Analyte monitoring methods, readable storage medium, and analyte monitoring systems

Abstract

The present disclosure describes an analyte monitoring method, a readable storage medium and an analyte monitoring system, the analyte monitoring method comprising: obtaining a first electrical signal and a second electrical signal; obtaining a correction factor for characterizing a deviation of a first interference signal and a second interference signal based on a ratio of a thickness of the second membrane layer and a thickness of the first membrane layer; obtaining an analyte electrical signal based on the first electrical signal, the second electrical signal and the correction factor. In this way, the accuracy of the monitored analyte electrical signal, i.e. the accuracy of the monitored analyte concentration value, can be improved.

Description

TECHNICAL FIELD

[0001] The present disclosure relates generally to the biopharmaceutical industry, and in particular to an analyte monitoring method, readable storage medium and analyte monitoring system. BACKGROUND

[0002] Monitoring the concentration of at least one analyte in a living body plays an important role in preventing and treating various diseases. The analyte can include, but is not limited to, glucose, lactic acid, blood ketone or other types of analyte. For example, for diabetic patients, timely acquisition of the patient's blood glucose level is beneficial for timely implementation of rescue measures. A continuous glucose monitoring system (CGM) is a mobile device for diabetic patients, which inserts a sensor with enzymes under the skin to react with glucose in tissue fluid or blood in the body to generate an electrical signal. According to the relationship between the detected electrical signal and the glucose concentration, the detection of the analyte is realized, which can test the blood glucose level all day long and obtain real-time blood glucose level information.

[0003] The accuracy of analyte concentration monitoring is very critical for patient treatment. For example, diabetic patients need to refer to the concentration of blood glucose monitoring for insulin injection treatment, so inaccurate blood glucose detection will bring very high risk to patients. In actual operation, a blank electrode without enzyme is arranged on the sensor for detecting interference signals, and the output of the working electrode is detected and compared with the output of the blank electrode to reduce the monitoring error caused by interference signals. Thus, the concentration of the analyte is obtained more accurately.

[0004] However, due to the slight differences in structure and other aspects between the working electrode and the blank electrode, there will be a certain shift or deviation between the interference signals measured by the blank electrode and the interference signals measured by the working electrode. Therefore, it is difficult to effectively reduce the measurement error of the analyte concentration by only comparing the output of the working electrode with the output of the blank electrode. SUMMARY

[0005] The present disclosure is proposed in view of the above situation, and aims to provide an analyte monitoring method, readable storage medium and analyte monitoring system, which can improve the accuracy of the monitored analyte electrical signal.

[0006] To this end, a first aspect of the present disclosure provides an analyte monitoring method, which is a method for obtaining 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 obtain a first electrical signal comprising the analyte electrical signal and a first interference signal, the blank electrode being configured to obtain a second electrical signal comprising 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: obtaining the first electrical signal and the second electrical signal; obtaining a correction factor for characterizing a deviation between the first interference signal and 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 obtaining the analyte electrical signal based on the first electrical signal, the second electrical signal, and the correction factor.

[0007] In the present disclosure, the sensor is capable of measuring the first electrical signal comprising the first interference signal and the second electrical signal comprising the second interference signal by the working electrode and the blank electrode respectively, and the first interference signal is negatively correlated with the thickness of the first membrane layer and the second interference signal can be negatively correlated with the thickness of the second membrane layer, in which case, the correction factor is obtained based on the ratio of the thickness of the second membrane layer to the thickness of the first membrane layer, so that the correction factor is capable of reducing the deviation between the first interference signal and the second interference signal caused by the difference between the thickness of the second membrane layer and the thickness of the first membrane layer, thereby obtaining a more accurate analyte electrical signal based on the first electrical signal, the second electrical signal, and the correction factor, i.e., improving the accuracy of the monitored analyte electrical signal.

[0008] In addition, in the analyte monitoring method of the first aspect of the present disclosure, optionally, the deviation between the first interference signal and the second interference signal further comprises a deviation caused by the difference between the surface area of the working electrode and the surface area of the blank electrode, and the analyte monitoring method further comprises: obtaining the correction factor based on the ratio of the surface area of the working electrode to the surface area of the blank electrode. In this case, considering that the surface area of the electrode is positively correlated with the size of the interference signal, the correction factor is obtained by dividing the surface area of the working electrode by the surface area of the blank electrode, so that the correction factor is capable of reducing the deviation between the first interference signal and the second interference signal caused by the difference between the surface area of the blank electrode and the surface area of the working electrode, thereby obtaining a more accurate analyte electrical signal based on the first electrical signal, the second electrical signal, and the correction factor, i.e., improving the accuracy of the monitored analyte electrical signal.

[0009] In addition, in the analyte monitoring method according to the first aspect of the present disclosure, optionally, a ratio of the thickness of the second membrane layer to the thickness of the first membrane layer is a first ratio, a ratio of the surface area of the working electrode to the surface area of the blank electrode is 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 electrical signal by comprehensively considering both the difference between the thicknesses of the membrane layers and the difference between the surface areas of the electrodes, the deviation between the first interference signal and the second interference signal caused by the difference between the surface areas of the working electrode and the blank electrode and the difference between the thickness of the first membrane layer and the thickness of the second membrane layer can be reduced, and thus the measurement accuracy of the concentration value of the analyte can be further improved.

[0010] In addition, in the analyte monitoring method according to the first aspect of the present disclosure, optionally, the deviation between the first interference signal and the second interference signal also includes a deviation caused by the difference between the background noise signal of the working electrode and the 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, considering that the background noise signal of the electrode is positively correlated with the size of the interference signal, the correction factor is obtained by dividing the background noise signal of the working electrode by 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, i.e., the accuracy of the monitored analyte electrical signal can be improved.

[0011] In addition, in the analyte monitoring method according to the first aspect of the present disclosure, optionally, a ratio of the thickness of the second membrane layer to the thickness of the first membrane layer is a first ratio, a ratio of the background noise signal of the working electrode to the background noise signal of the blank electrode is 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 electrical signal by comprehensively considering both the difference between the thicknesses of the membrane layers and the difference between the background noise signals of the electrodes, the deviation between the first interference signal and the second interference signal caused by the difference between the background noise signal of the working electrode and the background noise signal of the blank electrode and the difference between the thickness of the first membrane layer and the thickness of the second membrane layer can be reduced, and thus the measurement accuracy of the concentration value of the analyte can be further improved.

[0012] In addition, in the analyte monitoring method of the first aspect of the present disclosure, optionally, the deviation of the first interference signal from the second interference signal includes a deviation caused by 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: setting a ratio of the surface area of the working electrode to the surface area of the blank electrode as 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 from the second interference signal caused by a difference between a background noise signal of the working electrode and a background noise signal of the blank electrode, a difference between the surface area of the working electrode and the surface area of the blank electrode, and a difference between a thickness of the second membrane layer and a thickness of the first membrane layer. Thus, the measurement accuracy of the concentration value of the analyte can be further improved.

[0013] In addition, in the analyte monitoring method of 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 separating the working electrode and the blank electrode, the mutual interference between the working electrode and the blank electrode can be reduced, and thus the sensitivity of the sensor can be improved.

[0014] In addition, in the analyte monitoring method of the first aspect of the present disclosure, optionally, a corrected signal is obtained based on the second electric signal and the correction factor, and the analyte electric signal is obtained based on the first electric signal and the corrected signal. In this case, the corrected signal can be obtained based on the correction factor and the second electric signal, and the corrected signal can be substantially equivalent to the first interference signal. Thus, the analyte electric signal with high accuracy can be obtained based on the first electric signal and the corrected signal, and thus the measurement accuracy of the concentration value of the analyte can be improved.

[0015] The second aspect of the present disclosure provides a readable storage medium storing at least one instruction, and the at least one instruction is executed by a processor to implement the analyte monitoring method of any one of the first aspect. Thus, the analyte monitoring method can be automatically processed by using a computer device.

[0016] The third aspect of the present disclosure provides an analyte monitoring system, which obtains the analyte electrical signal by performing the analyte monitoring method according to any one of the first aspect. The analyte monitoring system comprises 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, i.e. 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.

[0017] According to the present disclosure, an analyte monitoring method, a readable storage medium and an analyte monitoring system can be provided, and the accuracy of analyte monitoring can be improved. BRIEF DESCRIPTION OF DRAWINGS

[0018] The present disclosure will now be explained in further detail by way of example only with reference to the accompanying drawings.

[0019] Figure 1A FIG. 1 is a diagram illustrating an application scenario of an analyte monitoring system according to an example of the present disclosure.

[0020] Figure 1B FIG. 2 is a schematic diagram illustrating a sensor according to an example of the present disclosure.

[0021] Figure 1C FIG. 3 is a block diagram illustrating an analyte monitoring system according to an example of the present disclosure.

[0022] Figure 1D FIG. 4 is a block diagram illustrating an electronic module according to an example of the present disclosure.

[0023] Figure 2 FIG. 5 is a schematic diagram illustrating an embodiment of a sensor according to an example of the present disclosure.

[0024] Figure 3A FIG. 6 is a first flowchart illustrating an analyte monitoring method according to an example of the present disclosure.

[0025] Figure 3B FIG. 7 is a second flowchart illustrating an analyte monitoring method according to an example of the present disclosure.

[0026] Figure 4 FIG. 8 is a diagram illustrating test results of Example 1 according to an example of the present disclosure.

[0027] Figure 5 FIG. 9 is a diagram illustrating test results of Example 2 according to an example of the present disclosure.

[0028] Figure 6 is a schematic diagram showing background noise signals of a working electrode and a blank electrode involved in the example of the present disclosure.

[0029] Figure 7 is a schematic diagram showing test results of Example 3 involved in the example of the present disclosure. DETAILED DESCRIPTION

[0030] The technical solutions in the embodiments of the present disclosure will be clearly and completely described below with reference to the drawings in the embodiments of the present disclosure. Obviously, the described embodiments are only part of the embodiments of the present disclosure, rather than all the embodiments. Based on the embodiments in the present disclosure, all other embodiments filled by those skilled in the art without creative labor are within the scope of protection of the present disclosure.

[0031] It should be noted that the terms "first", "second", "third", and "fourth" and the like in the specification and claims of the present disclosure and the above-described drawings are used to distinguish different objects, and are not used to describe a specific order. It should be noted that the terms "include" and "have" and any variations thereof in the present disclosure, such as a process, method, system, product, or device including or having a series of steps or units, do not necessarily limit to those clearly listed steps or units, but can include or have other steps or units not clearly listed or inherent to these processes, methods, products, or devices.

[0032] Hereinafter, preferred embodiments of the present disclosure will be described in detail with reference to the accompanying drawings. In the following description, the same parts are given the same reference numerals, and repeated description is omitted. In addition, the drawings are only schematic views, and the ratio of the size between the components or the shape of the components, etc. can be different from the actual ones.

[0033] In the present disclosure, unless otherwise explicitly specified and limited, the term "connection" should be understood broadly, for example, "connection" can be fixed connection, or detachable connection, or integral; can be directly connected, or indirectly connected through an intermediate medium. In addition, the term "coupling" can be an electrically connected manner for realizing signal transmission, and "coupling" can be direct electrically connected, or indirectly electrically connected through an intermediate medium. In addition, the term "accuracy" can be understood as the degree of conformity between the measured value and the true value (correct standard).

[0034] An electrochemical biosensor is a device that utilizes a biological reaction to detect a specific analyte. When a specific analyte (such as glucose, lactate, uric acid, protein, or a drug, etc.) has a biological reaction (such as an enzyme reaction or an immune reaction) with the sensor, an electrochemical reaction, such as the transfer of electrons, the transfer of ions, etc., will occur. These electrochemical reactions can be detected by the sensor and converted into an electrical signal, which can be referred to as an analyte electrical signal, and can be used to reflect the content of the specific analyte, i.e., the concentration value of the analyte. In some examples, the electrical signal can be a current signal or a voltage signal. In the present disclosure, the specific form of the electrical signal is not limited.

[0035] A first aspect of the present disclosure provides an analyte monitoring method, which can also be referred to as an analyte monitoring method for reducing interference signals or a method for improving analyte monitoring accuracy.

[0036] A second aspect of the present disclosure provides a readable storage medium, which can store at least one instruction. The at least one instruction can be executed by a processor to implement the analyte monitoring method of the first aspect of the present disclosure. Thus, it is convenient to use a computer device to implement the analyte monitoring method automatically.

[0037] A third aspect of the present disclosure provides an analyte monitoring system, which can also be referred to as an analyte monitoring device. The analyte monitoring system can obtain an analyte electrical signal by executing the analyte monitoring method according to the first aspect of the present disclosure.

[0038] In the present disclosure, the term "analyte" can be a chemical compound present in a solution. In some examples, the analyte can be one or more of acetylcholine, amylase, bilirubin, cholesterol, chorionic gonadotropin, creatine kinase, creatine, creatinine, DNA, fructosamine, glucose, glutamine, growth hormone, hormone, ketone body, lactate, oxygen, peroxide, prostate specific antigen, prothrombin, RNA, thyroid stimulating hormone, or troponin. In addition, the analyte can also be a drug in a solution. For example, the analyte can be digitalis glycoside, digoxin, theophylline, warfarin, or an antibiotic such as gentamicin or vancomycin, etc.

[0039] In some examples, the solution can be a body fluid of a human or an animal. In some examples, the solution can also be a test sample used in a laboratory environment. In the present disclosure, the human or the animal can be collectively referred to as a host.

[0040] Figure 1A FIG. 1 is a diagram illustrating an application scenario of an analyte monitoring system 10 according to an example of the present disclosure. Figure 1B FIG. 2 is a diagram illustrating a sensor 20 according to an example of the present disclosure. Figure 1Cis a block diagram illustrating an analyte monitoring system 10 according to an example of the present disclosure. Figure 1D is a block diagram illustrating an electronic module 30 according to an example of the present disclosure.

[0041] In some examples, referring to Figure 1A , the analyte monitoring system 10 can be applied to a host for monitoring a concentration value of an analyte in the host. In some examples, the analyte monitoring system 10 can be applied to a laboratory for in vitro experiments.

[0042] In some examples, referring to Figure 1A , the analyte monitoring system 10 can include a sensor 20. In this case, the sensor 20 is capable of generating an analyte electrical signal by electrochemically reacting with the analyte to represent a concentration value of the analyte.

[0043] In some examples, referring to Figure 1B , the sensor 20 can include a distal portion 20a and a proximal portion 20b, wherein the distal portion 20a can be placed at a selected site of the host, for example, the distal portion 20a can be implanted under a skin layer of the host to contact a body fluid in the host, and the proximal portion 20b can be provided with an electrical contact 201.

[0044] In some examples, referring to Figure 1C , the analyte monitoring system 10 can include an electronic module 30, and the sensor 20 can be electrically connected to the electronic module 30 through the electrical contact 201. Thus, the electrical signal measured by the sensor 20 can be transmitted to the electronic module 30 for processing.

[0045] In some examples, referring to Figure 1D , the electronic module 30 can 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 can be placed on a printed circuit board. Thus, the integration of the electronic module 30 can be improved.

[0046] In some examples, the signal processing element 32 can be an application specific integrated circuit (ASIC) chip. In some examples, the sensor 20 can be coupled to the signal processing element 32, and the signal processing element 32 can process the electrical signal measured by the sensor 20 and convert it into a third electrical signal. In some examples, the third electrical signal can be a digital signal. For example, the electrical signal obtained by the sensor 20 can be an analog signal, and the signal processing element 32 can convert the analog signal into a digital signal. Thus, the third electrical signal can be processed by digital processing techniques, such as digital filtering, etc.

[0047] In some examples, the signal transmission element 33 can transmit the third electrical signal to the outside through a communication link 331. In some examples, the communication link 331 can be a wireless transmission, in which case the form of the wireless transmission can be such that the data transmission is facilitated.

[0048] In some examples, the communication link 331 can be a wired transmission, for example, the communication link 331 can be a standard wired transmission cable such as a USB cable. In this way, the scope of application of the analyte monitoring system 10 can be improved.

[0049] In some examples, referring to Figure 1C , the analyte monitoring system 10 can further comprise a processing device 40 (see Figure 1C ), which can be configured to perform the analyte monitoring method proposed in the first aspect of the present disclosure (described in detail later).

[0050] In some examples, the processing device 40 can be integrated with the electronic module 30. In some examples, the processing device 40 can be a separate and independent device from the electronic module 30. In some examples, the processing device 40 can be integrated in the monitor 50 (described in detail later).

[0051] In some examples, referring to Figure 1D , the analyte monitoring system 10 can comprise a monitor 50. In this way, the concentration value of the analyte can be indicated by the monitor 50, facilitating the host to perceive the concentration value of the analyte.

[0052] In some examples, the monitor 50 can be coupled with the signal transmission element 33, and can receive, process and indicate the third electrical signal. In some examples, the monitor 50 can indicate the third electrical signal, i.e. the concentration value of the analyte, through an audible signal and / or a visual signal. In some examples, the audible signal can be a voice broadcast of the concentration value of the analyte or a voice alarm when the concentration value of the analyte exceeds a threshold value. In some examples, the visual signal can be a display of the concentration value of the analyte on the display screen of the monitor 50.

[0053] In some examples, the monitor 50 can be a smart terminal, for example, a smart mobile phone. In this way, the portability of the analyte monitoring system 10 can be improved, and the host can be able to monitor the concentration value of the analyte in daily life without the need to specially monitor the analyte in a hospital.

[0054] In some examples, the monitor 50 can also be an electronic measuring instrument, for example, the monitor 50 can be an oscilloscope, a current tester or other special measuring instrument. In this case, the concentration value of the analyte can be accurately measured by the special measuring instrument, and thus the analyte monitoring system 10 can be applicable to applications in a hospital environment or a laboratory environment.

[0055] Figure 2 is a schematic diagram showing an embodiment of a sensor 20 involved in examples of the present disclosure.

[0056] In some examples, referring to Figure 2 , the sensor 20 can include a working electrode 202, which can be used to obtain a first electrical signal, which can include an analyte electrical signal, which can also be referred to as a net analyte concentration value.

[0057] In some examples, the first electrical signal can also include a first interference signal, in other words, the first electrical signal can include an analyte electrical signal and a first interference signal. In this case, the analyte electrical signal can represent a concentration value of the analyte, and removing the first interference signal from the first electrical signal can obtain a more accurate concentration value of the analyte.

[0058] In some examples, the working electrode 202 can include a sensing layer 2021. In some examples, the sensing layer 2021 can facilitate an electrochemical reaction between the working electrode 202 and the analyte to generate the first electrical signal. Thus, the first electrical signal measured by the working electrode 202 can obtain a concentration value of the analyte.

[0059] In some examples, the sensing layer 2021 can also be referred to as a catalyst layer or an electroactive substance layer, and a catalyst layer corresponding to different analytes can be provided on the working electrode 202. In some examples, the sensing layer 2021 can be glucose oxidase or glucose dehydrogenase. In this case, for a glucose sensor, when the analyte is glucose or blood glucose, by providing glucose oxidase or glucose dehydrogenase on the working electrode 202, the working electrode 202 of the glucose sensor can electrochemically react with glucose or blood glucose, so that a first electrical signal including an analyte electrical signal can be obtained, where the analyte electrical signal can refer to an analyte electrical signal of a glucose concentration value.

[0060] In some examples, the sensor 20 can include a blank electrode 203, which can be used to obtain a second electrical signal, which can include a second interference signal.

[0061] In some examples, the blank electrode 203 can not include a sensing layer 2021. In other words, the blank electrode 203 can not electrochemically react with the analyte, i.e., the blank electrode 203 can not generate an analyte electrical signal related to the concentration value of the analyte. In this case, the second electrical signal measured by the blank electrode 203 can not include an electrical signal related to the analyte, i.e., the second electrical signal can be equivalent to the second interference signal.

[0062] In some examples, the first interference signal can include an electrical signal generated by an electrochemical reaction between a substance other than the analyte to be monitored in the solution and the working electrode 202. In some examples, the second interference signal can include an electrical signal generated by an electrochemical reaction between a substance other than the analyte to be monitored in the solution and the blank electrode 203.

[0063] In some examples, the first interference signal can also include a background noise signal generated by the working electrode 202 itself. In some examples, the second interference signal can also include a background noise signal generated by the blank electrode 203 itself. In the present disclosure, the background noise signal can be used to represent a noise signal that the working electrode 202 or the blank electrode 203 itself has, which can also be referred to as a bottom noise signal or bottom noise.

[0064] In some examples, compared with the working electrode 202, the blank electrode 203 is substantially the same as the working electrode 202 except that the blank electrode 203 does not have the sensing layer 2021. For example, the blank electrode 203 and the working electrode 202 can be made of the same material and have the same structure, and the working electrode 202 and the blank electrode 203 can 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, factors 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. Therefore, based on the first electrical signal and the second electrical signal, the analyte electrical signal, i.e., the net analyte concentration value, can be obtained more accurately from the first electrical signal.

[0065] In some examples, the sensor 20 can include a counter electrode 204. Thus, the working electrode 202 can form a first loop with the counter electrode 204 to generate the first electrical signal, and the blank electrode 203 can form a second loop with the counter electrode 204 to generate the second electrical signal.

[0066] In some examples, the working electrode 202 and the blank electrode 203 can be made of any one 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 have better electrical conductivity, so that the accuracy of the analyte monitoring system 10 can be improved.

[0067] In some examples, the working electrode 202 and the blank electrode 203 can be made of the same material. Thus, the deviation between the first interference signal and the second interference signal caused by the difference in the material of the working electrode 202 and the blank electrode 203 can be further reduced.

[0068] In some examples, the counter electrode 204 can be made of platinum, silver, silver chloride, palladium, titanium, or iridium. In this way, the electrochemical reaction at the working electrode 202 can be affected without affecting the electrical conductivity.

[0069] In some examples, the sensor 20 can include a 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 between the reference electrode 205 and the working electrode 202. In this way, the voltage generated by the working electrode 202 can be more accurately obtained. In this way, the voltage of the working electrode 202 can be automatically adjusted and maintained to be stable according to the pre-set 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, for example two.

[0070] In other examples, when the potential difference between the working electrode 202 and the solution does not fluctuate greatly, the reference electrode 205 can not be used. In this way, the manufacturing cost can be saved.

[0071] In some examples, referring to Figure 2 , the sensor 20 can include the working electrode 202, the blank electrode 203, the reference electrode 205, and the 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, and the blank electrode 203, the reference electrode 205, and the counter electrode 204 can form a second three-electrode system. By sharing the reference electrode 205 and the counter electrode 204, the related factors affecting the difference between the first interference signal and the second interference signal can be reduced, thereby facilitating the accurate obtaining of the analyte electrical signal from the first electrical signal.

[0072] In some examples, the sensor 20 can include a substrate 206. In this case, the substrate 206 can provide support for various electrodes of the sensor 20 and provide structural support for various electrodes, which can ensure the stability of the structure of the sensor 20 during use. In this way, the substrate 206 can enhance the mechanical strength of the sensor 20 and prevent the sensor 20 from deforming or breaking.

[0073] In some examples, the working electrode 202 and the blank electrode 203 can be located on two sides of the substrate 206, respectively. In this case, by separating the working electrode 202 and the blank electrode 203, the mutual interference between the working electrode 202 and the blank electrode 203 can be reduced, thereby improving the sensitivity of the sensor 20.

[0074] 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 disposing the various electrodes on the same substrate 206, the compactness of the sensor 20 can be improved, and the sensor 20 can be implanted in the skin layer of the host more easily.

[0075] In some examples, the working electrode 202, the blank electrode 203, the reference electrode 205, and the counter electrode 204 can be placed in a stacked structure on the substrate 206, see Figure 2 On one side of the substrate 206, the working electrode 202 and the reference electrode 205 can be stacked in sequence, and on the other side of the substrate 206, the blank electrode 203 and the counter electrode 204 can be stacked in sequence.

[0076] In this case, by arranging the electrodes in a stacked structure, the surface area of the working electrode 202 can be significantly increased, and a larger surface area can provide more sensing layer 2021, thereby improving the sensitivity of the sensor 20; the design of the stacked structure electrodes can allow the combination of different material layers, and the stacked structure of different material layers can complement each other, thereby improving the stability and durability of the sensor 20. For example, introducing a material with high stability as a protective layer can prevent oxidation, corrosion, or degradation of the electrodes, thereby prolonging the service life of the sensor 20; the sensor 20 usually needs to be small in size and portable, and by designing the stacked structure electrodes, more functional integration can be achieved in a limited space, and multiple functional layers can be integrated in a compact electrode structure, thereby improving the space utilization efficiency.

[0077] In some examples, see Figure 2 The sensor 20 can 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 layers, the occurrence of short circuits of the electrodes can be reduced.

[0078] In some examples, the substrate 206 can be a flexible substrate. The flexible substrate can be 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 can also be made of a metal foil, an ultrathin glass, a single-layer inorganic thin film, a multi-layer organic thin film, or a multi-layer inorganic thin film, etc.

[0079] In some examples, the sensor 20 can include a film layer covering at least part of the working electrode 202 and the blank electrode 203. The film layer covering the working electrode 202 can be a first film layer 211, and the film layer covering the blank electrode 203 can be a second film layer 212.

[0080] In some examples, the first membrane layer 211 and the second membrane layer 212 can have a thickness. In the present disclosure, the thickness of the first membrane layer 211 and the second membrane layer 212 can be obtained by selecting a plurality of predetermined points on the membrane layer, measuring the thickness of the positions where the predetermined points are located, and then taking the average of the thicknesses of the positions where the different predetermined points are located.

[0081] In some examples, the first membrane layer 211 and the second membrane layer 212 can include a semi-permeable membrane. In this case, the semi-permeable membrane can selectively allow the analyte to pass through while preventing other substances from passing through, thereby improving the accuracy of the monitoring; in addition, the membrane layers are arranged on the working electrode 202 and the blank electrode 203 at the same time, i.e., the working environment or structure of the working electrode 202 and the blank electrode 203 is kept consistent, thereby being able to reduce the deviation between the first interference signal and the second interference signal as much as possible.

[0082] In some examples, the semi-permeable membrane can include a diffusion control layer. In this case, the semi-permeable membrane can control the passing rate of the analyte, i.e., the semi-permeable membrane can limit the amount of analyte in the solution that reaches the sensing layer 2021, and can ensure that the sensing layer 2021 and other substances participating in the reaction are sufficient, so that the concentration of the analyte becomes the main factor (substantially the only factor) that limits the size of the first electrical signal, thereby enabling the size of the first electrical signal to accurately reflect the concentration of the analyte, and greatly increasing the linear range of the working electrode 202.

[0083] In some examples, the semi-permeable membrane can further include an anti-interference layer stacked on the diffusion control layer, and the anti-interference layer can prevent the diffusion of substances different from the analyte. In this way, the interference of substances different from the analyte on the detection of the concentration of the analyte can be reduced.

[0084] In some examples, the first membrane layer 211 and the second membrane layer 212 can include a biocompatible membrane, which can be arranged on the semi-permeable membrane. In this case, when the analyte monitoring system 10 is to be placed on a host body, and the sensor 20 is implanted into the skin layer of the host to be in contact with the body fluid or interstitial fluid, the immune response of the host to the sensor 20 can be reduced, thereby prolonging the service life of the sensor 20.

[0085] In some examples, when the analyte monitoring is performed on a solution containing an analyte, the solution often contains some interfering substances. For example, when a glucose sensor monitors glucose in a host, the blood or non-blood body fluid of the host often contains substances with strong reducing properties, such as ascorbic acid, uric acid, or acetaminophen. These interfering substances are prone to react with the working electrode 202 or the blank electrode 203, generating a first interference signal or a second interference signal. If the interference signal is large, it will cause the proportion of the first interference signal in the first electrical signal detected by the working electrode 202 to be large, thereby causing a large deviation between the first electrical signal and the analyte electrical signal in the first electrical signal, i.e., the accuracy of the first electrical signal in representing the concentration value of the analyte is low.

[0086] As described above, in some examples, the sensor 20 can include the blank electrode 203, so that the working electrode 202 and the blank electrode 203 participate in monitoring the concentration value of the analyte at the same time. After 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, a more accurate concentration value of the analyte can be obtained. In other words, the second interference signal can be equivalent to the first interference signal, and the value of the second electrical signal can be removed from the first electrical signal to obtain the analyte electrical signal.

[0087] However, in actual operation, there are usually differences between the blank electrode 203 and the working electrode 202, which cause the first interference signal to be usually not equal to the second interference signal, so that there is a deviation between the first interference signal and the second interference signal. In other words, assuming that the working electrode 202 and the blank electrode 203 are placed in the same solution environment at the same time and the solution does not contain the analyte, the electrical signals measured by the working electrode 202 and the blank electrode 203 are not the same, i.e., there is a deviation between the first interference signal and the second interference signal. In this case, when the analyte electrical signal is obtained by comparing the first electrical signal with the second electrical signal including the second interference signal, the accuracy of the obtained analyte electrical signal will be affected by the deviation between the first interference signal and the second interference signal.

[0088] The reason for the difference between the blank electrode 203 and the working electrode 202 can be the inconsistency caused by the error in the production process, or the difference caused by the different manufacturing processes of the blank electrode 203 and the working electrode 202. In the present disclosure, the reason for the difference between the blank electrode 203 and the working electrode 202 is not limited.

[0089] In some examples, the first interference signal can have a positive correlation with the surface area of the working electrode 202; the second interference signal can have a positive correlation with the surface area of the blank electrode 203. In this case, the greater the surface area of the working electrode 202, the greater the first interference signal generated by the electrochemical reaction of the interfering substance in the solution; similarly, the greater the surface area of the blank electrode 203, the greater the second interference signal generated by the electrochemical reaction of 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 deviation between the first interference signal and the second interference signal is large, and vice versa.

[0090] In some examples, the deviation between the first interference signal and the second interference signal can include a deviation caused by the difference between the surface area of the working electrode 202 and the surface area of the blank electrode 203, that is, when the surface area of the working electrode 202 is inconsistent with the surface area of the blank electrode 203, there will 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.

[0091] In some examples, the first interference signal can have a negative correlation with the thickness of the first film layer 211; the second interference signal can have a negative correlation with 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, thereby being able to cause the first interference signal generated by the electrochemical reaction of the working electrode 202 and the interfering substance to be smaller; similarly, the greater the thickness of the second film layer 212, the smaller the second interference signal. Thus, when the difference between the thickness of the first film layer 211 and the thickness of the second film layer 212 is large, the deviation between the first interference signal and the second interference signal is large, and vice versa.

[0092] In some examples, the deviation between the first interference signal and the second interference signal can include a deviation caused by the difference between the thickness of the second film layer 212 and the thickness of the first film layer 211, that is, when the thickness of the second film layer 212 is inconsistent with the thickness of the first film layer 211, there will 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.

[0093] In some examples, the first interference signal can have a positive correlation with the background noise signal of the working electrode 202; the second interference signal can have a positive correlation with the background noise signal of the blank electrode 203. In this case, the greater the background noise signal of the working electrode 202, the greater the first interference signal; the greater the background noise signal of the blank electrode 203, the greater the second interference signal.

[0094] In some examples, the deviation between the first interference signal and the second interference signal can include a deviation caused by a difference between 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 will 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.

[0095] 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 will be affected.

[0096] In the analyte monitoring method according to the first aspect of the present disclosure, the deviation between the first interference signal and the second interference signal can be corrected by using the correction factor, in other words, the corrected signal can 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 caused by the difference between the working electrode 202 and the blank electrode 203 can be reduced, and the corrected signal can be substantially equivalent to the first interference signal. Thus, a more accurate analyte electrical signal can be obtained by comparing the first electrical signal with the corrected signal, thereby improving the accuracy of analyte monitoring.

[0097] Figure 3A is a first flowchart illustrating an analyte monitoring method according to an example of the present disclosure. Figure 3B is a second flowchart illustrating an analyte monitoring method according to an example of the present disclosure.

[0098] In some examples, referring to Figure 3A , the analyte monitoring method can 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 membrane layer 212 to a thickness of the first membrane 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).

[0099] In the present disclosure, the sensor 20 can measure the first electrical signal including the first interference signal and the second electrical signal including the second interference signal by the working electrode 202 and the blank electrode 203 respectively, and the first interference signal can be negatively correlated with the thickness of the first film layer 211 and the second interference signal can be negatively correlated with the thickness of the second film layer 212, in which case, the correction factor can be obtained based on the 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 the deviation between the first interference signal and the second interference signal caused by the difference between the thickness of the second film layer 212 and the thickness of the first film layer 211, thereby 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.

[0100] In some examples, in step S200, the first electrical signal and the second electrical signal can be obtained, the first electrical signal can include the analyte electrical signal obtained by the working electrode 202 and the first interference signal, and the second electrical signal can include the second interference signal obtained by the blank electrode 203, thereby the analyte electrical signal can be obtained by comparing the first electrical signal and the second electrical signal.

[0101] In some examples, referring to Figure 3B , the analyte monitoring method can further include setting the working electrode 202 and the blank electrode 203 at a preset voltage potential (step S100). Thus, the electrochemical reactions of the working electrode 202 and the blank electrode 203 can be facilitated respectively, so as to generate the first electrical signal and the second electrical signal respectively.

[0102] In some examples, in step S100, the working electrode 202 and the blank electrode 203 can be set at a preset voltage potential by a potentiostat. In the present disclosure, the potentiostat can be understood as a circuit structure that can output the required constant voltage according to the actual needs.

[0103] In some examples, the electronic module 30 can include a potentiostat.

[0104] In some examples, the same preset voltage potential can be set on the working electrode 202 and the blank electrode 203. In this case, the deviation of the first interference signal and the second interference signal caused by the difference in potential between the working electrode 202 and the blank electrode 203 can be eliminated.

[0105] In some examples, different preset voltage potentials can be set on the working electrode 202 and the blank electrode 203. In this case, by setting different voltage potentials, the electrochemical reactions occurring on the working electrode 202 and the blank electrode 203 under different conditions can be facilitated.

[0106] In some examples, the preset voltage potential can be related to the type of the sensing layer 2021. For example, when the sensing layer 2021 is glucose dehydrogenase, the preset voltage potential applied on the working electrode 202 and the blank electrode 203 can be 50 mV, respectively.

[0107] In the present disclosure, for the 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, f1 represent the first ratio, f2 represent the second ratio, f3 represent the third ratio, I represent the analyte electrical signal, I1 represent the first electrical signal, I2 represent the second electrical signal, and I3 represent the corrected signal.

[0108] In some examples, in step S400, the correction factor can 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 can 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 can be equal to the first ratio, which can be Formula 1: f = f1. In this case, considering the negative correlation between the thickness of the film layer and the size of the interference signal, the correction factor is obtained by using the value of the thickness of the second film layer 212 divided by the thickness of the first film layer 211, and the corrected signal substantially equivalent to the first interference signal is obtained based on the correction factor and the second electrical signal, so that the correction factor can reduce the deviation of the first interference signal and the second interference signal caused by the difference between the thickness of the second film layer 212 and the thickness of the first film layer 211.

[0109] In some examples, the correction factor can be used to characterize the deviation of the first interference signal and the second interference signal. In this case, by introducing the correction factor and obtaining the corrected signal based on the correction factor and the second electrical signal, the corrected signal can be substantially equivalent to the first interference signal, that is, the correction factor can reduce the deviation of the first interference signal and the second interference signal caused by the difference between the working electrode 202 and the blank electrode 203 (such as the difference between the thickness of the second film layer 212 and the thickness of the first film layer 211), so that the measurement accuracy of the concentration value of the analyte can be improved by comparing the first electrical signal with the corrected signal.

[0110] In some examples, in step S400, the analyte monitoring method can comprise obtaining the correction factor based on a ratio of the surface area of the working electrode 202 to the surface area of the blank electrode 203. In other words, the correction factor can be equal to a value of the surface area of the working electrode 202 divided by the surface area of the blank electrode 203, i.e. the correction factor can be equal to the second ratio, which can be Formula 2: f = f2. In this case, considering that the surface area of the electrode is positively correlated with the size of the interference signal, the 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 between the first interference signal and the second interference signal caused by the difference between the surface area of the working electrode 202 and the surface area of the blank electrode 203, thereby obtaining a more accurate analyte electrical signal based on the first electrical signal, the second electrical signal, and the correction factor, i.e. improving the accuracy of the monitored analyte electrical signal.

[0111] In some examples, in step S400, the analyte monitoring method can comprise obtaining the correction factor based on a ratio of the surface area of the working electrode 202 to the surface area of the blank electrode 203, and a ratio of the thickness of the second membrane layer 212 to the thickness of the first membrane layer 211. In this case, the correction factor can reduce the deviation between the first interference signal and the second interference signal caused by 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 membrane layer 212 and the thickness of the first membrane layer 211.

[0112] In some examples, in step S400, the correction factor can be obtained based on a product of the first ratio and the second ratio, i.e. Formula 3: f = f1 x f2. In this case, by correcting the second electrical signal by comprehensively considering both the difference between the membrane thicknesses and the difference between the electrode surface areas, the deviation between the first interference signal and the second interference signal caused by the difference between the surface area of the blank electrode 203 and the working electrode 202, and the difference between the thickness of the first membrane layer 211 and the thickness of the second membrane layer 212 can be reduced, thereby further improving the measurement accuracy of the concentration value of the analyte.

[0113] In some examples, in step S400, the analyte monitoring method can comprise obtaining the correction factor based on a ratio of the background noise signal of the working electrode 202 to the background noise signal of the blank electrode 203. In other words, the correction factor can be equal to a 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 can be equal to the third ratio, which can be Formula 3: f = f3. In this case, considering that the background noise signal of the electrode is positively correlated with the size of the interference signal, the correction factor is obtained by dividing the background noise signal of the working electrode 202 by the background noise signal of the blank electrode 203, 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 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.

[0114] In some examples, in step S400, the analyte monitoring method can comprise obtaining the correction factor based on a ratio of the background noise signal of the working electrode 202 to the background noise signal of the blank electrode 203, a ratio of the thickness of the second membrane layer 212 to the thickness of the first membrane layer 211. In this case, 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 working electrode 202 and the background noise signal of the blank electrode 203, and the difference between the thickness of the second membrane layer 212 and the thickness of the first membrane layer 211.

[0115] In some examples, in step S400, the correction factor can be obtained based on a product of the first ratio and the third ratio, i.e. Formula 4: f = f1 x f3. In this case, by correcting the second electrical signal by comprehensively considering both the difference between the membrane layer thicknesses and the difference between the electrode background noise signals, the deviation between the first interference signal and the second interference signal caused by 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 first membrane layer 211 and the thickness of the second membrane layer 212 can be reduced, thereby further improving the measurement accuracy of the concentration value of the analyte.

[0116] In some examples, in step S400, the analyte monitoring method can include obtaining the correction factor based on a ratio of the background noise signal of the working electrode 202 to the background noise signal of the blank electrode 203, and a ratio of the surface area of the working electrode 202 to the surface area of the blank electrode 203. In this case, 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 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.

[0117] In some examples, in step S400, the correction factor can be obtained based on the product of the second ratio and the third ratio, i.e., there can be Formula 5: f = f2xf3. In this case, by correcting the second electrical signal by comprehensively considering both the difference between the electrode surface areas and the difference between the electrode background noise signals, the deviation between the first interference signal and the second interference signal caused by 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 can be reduced, thereby further improving the measurement accuracy of the concentration value of the analyte.

[0118] In some examples, in step S400, the analyte monitoring method can include 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 between the first interference signal and the second interference signal caused by 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 membrane layer 212 and the thickness of the first membrane layer 211. Thus, the measurement accuracy of the concentration value of the analyte can be further improved.

[0119] In some examples, in step S400, the correction factor can be obtained based on the product of the first ratio, the second ratio, and the third ratio, i.e., there can be Formula 6: f = f1xf2xf3. In this case, by correcting the second electrical signal by comprehensively considering three factors of 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 caused by 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 membrane layer 212 and the thickness of the first membrane layer 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, thereby further improving the measurement accuracy of the concentration value of the analyte.

[0120] In some examples, in step S400, the analyte monitoring method may include obtaining a correction factor based on at least one of the following: the ratio of the thickness of the second film layer 212 to the thickness of the first film layer 211, the ratio of the background noise signal of the working electrode 202 to the background noise signal of the blank electrode 203, and the ratio of the surface area of ​​the working electrode 202 to the surface area of ​​the blank electrode 203. In this case, the correction factor can include multiple factors that cause the deviation between the first interference signal and the second interference signal, thereby further improving the accuracy of analyte monitoring.

[0121] In some examples, in step S600, the analyte electrical signal can be obtained based on the first electrical signal, the second electrical signal, and the correction factor.

[0122] In some examples, in step S600, the correction signal can be obtained based on the second electrical signal and the correction factor.

[0123] In some examples, in step S600, the corrected signal can be obtained based on the product of the correction factor and the second electrical signal, that is, Formula 7: I3 = f × I2.

[0124] In some examples, in step S600, the analyte electrical signal can 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 electrical signal, which is essentially equivalent to the first interference signal. Thus, a highly accurate analyte electrical signal can be obtained based on the first electrical signal and the correction signal, thereby improving the measurement accuracy of the analyte concentration value.

[0125] In some examples, in step S600, the analyte electrical signal can be equal to the first electrical signal minus the correction signal, that is, it can be formula 8: I = I1 - I3.

[0126] The analyte monitoring method proposed in the first aspect will be described below using a glucose monitoring system as an example. In this embodiment, the glucose monitoring system can be a specific application of the analyte monitoring system 10 proposed in the second aspect of this disclosure.

[0127] In some examples, the glucose monitoring system may include a glucose sensor (referred to as sensor 20), which may employ, for example... Figure 2 The structure shown can be a glucose oxidase or a glucose dehydrogenase.

[0128] Figure 4 This is a schematic diagram illustrating the test results of Embodiment 1, which is an example of this disclosure. Figure 5 This is a schematic diagram illustrating the test results of Embodiment 2, which is an example of this disclosure. Figure 6is a schematic diagram showing background noise signals of a working electrode and a blank electrode involved in the example of the present disclosure. Figure 7 is a schematic diagram showing test results of Example 3 involved in the example of the present disclosure.

[0129]

Example 1

[0130] A sensor having a working electrode and a blank electrode of Example 1 was prepared, the surface of the working electrode was covered with a semi-permeable membrane (first membrane layer), and the surface of the blank electrode was covered with a semi-permeable membrane (second membrane layer).

[0131] First, the thicknesses of the first membrane layer and the second membrane layer on the sensor of Example 1 were measured by an optical measuring instrument, and the ratio of the thickness of the second membrane layer to the thickness of the first membrane layer, i.e., f1, was 1.04. Substituting f1 into Formula 1: f = f1, f was 1.04. Here, when measuring the thickness of the membrane layer, the data of multiple points on the membrane layer were measured and averaged to obtain the thickness of the membrane layer.

[0132] Second, the sensor of Example 1 was placed in a test solution containing 5 mM glucose, and a voltage of 50 mV was applied to the working electrode and the blank electrode for 20 minutes, obtaining a time-current graph (0 minute to 20 minute part in Figure 4 Figure 4

[0133] Next, the sensor was placed in a mixed solution containing 5 mM glucose and 0.085 mM ascorbic acid (interfering substance), and a voltage of 50 mV was applied to the working electrode and the blank electrode for 20 minutes, obtaining a time-current graph (20 minute to 40 minute part in Figure 4 Figure 4 Figure 4 is a schematic diagram showing test results of Example 1 involved in the example of the present disclosure.

[0134] In Figure 4 , the results (curve 1) from 0 minute to 20 minute were the test results of placing the sensor in a solution containing glucose and no interfering substance, and the results from 20 minute to 40 minute were the test results of placing the sensor in a solution containing glucose and an interfering substance. From Figure 4 ​​​​It can be seen that, in the period between 0 minute and 20 minute (curve 1), the current measured between the working electrode and the counter electrode is 5.7 nA (i.e. the analyte electrical signal representing the net analyte concentration is 5.7 nA). In the period between 20 minute and 40 minute, curve 2 is the curve of the first electrical signal measured by the working electrode, and the first electrical signal measured by the working electrode Ii is 7.8 nA after the measurement is stabilized; curve 3 is the curve of the second electrical signal measured by the blank electrode, and the second electrical signal measured by the blank electrode I2 is 1.9 nA after the measurement is stabilized; curve 4 is obtained by using the above-mentioned formula 7 and formula 8, i.e. I = Ii - f x I2, and the analyte electrical signal I is 5.82 nA.

[0135] It can be seen by comparison that, assuming that the sensor does not have the blank electrode, the measurement accuracy has an error of about 37% (calculated according to: (the first electrical signal - the analyte electrical signal) / the analyte electrical signal x 100%, (7.8 - 5.7) / 5.7 x 100% ≈ 37%), and in the case where the sensor includes the blank electrode and the correction factor is considered, the measurement accuracy has an error of about 2%. Thus, by providing the blank electrode in the sensor and considering 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.

[0136] [Example 2]

[0137] A sensor with a working electrode and a blank electrode of Example 2 is prepared, the surface of the working electrode is covered with a semi-permeable membrane (a first film layer), and the surface of the blank electrode is covered with a semi-permeable membrane (a second film layer).

[0138] First, the surface area of the working electrode and the surface area of the blank electrode of the sensor of Example 2, the thickness of the second film layer and the thickness of the first film layer are 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, i.e. f2 is 0.77, the ratio of the thickness of the second film layer to the thickness of the first film layer, i.e. f1 is 1.04, is obtained, and formula 3: f = f1 x f2, f is 0.8.

[0139] Secondly, the sensor of Example 2 is placed in a test solution containing 5 mM glucose, a voltage of 50 mV is applied to the working electrode and the blank electrode for 20 minutes, and a time-current graph (0 minute to 20 minute part) as shown in Figure 5 is obtained. Figure 5

[0140] Then, the sensor is placed in a mixed solution containing 5 mM glucose and 0.085 mM ascorbic acid (interfering substance), a voltage of 50 mV is applied to the working electrode and the blank electrode for 20 minutes, and a time-current graph (0 minute to 20 minute part) as shown in Figure 5 ​The time-current graph shown ( Figure 5 (The portion from 20 to 40 minutes). In other words, Figure 5 This is a schematic diagram illustrating the test results of Embodiment 2, which is an example of this disclosure.

[0141] exist Figure 5 In the figure, the results from 0 to 20 minutes (curve 5) represent the test results when the sensor was placed in a solution containing glucose and no interfering substances, while the results from 20 to 40 minutes represent the test results when the sensor was placed in a solution containing glucose and interfering substances. Figure 5 As can be seen, during the period from 0 to 20 minutes (curve 5), the current between the working electrode and the counter electrode was measured to be 5.7 nA (i.e., the analyte electrical signal representing the net analyte concentration was 5.7 nA). During the period from 20 to 40 minutes, curve 6 is the curve of the first electrical signal measured by the working electrode. After stabilization, the first electrical signal I1 measured by the working electrode was 7.4 nA. Curve 7 is the curve of the second electrical signal measured by the blank electrode. Similarly, after stabilization, the second electrical signal I2 measured by the blank electrode was 2.0 nA. Curve 8 is obtained by using the above formulas 7 and 8: I = I1 - f × I2, resulting in the analyte electrical signal I of 5.8 nA.

[0142] The comparison shows that, assuming the sensor has no blank electrode, the measurement accuracy is approximately 29.82% (this error is calculated based on: (first electrical signal - analyte electrical signal) / analyte electrical signal × 100%, (7.4 - 5.7) / 5.7 × 100% ≈ 29.82%). With the sensor including a blank electrode and considering the correction factor, the measurement accuracy is approximately 1.75%. Therefore, by incorporating a blank electrode into the sensor and considering the differences in surface area between the working electrode and the blank electrode, as well as the differences in thickness between the second and first films, the measurement accuracy of the sensor can be further improved.

[0143]

Example 3

[0144] Prepare a sensor with a working electrode and a blank electrode according to Example 3. The surface of the working electrode is covered with a semi-permeable membrane (first membrane layer), and the surface of the blank electrode is covered with a semi-permeable membrane (second membrane layer).

[0145] First, the thicknesses of the first and second films on the sensor of Example 3, the surface areas of the working electrode and the blank electrode are 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, i.e., f2 is 0.77, and the ratio of the thickness of the second film to the thickness of the first film, i.e., f1, is 1.04.

[0146] Next, the sensor from Example 3 was placed in phosphate buffer (also known as PBS buffer) (i.e., a solution free of glucose and interfering substances), and a voltage of 50 mV was applied to the working electrode and the blank electrode for 20 minutes to obtain the following results. Figure 6 The background noise signal time-current plots for the working electrode and the blank electrode are shown.

[0147] Next, the sensor from Example 3 was placed in a test solution containing 5 mM glucose, and a voltage of 50 mV was applied to the working electrode and the blank electrode for 20 minutes to obtain the following results. Figure 7 The time-current graph shown ( Figure 7 (0 to 20 minutes).

[0148] Then, the sensor was placed in a mixed solution containing 5 mM glucose and 0.085 mM ascorbic acid (interference substance), and a voltage of 50 mV was applied to the working electrode and the blank electrode for 20 minutes to obtain the following results. Figure 7 The time-current graph shown ( Figure 7 (The portion from 20 to 40 minutes). In other words, Figure 7 This is a schematic diagram illustrating the test results of Embodiment 3, which is an example of this disclosure.

[0149] exist Figure 6 In the process, 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. The stable current signal of the working electrode (curve 9) is 0.2nA, which means the background noise signal of the working electrode is 0.2nA. ​​The stable current signal of the blank electrode (curve 10) is 0.18nA, which means the background noise signal of the blank electrode is 0.18nA. Therefore, the ratio of the background noise signal of the working electrode to the background noise signal of the blank electrode, i.e., f3, is 1.11. Thus, in Example 3, substituting into Formula 6: f = f1 × f2 × f3, f is 0.89.

[0150] exist Figure 7 In the figures, the results from 0 to 20 minutes (curve 11) represent the test results when the sensor was placed in a solution containing glucose but without interfering substances, while the results from 20 to 40 minutes represent the test results when the sensor was placed in a solution containing glucose and interfering substances. Figure 7It can be seen that, in the stage between 0 minute and 20 minutes (curve 11), the current measured between the working electrode and the counter electrode is 5.9 nA (i.e. the analyte electrical signal representing the net analyte concentration is 5.9 nA). In the stage between 20 minutes and 40 minutes, curve 12 is the first electrical signal curve measured by the working electrode, and the first electrical signal I1 measured by the working electrode after stabilization is 7.67 nA; curve 13 is the second electrical signal curve measured by the blank electrode, and the second electrical signal I2 measured by the blank electrode after stabilization is 1.9 nA; curve 14 is obtained by using the above-mentioned formula 7 and formula 8, i.e. I = I1-f x I2, and the analyte electrical signal I is 5.98 nA.

[0151] It can be seen by comparison that, assuming that the sensor does not have the blank electrode, the measurement accuracy has an error of about 30% (calculated according to: (the first electrical signal-analyte electrical signal) / analyte electrical signal x 100%, (7.67-5.9) / 5.9 x 100% ≈ 30%), and in the case where the sensor includes the blank electrode and the correction factor is considered, the measurement accuracy has an error of about 1.36%. Thus, by providing the blank electrode in the sensor and considering 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, and the difference between the background noise signal of the working electrode and the background noise signal of the blank electrode, the measurement accuracy of the sensor can be further improved.

[0152] In the analyte monitoring system 10 of the third aspect of the present disclosure, the analyte monitoring system 10 can obtain the analyte electrical signal by performing the analyte monitoring method according to the first aspect, and the analyte monitoring system 10 can include a processing device 40 which can 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, i.e. 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, the first electrical signal measured by the working electrode 202 and the correction factor, thereby improving the accuracy of the analyte monitoring system 10.

[0153] Although the present disclosure has been specifically described above with reference to the drawings and examples, it should be understood that the above description does not limit the present disclosure in any form. Those skilled in the art can modify and change the present disclosure as needed without departing from the spirit and scope of the present disclosure, and such modifications and changes fall within the scope of the present disclosure.

Claims

1. A method for monitoring an analyte, characterized in that, it acquires the electrical signal of the analyte through a sensor. The sensor includes a working electrode, a blank electrode, and a film layer that at least partially covers 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 the first film layer, and the film layer covering the blank electrode is designated as the second film layer. The analyte monitoring method includes: acquiring the first electrical signal and the second electrical signal; setting the ratio of the thickness of the second film layer to the thickness of the first film layer as a first ratio, setting the ratio of the surface area of ​​the working electrode to the surface area of ​​the blank electrode as a second ratio, setting the ratio of the background noise signal of the working electrode to the background noise signal of the blank electrode as a third ratio, acquiring a correction factor based on the first ratio, the second ratio, and the third ratio to characterize the deviation between the first interference signal and the second interference signal; 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, characterized in that, 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 corrected 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 corrected 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 performing the analyte monitoring method according to any one of claims 1 to 3, the analyte monitoring system including a processing device configured to perform the analyte monitoring method.

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