CN119498833B

CN119498833B - Analyte monitoring method, readable storage medium, and analyte monitoring system

Info

Publication number: CN119498833B
Application number: CN202311070556.3A
Authority: CN
Inventors: 陈立果; 方骏飞; 陈志�
Original assignee: Shenzhen Guiji Sensing Technology Co ltd
Current assignee: Shenzhen Guiji Sensing Technology Co ltd
Priority date: 2023-08-23
Filing date: 2023-08-23
Publication date: 2025-11-21
Anticipated expiration: 2043-08-23
Also published as: CN119498833A

Abstract

The disclosure describes an analyte monitoring method, a readable storage medium, and an analyte monitoring system, the analyte monitoring method including obtaining a first electrical signal and a second electrical signal, obtaining a correction factor for characterizing a deviation of a first interference signal from a second interference signal based on a ratio of a thickness of the second film layer to a thickness of the first film layer, and obtaining the analyte electrical signal based on the first electrical signal, the second electrical signal, and the correction factor. Thereby, the accuracy of the monitored analyte electrical signal, i.e. the accuracy of the monitored analyte concentration value, can be improved.

Description

Analyte monitoring method, readable storage medium, and analyte monitoring system

Technical Field

The present disclosure relates generally to the biomedical industry, and more particularly, to an analyte monitoring method, a readable storage medium, and an analyte monitoring system.

Background

Monitoring the concentration of at least one analyte in an organism plays an important role in the prevention and treatment of various diseases. Wherein the analyte may include, but is not limited to, glucose, lactate, blood ketone, or other types of analytes. For example, for diabetics, timely acquisition of the blood glucose level of the patient is beneficial to timely implementation of treatment. A continuous blood glucose monitoring system (CGM) is a mobile device for diabetics, and is characterized in that a sensor fixed with enzyme is inserted under the skin to chemically react with tissue fluid in the body or glucose in blood, so that an electric signal is generated, the detection of an analyte is realized according to the relation between the detected electric signal and the concentration of the glucose, the blood glucose level can be tested all-weather, and the information of the real-time blood glucose level can be obtained.

The accuracy of analyte concentration monitoring is critical for patient treatment, e.g. diabetics need insulin injection therapy with reference to the concentration of blood glucose monitoring, so inaccuracy in blood glucose detection would present a very high risk to the patient. In actual operation, a blank electrode without enzyme is arranged on the sensor for detecting an interference signal, and the detection error caused by the interference signal is reduced by detecting the output of the working electrode and comparing with the output of the blank electrode. Thereby obtaining the concentration of the analyte more accurately.

However, due to the slight difference in structure between the working electrode and the blank electrode, there is a certain offset or deviation between the interference signal measured by the blank electrode and the interference signal measured by the working electrode. Therefore, it is difficult to effectively reduce the measurement error of the analyte concentration by merely comparing the output of the working electrode and the output of the blank electrode.

Disclosure of Invention

The present disclosure has been made in view of the above-described circumstances, and an object thereof is to provide an analyte monitoring method, a readable storage medium, and an analyte monitoring system capable of improving accuracy of monitored analyte electrical signals.

To this end, a first aspect of the present disclosure provides an analyte monitoring method, which is a method of acquiring an analyte electrical signal by a sensor, the sensor comprising a working electrode, a blank electrode, and a membrane layer at least partially covering the working electrode and the blank electrode, the working electrode being configured to acquire a first electrical signal including the analyte electrical signal and a first interference signal, the blank electrode being configured to acquire a second electrical signal including a second interference signal, the membrane layer covering the working electrode being a first membrane layer, the membrane layer covering the blank electrode being a second membrane layer, the analyte monitoring method comprising acquiring the first electrical signal and the second electrical signal, acquiring a correction factor for characterizing a deviation of the first interference signal from the second interference signal based on a ratio of a thickness of the second membrane layer to a thickness of the first membrane layer, and acquiring the analyte electrical signal based on the first electrical signal, the second electrical signal, and the correction factor.

In the present disclosure, the sensor can measure the first electrical signal including the first interference signal and the second electrical signal including the second interference signal, respectively, using the working electrode and the blank electrode, and the first interference signal and the thickness of the first film layer may be inversely related and the second interference signal and the thickness of the second film layer may be inversely related, in which case the correction factor is obtained based on the ratio of the thickness of the second film layer to the thickness of the first film layer, so that the correction factor can reduce the deviation between the first interference signal and the second interference signal due to the difference between the thickness of the second film layer and the thickness of the first film layer, and thus, a more accurate analyte electrical signal can be obtained based on the first electrical signal, the second electrical signal, and the correction factor, that is, the accuracy of the monitored analyte electrical signal can be improved.

In addition, in the analyte monitoring method according to the first aspect of the present disclosure, optionally, the deviation of the first interference signal from the second interference signal further includes a deviation due to a difference in surface area of the working electrode and surface area of the blank electrode, and the analyte monitoring method further includes obtaining the correction factor based on a ratio of the surface area of the working electrode to the surface area of the blank electrode. In this case, in consideration of the positive correlation between the surface area of the electrode and the magnitude of the interference signal, the correction factor is obtained by dividing the surface area of the working electrode by the value of the surface area of the blank electrode, so that the correction factor can reduce the deviation between the first interference signal and the second interference signal due to the difference between the surface area of the blank electrode and the surface area of the working electrode, whereby a more accurate analyte electrical signal can be obtained based on the first electrical signal, the second electrical signal, and the correction factor, that is, the accuracy of the monitored analyte electrical signal can be improved.

In addition, in the analyte monitoring method according to the first aspect of the present disclosure, a ratio of a thickness of the second film layer to a thickness of the first film layer is optionally set to a first ratio, a ratio of a surface area of the working electrode to a surface area of the blank electrode is set to a second ratio, and the correction factor is obtained based on a product of the first ratio and the second ratio. In this case, by correcting the analyte electric signal by combining two factors, i.e., the difference between the film thicknesses and the difference between the electrode surface areas, it is possible to simultaneously reduce the difference between the surface areas of the blank electrodes and the working electrodes, and the difference between the first interference signal and the second interference signal due to the difference between the thickness of the first film layer and the thickness of the second film layer, whereby the measurement accuracy of the concentration value of the analyte can be further improved.

In addition, in the analyte monitoring method according to the first aspect of the present disclosure, optionally, the deviation of the first interference signal from the second interference signal further includes a deviation due to a difference between a background noise signal of the working electrode and a background noise signal of the blank electrode, and the analyte monitoring method further includes obtaining the correction factor based on a ratio of the background noise signal of the working electrode to the background noise signal of the blank electrode. In this case, in consideration of the positive correlation between the magnitude of the background noise signal of the electrode and the magnitude of the interference signal, the correction factor is obtained by dividing the background noise signal of the working electrode by the value of the background noise signal of the blank electrode, so that the correction factor can reduce the deviation between the first interference signal and the second interference signal caused by the difference between the background noise signal of the blank electrode and the background noise signal of the working electrode, and thus, a more accurate analyte electrical signal can be obtained based on the first electrical signal, the second electrical signal, and the correction factor, that is, the accuracy of the monitored analyte electrical signal can be improved.

In addition, in the analyte monitoring method according to the first aspect of the present disclosure, optionally, a ratio of a thickness of the second film layer to a thickness of the first film layer is set to a first ratio, a ratio of a background noise signal of the working electrode to a background noise signal of the blank electrode is set to a third ratio, and the correction factor is obtained based on a product of the first ratio and the third ratio. In this case, by correcting the second electric signal by integrating two factors, i.e., the difference between the film thicknesses and the difference between the electrode background noise signals, it is possible to simultaneously reduce the difference between the background noise signal of the working electrode and the background noise signal of the blank electrode, and the deviation between the first interference signal and the second interference signal due to the difference between the thickness of the first film and the thickness of the second film, whereby the measurement accuracy of the concentration value of the analyte can be further improved.

In addition, in the analyte monitoring method according to the first aspect of the present disclosure, optionally, the deviation of the first interference signal from the second interference signal includes a deviation due to a difference between a surface area of the working electrode and a surface area of the blank electrode, and the analyte monitoring method further includes making a ratio of the surface area of the working electrode to the surface area of the blank electrode a second ratio, and obtaining the correction factor based on the first ratio, the second ratio, and the third ratio. In this case, the correction factor can reduce the deviation of the first interference signal and the second interference signal caused by the difference of the background noise signal of the working electrode and the background noise signal of the blank electrode, the difference of the surface area of the working electrode and the surface area of the blank electrode, and the difference of the thickness of the second film layer and the thickness of the first film layer. Thereby, the measurement accuracy of the concentration value of the analyte can be further improved.

In addition, in the analyte monitoring method according to the first aspect of the present disclosure, optionally, the sensor includes a substrate, and the working electrode and the blank electrode are located on two sides of the substrate. In this case, by providing the working electrode and the blank electrode separately, the mutual interference between the working electrode and the blank electrode can be reduced, and the sensitivity of the sensor can be improved.

In addition, in the analyte monitoring method according to the first aspect of the present disclosure, optionally, a correction signal is obtained based on the second electrical signal and the correction factor, and the analyte electrical signal is obtained based on the first electrical signal and the correction signal. In this case, the correction signal can be obtained using the correction factor and the second electric signal, which can be substantially equivalent to the first interference signal, whereby an analyte electric signal with high accuracy can be obtained based on the first electric signal and the correction signal, that is, the measurement accuracy of the concentration value of the analyte can be improved.

A second aspect of the present disclosure provides a readable storage medium storing at least one instruction which when executed by a processor implements the analyte monitoring method of any of the first aspects. Thereby, it can be facilitated to implement an automated process analyte monitoring method using a computer device.

A third aspect of the present disclosure provides an analyte monitoring system that obtains an analyte electrical signal by performing an analyte monitoring method according to any one of the first aspects, the analyte monitoring system comprising a processing device configured to perform the analyte monitoring method. In this case, the correction factor can reduce the deviation between the first interference signal measured by the working electrode and the second interference signal measured by the blank electrode due to the difference between the working electrode and the blank electrode, so that the analyte monitoring system can obtain a more accurate analyte electrical signal, that is, a more accurate concentration value of the analyte, from the first electrical signal based on the second interference signal measured by the blank electrode, the first electrical signal measured by the working electrode, and the correction factor, thereby improving the accuracy of the analyte monitoring system.

According to the present disclosure, an analyte monitoring method, a readable storage medium, and an analyte monitoring system can be provided, which can improve the accuracy of analyte monitoring.

Drawings

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

Fig. 1A is an application scenario diagram illustrating an analyte monitoring system according to an example of the present disclosure.

Fig. 1B is a schematic diagram illustrating a sensor to which examples of the present disclosure relate.

Fig. 1C is a block diagram illustrating an analyte monitoring system in accordance with examples of the present disclosure.

Fig. 1D is a block diagram illustrating an electronic module to which examples of the present disclosure relate.

Fig. 2 is a schematic diagram illustrating an embodiment of a sensor to which examples of the present disclosure relate.

Fig. 3A is a first flow chart illustrating an analyte monitoring method according to an example of the present disclosure.

Fig. 3B is a second flow chart illustrating an analyte monitoring method according to an example of the present disclosure.

Fig. 4 is a schematic diagram showing test results of embodiment 1 related to examples of the present disclosure.

Fig. 5 is a schematic diagram showing test results of embodiment 2 related to examples of the present disclosure.

Fig. 6 is a schematic diagram showing background noise signals of a working electrode and a blank electrode according to an example of the present disclosure.

Fig. 7 is a schematic diagram showing test results of embodiment 3 related to an example of the present disclosure.

Detailed Description

The following description of the technical solutions in the embodiments of the present disclosure will be made clearly and completely with reference to the accompanying drawings in the embodiments of the present disclosure, and it is apparent that the described embodiments are only some embodiments of the present disclosure, not all embodiments. All other embodiments, which are filled by those of ordinary skill in the art without undue burden based on the embodiments in this disclosure, are within the scope of the present disclosure.

It should be noted that the terms "first," "second," "third," and "fourth," etc. in the description and claims of the present disclosure and in the above figures are used for distinguishing between different objects and not for describing a particular sequential order. It should be noted that the terms "comprises" and "comprising," and any variations thereof, in this disclosure, such as a process, method, system, article, or apparatus that comprises or has a list of steps or elements is not necessarily limited to those steps or elements expressly listed or inherent to such process, method, article, or apparatus, but may include or have other steps or elements not expressly listed or inherent to such process, method, article, or apparatus.

Hereinafter, preferred embodiments of the present disclosure will be described in detail with reference to the accompanying drawings. In the following description, the same members are denoted by the same reference numerals, and overlapping description thereof is omitted. In addition, the drawings are schematic, and the ratio of the sizes of the components to each other, the shapes of the components, and the like may be different from actual ones.

In the present disclosure, unless explicitly stated and limited otherwise, the term "coupled" is to be construed broadly, and for example, the term "coupled" may be a fixed connection, a removable connection, or an integral unit, and may be directly or indirectly coupled via an intervening medium. In addition, the term "coupled" may be used to describe an electrical connection for signal transmission, where "coupled" may be a direct electrical connection or an indirect electrical connection via an intermediary. In addition, the term "accuracy" can be understood as the degree of coincidence between a measured value and a true value (correct standard).

Electrochemical biosensors are devices that use biological reactions to detect a specific analyte, and when a specific analyte (e.g., glucose, lactic acid, uric acid, protein, or drug) reacts with the sensor (e.g., an enzymatic reaction or an immunological reaction), electrochemical reactions, such as electron transfer, ion transfer, etc., are generated. These electrochemical reactions can be detected by a sensor and converted into an electrical signal, which may be referred to as an analyte electrical signal, which can be used to reflect the content of a particular analyte, i.e., the concentration value of the analyte. In some examples, the electrical signal may be a current signal or a voltage signal. In the present disclosure, the specific form of the electrical signal is not limited.

A first aspect of the present disclosure proposes an analyte monitoring method, which may also be referred to as an analyte monitoring method for reducing interfering signals or a method for improving the accuracy of analyte monitoring.

A second aspect of the present disclosure proposes a readable storage medium, which may store at least one instruction, which when executed by a processor, implements the analyte monitoring method of the first aspect of the present disclosure. Thereby, it can be facilitated to implement an automated process analyte monitoring method using a computer device.

A third aspect of the present disclosure proposes an analyte monitoring system, which may also be referred to as an analyte monitoring device, which may obtain an analyte electrical signal by performing an analyte monitoring method according to the first aspect of the present disclosure.

In the present disclosure, the term "analyte" may be a chemical compound that is present in a solution. In some examples, the analyte may be one or more of glucose, acetylcholine, amylase, bilirubin, cholesterol, chorionic gonadotrophin, creatine kinase, creatine, DNA, fructosamine, glucose, glutamine, growth hormone, ketone body, lactate, oxygen, peroxide, prostate specific antigen, prothrombin, RNA, thyroid stimulating hormone, or troponin. In addition, the analyte may also be a drug in solution. For example, the analyte may be digitoxin, digoxin, theophylline, warfarin, or an antibiotic (such as gentamicin or vancomycin, etc.).

In some examples, the solution may be a bodily fluid of a human or animal. In some examples, the solution may also be a test sample used in a laboratory environment. In this disclosure, a human or animal may be collectively referred to as a host.

Fig. 1A is a diagram illustrating an application scenario of an analyte monitoring system 10 in accordance with examples of the present disclosure. Fig. 1B is a schematic diagram illustrating a sensor 20 to which examples of the present disclosure relate. Fig. 1C is a block diagram illustrating an analyte monitoring system 10 in accordance with examples of the present disclosure. Fig. 1D is a block diagram illustrating an electronic module 30 to which examples of the present disclosure relate.

In some examples, referring to fig. 1A, analyte monitoring system 10 may be applied to a host for monitoring concentration values of an analyte within the host. In some examples, analyte monitoring system 10 may be used in a laboratory for in vitro experiments.

In some examples, referring to fig. 1A, analyte monitoring system 10 may include a sensor 20. In this case, the sensor 20 is capable of electrochemically reacting with the analyte to generate an analyte electrical signal to characterize the concentration value of the analyte.

In some examples, referring to fig. 1B, sensor 20 may include a distal portion 20a and a proximal portion 20B, wherein distal portion 20a may be placed at a selected site in the host, e.g., distal portion 20a may be implanted under a skin layer of the host in contact with bodily fluids within the host, and proximal portion 20B may be provided with electrical contacts 201.

In some examples, referring to fig. 1C, analyte monitoring system 10 may include an electronic module 30 and sensor 20 may be electrically connected to electronic module 30 via electrical contacts 201. Thus, the electrical signal measured by the sensor 20 can be transmitted to the electronic module 30 for processing.

In some examples, referring to fig. 1D, the electronic module 30 may include a power supply 31, a signal processing element 32, and a signal transmission element 33. In some examples, the power supply 31, the signal processing element 32, and the signal transmission element 33 may be placed on a printed circuit board. This can improve the integration of the electronic module 30.

In some examples, signal processing element 32 may be an Application Specific Integrated Circuit (ASIC) chip. In some examples, the sensor 20 may be coupled with a signal processing element 32, and the signal processing element 32 may process the electrical signal from the sensor 20 measurement and convert to a third electrical signal. In some examples, the third electrical signal may be a digital signal. For example, the electrical signal obtained by the sensor 20 may be an analog signal, and the signal processing element 32 may convert the analog signal into a digital signal, whereby signal processing, such as digital filtering, etc., of the third electrical signal using digital processing techniques can be facilitated.

In some examples, signal transmission element 33 may send the third electrical signal out through communication link 331. In some examples, communication link 331 may be a wireless transmission, in which case the form of the wireless transmission can facilitate data transmission.

In some examples, communication link 331 may be a wired transmission, for example communication link 331 may be a standard wired transmission cable such as a USB cable. Thereby, the application range of the analyte monitoring system 10 can be improved.

In some examples, referring to fig. 1C, analyte monitoring system 10 may further include a processing device 40 (referring to fig. 1C), and processing device 40 may be configured to perform the analyte monitoring method set forth in the first aspect of the present disclosure (described in detail later).

In some examples, processing device 40 may be integrated with electronic module 30. In some examples, processing device 40 may be a separate and independent device from electronic module 30. In some examples, the processing device 40 may be integrated in the monitor 50 (described in detail later).

In some examples, referring to fig. 1D, analyte monitoring system 10 may include monitor 50. Thus, the concentration value of the analyte can be indicated by the monitor 50, facilitating host perception of the concentration value of the analyte.

In some examples, monitor 50 may be coupled to signal transmission element 33 and may receive, process, and indicate a third electrical signal. In some examples, monitor 50 may indicate the third electrical signal, i.e., the concentration value of the analyte, by an audible signal and/or a visual signal. In some examples, the audible signal may be a voice broadcast of the concentration value of the analyte or a voice alarm message when the concentration value of the analyte exceeds a threshold. In some examples, the visual signal may be displaying a concentration value of the analyte on a display screen of monitor 50.

In some examples, monitor 50 may be a smart terminal, such as a smart mobile phone. Thereby facilitating the portability of the analyte monitoring system 10, enabling the host to monitor the concentration value of the analyte on a daily basis without the need for special monitoring of the analyte at a hospital.

In some examples, monitor 50 may also be an electronic measurement instrument, for example monitor 50 may be a dedicated measurement instrument such as an oscilloscope, a current tester, or the like. In this case, the concentration value of the analyte can be accurately measured by a dedicated measuring instrument, whereby the analyte monitoring system 10 can be adapted for use in a hospital environment or laboratory environment.

Fig. 2 is a schematic diagram illustrating an embodiment of a sensor 20 according to an example of the present disclosure.

In some examples, referring to fig. 2, sensor 20 may include a working electrode 202, where working electrode 202 may be used to obtain a first electrical signal, which may include an analyte electrical signal, which may also be referred to as a net analyte concentration value.

In some examples, the first electrical signal may also include a first interfering signal, in other words, the first electrical signal may include a characteristic analyte electrical signal and the first interfering signal. In this case, the analyte electrical signal is capable of characterizing the concentration value of the analyte, such that removal of the first interfering signal from the first electrical signal results in a more accurate concentration value of the analyte.

In some examples, working electrode 202 may include a sensing layer 2021. In some examples, the sensing layer 2021 may facilitate an electrochemical reaction of the working electrode 202 with the analyte to generate a first electrical signal. Thus, the concentration value of the analyte can be obtained by the first electrical signal measured by the working electrode 202.

In some examples, the sensing layer 2021 may also be referred to as a catalyst layer or electroactive species layer, and a catalyst layer for a corresponding analyte may be disposed on the working electrode 202 for a different analyte. In some examples, the sensing layer 2021 may be glucose oxidase or glucose dehydrogenase. In this case, in the case where the analyte is glucose or blood glucose with respect to the glucose sensor, by providing glucose oxidase or glucose dehydrogenase on the working electrode 202, the working electrode 202 of the glucose sensor can be electrochemically reacted with glucose or blood glucose, so that a first electrical signal including an analyte electrical signal, which can refer to an analyte electrical signal of a glucose concentration value, can be obtained.

In some examples, the sensor 20 may include a blank electrode 203, the blank electrode 203 may be used to acquire a second electrical signal, and the second electrical signal may include a second interference signal.

In some examples, the blank electrode 203 may not include the sensing layer 2021. In other words, the blank electrode 203 may not electrochemically react with the analyte, i.e., the blank electrode 203 may not generate an analyte electrical signal that is related to the concentration value of the analyte. In this case, the second electrical signal measured by the blank electrode 203 can include no electrical signal related to the analyte, i.e., the second electrical signal can be equated with the second interference signal.

In some examples, the first interfering signal may include an electrical signal generated by an electrochemical reaction of a substance in the solution other than the analyte to be monitored with the working electrode 202. In some examples, the second interfering signal may include an electrical signal generated by an electrochemical reaction of other substances in the solution than the analyte to be monitored with the blank electrode 203.

In some examples, the first interference signal may also include a background noise signal generated by the working electrode 202 itself. In some examples, the second interference signal may also include a background noise signal generated by the blank electrode 203 itself. In this disclosure, the background noise signal may be used to characterize the noise signal that the working electrode 202 or the blanking electrode 203 has by its nature, and may also be referred to as the bottom noise signal or the bottom noise.

In some examples, the blank electrode 203 is substantially the same as the working electrode 202 except that the sensing layer 2021 is not provided, as compared to the working electrode 202, for example, the blank electrode 203 and the working electrode 202 may be made of the same material and have the same structure, and the working electrode 202 and the blank electrode 203 may be manufactured using the same manufacturing process. In this case, by reducing the difference between the blank electrode 203 and the working electrode 202 as much as possible, on the one hand, the deviation between the first interference signal and the second interference signal can be reduced, and on the other hand, the factor affecting the deviation between the first interference signal and the second interference signal can be reduced as much as possible, so that the relationship between the first interference signal and the second interference signal can be obtained more accurately, and thus, the analyte electric signal, that is, the net analyte concentration value, can be obtained from the first electric signal more accurately based on the first electric signal and the second electric signal.

In some examples, the sensor 20 may include a counter electrode 204. Thus, the working electrode 202 can form a first circuit with the counter electrode 204 to generate a first electrical signal, and the blank electrode 203 can form a second circuit with the counter electrode 204 to generate a second electrical signal.

In some examples, working electrode 202 and blank electrode 203 may be made of any of platinum, gold, silver, lead, mercury, a glassy carbon electrode, conductive glass, palladium, titanium, or iridium. Thus, the working electrode 202 and the blank electrode 203 can be provided with good conductivity, and the accuracy of the analyte monitoring system 10 can be improved.

In some examples, the working electrode 202 and the blank electrode 203 may be made of the same material. This can further reduce the deviation between the first interference signal and the second interference signal due to the difference in the material of the working electrode 202 and the blank electrode 203.

In some examples, the counter electrode 204 may be made of platinum, silver chloride, palladium, titanium, or iridium. Thus, the electrochemical reaction at the working electrode 202 can be unaffected with good conductivity.

In some examples, sensor 20 may include reference electrode 205. In some examples, the reference electrode 205 can form a known and fixed potential difference with the solution. In this case, the potential difference between the working electrode 202 and the solution can be measured by the potential difference formed by the reference electrode 205 and the working electrode 202. Thus, the voltage generated by the working electrode 202 can be obtained more accurately. Thus, the voltage of the working electrode 202 can be automatically adjusted and maintained stable according to the preset voltage value, so that the measured electrical signal, i.e., the first electrical signal, can more accurately reflect the concentration of the analyte in the solution. In some examples, the number of reference electrodes 205 can be one or more, such as two.

In other examples, reference electrode 205 may not be used when the variation in potential difference between working electrode 202 and the solution does not fluctuate much. Thus, the manufacturing cost can be saved.

In some examples, referring to fig. 2, sensor 20 can include a working electrode 202, a blank electrode 203, a reference electrode 205, and a counter electrode 204. In this case, the working electrode 202, the reference electrode 205, and the counter electrode 204 can form a first three-electrode system, the blank electrode 203, the reference electrode 205, and the counter electrode 204 can form a second three-electrode system, and by sharing the reference electrode 205 and the counter electrode 204, correlation factors that affect the difference between the first interference signal and the second interference signal can be reduced, whereby accurate acquisition of the analyte electric signal from the first electric signal can be facilitated.

In some examples, the sensor 20 may include a substrate 206. In this case, the substrate 206 can provide support for the various electrodes of the sensor 20, and structural support for the various electrodes, which can ensure that the sensor 20 maintains structural stability during use. Thus, the substrate 206 can enhance the mechanical strength of the sensor 20, preventing the sensor 20 from being deformed or broken.

In some examples, the working electrode 202 and the blank electrode 203 may be located on both sides of the substrate 206, respectively. In this case, by providing the working electrode 202 and the blank electrode 203 separately, the mutual interference between the working electrode 202 and the blank electrode 203 can be reduced, and the sensitivity of the sensor 20 can be improved.

In some examples, the working electrode 202, the blank electrode 203, the reference electrode 205, and the counter electrode 204 can be disposed on the substrate 206. In this case, by providing the various electrodes on the same substrate 206, the compactness of the sensor 20 can be improved, and the sensor 20 can be easily implanted in the skin layer of the host.

In some examples, the working electrode 202, the blank electrode 203, the reference electrode 205, and the counter electrode 204 may be placed on the substrate 206 in a stacked configuration, referring to fig. 2, the working electrode 202 and the reference electrode 205 may be stacked in sequence on one side of the substrate 206, and the blank electrode 203 and the counter electrode 204 may be stacked in sequence on the other side of the substrate 206.

In this case, the surface area of the working electrode 202 can be significantly increased by arranging the electrodes in a laminated structure, a larger surface area can provide more sensing layers 2021, and the sensitivity of the sensor 20 can be improved, and the design of the laminated structure electrode can allow the combination of different material layers, and the laminated structure of the different material layers can complement each other, and the stability and durability of the sensor 20 can be improved. For example, the sensor 20 generally needs small size and portability, and through the design of the electrode with a laminated structure, more functional integration can be realized in a limited space, and a plurality of functional layers are integrated in a compact electrode structure, thereby improving the space utilization efficiency.

In some examples, referring to fig. 2, sensor 20 may further include a first electrically insulating layer 207, a second electrically insulating layer 208, a third electrically insulating layer 209, and a fourth electrically insulating layer 210. In this case, by providing the electrically insulating layer, the occurrence of short-circuiting of the electrodes can be reduced.

In some examples, the substrate 206 may be a flexible substrate. The flexible substrate may be generally 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 flexible substrate may also be made substantially of metal foil, ultra-thin glass, single-layer inorganic film, multi-layer organic film, multi-layer inorganic film, or the like.

In some examples, sensor 20 may include a film that at least partially covers working electrode 202 and blank electrode 203, and the film that covers working electrode 202 may be made a first film 211 and the film that covers blank electrode 203 may be made a second film 212.

In some examples, the first film layer 211 and the second film layer 212 may have a thickness. In the present disclosure, the thickness of the first film layer 211 and the second film layer 212 may be obtained by selecting a plurality of predetermined points on the film layer to measure, measuring the thickness of the position where the predetermined point is located, and then taking an average value of the thicknesses of the positions where different predetermined points are located.

In some examples, the first membrane layer 211 and the second membrane layer 212 may include semi-permeable membranes. In this case, the semipermeable membrane can selectively permeate the analyte and prevent other substances from passing therethrough, thereby improving the accuracy of monitoring, and in addition, the membrane layers are arranged on the working electrode 202 and the blank electrode 203 at the same time, that is, the working environments or structures of the working electrode 202 and the blank electrode 203 are kept consistent, so that the deviation between the first interference signal and the second interference signal can be reduced as much as possible.

In some examples, the semipermeable membrane may include a diffusion control layer. In this case, the semipermeable membrane can control the rate of passage of the analyte, i.e., the semipermeable membrane can limit the amount of analyte in solution reaching the sensing layer 2021, can ensure that the sensing layer 2021 and other substances involved in the reaction are in sufficient quantities that the concentration of the analyte is the primary (substantially the only) factor limiting the magnitude of the first electrical signal, so that the magnitude of the first electrical signal can accurately reflect the concentration of the analyte, and can greatly increase the linear range of the working electrode 202.

In some examples, the semipermeable membrane may further include an anti-interference layer laminated over the diffusion control layer, the anti-interference layer may prevent diffusion of a substance other than the analyte. Thus, the interference of detection of the analyte concentration by a substance different from the analyte can be reduced.

In some examples, the first membrane layer 211 and the second membrane layer 212 may include a biocompatible membrane, which may be disposed on the semi-permeable membrane. In this case, when the analyte monitoring system 10 is to be placed on a host, the sensor 20 is implanted in the cortex of the host in contact with body fluid or interstitial fluid, the host's immune response to the sensor 20 can be reduced, and the service life of the sensor 20 can be extended.

In some examples, when monitoring an analyte-containing solution, the solution often contains interfering substances, for example, when the glucose sensor monitors glucose in the host, the blood or non-blood body fluid in the host often contains interfering substances, such as ascorbic acid, uric acid, or acetaminophen, which are more reducing substances, and these interfering substances are easy to react with the working electrode 202 or the blank electrode 203 to generate a first interfering signal or a second interfering signal, if the interfering signal is larger, the first interfering signal is larger in the first electrical signal detected by the working electrode 202, so that the deviation between the first electrical signal and the analyte electrical signal in the first electrical signal is larger, that is, the accuracy that the first electrical signal refers to the concentration value of the analyte is lower.

As described above, in some examples, the sensor 20 may include the blank electrode 203, where the working electrode 202 and the blank electrode 203 are simultaneously involved in monitoring the concentration value of the analyte, and comparing the first electrical signal measured by the working electrode 202 with the second electrical signal (i.e., the second interference signal) measured by the blank electrode 203 may obtain a more accurate concentration value of the analyte, in other words, the second interference signal may be equivalent to the first interference signal, and removing the value of the second electrical signal from the first electrical signal may obtain the analyte electrical signal.

In practice, however, there is typically a difference between the blank electrode 203 and the working electrode 202, resulting in that the first interference signal is typically not equal to the second interference signal, such that the first interference signal is offset from the second interference signal. In other words, it is assumed that the working electrode 202 and the blank electrode 203 are simultaneously placed in the same solution environment containing no analyte, and the electrical signals measured by the working electrode 202 and the blank electrode 203 are not identical, i.e., the first interference signal and the second interference signal deviate. In this case, when the analyte electrical signal is obtained by comparing the first electrical signal with the second electrical signal including the second interfering signal, the accuracy of the obtained analyte electrical signal will be affected by the deviation between the first interfering signal and the second interfering signal.

The difference between the blank electrode 203 and the working electrode 202 may be caused by an error in the manufacturing process or may be caused by a difference in the manufacturing process between the blank electrode 203 and the working electrode 202. In the present disclosure, the cause of the difference between the blank electrode 203 and the working electrode 202 is not limited at all.

In some examples, the first interference signal may be in positive correlation with the surface area of the working electrode 202 and the second interference signal may be in positive correlation with the surface area of the blank electrode 203. In this case, the larger the surface area of the working electrode 202, the larger the first interference signal generated by the electrochemical reaction with the interfering substance in the solution, and the larger the surface area of the blank electrode 203, the larger the second interference signal generated by the electrochemical reaction with the interfering substance in the solution. Thus, when the difference between the surface area of the working electrode 202 and the surface area of the blank electrode 203 is large, the larger the deviation of the first interference signal from the second interference signal is, and conversely, the smaller the deviation of the first interference signal from the second interference signal is.

In some examples, the deviation of the first interference signal from the second interference signal may include a deviation due to a difference between a surface area of the working electrode 202 and a surface area of the blank electrode 203, in other words, when the surface area of the working electrode 202 is inconsistent with the surface area of the blank electrode 203, there may be a deviation between the first interference signal measured by the working electrode 202 and the second interference signal measured by the blank electrode 203.

In some examples, the first interference signal may be inversely related to the thickness of the first film layer 211 and the second interference signal may be inversely related to the thickness of the second film layer 212. In this case, the greater the thickness of the first film layer 211, the smaller the concentration of the interfering substance penetrating through the first film layer 211, so that the first interfering signal generated by the electrochemical reaction between the working electrode 202 and the interfering substance can be caused to be smaller, and the greater the thickness of the second film layer 212, the smaller the second interfering signal. Thus, when the difference between the thickness of the first film layer 211 and the thickness of the second film layer 212 is larger, the larger the deviation of the first interference signal and the second interference signal is, and conversely, the smaller the deviation of the first interference signal and the second interference signal is.

In some examples, the deviation of the first interference signal from the second interference signal may include a deviation caused by a difference between the thickness of the second film layer 212 and the thickness of the first film layer 211, in other words, when the thickness of the second film layer 212 is inconsistent with the thickness of the first film layer 211, there may be a deviation between the first interference signal measured by the working electrode 202 and the second interference signal measured by the blank electrode 203.

In some examples, the first interference signal may be in positive correlation with the background noise signal of working electrode 202 and the second interference signal may be in positive correlation with the background noise signal of blanking electrode 203. In this case, the larger the background noise signal of the working electrode 202, the larger the first interference signal, and the larger the background noise signal of the blank electrode 203, the larger the second interference signal.

In some examples, the deviation of the first interference signal from the second interference signal may include a deviation due to a difference in the background noise signal of the blank electrode 203 and the background noise signal of the working electrode 202. In other words, when the background noise signal of the blank electrode 203 is inconsistent with the background noise signal of the working electrode 202, there is a deviation between the first interference signal measured by the working electrode 202 and the second interference signal measured by the blank electrode 203.

As can be seen from the above description, due to the difference between the working electrode 202 and the blank electrode 203, there is a difference between the first interference signal and the second interference signal, and the accuracy of the analyte electrical signal obtained by directly comparing the first electrical signal with the second electrical signal may be affected.

In the analyte monitoring method set forth in the first aspect of the present disclosure, the deviation between the first interference signal and the second interference signal may be corrected by using the correction factor, in other words, the correction signal may be obtained based on the second electrical signal and the correction factor, that is, by using the correction factor, the deviation between the first interference signal and the second interference signal due to the difference between the working electrode 202 and the blank electrode 203 may be reduced, and the correction signal may be substantially identical to the first interference signal. Thus, by comparing the first electrical signal with the correction signal, a more accurate analyte electrical signal can be obtained, and the accuracy of analyte monitoring can be improved.

Fig. 3A is a first flow chart illustrating an analyte monitoring method according to an example of the present disclosure. Fig. 3B is a second flow chart illustrating an analyte monitoring method according to an example of the present disclosure.

In some examples, referring to FIG. 3A, an analyte monitoring method may include obtaining a first electrical signal and a second electrical signal (step S200), obtaining a correction factor based on a ratio of a thickness of the second film layer 212 to a thickness of the first film layer 211 (step S400), and obtaining an analyte electrical signal based on the first electrical signal, the second electrical signal, and the correction factor (S600).

In the present disclosure, the sensor 20 may measure the first electrical signal including the first interference signal and the second electrical signal including the second interference signal using the working electrode 202 and the blank electrode 203, respectively, and the thickness of the first interference signal and the first film layer 211 may be inversely related and the thickness of the second interference signal and the second film layer 212 may be inversely related, in which case, a correction factor is obtained based on a ratio of the thickness of the second film layer 212 to the thickness of the first film layer 211, so that the correction factor can reduce a deviation between the first interference signal and the second interference signal due to a difference between the thickness of the second film layer 212 and the thickness of the first film layer 211, and thus, a more accurate analyte electrical signal can be obtained based on the first electrical signal, the second electrical signal, and the correction factor, that is, the accuracy of the monitored analyte electrical signal can be improved.

In some examples, in step S200, a first electrical signal may be acquired, which may include the analyte electrical signal acquired by the working electrode 202 and the first interference signal, and a second electrical signal may include the second interference signal acquired by the blank electrode 203, whereby the analyte electrical signal can be acquired by comparing the first electrical signal and the second electrical signal.

In some examples, referring to fig. 3B, the analyte monitoring method may further include setting the working electrode 202 and the blank electrode 203 at a preset voltage potential (step S100). This promotes the electrochemical reaction between the working electrode 202 and the blank electrode 203, and generates the first electric signal and the second electric signal, respectively.

In some examples, in step S100, the working electrode 202 and the blank electrode 203 may be set at a preset voltage potential by a potentiostat. In the present disclosure, a potentiostat may be understood as a circuit structure capable of outputting a desired constant voltage according to actual needs.

In some examples, the electronic module 30 may include a potentiostat.

In some examples, the same preset voltage potential may be set on the working electrode 202 and the blank electrode 203. In this case, the deviation of the first interference signal from the second interference signal caused by the difference in potential between the working electrode 202 and the blank electrode 203 can be eliminated.

In some examples, different preset voltage potentials may be set on the working electrode 202 and the blank electrode 203. In this case, it is possible to facilitate the study of electrochemical reactions occurring on the working electrode 202 and the blank electrode 203 under different conditions by setting different voltage potentials.

In some examples, the preset voltage potential may be related to the type of sensing layer 2021. For example, when the sensor layer 2021 is glucose dehydrogenase, the preset voltage potential applied to the working electrode 202 and the blank electrode 203 may be 50mV.

In this disclosure, for convenience of description, let the ratio of the thickness of the second film layer 212 to the thickness of the first film layer 211 be a first ratio, let the ratio of the surface area of the working electrode 202 to the surface area of the blank electrode 203 be a second ratio, let the ratio of the background noise signal of the working electrode 202 to the background noise signal of the blank electrode 203 be a third ratio, let f represent the correction factor, f ₁ represent the first ratio, f ₂ represent the second ratio, f ₃ represent the third ratio, I represent the analyte electrical signal, I ₁ represent the first electrical signal, I ₂ represent the second electrical signal, and I ₃ represent the correction signal.

In some examples, in step S400, the correction factor may be obtained based on the ratio of the thickness of the second film layer 212 to the thickness of the first film layer 211, in other words, the correction factor may be equal to the value of the thickness of the second film layer 212 divided by the thickness of the first film layer 211, that is, the correction factor may be equal to the first ratio, and may have the formula 1:f =f ₁. In this case, in consideration of the relationship in which the thickness of the film layer is inversely related to the magnitude of the interference signal, a correction factor is obtained by dividing the thickness of the second film layer 212 by the thickness of the first film layer 211, and a correction signal substantially equivalent to the first interference signal is obtained based on the correction factor and the second electric signal, so that the correction factor can reduce the deviation of the first interference signal from the second interference signal due to the difference in the thickness of the second film layer 212 and the thickness of the first film layer 211.

In some examples, the correction factor may be used to characterize the deviation of the first interference signal from the second interference signal. In this case, by introducing a correction factor and obtaining a correction signal based on the correction factor and the second electric signal, the correction signal can be substantially equivalent to the first interference signal, that is, the correction factor can reduce the deviation of the first interference signal from the second interference signal due to the difference between the working electrode 202 and the blank electrode 203 (for example, the difference between the thickness of the second film layer 212 and the thickness of the first film layer 211), whereby the measurement accuracy of the concentration value of the analyte can be improved by comparing the first electric signal with the correction signal.

In some examples, in step S400, the analyte monitoring method may include obtaining a correction factor based on a ratio of a surface area of the working electrode 202 to a surface area of the blank electrode 203. In other words, the correction factor may be equal to the surface area of the working electrode 202 divided by the surface area of the blank electrode 203, i.e., the correction factor may be equal to the second ratio, and may have the formula 2:f =f ₂. In this case, in consideration of the positive correlation between the surface area of the electrode and the magnitude of the interference signal, a correction factor is obtained by dividing the surface area of the working electrode 202 by the surface area of the blank electrode 203, so that the correction factor can reduce the deviation of the first interference signal from the second interference signal due to the difference between the surface area of the working electrode 202 and the surface area of the blank electrode 203, whereby a more accurate analyte electrical signal can be obtained based on the first electrical signal, the second electrical signal, and the correction factor, that is, the accuracy of the monitored analyte electrical signal can be improved.

In some examples, in step S400, the analyte monitoring method may include obtaining a correction factor based on a ratio of a surface area of the working electrode 202 to a surface area of the blank electrode 203, a ratio of a thickness of the second film layer 212 to a thickness of the first film layer 211. In this case, the correction factor can reduce the deviation of the first interference signal from the second interference signal due to the difference in the surface area of the working electrode 202 and the surface area of the blank electrode 203, and the difference in the thickness of the second film layer 212 and the thickness of the first film layer 211.

In some examples, in step S400, the correction factor may be obtained based on the product of the first ratio and the second ratio, that is, may have the formula 3:f =f ₁×f₂. In this case, by correcting the second electric signal by combining two factors, i.e., the difference between the film thicknesses and the difference between the electrode surface areas, the difference between the surface areas of the blank electrode 203 and the working electrode 202, and the difference between the first interference signal and the second interference signal due to the difference between the thickness of the first film 211 and the thickness of the second film 212 can be reduced at the same time, whereby the measurement accuracy of the concentration value of the analyte can be further improved.

In some examples, in step S400, the analyte monitoring method may include obtaining a correction factor based on a ratio of a background noise signal of the working electrode 202 to a background noise signal of the blank electrode 203. In other words, the correction factor may be equal to the value of the background noise signal of the working electrode 202 divided by the background noise signal of the blank electrode 203, i.e., the correction factor may be equal to the third ratio, and may have the formula 3:f =f ₃. In this case, in consideration of the positive correlation between the magnitude of the background noise signal of the electrode and the magnitude of the interference signal, a correction factor is obtained by dividing the background noise signal of the working electrode 202 by the value of the background noise signal of the blank electrode 203, so that the correction factor can reduce the deviation of the first interference signal and the second interference signal due to the difference between the background noise signal of the working electrode 202 and the background noise signal of the blank electrode 203. Thus, a more accurate analyte electrical signal can be obtained based on the first electrical signal, the second electrical signal, and the correction factor, i.e., the accuracy of the monitored analyte electrical signal can be improved.

In some examples, in step S400, the analyte monitoring method may include obtaining a correction factor based on a ratio of a background noise signal of the working electrode 202 to a background noise signal of the blank electrode 203, a ratio of a thickness of the second film layer 212 to a thickness of the first film layer 211. In this case, the correction factor can reduce the deviation of the first interference signal and the second interference signal due to the difference between the background noise signal of the working electrode 202 and the background noise signal of the blank electrode 203, and the difference between the thickness of the second film layer 212 and the thickness of the first film layer 211.

In some examples, in step S400, the correction factor may be obtained based on the product of the first ratio and the third ratio, that is, may have the formula 4:f =f ₁×f₃. In this case, by correcting the second electric signal by combining two factors, that is, the difference between the film thickness and the difference between the electrode background noise signals, the difference between the background noise signal of the working electrode 202 and the background noise signal of the blank electrode 203 and the deviation between the first interference signal and the second interference signal due to the difference between the thickness of the first film 211 and the thickness of the second film 212 can be reduced at the same time, whereby the measurement accuracy of the concentration value of the analyte can be further improved.

In some examples, in step S400, the analyte monitoring method may include obtaining a correction factor based on a ratio of a background noise signal of the working electrode 202 to a background noise signal of the blank electrode 203, a ratio of a surface area of the working electrode 202 to a surface area of the blank electrode 203. In this case, the correction factor can reduce the deviation of the first interference signal from the second interference signal due to the difference between the background noise signal of the working electrode 202 and the background noise signal of the blank electrode 203, and the difference between the surface area of the working electrode 202 and the surface area of the blank electrode 203.

In some examples, in step S400, the correction factor may be obtained based on the product of the second ratio and the third ratio, that is, may have the formula 5:f =f ₂×f₃. In this case, by correcting the second electric signal by combining two factors, i.e., the difference between the electrode surface areas and the difference between the electrode background noise signals, it is possible to simultaneously reduce the deviation between the first and second disturbance signals due to the difference between the background noise signal of the working electrode 202 and the background noise signal of the blank electrode 203, and the difference between the surface areas of the working electrode 202 and the blank electrode 203, whereby the measurement accuracy of the concentration value of the analyte can be further improved.

In some examples, in step S400, the analyte monitoring method may include obtaining a correction factor based on the first ratio, the second ratio, and the third ratio. In this case, the correction factor can reduce the deviation of the first interference signal and the second interference signal due to the difference between the background noise signal of the working electrode 202 and the background noise signal of the blank electrode 203, the difference between the surface area of the working electrode 202 and the surface area of the blank electrode 203, and the difference between the thickness of the second film 212 and the thickness of the first film 211. Thereby, the measurement accuracy of the concentration value of the analyte can be further improved.

In some examples, in step S400, the correction factor may be obtained based on the product of the first ratio, the second ratio, and the third ratio, that is, may have the formula 6:f =f ₁×f₂×f₃. In this case, by correcting the second electric signal by integrating three factors, that is, the difference between the electrode surface areas, the difference between the electrode background noise signals, and the difference between the electrode surface areas, the deviation between the first interference signal and the second interference signal due to the difference between the background noise signal of the working electrode 202 and the background noise signal of the blank electrode 203, the difference between the thickness of the second film 212 and the thickness of the first film 211, and the difference between the surface area of the working electrode 202 and the surface area of the blank electrode 203 can be reduced at the same time, whereby the measurement accuracy of the concentration value of the analyte can be further improved.

In some examples, in step S400, the analyte monitoring method may include obtaining a correction factor based on at least one of a ratio of a thickness of the second film layer 212 to a thickness of the first film layer 211, a ratio of a background noise signal of the working electrode 202 to a background noise signal of the blanking electrode 203, and a ratio of a surface area of the working electrode 202 to a surface area of the blanking electrode 203. In this case, the correction factor can include a plurality of factors that cause a deviation between the first interference signal and the second interference signal, whereby the accuracy of analyte monitoring can be further improved.

In some examples, in step S600, an analyte electrical signal may be obtained based on the first electrical signal, the second electrical signal, and the correction factor.

In some examples, in step S600, a correction signal may be obtained based on the second electrical signal and the correction factor.

In some examples, in step S600, the correction signal may be obtained based on the product of the correction factor and the second electrical signal, i.e., may have formula 7:I ₃＝f×I₂.

In some examples, in step S600, an analyte electrical signal may be obtained based on the first electrical signal and the correction signal. In this case, the correction signal can be obtained using the correction factor and the second electric signal, which can be substantially equivalent to the first interference signal, whereby an analyte electric signal with high accuracy can be obtained based on the first electric signal and the correction signal, that is, the measurement accuracy of the concentration value of the analyte can be improved.

In some examples, in step S600, the analyte electrical signal may be equal to the first electrical signal minus the correction signal, i.e., may have the formula 8:I =i ₁-I₃.

The analyte monitoring method according to the first aspect will be described below by way of example with respect to a glucose monitoring system. In this embodiment, the glucose monitoring system may be one specific application of the analyte monitoring system 10 set forth in the second aspect of the present disclosure.

In some examples, the glucose monitoring system may include a glucose sensor (simply referred to as sensor 20), and the sensor 20 may take the configuration shown in fig. 2, wherein the sensing layer 2021 may be glucose oxidase or glucose dehydrogenase.

Fig. 4 is a schematic diagram showing test results of embodiment 1 related to examples of the present disclosure. Fig. 5 is a schematic diagram showing test results of embodiment 2 related to examples of the present disclosure. Fig. 6 is a schematic diagram showing background noise signals of a working electrode and a blank electrode according to an example of the present disclosure. Fig. 7 is a schematic diagram showing test results of embodiment 3 related to an example of the present disclosure.

[ Example 1]

A sensor of example 1 having a working electrode and a blank electrode was prepared, the surface of the working electrode being covered with a semipermeable membrane (first membrane layer) and the surface of the blank electrode being covered with a semipermeable membrane (second membrane layer).

First, the thicknesses of the first film layer and the second film layer on the sensor of example 1 were measured by an optical measuring instrument, and the ratio of the thickness of the second film layer to the thickness of the first film layer, i.e., f ₁, was 1.04, and was substituted into the formula 1:f =f ₁, where f was 1.04. The film thickness is measured by taking the average value of data of a plurality of sites on the film as the film thickness.

Next, the sensor of example 1 was placed in a test solution containing 5mM glucose, and a voltage of 50mV was applied to the working electrode and the blank electrode for 20 minutes, to obtain a time-current diagram (0 minutes to 20 minutes section in fig. 4) as shown in fig. 4.

Next, the sensor was placed in a mixed solution containing 5mM glucose and 0.085mM ascorbic acid (interfering substance), and a voltage of 50mV was applied to the working electrode and the blank electrode for 20 minutes, to obtain a time-current diagram (20 minutes to 40 minutes section in fig. 4) as shown in fig. 4. In other words, fig. 4 is a schematic diagram showing the test results of embodiment 1 related to the examples of the present disclosure.

In fig. 4, the results (curve 1) of 0 to 20 minutes are test results of placing the sensor in a solution containing glucose and no interfering substance, and the results of 20 to 40 minutes are test results of placing the sensor in a solution containing glucose and no interfering substance. As can be seen from fig. 4, the current between the working electrode and the counter electrode was measured to be 5.7nA (i.e., the analyte electrical signal representing the net analyte concentration was 5.7 nA) at a period between 0 minutes and 20 minutes (curve 1). In the period between 20 minutes and 40 minutes, curve 2 is the curve of the first electrical signal measured by the working electrode, the first electrical signal I ₁ measured by the working electrode is 7.8nA after stabilization, curve 3 is the curve of the second electrical signal measured by the blank electrode, the second electrical signal I ₂ measured by the blank electrode is 1.9nA after stabilization, and curve 4 is the result of i=i ₁-f×I₂ using the above-mentioned formula 7 and formula 8, resulting in the analyte electrical signal I being 5.82nA.

As can be seen by comparison, assuming that the sensor does not have a blank electrode, the measurement accuracy is about 37% error (this error is calculated from (first electric signal-analyte electric signal)/analyte electric signal×100% (7.8-5.7)/5.7X100% ≡37%), and the measurement accuracy is about 2% error with the sensor including a blank electrode and taking the correction factor into consideration. Thus, by providing the blank electrode in the sensor, and taking into consideration the difference between the thickness of the first film layer covering the working electrode and the thickness of the second film layer covering the blank electrode, the measurement accuracy of the sensor can be improved.

[ Example 2]

A sensor of example 2 having a working electrode and a blank electrode was prepared, the surface of the working electrode being covered with a semipermeable membrane (first membrane layer) and the surface of the blank electrode being covered with a semipermeable membrane (second membrane layer).

First, the surface area of the working electrode and the surface area of the blank electrode, the thickness of the second film layer and the thickness of the first film layer on the sensor of example 2 were measured by an optical measuring instrument, and the ratio of the surface area of the working electrode to the surface area of the blank electrode, that is, f ₂ was 0.77, the ratio of the thickness of the second film layer to the thickness of the first film layer, that is, f ₁ was 1.04, was substituted into the formula 3:f =f ₁×f₂, and f was 0.8.

Next, the sensor of example 2 was placed in a test solution containing 5mM glucose, and a voltage of 50mV was applied to the working electrode and the blank electrode for 20 minutes, to obtain a time-current diagram (0 minutes to 20 minutes part in fig. 5) as shown in fig. 5.

Next, the sensor was placed in a mixed solution containing 5mM glucose and 0.085mM ascorbic acid (interfering substance), and a voltage of 50mV was applied to the working electrode and the blank electrode for 20 minutes, to obtain a time-current diagram (20 minutes to 40 minutes section in fig. 5) as shown in fig. 5. In other words, fig. 5 is a schematic diagram showing the test results of embodiment 2 related to the examples of the present disclosure.

In fig. 5, the results (curve 5) of 0 to 20 minutes are test results of placing the sensor in a solution containing glucose and no interfering substance, and the results of 20 to 40 minutes are test results of placing the sensor in a solution containing glucose and no interfering substance. As can be seen from fig. 5, the current between the working electrode and the counter electrode was measured to be 5.7nA (i.e., the analyte electrical signal representing the net analyte concentration was 5.7 nA) at a period between 0 minutes and 20 minutes (curve 5). In the period between 20 minutes and 40 minutes, curve 6 is a graph of a first electrical signal measured by the working electrode, the first electrical signal I ₁ measured by the working electrode is 7.4nA after stabilization, curve 7 is a graph of a second electrical signal measured by the blank electrode, the second electrical signal I ₂ measured by the blank electrode is 2.0nA after stabilization, and curve 8 is a graph obtained by using the above-mentioned formula 7 and formula 8, i=i ₁-f×I₂, and the analyte electrical signal I is 5.8nA.

As can be seen by comparison, assuming that the sensor does not have a blank electrode, there is an error of about 29.82% (this error is calculated from (first electrical signal-analyte electrical signal)/analyte electrical signal x 100%, (7.4-5.7)/5.7x100% ≡29.82%), and the measurement accuracy is about 1.75% error with the sensor including a blank electrode and taking the correction factor into account. Thus, by providing the blank electrode in the sensor, and taking into consideration the difference between the surface area of the working electrode and the surface area of the blank electrode, the difference between the thickness of the second film layer and the thickness of the first film layer, the measurement accuracy of the sensor can be further improved.

[ Example 3]

A sensor of example 3 was prepared having a working electrode and a blank electrode, the surface of the working electrode being covered with a semipermeable membrane (first membrane layer) and the surface of the blank electrode being covered with a semipermeable membrane (second membrane layer).

First, the thicknesses of the first film layer and the second film layer, the surface area of the working electrode and the surface area of the blank electrode, and the ratio of the surface area of the working electrode to the surface area of the blank electrode, that is, f ₂, was 0.77, and the ratio of the thickness of the second film layer to the thickness of the first film layer, that is, f ₁, was 1.04 were measured on the sensor of example 3 by an optical measuring instrument.

Next, the sensor of example 3 was placed in a phosphate buffer (also referred to as PBS buffer) (i.e., a solution containing no glucose and interfering substances), and a 50mV voltage was applied to the working electrode and the blank electrode for 20 minutes, to obtain a background noise signal time-current diagram of the working electrode and the blank electrode as shown in fig. 6.

Next, the sensor of example 3 was placed in a test solution containing 5mM glucose, and a 50mV voltage was applied to the working electrode and the blank electrode for 20 minutes, to obtain a time-current diagram (0 minutes to 20 minutes portion in fig. 7) as shown in fig. 7.

Then, the sensor was placed in a mixed solution containing 5mM glucose and 0.085mM ascorbic acid (interfering substance), and a voltage of 50mV was applied to the working electrode and the blank electrode for 20 minutes, to obtain a time-current diagram (20 minutes to 40 minutes section in FIG. 7) as shown in FIG. 7. In other words, fig. 7 is a schematic diagram showing the test results of embodiment 3 related to the example of the present disclosure.

In fig. 6, the current signal between the working electrode and the counter electrode (curve 9) and the current signal between the blank electrode and the counter electrode (curve 10) were measured, wherein the current signal for the working electrode stabilization (curve 9) was 0.2nA, i.e., the background noise signal for the working electrode was 0.2nA, the current signal for the blank electrode stabilization (curve 10) was 0.18nA, i.e., the background noise signal for the blank electrode was 0.18nA, whereby the ratio of the background noise signal for the working electrode to the background noise signal for the blank electrode, i.e., f ₃, was 1.11, and therefore in example 3, the substitution formula 6:f =f ₁×f₂×f₃, f was 0.89.

In fig. 7, the results (curve 11) of 0 to 20 minutes are test results of placing the sensor in a solution containing glucose and no interfering substance, and 20 to 40 minutes are test results of placing the sensor in a solution containing glucose and no interfering substance. As can be seen from fig. 7, at a period between 0 minutes and 20 minutes (curve 11), the current between the working electrode and the counter electrode was measured to be 5.9nA (i.e., the analyte electrical signal representing the net analyte concentration was 5.9 nA). In the period between 20 minutes and 40 minutes, curve 12 is a graph of the first electrical signal measured by the working electrode, after stabilization, the first electrical signal I ₁ measured by the working electrode is measured to be 7.67nA, curve 13 is a graph of the second electrical signal measured by the blank electrode, similarly, the second electrical signal I ₂ measured by the blank electrode is measured to be 1.9nA, and curve 14 is obtained by using the above-mentioned formula 7 and formula 8, i=i ₁-f×I₂, and the analyte electrical signal I is obtained to be 5.98nA.

As can be seen by comparison, assuming that the sensor does not have a blank electrode, there is an error of about 30% (this error is calculated from (first electric signal-analyte electric signal)/analyte electric signal×100%) (7.67-5.9)/5.9×100% ≡30%), and the measurement accuracy is about 1.36% error with the sensor including a blank electrode and taking the correction factor into consideration. Therefore, by arranging the blank electrode in the sensor, and taking the difference between the surface area of the working electrode and the surface area of the blank electrode, the difference between the thickness of the second film layer and the thickness of the first film layer into consideration, the measuring accuracy of the sensor can be further improved under the condition of the difference between the background noise signal of the working electrode and the background noise signal of the blank electrode.

In one analyte monitoring system 10 of the third aspect of the present disclosure, the analyte monitoring system 10 may obtain an analyte electrical signal by performing the analyte monitoring method according to the first aspect, the analyte monitoring system 10 may comprise a processing device 40, and the processing device 40 may be configured to perform the analyte monitoring method. In this case, the correction factor can reduce the deviation between the first interference signal measured by the working electrode 202 and the second interference signal measured by the blank electrode 203 due to the difference between the working electrode 202 and the blank electrode 203, so that the analyte monitoring system 10 can obtain a more accurate analyte electrical signal, that is, a more accurate concentration value of the analyte, from the first electrical signal based on the second interference signal measured by the blank electrode 203, and the correction factor measured by the working electrode 202, thereby improving the accuracy of the analyte monitoring system 10.

While the disclosure has been described in detail in connection with the drawings and examples, it is to be understood that the foregoing description is not intended to limit the disclosure in any way. Modifications and variations of the present disclosure may be made as desired by those skilled in the art without departing from the true spirit and scope of the disclosure, and such modifications and variations fall within the scope of the disclosure.

Claims

1. An analyte monitoring method, comprising acquiring an analyte electrical signal via a sensor, characterized in that the sensor includes a working electrode, a blank electrode, and a film layer at least partially covering the working electrode and the blank electrode; the working electrode is used to acquire a first electrical signal including the analyte electrical signal and a first interference signal; the blank electrode is used to acquire a second electrical signal including a second interference signal; the film layer covering the working electrode is designated as a first film layer; and the film layer covering the blank electrode is designated as a second film layer; the analyte monitoring method comprises: acquiring the first electrical signal and the second electrical signal; setting a first ratio for the thickness of the second film layer to the thickness of the first film layer; setting a second ratio for the surface area of the working electrode to the surface area of the blank electrode; setting a third ratio for the background noise signal of the working electrode to the background noise signal of the blank electrode; acquiring a correction factor characterizing the deviation between the first interference signal and the second interference signal based on the first ratio, the second ratio, and the third ratio; and obtaining the analyte electrical signal based on the first electrical signal, the second electrical signal, and the correction factor.

2. The analyte monitoring method according to claim 1, wherein the sensor includes a substrate, and the working electrode and the blank electrode are located on opposite sides of the substrate.

3. The analyte monitoring method according to any one of claims 1 to 2, characterized in that a correction signal is obtained based on the second electrical signal and the correction factor, and the analyte electrical signal is obtained based on the first electrical signal and the correction signal.

4. A readable storage medium, characterized in that the readable storage medium stores at least one instruction, which, when executed by a processor, implements the analyte monitoring method as described in any one of claims 1 to 3.

5. An analyte monitoring system, characterized in that the analyte monitoring system acquires an analyte electrical signal by executing the analyte monitoring method according to any one of claims 1 to 3, the analyte monitoring system comprising a processing device configured to execute the analyte monitoring method.