C, 36.5°C, 37°C, 37.5°C, 38°C, 39°C, 40°C, or 41°C.

In some examples, the reference temperature may have a range. For example, the reference temperature may range from 34°C to 41°C. In some examples, the reference temperature may select a point in the temperature range. For example, the reference temperature may be 34°C, 36°C, 36.5°C, 37°C, or 41°C.

In some examples, the reference background signal can be obtained by experiment according to a preset reference temperature. Specifically, the reference temperature can be preset, and the reference background signal at the set reference temperature can be obtained by experiment. In some examples, the reference background signal can be obtained according to a selected reference temperature and data that can reflect the corresponding relationship between the target temperature and the background signal.

In some examples, in step S130, the preset relationship may refer to a mapping relationship obtained through the correlation between the background signal change and the target temperature change.

In some examples, in step S130, the preset relationship may be a linear relationship. In this case, a mathematical formula with low complexity can be used to reflect the corresponding relationship between the background signal and the monitored temperature, so that the relationship between the background signal and the monitored temperature can be more intuitive.

In some examples, in step S130, the preset relationship can be obtained by experiment. Thus, the preset relationship can be determined by experiment. Specifically, background signals at different monitoring temperatures can be obtained by experiment, and the background signals at different monitoring temperatures can be fitted to obtain the preset relationship.

In some examples, the preset relationship between the background signal change and the monitored temperature change under different environments can be obtained based on different experiments, and the preset relationships corresponding to multiple experiments can be comprehensively judged to obtain the preset relationship for determining the background signal. In this way, the preset relationship can be made more accurate.

In some examples, in step S130, the reference background signal and the reference temperature (i.e., the reference data) can be combined with the above linear relationship to obtain a relationship for determining the background signal in the monitoring signal. Specifically, in some examples, the reference background signal and the reference temperature can be used as boundary conditions of the linear relationship to obtain a relationship for determining the background signal in the monitoring signal.

Specifically, in some examples, the linear relationship can be in the form of a numerical relationship between the change in the background signal and the change in the monitored temperature (that is, the slope of the straight line). At this time, the baseline data can be substituted into the numerical relationship as a boundary condition to obtain a mathematical formula for the relationship between the monitored temperature and the background signal (that is, the straight line is determined by the slope and a point on the straight line).

In summary, in the method for obtaining background signals involved in the present disclosure, the background signal in the monitoring signal can be obtained based on the monitoring temperature. In this case, it is possible to obtain the corresponding background signal as the monitoring temperature changes, so that the background signal can be obtained more accurately. In addition, the present disclosure can obtain the background signal based on the temperature, so that the process of obtaining the background signal can be more convenient.

In some examples, temperature can affect the relevant chemical reactions of the analyte, thereby affecting the accuracy of the analyte concentration. In some examples, the monitoring temperature can be used to determine the background signal while being used to process (e.g., calibrate) the analyte concentration to improve the accuracy of the analyte concentration. In this case, using the monitoring temperature to determine the background signal can reuse temperature data or reuse temperature measurement equipment (e.g., temperature sensors), so that a more accurate background signal can be obtained without introducing additional components for the background signal.

In addition, the method for obtaining background signals disclosed herein can save costs compared to obtaining background signals using additional components that do not react with analytes (such as blank electrodes). In addition, reducing the arrangement of additional components (such as implanting blank electrodes in the body) can improve user experience.

In addition, the present disclosure also provides a system for acquiring a background signal in a monitoring signal based on temperature (referred to as an acquisition system for short), and the acquisition system may include a monitoring signal acquisition module, a temperature measurement module, and a background signal acquisition module.

FIG. 2 is a schematic block diagram showing an acquisition system 400 involved in an example of the present disclosure.

As shown in FIG. 2 , the acquisition system 400 may include a monitoring signal acquisition module 410 , a temperature measurement module 420 , and a background signal acquisition module 430 .

In some examples, the monitoring signal acquisition module 410 may be used to acquire a monitoring signal, which may be obtained by monitoring the analyte and may include a background signal and a target signal related to the concentration of the analyte. For details, see the relevant description in step S110.

In some examples, the temperature measurement module 420 may be used to obtain a monitoring temperature, which is related to the temperature of the environment in which the analyte is located. For details, see the relevant description in step S120.

In some examples, the background signal acquisition module 430 may determine the background signal based on the monitoring temperature corresponding to the monitoring signal. For details, refer to the relevant description in step S130.

In addition, the present disclosure also provides a method for obtaining a target signal in a monitoring signal, and the target signal in the monitoring signal can be obtained using the above-mentioned identification method. Specifically, the method for obtaining a target signal can include obtaining a monitoring signal, obtaining a background signal from the monitoring signal using one or more steps in the identification method provided by the example of the present disclosure, and obtaining a target signal based on the monitoring signal and the background signal.

In some examples, the target signal can be used to obtain the concentration of the analyte. In this case, a more accurate background signal can be obtained by monitoring the temperature, and the monitoring signal is processed with the background signal, which can improve the accuracy of obtaining the target signal, thereby obtaining a more accurate analyte concentration.

In addition, in some examples, the method for obtaining background signals provided by the present disclosure can be used in an analyte monitoring system. For ease of understanding, the present disclosure first introduces an analyte monitoring system to which the method provided by the present disclosure can be applied.

In some examples, the analyte monitoring system may include an implantable analyte monitoring system and a continuous analyte monitoring system, etc. It should be noted that the above-listed systems are not intended to limit the applicable scenarios of the methods involved in the present disclosure.

In some examples, an analyte monitoring system may include an implant portion that is positionable subcutaneously and includes a probe, an application portion that is positionable on the body surface and includes a temperature sensor, and a processing module.

In some examples, the probe can be used to obtain a monitoring signal; the temperature sensor can obtain a monitoring temperature; the processing module can be used to receive the monitoring signal and the monitoring temperature and use the method for obtaining a background signal provided by the present disclosure to obtain a background signal and obtain the analyte concentration based on the background signal. In this case, a more accurate background signal can be obtained using the monitoring temperature, and the monitoring signal can be processed with the background signal, so that a more accurate analyte concentration can be obtained.

As described above, temperature can affect the relevant chemical reactions of the analyte, thereby affecting the accuracy of the analyte concentration. In some examples, the monitoring temperature obtained by the temperature sensor in the analyte monitoring system can be used to process the analyte concentration to improve accuracy. In this case, the background signal is determined by using the monitoring temperature, and the temperature sensor can be reused, thereby reducing the complexity of the structural design of the analyte monitoring system.

In addition, the present disclosure also provides another analyte monitoring system using the above method for obtaining background signals. The system includes: an implantable part that can be placed subcutaneously and includes a probe, an application part that can be placed on the body surface and has a temperature sensor, and an electronic device.

In some examples, the probe can be used to obtain the monitoring signal. In some examples, the temperature sensor can be used to obtain the monitoring temperature. In some examples, the electronic device can be used to receive the monitoring signal and the monitoring temperature. The above method for obtaining the background signal obtains the background signal to obtain the concentration of the analyte. In this case, the monitoring temperature can be used to obtain a more accurate background signal, and the monitoring signal is processed with the background signal, so that the analyte concentration can be measured more accurately.

In addition, in some examples, the analyte of the analyte monitoring system may be glucose, and the probe may be a glucose sensor, so that the continuous glucose monitoring system can conveniently and accurately obtain background signals, and thus obtain a more accurate glucose concentration.

FIG. 3 is a schematic diagram showing a wearing state of the analyte monitoring system 1 according to an example of the present disclosure.

In some examples, referring to FIG. 3 , the analyte monitoring system 1 may include an implant portion 2 that can be placed subcutaneously and an application portion 3 that can be placed on the body surface.

In some examples, implant portion 2 may include a probe, and implant portion 2 may be implanted subcutaneously.

In some examples, when the implant portion 2 is implanted subcutaneously, the implant portion 2 can obtain a monitoring signal related to the concentration of the analyte. In some examples, the implant portion 2 can obtain a monitoring signal by participating in a relevant chemical reaction of the subcutaneous analyte. In some examples, the relevant chemical reaction can be an electrochemical reaction. In some examples, the monitoring signal obtained by the implant portion 2 can be a current signal. At this time, the background signal in the monitoring signal can also be called background current or noise current.

In some examples, the application portion 3 may have a temperature sensor 32 (see FIG. 3 ). In some examples, when the application portion 3 is placed on the body surface, the temperature sensor 32 may monitor the temperature of the body surface and output the body surface temperature.

In some examples, the processing module 33 can receive the monitoring signal output by the implanted part 2 and the monitoring temperature output by the temperature sensor 32, and obtain the background signal in the monitoring signal according to the monitoring temperature, and then obtain the analyte concentration according to the background signal and the monitoring signal. In some examples, the implanted part 2 can continuously output the monitoring signal, the temperature sensor 32 can continuously output the monitoring temperature, and then the processing module 33 can continuously obtain the background signal in the monitoring signal based on the monitoring temperature.

FIG. 4 is a schematic diagram showing the structure of the implanted portion 2 of the analyte monitoring system 1 according to the example of the present disclosure.

In some examples, as described above, the analyte monitoring system 1 can include an implant portion 2 (see FIG. 3 ). In some examples, the implant portion 2 of the analyte monitoring system 1 can be placed subcutaneously and in contact with the subcutaneous tissue fluid (see FIG. 3 ). The implant portion 2 can obtain a monitoring signal related to the concentration of the analyte and output the monitoring signal.

In some examples, the implant portion 2 may be flexible. The implant portion 2 may be disposed in a puncture needle (not shown), and the implant portion 2 may be detachable from the puncture needle. When the analyte monitoring system 1 is worn, the puncture needle wrapped with the implant portion 2 may be inserted into the tissue, and then the puncture needle may be pulled out and separated from the implant portion 2, so that the implant portion 2 is placed subcutaneously.

In some examples, the implant portion 2 can be disposed in the arm (see FIG. 3 ), abdomen, waist, leg, or the like.

In some examples, the implant portion 2 can be inserted 3mm to 20mm under the skin. In some examples, the depth of the implant portion 2 inserted under the skin is determined according to the insertion position. When the fat layer is thicker, the implant portion 2 is inserted deeper, such as in the abdomen of the human body, and the insertion depth can be about 10mm to 15mm. When the fat layer is thinner, the implant portion 2 is inserted shallower, such as in the arm, and the insertion depth can be about 5mm to 10mm.

In some examples, implant portion 2 can include substrate S (see FIG. 4 ).

In some examples, the substrate S may be flexible. The substrate S may be substantially made of at least one of polyethylene (PE), polypropylene (PP), polyimide (PI), polystyrene (PS), polyethylene terephthalate (PET), and polyethylene naphthalate (PEN). In addition, in other examples, the substrate S may also be substantially made of metal foil, ultra-thin glass, a single-layer inorganic film, a multi-layer organic film, or a multi-layer inorganic film. In some examples, the substrate S may also be non-flexible.

In some examples, implant portion 2 may include working electrode 21 and counter electrode 23 (see FIG. 4 ). In some examples, working electrode 21 may form a loop with counter electrode 23. Thus, implant portion 2 is capable of sensing analyte concentration.

In some examples, the implant part 2 may further include a reference electrode 22. In some examples, the implant part 2 may further include a contact 24 (see FIG. 4 ) connected to the working electrode 21 via a lead. Thus, the implant part 2 may transmit a response signal to the outside via the contact 24.

In some examples, the working electrode 21, the reference electrode 22, and the counter electrode 23 may be disposed on a substrate S (see FIG. 4).

In some examples, using the method of obtaining background signals involved in the examples of the present disclosure, the implanted part 2 may not have a blank electrode (i.e., an electrode used to obtain background signals but not participating in the relevant chemical reaction of the analyte). In this case, the cost of the analyte monitoring system can be saved. In addition, not using a blank electrode can reduce the discomfort during implantation.

FIG5 is a schematic diagram showing the structure of the working electrode 21 of the implanted portion 2 of the analyte monitoring system 1 according to the example of the present disclosure.

In some examples, as described above, the implant portion 2 may include a working electrode 21 (see FIG. 4 ). In some examples, the working electrode 21 may include a substrate layer 110, a nanoparticle layer 120, an analyte enzyme sensing layer 130, a semipermeable membrane 140, and a biocompatible membrane 150. The substrate layer 110, the nanoparticle layer 120, the analyte enzyme sensing layer 130, the semipermeable membrane 140, and the biocompatible membrane 150 may be stacked in sequence (see FIG. 5 ).

In some examples, the substrate layer 110 may be provided with an analyte enzyme sensing layer 130 .

In some examples, the concentration of multiple analytes can be obtained by changing the analyte enzyme sensing layer 130 on the implant portion 2. For example, the analyte can be one or more of blood ketones, acetylcholine, amylase, bilirubin, cholesterol, chorionic gonadotropin, creatine kinase, creatine, creatinine, DNA, fructosamine, glucose, glutamine, growth hormone, hormone, lactate, peroxide, prostate specific antigen, prothrombin, RNA, thyroid stimulating hormone and troponin.

In some examples, when the analyte is glucose, the analyte enzyme sensing layer 130 may contain glucose oxidase or glucose dehydrogenase. In this case, the analyte monitoring system 1 is a continuous glucose monitoring system. The method for obtaining a background signal in a monitoring signal based on temperature according to the present disclosure can be applied to the system to achieve more accurate monitoring of the glucose concentration in the tissue fluid.

In some examples, a nanoparticle layer 120 may be disposed on the substrate layer 110. That is, a nanoparticle layer 120 may be disposed between the substrate layer 110 and the analyte enzyme sensing layer 130. In this case, the nanoparticles can further catalyze the analyte reaction, reduce the operating voltage required for the analyte reaction, and increase the reaction rate.

FIG. 6 is a schematic diagram showing the electrochemical reaction of the analyte enzyme sensing layer 130 of the analyte monitoring system 1 according to an example of the present disclosure.

6 , specifically, taking glucose oxidase (GO _x (FAD)) as an example, in the analyte enzyme sensing layer 130 , when GO _x (FAD) encounters glucose in the tissue, the following reaction occurs:

Glucose + GO _x (FAD) → Gluconolactone + GO _x (FADH ₂ ) ... Reaction formula (I)

GO _x (FADH ₂ )+O ₂ →GO _x (FAD)+H ₂ O ₂ ……Reaction formula (II)

In the above reaction process, H ₂ O ₂ will be generated in reaction formula (II), and the accumulation of H ₂ O ₂ will reduce the enzyme activity in the analyte enzyme sensing layer 130 .

The nanoparticle layer 120 can act as a catalyst to cause H ₂ O ₂ to undergo a decomposition reaction. The specific reaction is as follows:

H ₂ O ₂ →2H ⁺ +O ₂ +2e ^- ……Reaction formula (III)

Through the above reaction formula (I) to reaction formula (III), the reaction between the implant part 2 and glucose can be continuously carried out. In addition, by catalyzing the decomposition of hydrogen peroxide by the nanoparticle layer 120, the voltage required to be applied during the reaction can be reduced, which is conducive to improving the sensitivity of the implant part 2, extending the service life of the analyte monitoring system 1, and obtaining a low operating voltage. In other words, through the nanoparticle layer 120, a high-sensitivity sensing signal of tissue glucose can be continuously obtained, the service life of the analyte monitoring system 1 can be extended, and the low operating voltage is conducive to improving the anti-interference performance.

In some examples, the semipermeable membrane 140 may be disposed on the analyte enzyme sensing layer 130. In some examples, the semipermeable membrane 140 may further include a diffusion control layer and an anti-interference layer stacked on the diffusion control layer.

In some examples, the biocompatible membrane 150 can be disposed on the semipermeable membrane 140. In some examples, the biocompatible membrane 150 can be made of plant materials. In other examples, the biocompatible membrane 150 can also be made of artificial synthetic materials. Thus, the immune response of the human body to the implant part 2 can be reduced, and the service life of the implant part 2 can be extended.

In some examples, as described above, the implant portion 2 may include a counter electrode 23 (see FIG. 4 ). In some examples, the counter electrode 23 may be made of platinum, silver, silver chloride, palladium, titanium, or iridium. Thus, the electrochemical reaction at the working electrode 21 may not be affected while having good electrical conductivity. However, the present embodiment is not limited thereto, and in other examples, the counter electrode 23 may also be made of at least one selected from gold, glassy carbon, graphite, silver, silver chloride, palladium, titanium, or iridium. Thus, the influence on the working electrode 21 may be reduced while having good electrical conductivity.

In some examples, the implanted portion 2 involved in this embodiment can realize continuous monitoring, thereby achieving the purpose of continuously monitoring the concentration value of human analytes for a long time (for example, 1 day to 24 days).

In some examples, as described above, analyte monitoring system 1 also includes an application portion 3 (see FIGS. 3 and 4 ).

In some examples, the application portion 3 may have a housing 31 (see FIG. 3 ). In some examples, the application portion 3 may have a temperature sensor 32 located within the housing 31 (see FIG. 3 ).

In some examples, the temperature sensor 32 may be disposed on an inner wall surface of the housing 31 close to the body surface (see FIG. 3 ). In other examples, the temperature sensor 32 may be disposed on any wall surface of the housing 31 .

In some examples, the number of temperature sensors 32 of the application part 3 may be one. In other examples, the number of temperature sensors 32 of the application part 3 may be multiple, thereby improving the accuracy of body surface temperature sensing, thereby improving the accuracy of subcutaneous temperature obtained based on body surface temperature.

In some examples, the application part 3 can be connected to the implant part 2. In some examples, the part of the implant part 2 located on the body surface can be connected to the application part 3 through the contact 24 (see FIG. 4). Thus, the current signal generated by the implant part 2 can be transmitted to the application part 3 through the base layer 110 and the transmission wire via the contact 24.

In some examples, the application part 3 can be made of a flexible PCB and a flexible battery, so that it can be closely attached to the skin and reduce the impact on the user's daily life.

In some examples, as described above, the analyte monitoring system 1 also includes a processing module 33 .

In some examples, the processing module 33 can be installed in the application part 3. Thus, the current signal generated by the implant part 2 can be transmitted to the processing module 33 through the contact 24 for analysis, and the body surface temperature output by the temperature sensor 32 can be transmitted to the processing module 33 for analysis.

In some examples, the processing module 33 may not be installed in the application part 3. For example, the processing module 33 may be installed outside the application part 3 to receive signals from the implant part 2 and the temperature sensor 32. In other examples, the processing module 33 may also be any system that can receive signals from the implant part 2 and the temperature sensor 32 and process the signals, for example, the processing module 33 may be a physiological parameter monitor, a smart phone, or a desktop computer.

In some examples, if the processing module 33 is not installed in the application part 3, the processing module 33 can be connected to the implant part 2 and the temperature sensor 32 in a wired or wireless manner and obtain signals from the implant part 2 and the temperature sensor 32.

FIG. 7 is a schematic flow chart showing the process of obtaining glucose concentration by the analyte monitoring system 1 according to an example of the present disclosure.

The process of obtaining glucose concentration is described by taking the analyte as glucose, the analyte monitoring system 1 as a continuous glucose monitoring system, and the implanted part of the continuous glucose monitoring system being located in the tissue fluid as an example. It should be noted that the above examples do not limit the present disclosure and are also applicable to other analytes unless there is a contradiction.

Specifically, as shown in FIG. 7 , the steps for the continuous glucose monitoring system to obtain the glucose concentration of tissue fluid include: the implanted part obtains the monitoring current (step S210), the temperature sensor obtains the body surface temperature (step S220), the processing module obtains the background current in the monitoring current based on the body surface temperature (step S230), the processing module obtains the target current based on the monitoring current and the background current (step S240), and the processing module obtains the glucose concentration based on the target current (step S250).

In step S210, the implanted part 2 may acquire a monitoring current. As described above, in some examples, the implanted part 2 may participate in the electrochemical reaction of glucose in the tissue fluid to acquire a current, that is, a target current (also referred to as a glucose current). In some examples, the monitoring current acquired by the implanted part 2 also includes a background current, which is independent of the target current, so the background current may be processed when the target current is subsequently acquired to improve the measurement accuracy of the glucose concentration.

In some examples, the implanted portion 2 may be placed 3 mm to 20 mm below the skin. It is understandable that the distance between 3 mm below the skin and 20 mm below the skin is small, and the temperature is roughly the same, which will not cause the response signal output by the implanted portion 2 to have a statistical difference.

In step S220, the temperature sensor 32 may acquire the body surface temperature. In some examples, the location of the body surface temperature acquired by the temperature sensor 32 is relatively close to the location of the implanted part 2. In this case, the temperature difference between the body surface temperature acquired by the temperature sensor 32 and the temperature at the location of the implanted part 2 is small, so the correlation between the temperatures at the two locations is large.

In some examples, the body surface temperature and the temperature of the subcutaneous tissue fluid are affected by both the ambient temperature and the internal temperature. The body surface temperature is affected by the ambient temperature faster than the temperature of the subcutaneous tissue fluid is affected by the ambient temperature, and the body surface temperature is affected by the internal temperature slower than the temperature of the subcutaneous tissue fluid is affected by the internal temperature. There is a delay between the change in body surface temperature and the change in subcutaneous tissue fluid temperature. Therefore, in subsequent steps, the processing module 33 can store and process the body surface temperature obtained by the temperature sensor 32 to obtain temperature information that is more consistent with the location of the implanted part 2.

In step S230 , the processing module 33 may obtain the background current in the monitoring current based on the body surface temperature.

FIG. 8 is a flow chart showing the process of obtaining background current by the processing module 33 according to the example of the present disclosure.

As shown in Figure 8, the step of the processing module 33 obtaining the background current may include: the processing module obtains the temperature data of the temperature sensor (step S231), the processing module filters the temperature data to obtain the body surface temperature corresponding to the monitoring current (step S232), and the processing module obtains the background current based on the temperature data, the reference data, and the preset relationship between the background current change and the body surface temperature change (step S233).

In step S231, the processing module 33 may obtain temperature data of the temperature sensor 32. In some examples, if the processing module 33 is installed in the application portion 3, the temperature sensor 32 may transmit data to the processing module 33 through a circuit connection. In other examples, if the processing module 33 is not installed in the application portion 3, the temperature sensor 32 may transmit data to the processing module 33 through a wired or wireless manner.

In some examples, as described above, there may be a delay between the temperature data of the temperature sensor 32 and the temperature of the environment in which the implanted portion 2 is located, and the temperature data needs to be processed to reduce the impact of the delay.

In step S232, the processing module 33 may filter the temperature data to obtain the body surface temperature corresponding to the monitoring current. For details, see the description of filtering in step S130.

In step S233, the processing module 33 can obtain the background current based on the temperature data, the reference data, and the preset relationship between the background current change and the body surface temperature change. In addition, the reference data can include a reference background current and a reference temperature. For details, see the relevant description of determining the background signal in step S130.

FIG. 9 is an example diagram showing the correlation between background current changes and monitored temperature changes in an environment of tissue fluid of a human body involved in examples of the present disclosure.

As shown in FIG9 , in some examples, the background current data may be the relationship between the background current and time monitored in an environment simulating the tissue fluid of the human body (for example, a blank electrode may be used to monitor the relationship between the background current and time), and the unit of the current is nanoampere (nA). The temperature data may be the relationship between the simulated body surface temperature and time. As can be seen from the figure, the trend of the background current changing over time and the trend of the monitored temperature changing over time have similar fluctuations, and the preset relationship (for example, a linear relationship) between the background current change and the monitored temperature change can be obtained by fitting the fluctuations.

As described above, the processing module 33 can store the preset relationship for use in step S233 to obtain the background current in the monitoring current. In some examples, referring to the above description of step S130 in FIG. 1 , in step S233, the processing module 33 can combine the reference data with the preset relationship to obtain a relationship formula for determining the background current in the monitoring current.

Referring back to Fig. 7, in step S240, the processing module 33 may obtain the target current based on the monitoring current and the background current. In some examples, the processing module 33 may obtain the target current by subtracting the background current from the monitoring current.

7 , in step S250 , the processing module 33 may obtain the glucose concentration based on the target current. In some examples, the processing module 33 may calculate the glucose concentration based on the conversion relationship between the target current and the glucose concentration.

In some examples, the glucose concentration signal obtained by the processing module 33 can be sent out via wireless communication such as Bluetooth, Wi-Fi, etc. An external reading device, such as a mobile phone or a computer (not shown), can receive the glucose concentration signal sent by the processing module 33 and display the glucose concentration.

Although the present disclosure is specifically described above in conjunction with the accompanying drawings and examples, it is to be understood that the above description does not limit the present disclosure in any form. Those skilled in the art may modify and change the present disclosure as needed without departing from the essential spirit and scope of the present disclosure, and these modifications and changes all fall within the scope of the present disclosure.

Claims (13)

1. A method of acquiring a background signal in a monitoring signal based on temperature, the method comprising:

Acquiring a monitoring temperature corresponding to a monitoring signal, wherein the monitoring signal is obtained by monitoring an analyte and comprises a background signal and a target signal related to the concentration of the analyte, and the monitoring temperature is related to the temperature of the environment in which the analyte is located; and determining the background signal based on the monitored temperature.

2. The method of claim 1, wherein the step of determining the position of the substrate comprises,

The background signal is determined based on the monitored temperature, reference data including a reference temperature and a reference background signal corresponding to the reference temperature, and a preset relationship between background signal changes and monitored temperature changes.

3. The method of claim 2, wherein the step of determining the position of the substrate comprises,

The preset relationship is a linear relationship.

4. The method of claim 2, wherein the step of determining the position of the substrate comprises,

The preset relationship is obtained through experiments.

5. The method of claim 1, wherein the step of determining the position of the substrate comprises,

The monitoring signal is acquired by an analyte sensor, wherein the analyte sensor acquires the monitoring signal by participating in a related chemical reaction of the analyte in the environment.

6. The method of claim 5, wherein the step of determining the position of the probe is performed,

The monitoring signal is a current signal, and the environment is a solution environment.

7. The method of claim 6, wherein the step of providing the first layer comprises,

The analyte is glucose and the environment is a body fluid environment under the skin of a human body.

8. The method of claim 5, wherein the step of determining the position of the probe is performed,

The analyte sensor may be implanted subcutaneously, and the monitored temperature is a body surface temperature or a temperature at which the analyte sensor is located.

9. The method of claim 1, wherein the step of determining the position of the substrate comprises,

And if the temperature change between the measuring position of the monitoring temperature and the environment is delayed, filtering the temperature data to correct the delay, and further obtaining the monitoring temperature corresponding to the monitoring signal, wherein the temperature data comprises the monitoring temperature before the monitoring time of the monitoring signal.

10. A system for acquiring a background signal in a monitored signal based on temperature, comprising: the device comprises a monitoring signal acquisition module, a temperature measurement module and a background signal acquisition module;

The monitoring signal acquisition module is used for acquiring a monitoring signal, wherein the monitoring signal is obtained by monitoring an analyte and comprises a target signal and a background signal which are related to the concentration of the analyte;

the temperature measurement module is used for acquiring a monitoring temperature, and the monitoring temperature is related to the temperature of the environment where the analyte is located;

the background signal acquisition module determines the background signal based on the monitored temperature corresponding to the monitored signal.

11. A method of acquiring a target signal in a monitoring signal, comprising:

Obtaining a background signal from the monitoring signal using the method of any one of claims 1 to 9; and

The target signal is acquired based on the monitoring signal and the background signal, the target signal being used to acquire the concentration of the analyte.

12. An analyte monitoring system, comprising:

an subcutaneously positionable implant portion including a probe, an applicator portion positionable on a body surface and having a temperature sensor, and a processing module;

the probe is used to acquire a monitoring signal,

The temperature sensor is used for acquiring the monitoring temperature,

The processing module is configured to receive the monitoring signal and the monitoring temperature and to obtain a background signal using the method of any one of claims 1 to 9 to obtain the concentration of the analyte.

13. The analyte monitoring system of claim 12, wherein the analyte monitoring device comprises a plurality of sensors,

The analyte is glucose and the probe is a glucose sensor.