Sensor-based analyte monitoring methods and related media and devices

Abstract

The invention discloses an analyte monitoring method based on a sensor and a related medium and device. The analyte monitoring method comprises the following steps: acquiring a first electric signal and a second electric signal; the ratio of the background noise signal of the working electrode to the background noise signal of the blank electrode is a noise ratio; acquiring a correction factor for representing the deviation between the first interference signal and the second interference signal based on the noise ratio; an analyte electrical signal is obtained based on the first electrical signal, the second electrical signal, and a correction factor. Therefore, the accuracy of the monitored analyte electric signal can be improved.

Description

[0001] This application is a divisional application of the patent application filed on August 23, 2023, with application number 2023110705563, entitled "Analytic Monitoring Method, Readable Storage Medium and Analytic Monitoring System". Technical Field

[0002] This disclosure generally relates to the biopharmaceutical industry, and in particular to a sensor-based analyte monitoring method and related media and apparatus. Background Technology

[0003] Monitoring the concentration of at least one analyte in an organism plays a crucial role in the prevention and treatment of various diseases. These analytes can include, but are not limited to, glucose, lactate, blood ketones, or other types of analytes. For example, for diabetic patients, timely access to their blood glucose levels is essential for prompt treatment. Continuous glucose monitoring (CGM) systems are mobile devices used by diabetic patients. They work by inserting a sensor immobilized with an enzyme under the skin, which reacts chemically with glucose in the body's tissue fluid or blood to generate an electrical signal. Based on the relationship between the detected electrical signal and glucose concentration, the analyte can be detected, allowing for continuous 24 / 7 blood glucose level monitoring and real-time blood glucose information.

[0004] The accuracy of analyte concentration monitoring is crucial for patient treatment. For example, diabetic patients need to administer insulin injections based on blood glucose monitoring concentrations, so inaccurate blood glucose testing can pose significant risks. In practice, a blank electrode without enzymes is placed on the sensor to detect interference signals. By detecting the output of the working electrode and comparing it with the output of the blank electrode, monitoring errors caused by interference signals are reduced, thus obtaining a more accurate analyte concentration.

[0005] However, due to subtle differences in structure and other aspects between the working electrode and the blank electrode, there will be a certain offset or deviation between the interference signal measured by the blank electrode and the interference signal measured by the working electrode. Therefore, simply comparing the outputs of the working electrode and the blank electrode is insufficient to effectively reduce the measurement error of the analyte concentration. Summary of the Invention

[0006] This disclosure is made in view of the above-mentioned situation, and its purpose is to provide an analyte monitoring method, a readable storage medium, and an analyte monitoring system that can improve the accuracy of the monitored analyte electrical signals.

[0007] Therefore, a first aspect of this disclosure provides an analyte monitoring method, which is a method for acquiring an analyte electrical signal 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; acquiring a correction factor based on the ratio of the thickness of the second film layer to the thickness of the first film layer 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.

[0008] In this disclosure, the sensor can measure a first electrical signal including a first interference signal and a second electrical signal including a second interference signal using a working electrode and a blank electrode, respectively. The first interference signal is negatively correlated with the thickness of the first film layer, and the second interference signal is negatively correlated with the thickness of the second film layer. In this case, a correction factor is obtained based on the ratio of the thickness of the second film layer to the thickness of the first film layer. 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 and the thickness of the first film layer. Thus, based on the first electrical signal, the second electrical signal, and the correction factor, a more accurate analyte electrical signal can be obtained, that is, the accuracy of the monitored analyte electrical signal can be improved.

[0009] Furthermore, in the analyte monitoring method according to the first aspect of this disclosure, optionally, the deviation between the first interference signal and the second interference signal also includes the deviation caused by the difference between the surface area of ​​the working electrode and the surface area of ​​the blank electrode. The analyte monitoring method further includes: 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 magnitude 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. Therefore, the correction factor can reduce the deviation between the first interference signal and the second interference signal caused by the difference between the surface areas of the blank electrode and the working electrode. Thus, a more accurate analyte electrical signal can be obtained based on the first electrical signal, the second electrical signal, and the correction factor, thereby improving the accuracy of the monitored analyte electrical signal.

[0010] Furthermore, in the analyte monitoring method according to the first aspect of this disclosure, optionally, the ratio of the thickness of the second film layer to the thickness of the first film layer is set as a first ratio, and the ratio of the surface area of ​​the working electrode to the surface area of ​​the blank electrode is set as a second ratio, and the correction factor is obtained based on the product of the first ratio and the second ratio. In this case, by correcting the analyte electrical signal by combining the differences between film layer thicknesses and the differences between electrode surface areas, the deviation between the first interference signal and the second interference signal caused by the differences in surface area between the blank electrode and the working electrode, as well as the differences in thickness of the first film layer and the second film layer, can be reduced simultaneously, thereby further improving the measurement accuracy of the analyte concentration value.

[0011] Furthermore, in the analyte monitoring method according to the first aspect of this disclosure, optionally, the deviation between the first interference signal and the second interference signal also includes the deviation caused by the difference between the background noise signal of the working electrode and the background noise signal of the blank electrode. The analyte monitoring method further includes: obtaining the correction factor based on the 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 magnitude of the background noise signal of the electrode is positively correlated with the magnitude 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. Therefore, 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. Thus, based on the first electrical signal, the second electrical signal, and the correction factor, a more accurate analyte electrical signal can be obtained, that is, the accuracy of the monitored analyte electrical signal can be improved.

[0012] Furthermore, in the analyte monitoring method according to the first aspect of this disclosure, optionally, the ratio of the thickness of the second membrane layer to the thickness of the first membrane layer is set as a first ratio, and the ratio of the background noise signal of the working electrode to the background noise signal of the blank electrode is set as a third ratio. The correction factor is obtained based on the product of the first ratio and the third ratio. In this case, by correcting the second electrical signal by combining the differences between the membrane layer thicknesses and the differences between the electrode background noise signals, the deviation between the first interference signal and the second interference signal caused by the differences between the background noise signals of the working electrode and the blank electrode, as well as the differences between the thicknesses of the first membrane layer and the second membrane layer, can be reduced simultaneously. This further improves the measurement accuracy of the analyte concentration value.

[0013] 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 includes a deviation caused by the difference in the surface area of the working electrode and the surface area of the blank electrode. The analyte monitoring method further includes: making the ratio of the surface area of the working electrode to the surface area of the blank electrode be 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 between the first interference signal and the second interference signal jointly caused by the difference in the background noise signal between the working electrode and the blank electrode, the difference in the surface area of the working electrode and the surface area of the blank electrode, and the difference in 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.

[0014] 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 both 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.

[0015] 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 factor and the second electrical signal can be used to obtain a correction signal, and this correction signal is substantially equivalent to the first interference signal. Thereby, a relatively accurate analyte electrical signal can be obtained based on the first electrical signal and the correction signal, that is, the measurement accuracy of the concentration value of the analyte can be improved.

[0016] The second aspect of the present disclosure provides a readable storage medium storing at least one instruction, and when the at least one instruction is executed by a processor, the analyte monitoring method described in any item of the first aspect is implemented. Thereby, it is convenient to use a computer device to implement an automated processing of the analyte monitoring method.

[0017] A third aspect of this disclosure provides an analyte monitoring system that acquires an analyte electrical signal by performing an analyte monitoring method according to any one of the first aspects. The analyte monitoring system includes a processing unit configured to perform the analyte monitoring method. In this case, a correction factor can reduce the deviation between a first interference signal measured by the working electrode and a second interference signal measured by the blank electrode due to differences between the working electrode and the blank electrode. Therefore, the analyte monitoring system can obtain a more accurate analyte electrical signal, i.e., a more accurate analyte concentration value, 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.

[0018] According to this 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. Attached Figure Description

[0019] This disclosure will now be explained in further detail by way of example only with reference to the accompanying drawings.

[0020] Figure 1A This is a diagram illustrating an application scenario of the analyte monitoring system described in this disclosure.

[0021] Figure 1B This is a schematic diagram illustrating the sensor involved in the example of this disclosure.

[0022] Figure 1C This is a block diagram illustrating an analyte monitoring system as described in this disclosure example.

[0023] Figure 1D This is a block diagram illustrating the electronic module involved in the example of this disclosure.

[0024] Figure 2 This is a schematic diagram illustrating an embodiment of a sensor as described in this disclosure.

[0025] Figure 3A This is a first flowchart illustrating the analyte monitoring method described in this disclosure.

[0026] Figure 3B This is a second flowchart illustrating the analyte monitoring method described in this disclosure.

[0027] Figure 4 This is a schematic diagram illustrating the test results of Embodiment 1, which is an example of this disclosure.

[0028] Figure 5 This is a schematic diagram illustrating the test results of Embodiment 2, which is an example of this disclosure.

[0029] Figure 6 This is a schematic diagram illustrating the background noise signals of the working electrode and the blank electrode involved in the examples of this disclosure.

[0030] Figure 7 This is a schematic diagram illustrating the test results of Embodiment 3, which is an example of this disclosure. Detailed Implementation

[0031] The technical solutions of the embodiments of this disclosure will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this disclosure, and not all embodiments. Based on the embodiments of this disclosure, all other embodiments filled in by those of ordinary skill in the art without creative effort are within the scope of protection of this disclosure.

[0032] It should be noted that the terms "first," "second," "third," and "fourth," etc., in the specification, claims, and accompanying drawings of this disclosure are used to distinguish different objects, not to describe a specific order. It should also be noted that the terms "comprising" and "having," and any variations thereof, meaning that a process, method, system, product, or apparatus comprising or having a series of steps or units, is not necessarily limited to those steps or units explicitly listed, but may include or have other steps or units not explicitly listed or inherent to these processes, methods, products, or apparatuses.

[0033] Hereinafter, preferred embodiments of the present disclosure will be described in detail with reference to the accompanying drawings. In the following description, the same reference numerals are used for the same components, and repeated descriptions are omitted. Furthermore, the drawings are merely schematic diagrams, and the proportions of the components or the shapes of the components may differ from actual figures.

[0034] In this disclosure, unless otherwise expressly specified and limited, the term "connection" should be interpreted broadly. For example, "connection" can be a fixed connection, a detachable connection, or an integral part; it can be a direct connection or an indirect connection through an intermediate medium. Furthermore, the term "coupled" can refer to a method of electrical connection for signal transmission; "coupled" can be a direct electrical connection or an indirect electrical connection through an intermediate medium. Additionally, the term "accuracy" can be understood as the degree of conformity between the measured value and the true value (the correct standard).

[0035] An electrochemical biosensor is a device that uses biological reactions to detect specific analytes. When a specific analyte (such as glucose, lactic acid, uric acid, protein, or drug) reacts with the sensor (e.g., an enzymatic reaction or an immune reaction), an electrochemical reaction occurs, such as the transfer of electrons or ions. These electrochemical reactions can be detected by the sensor and converted into an electrical signal, which can be called 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. This disclosure does not limit the specific form of the electrical signal.

[0036] The first aspect of this disclosure proposes an analyte monitoring method, which may also be referred to as an analyte monitoring method for reducing interference signals or a method for improving the accuracy of analyte monitoring.

[0037] A second aspect of this disclosure provides a readable storage medium that can store at least one instruction, which, when executed by a processor, implements the analyte monitoring method of the first aspect of this disclosure. This facilitates the automation of the analyte monitoring method using computer equipment.

[0038] The third aspect of this disclosure provides an analyte monitoring system, also known as an analyte monitoring device, which can acquire analyte electrical signals by executing the analyte monitoring method according to the first aspect of this disclosure.

[0039] In this disclosure, the term "analyte" can refer to a chemical compound present in solution. In some examples, the analyte can be one or more of glucose, acetylcholine, amylase, bilirubin, cholesterol, human chorionic gonadotropin, creatine kinase, creatine, creatine anhydride, DNA, fructosamine, glucose, glutamine, growth hormone, hormones, ketone bodies, lactate, oxygen, peroxides, prostate-specific antigen, prothrombin, RNA, thyroid-stimulating hormone, or troponin. Furthermore, the analyte can also be a drug in solution. For example, the analyte can be digoxin, theophylline, warfarin, or an antibiotic (such as gentamicin or vancomycin).

[0040] In some examples, the solution may be bodily fluids from a human or animal. In some examples, the solution may also be a test sample used in a laboratory setting. In this disclosure, human or animal may be collectively referred to as the host.

[0041] Figure 1A This is a diagram illustrating an application scenario of the analyte monitoring system 10 as described in this disclosure example. Figure 1B This is a schematic diagram illustrating the sensor 20 involved in the example of this disclosure. Figure 1Cis a block diagram showing an analyte monitoring system 10 according to an example of the present disclosure. Figure 1D is a block diagram showing an electronic module 30 according to an example of the present disclosure.

[0042] In some examples, referring to Figure 1A , the analyte monitoring system 10 can be applied to a host for monitoring the concentration value of an analyte in the host. In some examples, the analyte monitoring system 10 can be used in a laboratory for in vitro experiments.

[0043] In some examples, referring to Figure 1A , the analyte monitoring system 10 can include a sensor 20. In this case, the sensor 20 can generate an analyte electrical signal through an electrochemical reaction with the analyte to characterize the concentration value of the analyte.

[0044] In some examples, referring to Figure 1B , the sensor 20 can include a distal portion 20a and a proximal portion 20b, where the distal portion 20a can be placed at a selected site of the host. For example, the distal portion 20a can be implanted under the skin layer of the host to contact the body fluid in the host, and the proximal portion 20b can be provided with electrical contacts 201.

[0045] 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 contacts 201. Thus, the electrical signal measured by the sensor 20 can be sent to the electronic module 30 for processing.

[0046] 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 degree of the electronic module 30 can be improved.

[0047] 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, it is convenient to use digital processing technology to process the third electrical signal, such as digital filtering, etc.

[0048] In some examples, the signal transmission element 33 can transmit a third electrical signal externally via the communication link 331. In some examples, the communication link 331 can be a wireless transmission, in which case the wireless transmission method makes data transmission more convenient.

[0049] In some examples, the communication link 331 can be a wired transmission, such as a standard wired transmission cable like a USB cable. This expands the applicability of the analyte monitoring system 10.

[0050] See in some examples Figure 1C The analyte monitoring system 10 may also include a processing unit 40 (see...) Figure 1C The processing device 40 can be configured to perform the analyte monitoring method proposed in the first aspect of this disclosure (described in detail later).

[0051] In some examples, the processing device 40 may be integrated with the electronic module 30. In some examples, the processing device 40 may be a separate and independent device from the electronic module 30. In some examples, the processing device 40 may be integrated into the monitor 50 (described in detail later).

[0052] See in some examples Figure 1D The analyte monitoring system 10 may include a monitor 50. Thus, the monitor 50 can indicate the concentration value of the analyte, facilitating the host's perception of the analyte concentration.

[0053] In some examples, monitor 50 may be coupled to signal transmission element 33 to 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, via auditory and / or visual signals. In some examples, the auditory signal may be a voice announcement of the analyte concentration value or a voice alarm message issued when the analyte concentration value exceeds a threshold. In some examples, the visual signal may be the display of the analyte concentration value on the monitor 50's display screen.

[0054] In some examples, the monitor 50 can be a smart terminal, such as a smartphone. This improves the portability of the analyte monitoring system 10, enabling the host to monitor analyte concentrations routinely without the need for specialized analyte monitoring in a hospital setting.

[0055] In some examples, the monitor 50 can also be an electronic measuring instrument, such as an oscilloscope, current meter, or other specialized measuring instrument. In this case, the concentration value of the analyte can be accurately measured using a specialized measuring instrument, thus making the analyte monitoring system 10 suitable for applications in hospital or laboratory environments.

[0056] Figure 2 This is a schematic diagram illustrating an embodiment of a sensor 20 according to an example of this disclosure.

[0057] See in some examples Figure 2 The sensor 20 may include a working electrode 202, which can be used to acquire a first electrical signal. The first electrical signal may include an analyte electrical signal, which may also be referred to as the net analyte concentration value.

[0058] In some examples, the first electrical signal may also include a first interference signal; in other words, the first electrical signal may include both an analyte electrical signal and a first interference signal. In this case, the analyte electrical signal can characterize the concentration value of the analyte, so removing the first interference signal from the first electrical signal can yield a more accurate concentration value of the analyte.

[0059] In some examples, the working electrode 202 may include a sensing layer 2021. In some examples, the sensing layer 2021 may facilitate an electrochemical reaction between the working electrode 202 and the analyte to generate a first electrical signal. Thus, the concentration value of the analyte can be obtained by measuring the first electrical signal through the working electrode 202.

[0060] In some examples, the sensing layer 2021 may also be referred to as a catalyst layer or an electroactive material layer. A catalyst layer corresponding to the analyte can be provided on the working electrode 202 for different analytes. 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 undergo an electrochemical reaction with glucose or blood glucose, thereby obtaining a first electrical signal including an analyte electrical signal, wherein the analyte electrical signal can refer to the glucose concentration value.

[0061] In some examples, sensor 20 may include a blank electrode 203, which may be used to acquire a second electrical signal, which may include a second interference signal.

[0062] In some examples, the blank electrode 203 may not include the sensing layer 2021. In other words, the blank electrode 203 may not undergo an electrochemical reaction with the analyte, meaning it may not generate an analyte electrical signal related to the concentration of the analyte. In this case, the second electrical signal measured by the blank electrode 203 may not include the analyte-related electrical signal, meaning the second electrical signal can be equated to a second interference signal.

[0063] In some examples, the first interference signal may include an electrical signal generated by the electrochemical reaction between the working electrode 202 and substances in the solution other than the analyte to be monitored. In some examples, the second interference signal may include an electrical signal generated by the electrochemical reaction between the blank electrode 203 and substances in the solution other than the analyte to be monitored.

[0064] In some examples, the first interference signal may also include background noise signals generated by the working electrode 202 itself. In some examples, the second interference signal may also include background noise signals generated by the blank electrode 203 itself. In this disclosure, the background noise signal can be used to characterize the noise signal inherent in the characteristics of the working electrode 202 or the blank electrode 203 itself, and may also be referred to as the bottom noise signal or noise floor.

[0065] In some examples, compared to the working electrode 202, the blank electrode 203 is largely the same as the working electrode 202, except that it lacks 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 can be manufactured using the same manufacturing process. In this case, by minimizing the differences between the blank electrode 203 and the working electrode 202, the deviation between the first interference signal and the second interference signal can be reduced, and the factors affecting the deviation between the first interference signal and the second interference signal can also be minimized. This allows for a more accurate determination of the relationship between the first interference signal and the second interference signal. Consequently, 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.

[0066] In some examples, sensor 20 may include counter electrode 204. Thus, working electrode 202 can form a first circuit with counter electrode 204 to generate a first electrical signal; and blank electrode 203 can form a second circuit with counter electrode 204 to generate a second electrical signal.

[0067] In some examples, the working electrode 202 and the blank electrode 203 can be made of any one of the following materials: platinum, gold, silver, lead, mercury, glassy carbon electrode, conductive glass, palladium, titanium, or iridium. This allows the working electrode 202 and the blank electrode 203 to possess good conductivity, thereby improving the accuracy of the analyte monitoring system 10.

[0068] In some examples, the working electrode 202 and the blank electrode 203 can be made of the same material. This further reduces the deviation between the first interference signal and the second interference signal caused by the difference in materials between the working electrode 202 and the blank electrode 203.

[0069] In some examples, the counter electrode 204 can be made of platinum, silver, silver chloride, palladium, titanium, or iridium. This allows for good conductivity without affecting the electrochemical reaction at the working electrode 202.

[0070] In some examples, sensor 20 may include a reference electrode 205. In some examples, the reference electrode 205 may 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 between the reference electrode 205 and the working electrode 202. This allows for a more accurate determination of the voltage generated by the working electrode 202. Consequently, the voltage of the working electrode 202 can be automatically adjusted and maintained stable according to a 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 may be one or more, for example, two.

[0071] In other examples, when the potential difference between the working electrode 202 and the solution does not fluctuate significantly, the reference electrode 205 may not be used. This can save on manufacturing costs.

[0072] See in some examples Figure 2 The sensor 20 may 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, 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 factors affecting the difference between the first interference signal and the second interference signal can be reduced, thereby facilitating the accurate acquisition of the analyte electrical signal from the first electrical signal.

[0073] In some examples, sensor 20 may include substrate 206. In this case, substrate 206 can provide support for the various electrodes of sensor 20, providing structural support for the various electrodes and ensuring that sensor 20 maintains structural stability during use. Thus, substrate 206 can enhance the mechanical strength of sensor 20 and prevent sensor 20 from deforming or breaking.

[0074] In some examples, the working electrode 202 and the blank electrode 203 can be located on opposite sides of the substrate 206. In this case, by separating the working electrode 202 and the blank electrode 203, mutual interference between the working electrode 202 and the blank electrode 203 can be reduced, thereby improving the sensitivity of the sensor 20.

[0075] 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 of the various electrodes on the same substrate 206, the compactness of the sensor 20 can be improved, making it easier to implant the sensor 20 into the host's skin layer.

[0076] 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 structure, see [reference]. Figure 2 On one side of the substrate 206, a working electrode 202 and a reference electrode 205 can be stacked in sequence, and on the other side of the substrate 206, a blank electrode 203 and a counter electrode 204 can be stacked in sequence.

[0077] In this context, arranging electrodes in a stacked structure significantly increases the surface area of ​​the working electrode 202. A larger surface area allows for more sensing layers 2021, improving the sensitivity of the sensor 20. The stacked electrode design also allows for combinations of different material layers, which complement each other, enhancing the stability and durability of the sensor 20. For example, introducing a highly stable material as a protective layer can prevent oxidation, corrosion, or degradation of the electrode, extending the lifespan of the sensor 20. Since the sensor 20 typically requires small size and portability, the stacked electrode design enables greater functional integration within a limited space, integrating multiple functional layers into a compact electrode structure and improving space utilization efficiency.

[0078] See in some examples Figure 2 The sensor 20 may also 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 electrically insulating layers, the possibility of short circuits occurring at the electrodes can be reduced.

[0079] In some examples, substrate 206 may be a flexible substrate. The flexible substrate may be made generally of at least one of polyethylene (PE), polypropylene (PP), polyimide (PI), polystyrene (PS), polyethylene terephthalate (PET), and polyethylene terephthalate (PEN). Alternatively, in other examples, the flexible substrate may also be made generally of metal foil, ultrathin glass, a single-layer inorganic film, a multilayer organic film, or a multilayer inorganic film.

[0080] In some examples, sensor 20 may include a film layer that at least partially covers the working electrode 202 and the blank electrode 203, wherein the film layer covering the working electrode 202 may be a first film layer 211 and the film layer covering the blank electrode 203 may be a second film layer 212.

[0081] In some examples, the first film layer 211 and the second film layer 212 may have thickness. In this disclosure, the thickness of the first film layer 211 and the second film layer 212 can be obtained by selecting multiple predetermined points on the film layer for measurement, measuring the thickness at the location of the predetermined point, and then taking the average of the thicknesses at different predetermined points.

[0082] In some examples, the first membrane layer 211 and the second membrane layer 212 may include a semi-permeable membrane. In this case, the semi-permeable membrane can selectively allow the analyte to pass through while blocking other substances, thereby improving the accuracy of monitoring; in addition, by simultaneously providing membrane layers on the working electrode 202 and the blank electrode 203, that is, by keeping the working environment or structure of the working electrode 202 and the blank electrode 203 consistent, the deviation between the first interference signal and the second interference signal can be minimized.

[0083] In some examples, the semipermeable membrane may include a diffusion control layer. In this case, the semipermeable membrane can control the permeability of the analyte, that is, the semipermeable membrane can limit the amount of analyte in the solution that reaches the sensing layer 2021, ensuring that the sensing layer 2021 and other substances participating in the reaction are in sufficient quantity, so that the concentration of the analyte becomes the main (basically the only) limiting factor for the magnitude of the first electrical signal, thereby enabling the magnitude of the first electrical signal to accurately reflect the concentration of the analyte, and greatly increasing the linear range of the working electrode 202.

[0084] In some examples, the semipermeable membrane may also include an anti-interference layer stacked on the diffusion control layer, which prevents the diffusion of substances different from the analyte. This reduces interference from substances different from the analyte in the detection of analyte concentration.

[0085] In some examples, the first membrane layer 211 and the second membrane layer 212 may include a biocompatible membrane, which may be disposed on a semipermeable membrane. In this case, when the analyte monitoring system 10 is placed on a host body and the sensor 20 is implanted in the host's skin and comes into contact with body fluids or tissue fluids, the host's immune response to the sensor 20 can be reduced, thereby extending the lifespan of the sensor 20.

[0086] In some examples, when monitoring analytes in solutions containing analytes, the solutions often contain interfering substances. For instance, when a glucose sensor monitors glucose levels in a host, the host's blood or non-blood fluids often contain interfering substances such as ascorbic acid, uric acid, or acetaminophen, which are highly reducing agents. These interfering substances readily 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 result in a large proportion of the first interference signal in the first electrical signal detected by the working electrode 202, thus 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 concentration value of the analyte indicated by the first electrical signal is low.

[0087] As described above, in some examples, sensor 20 may include blank electrode 203, so that working electrode 202 and blank electrode 203 participate in monitoring the concentration value of analyte. After comparing the first electrical signal measured by working electrode 202 with the second electrical signal (i.e. the second interference signal) measured by blank electrode 203, a more accurate concentration value of analyte can be obtained. In other words, the second interference signal can be equated with the first interference signal, and the value of the second electrical signal can be obtained by removing the value of the second electrical signal from the first electrical signal.

[0088] However, in practice, there is usually a difference between the blank electrode 203 and the working electrode 202, causing the first interference signal to be unequal to the second interference signal, resulting in a deviation between the two. In other words, assuming that the working electrode 202 and the blank electrode 203 are simultaneously placed in the same solution environment free of analyte, the electrical signals measured by the working electrode 202 and the blank electrode 203 will not be the same, meaning there is a deviation between the first and second interference signals. In this case, when the analyte electrical signal is obtained by comparing the first electrical signal with a second electrical signal that includes the second interference signal, the accuracy of the obtained analyte electrical signal will be affected by the deviation between the first and second interference signals.

[0089] The difference between the blank electrode 203 and the working electrode 202 can be caused by inconsistencies due to errors in the manufacturing process, or by differences in the manufacturing processes used to produce the blank electrode 203 and the working electrode 202. This disclosure does not limit the causes of the difference between the blank electrode 203 and the working electrode 202.

[0090] In some examples, the first interference signal may be positively correlated with the surface area of ​​the working electrode 202; the second interference signal may be positively correlated with the surface area of ​​the blank electrode 203. In this case, the larger the surface area of ​​the working electrode 202, the stronger the first interference signal generated by the electrochemical reaction with the interfering substance in the solution; similarly, the larger the surface area of ​​the blank electrode 203, the stronger the second interference signal generated by the electrochemical reaction with the interfering substance in the solution. Therefore, when the surface area of ​​the working electrode 202 and the surface area of ​​the blank electrode 203 differ significantly, the deviation between the first and second interference signals is greater, and vice versa.

[0091] In some examples, the deviation between the first interference signal and the second interference signal may include the deviation caused by the difference between the surface area of ​​the working electrode 202 and the 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 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.

[0092] In some examples, the first interference signal may be negatively correlated with the thickness of the first film layer 211; the second interference signal may be negatively correlated with the thickness of the second film layer 212. In this case, the greater the thickness of the first film layer 211, the lower the concentration of the interfering substance permeating through the first film layer 211, thus resulting in a smaller first interference signal generated by the electrochemical reaction between the working electrode 202 and the interfering substance; similarly, the greater the thickness of the second film layer 212, the smaller the second interference signal. Therefore, 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 larger, and vice versa.

[0093] In some examples, the deviation between the first interference signal and the second interference signal may include the deviation caused by the 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 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.

[0094] In some examples, the first interference signal may be positively correlated with the background noise signal of the working electrode 202; the second interference signal may be positively correlated 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.

[0095] In some examples, the deviation between the first interference signal and the second interference signal may include the deviation caused by the 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.

[0096] As can be seen from the above explanation, 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. The accuracy of the analyte electrical signal obtained by directly comparing the first electrical signal and the second electrical signal will be affected.

[0097] In the analyte monitoring method proposed in the first aspect of this disclosure, the deviation between the first interference signal and the second interference signal can be corrected by using a correction factor. In other words, a 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. Therefore, a more accurate analyte electrical signal can be obtained by comparing the first electrical signal and the corrected signal, thereby improving the accuracy of analyte monitoring.

[0098] Figure 3A This is a first flowchart illustrating the analyte monitoring method described in this disclosure. Figure 3B This is a second flowchart illustrating the analyte monitoring method described in this disclosure.

[0099] See in some examples Figure 3A The analyte monitoring method may include: acquiring a first electrical signal and a second electrical signal (step S200); acquiring a correction factor based on the ratio of the thickness of the second film layer 212 to the thickness of the first film layer 211 (step S400); and acquiring an analyte electrical signal based on the first electrical signal, the second electrical signal, and the correction factor (S600).

[0100] In this disclosure, the sensor 20 can use the working electrode 202 and the blank electrode 203 to measure a first electrical signal including a first interference signal and a second electrical signal including a second interference signal, respectively. The first interference signal may be negatively correlated with the thickness of the first film layer 211 and the second interference signal may be negatively correlated with the thickness of the second film layer 212. In this case, a correction factor is obtained based on the ratio of the thickness of the second film layer 212 to the thickness of the first film layer 211. The correction factor can reduce the deviation between the first interference signal and the second interference signal caused by the difference in thickness between the second film layer 212 and the first film layer 211. Thus, based on the first electrical signal, the second electrical signal, and the correction factor, a more accurate analyte electrical signal can be obtained, that is, the accuracy of the monitored analyte electrical signal can be improved.

[0101] In some examples, in step S200, a first electrical signal and a second electrical signal can be acquired. The first electrical signal may include the analyte electrical signal and a first interference signal acquired by the working electrode 202, and the second electrical signal may include the second interference signal acquired by the blank electrode 203. Thus, the analyte electrical signal can be obtained by comparing the first electrical signal and the second electrical signal.

[0102] See in some examples Figure 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 electrochemical reactions in the working electrode 202 and the blank electrode 203, thereby generating a first electrical signal and a second electrical signal, respectively.

[0103] In some examples, in step S100, the working electrode 202 and the blank electrode 203 can be set to a preset voltage potential using a potentiostat. In this disclosure, a potentiostat can be understood as a circuit structure capable of outputting a constant voltage as required by actual needs.

[0104] In some examples, electronic module 30 may include a potentiostat.

[0105] 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 between 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.

[0106] 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, it is convenient to study the electrochemical reactions that occur on the working electrode 202 and the blank electrode 203 under different conditions.

[0107] In some examples, the preset voltage potential can be related to the type of sensing layer 2021. For example, when sensing layer 2021 is glucose dehydrogenase, the preset voltage potential applied to the working electrode 202 and the blank electrode 203 can be 50mV respectively.

[0108] In this disclosure, for ease of description, the ratio of the thickness of the second film layer 212 to the thickness of the first film layer 211 is defined as the first ratio, the ratio of the surface area of ​​the working electrode 202 to the surface area of ​​the blank electrode 203 is defined as the second ratio, and the ratio of the background noise signal of the working electrode 202 to the background noise signal of the blank electrode 203 is defined as the 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 correction signal.

[0109] In some examples, in step S400, a 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, i.e., the correction factor can be equal to the first ratio, which can be expressed by formula 1: f = f1. In this case, considering that the thickness of the film layer is negatively correlated with the magnitude of the interference signal, the correction factor is obtained by dividing the thickness of the second film layer 212 by the thickness of the first film layer 211. Based on the correction factor and the second electrical signal, a correction signal that is essentially equivalent to the first interference signal is obtained. Thus, the correction factor can reduce the deviation between the first interference signal and the second interference signal caused by the difference in thickness between the second film layer 212 and the first film layer 211.

[0110] In some examples, a correction factor can be used to characterize the deviation between the first interference signal and the second interference signal. In this case, by introducing a correction factor and obtaining a 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 between the first interference signal and the second interference signal caused by the difference between the working electrode 202 and the blank electrode 203 (e.g., the difference between the thickness of the second film layer 212 and the thickness of the first film layer 211). Thus, by comparing the first electrical signal and the corrected signal, the measurement accuracy of the analyte concentration value can be improved.

[0111] In some examples, in step S400, the analyte monitoring method may include obtaining a correction factor based on the 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 may be equal to the 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 may be equal to a second ratio, which can be expressed by formula 2: f = f2. In this case, considering that the surface area of ​​the electrode is positively correlated with the magnitude 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. Thus, the correction factor can reduce the deviation between the first interference signal and the second interference signal caused by the difference in the surface areas of the working electrode 202 and the blank electrode 203. Therefore, based on the first electrical signal, the second electrical signal, and the correction factor, a more accurate analyte electrical signal can be obtained, i.e., the accuracy of the monitored analyte electrical signal can be improved.

[0112] In some examples, in step S400, the analyte monitoring method may include obtaining a correction factor based on the ratio of the surface area of ​​the working electrode 202 to the surface area of ​​the blank electrode 203, and the ratio of the thickness of the second film layer 212 to the thickness of the first film 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 combined difference in the surface area of ​​the working electrode 202 and the blank electrode 203, and the difference in the thickness of the second film layer 212 and the first film layer 211.

[0113] In some examples, in step S400, a correction factor can be obtained based on the product of the first ratio and the second ratio, i.e., Formula 3: f = f1 × f2. In this case, by correcting the second electrical signal by combining the differences between the film thicknesses and the electrode surface areas, the deviation between the first interference signal and the second interference signal caused by the differences in surface area between the blank electrode 203 and the working electrode 202, as well as the differences in thickness between the first film layer 211 and the second film layer 212, can be reduced simultaneously. This further improves the accuracy of analyte concentration measurement.

[0114] In some examples, in step S400, the analyte monitoring method may include obtaining a correction factor based on the 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 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 a third ratio, as per Formula 3: f = f3. In this case, considering the positive correlation between the magnitude of the background noise signal of the electrodes and the interference signal, obtaining the correction factor by dividing the background noise signal of the working electrode 202 by the background noise signal of the blank electrode 203 reduces the deviation between the first interference signal and the second interference signal caused by the difference between the background noise signals of the working electrode 202 and the blank electrode 203. Therefore, based on the first electrical signal, the second electrical signal, and the correction factor, a more accurate analyte electrical signal can be obtained, thus improving the accuracy of the monitored analyte electrical signal.

[0115] In some examples, in step S400, the analyte monitoring method may include obtaining a correction factor based on 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 thickness of the second film layer 212 to the thickness of the first film 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 signals of the working electrode 202 and 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.

[0116] In some examples, in step S400, the correction factor can be obtained based on the product of the first ratio and the third ratio, i.e., Formula 4: f = f1 × f3. In this case, by correcting the second electrical signal by combining the differences between the film thicknesses and the differences between the electrode background noise signals, the deviation between the first interference signal and the second interference signal caused by the differences between the background noise signals of the working electrode 202 and the blank electrode 203, as well as the differences in the thickness of the first film layer 211 and the second film layer 212, can be reduced simultaneously. This further improves the measurement accuracy of the analyte concentration value.

[0117] In some examples, in step S400, the analyte monitoring method may include obtaining a correction factor based on 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 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.

[0118] 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., Formula 5: f = f2 × f3. In this case, by correcting the second electrical signal by combining the differences between the electrode surface areas and the differences between the electrode background noise signals, the deviation between the first interference signal and the second interference signal caused by the differences between the background noise signals of the working electrode 202 and the blank electrode 203, as well as the differences between the surface areas of the working electrode 202 and the blank electrode 203, can be reduced simultaneously. This further improves the accuracy of the analyte concentration measurement.

[0119] In some examples, in step S400, the analyte monitoring method may include obtaining a correction factor based on a first ratio, a second ratio, and a 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 differences in background noise signals between the working electrode 202 and the blank electrode 203, the differences in surface area between the working electrode 202 and the blank electrode 203, and the differences in thickness between the second film layer 212 and the first film layer 211. This further improves the accuracy of analyte concentration measurement.

[0120] 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., Formula 6: f = f1 × f2 × f3. In this case, by comprehensively correcting the second electrical signal based on three factors—the difference between electrode surface areas, the difference between electrode background noise signals, and the difference between 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 film layer 212 and the thickness of the first film 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 simultaneously. Thus, the measurement accuracy of the analyte concentration value can be further improved.

[0121] 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.

[0122] 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.

[0123] In some examples, in step S600, the correction signal can be obtained based on the second electrical signal and the correction factor.

[0124] 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.

[0125] 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.

[0126] 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.

[0127] 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.

[0128] 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.

[0129] 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 6This is a schematic diagram illustrating the background noise signals of the working electrode and the blank electrode involved in the examples of this disclosure. Figure 7 This is a schematic diagram illustrating the test results of Embodiment 3, which is an example of this disclosure.

[0130]

Example 1

[0131] First, the thicknesses of the first and second films on the sensor of Example 1 are measured using an optical measuring instrument. The ratio of the thickness of the second film to the thickness of the first film, i.e., f1, is 1.04. Substituting this into Formula 1: f = f1, f = 1.04. The film thickness is measured by averaging data from multiple points on the film.

[0132] Secondly, the sensor of Example 1 was placed in a 5mM glucose test solution, and a voltage of 50mV was applied to the working electrode and the blank electrode for 20 minutes to obtain the following result. Figure 4 The time-current graph shown ( Figure 4 (0 to 20 minutes).

[0133] Next, 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 both the working electrode and the blank electrode for 20 minutes to obtain the following results. Figure 4 The time-current graph shown ( Figure 4 (The portion from 20 to 40 minutes). In other words, Figure 4 This is a schematic diagram illustrating the test results of Embodiment 1, which is an example of this disclosure.

[0134] exist Figure 4 In the figures, the results from 0 to 20 minutes (curve 1) 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 4It can be seen that during the period from 0 to 20 minutes (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). During the period from 20 to 40 minutes, curve 2 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 is 7.8 nA; curve 3 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 is 1.9 nA; curve 4 is obtained by using the above formulas 7 and 8: I = I1 - f × I2, resulting in an analyte electrical signal I of 5.82 nA.

[0135] The comparison shows that, assuming the sensor has no blank electrode, the measurement accuracy has an error of approximately 37% (this error is calculated as: (first electrical signal - analyte electrical signal) / analyte electrical signal × 100%, (7.8 - 5.7) / 5.7 × 100% ≈ 37%). With the sensor including a blank electrode and considering the correction factor, the measurement accuracy has an error of approximately 2%. Therefore, by incorporating a blank electrode into 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] First, the surface area of ​​the working electrode and the surface area of ​​the blank electrode on the sensor of Example 2 are measured by an optical measuring instrument, and the thickness of the second film layer and the thickness of the first film layer are measured. 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 layer to the thickness of the first film layer, i.e., f1 is 1.04. Substituting these values ​​into Formula 3: f = f1 × f2, f is 0.8.

[0138] Secondly, the sensor in Example 2 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 5 The time-current graph shown ( Figure 5 (0 to 20 minutes).

[0139] Next, 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 both the working electrode and the blank electrode for 20 minutes to obtain the following results. 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.

[0140] 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 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 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.

[0141] The comparison shows that, assuming the sensor has no blank electrode, the measurement accuracy is approximately 29.82% (this error is calculated as: (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.

[0142]

Example 3

[0143] 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.

[0144] 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.

[0145] 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).

[0146] 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.

[0147] 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.

[0148] 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 7As can be seen, during the period from 0 to 20 minutes (curve 11), the current between the working electrode and the counter electrode was measured to be 5.9 nA (i.e., the analyte electrical signal representing the net analyte concentration was 5.9 nA). During the period from 20 to 40 minutes, curve 12 is the first electrical signal curve measured by the working electrode. After stabilization, the first electrical signal I1 measured by the working electrode was 7.67 nA. Curve 13 is the second electrical signal curve measured by the blank electrode. Similarly, after stabilization, the second electrical signal I2 measured by the blank electrode was 1.9 nA. Curve 14 is obtained by using the above formulas 7 and 8, which yields: I = I1 - f × I2, resulting in an analyte electrical signal I of 5.98 nA.

[0149] The comparison shows that, assuming the sensor has no blank electrode, the measurement accuracy is approximately 30% (this error is calculated as: (first electrical signal - analyte electrical signal) / analyte electrical signal × 100%, (7.67 - 5.9) / 5.9 × 100% ≈ 30%). With the sensor including a blank electrode and considering the correction factor, the measurement accuracy is approximately 1.36%. Therefore, by incorporating a blank electrode into the sensor and considering the differences in surface area between the working electrode and the blank electrode, the differences in thickness between the second and first films, and the differences in background noise signals between the working and blank electrodes, the measurement accuracy of the sensor can be further improved.

[0150] In an analyte monitoring system 10 according to a third aspect of this disclosure, the analyte monitoring system 10 can acquire an analyte electrical signal by executing an analyte monitoring method according to the first aspect. The analyte monitoring system 10 may include a processing device 40, which may be configured to execute the analyte monitoring method. In this case, a 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. Therefore, the analyte monitoring system 10 can obtain a more accurate analyte electrical signal, i.e., a more accurate analyte concentration value, 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.

[0151] While the present disclosure has been specifically described above in conjunction with the accompanying drawings and examples, it is to be understood that the foregoing description does not limit the present disclosure in any way. Those skilled in the art can make modifications and variations to the present disclosure as needed without departing from its essential spirit and scope, and all such modifications and variations shall fall within the scope of the present disclosure.

Claims

1. A sensor-based analyte monitoring method, characterized in that, The sensor includes a working electrode and a blank electrode. The working electrode includes a sensing layer and is used to acquire a first electrical signal including an electrical signal of the analyte and a first interference signal. The blank electrode is used to acquire a second electrical signal including a second interference signal. The analyte monitoring method includes: Acquire the first electrical signal and the second electrical signal; Let the ratio of the background noise signal of the working electrode to the background noise signal of the blank electrode be the noise ratio value; A correction factor is obtained based on the noise ratio to characterize the deviation between the first interference signal and the second interference signal; The analyte electrical signal is obtained 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 preferably includes a film layer that at least partially covers the working electrode and the blank electrode. The film layer covering the working electrode is called the first film layer, and the film layer covering the blank electrode is called the second film layer. The ratio of the thickness of the second film layer to the thickness of the first film layer is called the thickness ratio. The correction factor is obtained based on the noise ratio and the thickness ratio. or Let the ratio of the surface area of ​​the working electrode to the surface area of ​​the blank electrode be the area ratio, and obtain the correction factor based on the noise ratio and the area ratio.

3. The analyte monitoring method according to claim 2, characterized in that, Let the ratio of the surface area of ​​the working electrode to the surface area of ​​the blank electrode be the area ratio; The correction factor is obtained based on the noise ratio, the thickness ratio, and the area ratio.

4. The analyte monitoring method according to any one of claims 2 to 3, characterized in that, The correction factor is obtained by multiplying the ratios on which it is based.

5. The analyte monitoring method according to claim 1, characterized in that, The ways to reduce the factors affecting the deviation include at least one of the following: Compared with the working electrode, the blank electrode is the same as the working electrode in terms of material, structure and manufacturing process, except that it does not have a sensing layer. The same preset voltage potential is set on the working electrode and the blank electrode; The sensor also includes a counter electrode and a reference electrode. The working electrode and the counter electrode share the reference electrode and the counter electrode to form a first three-electrode system and a second three-electrode system, respectively.

6. The analyte monitoring method according to claim 1, characterized in that, The sensor also includes a counter electrode, a reference electrode, and a substrate, wherein the working electrode, the blank electrode, the reference electrode, and the counter electrode are stacked on the substrate.

7. 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.

8. The analyte monitoring method according to claim 1, 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.

9. 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 8.

10. A processing apparatus, characterized in that, It is configured to perform the analyte monitoring method according to any one of claims 1 to 8.

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