Biosensor and system for measuring concentration of salivary glucose

Abstract

The present invention relates to a biosensor for detecting glucose in saliva, comprising: a lower plate including a working electrode for detecting glucose in saliva, the working electrode including at least one working electrode protrusion, and a reference electrode for detecting glucose in saliva, the reference electrode including at least one reference electrode protrusion; a middle plate which is disposed on the upper surface of the lower plate and which has a saliva inflow path perforated therein; an upper plate disposed on the upper surface of the middle plate; and a reagent layer disposed in the saliva inflow path, wherein the area of a portion of the working electrode protrusion that is covered by the saliva inflow path is formed to be larger than the area of a portion of the reference electrode protrusion that is covered by the saliva inflow path.

Description

Biosensor and system for measuring salivary glucose concentration

[0001] Embodiments of the present invention relate to a biosensor for detecting salivary sugar and a system for measuring the concentration of salivary sugar.

[0002] Previously, medical self-diagnosis tests for users were often conducted using blood samples. However, such tests required the prior extraction of a blood sample, inevitably involving skin damage during the process. Consequently, self-diagnosis testing via blood samples increased the risk of infection, caused pain and fear in users, and heightened resistance to the testing procedure.

[0003] To address the shortcomings of existing self-diagnosis testing methods mentioned above, there is an increasing trend in the development of self-diagnosis testing devices and methods utilizing non-blood body fluids such as saliva, tears, and sweat.

[0004] Embodiments of the present invention can provide a biosensor and a salivary glucose measurement system that improve the accuracy and reproducibility of measuring glucose concentration in saliva through an optimal area ratio and arrangement between a working electrode protrusion and a reference electrode protrusion.

[0005] To solve the problem of the present invention, a biosensor for detecting glucose in saliva is provided, comprising: a lower plate including a working electrode for detecting glucose in saliva—the working electrode including at least one working electrode protrusion—and a reference electrode for detecting glucose in saliva—the reference electrode including at least one reference electrode protrusion; a middle plate disposed on the upper surface of the lower plate and having a saliva inflow channel perforated therein; an upper plate disposed on the upper surface of the middle plate; and a reagent layer disposed within the saliva inflow channel; wherein the area of ​​the portion of the working electrode protrusion that is covered by the saliva inflow channel is formed to be larger than the area of ​​the portion of the reference electrode protrusion that is covered by the saliva inflow channel.

[0006] To solve the problem of the present invention, a biosensor for detecting glucose in saliva is provided, comprising: a lower plate including a working electrode for detecting glucose in saliva—the working electrode including at least one working electrode protrusion—and a reference electrode for detecting glucose in saliva—the reference electrode including at least one reference electrode protrusion; a middle plate disposed on the upper surface of the lower plate and having a saliva inflow channel perforated therein; an upper plate disposed on the upper surface of the middle plate; and a reagent layer disposed within the saliva inflow channel; wherein the area of ​​the portion of the working electrode protrusion that contacts the reagent layer is formed to be larger than the area of ​​the portion of the reference electrode protrusion that contacts the reagent layer.

[0007] To solve the problem of the present invention, a biosensor for detecting glucose in saliva comprises: a lower plate including a working electrode for detecting glucose in saliva—the working electrode includes at least one working electrode protrusion—; a middle plate disposed on the upper surface of the lower plate and having a saliva inflow channel perforated therein; an upper plate disposed on the upper surface of the middle plate and including a reference electrode for detecting glucose in saliva—the reference electrode includes at least one reference electrode protrusion—; and a reagent layer disposed within the saliva inflow channel; wherein the area of ​​the portion of the working electrode protrusion that is covered by the saliva inflow channel is formed to be larger than the area of ​​the portion of the reference electrode protrusion that is covered by the saliva inflow channel.

[0008] To solve the problem of the present invention, a biosensor for detecting glucose in saliva is provided, comprising: a lower plate including a working electrode for detecting glucose in saliva—the working electrode includes at least one working electrode protrusion—; a middle plate disposed on the upper surface of the lower plate and having a saliva inflow channel perforated therein; an upper plate disposed on the upper surface of the middle plate and including a reference electrode for detecting glucose in saliva—the reference electrode includes at least one reference electrode protrusion—; and a reagent layer disposed within the saliva inflow channel; wherein the area of ​​the portion of the working electrode protrusion that contacts the reagent layer is formed to be larger than the area of ​​the portion of the reference electrode protrusion that contacts the reagent layer.

[0009] According to one embodiment of the present invention, the ratio of the area of ​​the portion of the working electrode protrusion covered by the saliva inflow path to the area of ​​the portion of the reference electrode protrusion covered by the saliva inflow path may be included in the numerical range of [3, 9].

[0010]

[0011] According to one embodiment of the present invention, the area ratio of the area of ​​the portion of the working electrode protrusion that contacts the reagent layer to the area of ​​the portion of the reference electrode protrusion that contacts the reagent layer may be included in the numerical range of [3, 9].

[0012] According to one embodiment of the present invention, the area ratio may be included in the numerical range of [5, 9].

[0013] According to one embodiment of the present invention, the biosensor is inserted into a salivary glucose measuring device for measuring the concentration of glucose in saliva, and is configured to receive a voltage from the salivary glucose measuring device through the working electrode and the reference electrode when inserted into the salivary glucose measuring device, and based on the received voltage, an oxidation / reduction reaction of the glucose in the saliva introduced through the reagent layer and the saliva inflow channel occurs, and a current signal generated based on the oxidation / reduction reaction is proportional to the concentration of the glucose in the introduced saliva and is transmitted to the salivary glucose measuring device through the working electrode and the reference electrode, and the salivary glucose measuring device may be configured to measure the concentration of the glucose in the introduced saliva based on the transmitted current signal.

[0014] According to one embodiment of the present invention, the numerical range may be configured to increase the rate of increase of the measured value of the current signal measured by the saliva glucose measuring device with respect to the concentration of glucose in the incoming saliva, compared to the case where the area ratio is not included in the numerical range.

[0015] According to one embodiment of the present invention, the numerical range may be configured to reduce the coefficient of variation of the measured value of the current signal measured by the saliva-per-measuring device compared to the case where the area ratio is not included in the numerical range.

[0016] According to one embodiment of the present invention, the numerical range may be configured to increase the linear correlation of the measured value of the current signal measured by the saliva glucose measuring device with respect to the concentration of glucose in the incoming saliva, compared to the case where the area ratio is not included in the numerical range.

[0017] To solve the problem of the present invention, a system for measuring the concentration of glucose in saliva comprises: a biosensor as described in the specification of the present invention; a saliva collection device for collecting saliva and dropping the collected saliva onto the biosensor; and a saliva glucose measuring device configured to insert the biosensor, which applies a voltage to the inserted biosensor through the working electrode and the reference electrode, receives a current signal from the biosensor, and calculates the concentration of glucose in the saliva introduced through the saliva inflow channel based on the received current signal; wherein, based on the voltage applied by the saliva glucose measuring device, an oxidation / reduction reaction occurs between the reagent layer and the glucose in the introduced saliva, and the current signal is generated based on the oxidation / reduction reaction and is proportional to the concentration of glucose in the introduced saliva.

[0018] According to one embodiment of the present invention, the ratio of the area of ​​the portion of the working electrode protrusion covered by the saliva inflow path to the area of ​​the portion of the reference electrode protrusion covered by the saliva inflow path may be included in the numerical range of [3, 9].

[0019] According to one embodiment of the present invention, the area ratio of the area of ​​the portion of the working electrode protrusion that contacts the reagent layer to the area of ​​the portion of the reference electrode protrusion that contacts the reagent layer may be included in the numerical range of [3, 9].

[0020] According to one embodiment of the present invention, the area ratio may be included in the numerical range of [5, 9].

[0021] According to one embodiment of the present invention, the numerical range may be configured to increase the rate of increase of the measured value of the current signal measured by the saliva glucose measuring device with respect to the concentration of glucose in the incoming saliva, compared to the case where the area ratio is not included in the numerical range.

[0022] According to one embodiment of the present invention, the numerical range may be configured to reduce the coefficient of variation of the measured value of the current signal measured by the saliva-per-measuring device compared to the case where the area ratio is not included in the numerical range.

[0023] According to one embodiment of the present invention, the numerical range may be configured to increase the linear correlation of the measured value of the current signal measured by the saliva glucose measuring device with respect to the concentration of glucose in the incoming saliva, compared to the case where the area ratio is not included in the numerical range.

[0024] The biosensor according to the embodiments of the present invention can improve accuracy and reproducibility in measuring the concentration of glucose in saliva.

[0025] The biosensor according to the embodiments of the present invention can improve accuracy and reproducibility in measuring the concentration of glucose in saliva by configuring the total area of ​​the working electrode protrusions to be larger than the total area of ​​the reference electrode protrusions.

[0026] The biosensor according to the embodiments of the present invention can improve accuracy and reproducibility in measuring the concentration of glucose in saliva through the area ratio and arrangement between the working electrode protrusion and the reference electrode protrusion.

[0027] FIG. 1 is a drawing showing a saliva sugar measuring system including a saliva collection device, a biosensor, and a saliva sugar measuring device according to one embodiment of the present invention.

[0028] FIG. 2 is a schematic diagram showing the structure of a biosensor according to one embodiment of the present invention.

[0029] FIG. 3 illustrates the electrode structure of a lower plate according to one embodiment of the present invention.

[0030] FIG. 4 is a drawing showing another embodiment of the structure of a biosensor and the electrode structure of a bottom plate according to the present invention.

[0031] FIG. 5 illustrates the slope and Y-intercept of a trend line plotting the measured values ​​of a current signal according to the concentration of glucose in relation to embodiments of the present invention, according to the area ratio and arrangement between the working electrode protrusion and the reference electrode protrusion.

[0032] FIG. 6 shows the slope of the trend line and the coefficient of determination (R²) plotting the measured values ​​of the current signal according to the concentration of glucose in relation to embodiments of the present invention. 2 The coefficient of variation (CV) for measuring the concentration of ) and glucose is plotted according to the area ratio between the working electrode protrusions and the reference electrode protrusions arranged in a predetermined manner.

[0033] FIG. 7 shows the slope, Y-intercept, and coefficient of determination (R²) of a trend line plotting the measured values ​​of a current signal according to glucose concentration in relation to embodiments of the present invention. 2 ) is illustrated according to the area ratio between the working electrode protrusion and the reference electrode protrusion.

[0034] FIG. 8 shows the slope, Y-intercept, and coefficient of determination (R) of a trend line plotting the measured values ​​of a current signal according to glucose concentration in relation to embodiments of the present invention. 2 ) is illustrated according to the vertical lengths of the working electrode protrusion and the reference electrode protrusion.

[0035] Hereinafter, a biosensor and system for measuring salivary sugar concentration according to embodiments of the present invention will be described in detail with reference to the attached drawings. However, it will be readily apparent to those skilled in the art that the attached drawings are provided merely to facilitate the disclosure of the content of the present invention, and that the scope of the present invention is not limited to the scope of the attached drawings.

[0036] Hereinafter, salivary glucose refers to glucose contained in saliva, and blood glucose refers to glucose contained in blood.

[0037] A salivary glucose measurement system may include a biosensor and a salivary glucose measurement device. The salivary glucose measurement device may apply voltage to an electrode on the biosensor to which saliva is applied. Due to the voltage applied from the salivary glucose measurement device to the electrode on the biosensor, an oxidation / reduction reaction may occur between the reagent layer located on the electrode of the biosensor and the glucose in the saliva applied thereto. The current signal generated through this oxidation / reduction reaction may be transmitted (i.e., delivered) to the salivary glucose measurement device through the electrode on the biosensor. The salivary glucose measurement device may calculate the concentration of salivary glucose based on the received current signal and predict and determine the concentration of blood glucose based on the calculated concentration of salivary glucose.

[0038] A biosensor used for electrochemical detection of saliva sugar may include a working electrode and a reference electrode.

[0039] At least one of the working electrode and the reference electrode may be placed in the biosensor in contact with a reagent layer included in the biosensor. Here, the reagent layer is the part where the major reaction necessary for electrochemical salivary glucose detection occurs in relation to glucose in saliva dropped onto the reagent layer, specifically the part where oxidation / reduction reactions occur. At this time, the surface area of ​​the working electrode in contact with the reagent layer affects the rate of the oxidation / reduction reaction, the magnitude of the current signal resulting from such reaction, and the reproducibility of salivary glucose detection.

[0040] The reference electrode is an electrode used as a reference point for measuring the potential of the working electrode. Specifically, the reference electrode can maintain a constant potential during oxidation / reduction reactions. In particular, to minimize such potential fluctuations and increase the accuracy of saliva detection, the area of ​​the reference electrode can typically be designed to be equal to or larger than the area of ​​the working electrode.

[0041] Generally, blood glucose measurement systems are designed to measure blood glucose concentrations in a numerical range of 10 mg / dL to 600 mg / dL. In contrast, since the concentration of glucose in saliva is significantly lower than that in blood, salivary glucose measurement systems need to be designed to be able to distinguish glucose concentrations of 10 mg / dL or lower.

[0042] Meanwhile, if the area of ​​the working electrode is significantly larger than the area of ​​the reference electrode, an overcharge may occur on the electrode surface due to a sudden change in current density. Consequently, the potential of the reference electrode may also fluctuate, which may reduce the accuracy and reliability of saliva detection.

[0043] Since the space available for arranging the working electrode and reference electrode on the biosensor is limited, the area of ​​the working electrode and reference electrode is also designed under the influence of these spatial limitations.

[0044] Embodiments of the present invention provide a biosensor and a system for measuring the concentration of salivary glucose, wherein a working electrode and a reference electrode have an optimal area ratio and arrangement to detect low concentrations of glucose in saliva within a limited space on the biosensor and to improve the accuracy and reproducibility of measuring the glucose concentration in saliva.

[0045] Overall structure

[0046] FIG. 1 is a drawing showing a saliva sugar measuring system including a saliva collection device, a biosensor, and a saliva sugar measuring device according to one embodiment of the present invention.

[0047] As illustrated in FIG. 1, the saliva-percentage measuring system (10) may include a saliva collection device (100), a biosensor (200), and a saliva-percentage measuring device (300).

[0048] Specifically, the salivary glucose measuring system (10) is a system for measuring the concentration of glucose contained in saliva. More specifically, the salivary glucose measuring system (10) is for calculating the concentration of salivary glucose from saliva and for predicting and determining the blood glucose concentration through the concentration of salivary glucose.

[0049] Specifically, the saliva collection device (100) is intended to collect saliva. More specifically, a user can collect saliva using the saliva collection device (100). For example, the user can collect saliva by inserting the saliva collection device (100) into the oral cavity. Additionally, the user can apply the saliva collected using the saliva collection device (100) to the biosensor (200).

[0050] Specifically, the biosensor (200) is intended to drop saliva, cause glucose in the dropped saliva to undergo an oxidation / reduction reaction with a reagent layer, and transmit a current signal generated by the oxidation / reduction reaction to a saliva glucose measuring device (300). Detailed information regarding the biosensor (200) will be described later.

[0051] Specifically, the salivary sugar measuring device (300) applies voltage to the biosensor (200), receives a current signal from the biosensor (200), and calculates the concentration of salivary sugar based on the received current signal. Additionally, the salivary sugar measuring device (300) is intended to predict and determine the blood sugar concentration based on the concentration of salivary sugar.

[0052] According to one embodiment of the present invention, a user can collect saliva using a saliva collection device (100). A biosensor (200) can be inserted into a saliva-percentage measuring device (300). When the biosensor (200) is inserted into the saliva-percentage measuring device (300), the biosensor (200) can receive voltage from the saliva-percentage measuring device (300). The user can use the saliva collection device (100) to drop saliva onto the biosensor (200) inserted into the saliva-percentage measuring device (300). When the biosensor (200) with the dropped saliva receives voltage, the biosensor (200) can cause an oxidation / reduction reaction of glucose in the saliva dropped onto the biosensor (200). The biosensor (200) can transmit a current signal generated by the oxidation / reduction reaction to the saliva-percentage measuring device (300). The salivary glucose measuring device (300) can calculate the concentration of glucose in saliva based on the current signal received from the biosensor (200). The salivary glucose measuring device (300) can predict and determine the blood glucose concentration based on the concentration of salivary glucose.

[0053] Structure of biosensors

[0054] FIG. 2 is a schematic diagram showing the structure of a biosensor according to one embodiment of the present invention.

[0055] As illustrated in FIG. 2, the biosensor (200) may include a bottom plate (210), a middle plate (220), and a top plate (230). Specifically, the bottom plate (210), the middle plate (220), and the top plate (230) may form a stacked structure in sequence. More specifically, the top plate (230) may be placed on top of the middle plate (220), and the middle plate (220) may be placed on top of the bottom plate (210). However, the present invention is not limited to a biosensor (200) in which the bottom plate (210), the middle plate (220), and the top plate (230) form a stacked structure in sequence, and the present invention may also include a biosensor (200) in which two or more of the bottom plate (210), the middle plate (220), and the top plate (230) form an integral structure.

[0056] As illustrated in FIG. 2, the top plate (230) may have a saliva inlet (231) and an air outlet (232) formed therein. More specifically, the saliva inlet (231) may be a location where saliva collected by the saliva collection device (100) is applied. Additionally, the saliva inlet (231) is an opening through which saliva applied to the biosensor (200) can pass. Additionally, the air outlet (232) is a passage through which air inside the biosensor (200) can be discharged to the outside. When air is discharged through the air outlet (232), the generation of bubbles in the saliva may be prevented when the saliva applied to the biosensor (200) through the saliva inlet (231) flows into the saliva inlet (221). Additionally, saliva applied to the biosensor (200) can be diffused by the flow of air discharged through the air outlet (232). In this case, the oxidation / reduction reaction between the reagent layer and the saliva can occur uniformly.

[0057] According to one embodiment of the present invention, the top plate (230) may comprise at least one material selected from the group comprising polyethylene terephthalate (PET), polypropylene (PP), polytetrafluoroethylene (PTFE), polyethylene (PE), silicone, and polyurethane (PU). However, it is not limited thereto.

[0058] According to one embodiment of the present invention, the surface of the top plate (230) may be coated with a material comprising a hydrophilic material. For example, the coating may be at least one coating selected from the group comprising physical vapor deposition, chemical vapor deposition, nano coating, polymer coating, sol-gel coating, diamond coating, and UV-curing coating. However, it is not limited thereto.

[0059] As illustrated in FIG. 2, the middle plate (220) can be placed at the bottom of the top plate (230) and perforated to form a saliva inflow channel (221). The saliva inflow channel (221) is a channel into which saliva, which is applied to the biosensor (200), flows after passing through the saliva inlet (231) formed in the top plate (210).

[0060] As shown in FIG. 2, a reagent layer (222) may be placed in the saliva inflow channel (221). The reagent layer (222) is intended to perform an oxidation / reduction reaction with glucose in the saliva.

[0061] Specifically, the saliva inlet channel (221) may be a portion where an oxidation / reduction reaction occurs between glucose in the incoming saliva and the reagent layer (222). More specifically, the oxidation / reduction reaction may occur at an electrode located in a portion corresponding to the saliva inlet channel (221) on the lower plate (210). That is, the saliva inlet channel (221) may serve as a reference for determining the area of ​​the electrode on the lower plate (210) where the oxidation / reduction reaction occurs. Additionally, the user may drop saliva into the biosensor (200) in an amount equal to the volume formed by the saliva inlet channel (221). That is, the saliva inlet channel (221) may serve as a reference for determining the amount of saliva inflow. Furthermore, the saliva inflow into the saliva inlet channel (221) may be stored within the saliva inlet channel (221). That is, the saliva inlet channel (221) may prevent the flow of saliva while the oxidation / reduction reaction occurs. Thus, oxidation / reduction reactions can occur stably.

[0062] Specifically, the reagent layer (222) may include an enzyme compound and an electron transfer mediator.

[0063] More specifically, the enzyme compound is intended to specifically react with glucose in saliva to generate electrons. For example, the enzyme compound may comprise at least one oxidoreductase selected from the group comprising glucose oxidase (GOD) and glucose dehydrogenase (GDH). The enzyme compound may be glucose dehydrogenase (GDH), but is not limited thereto.

[0064] According to one embodiment of the present invention, the enzyme compound may further include a cofactor. Specifically, the cofactor is intended to assist the function of the redox enzyme. For example, the cofactor may include at least one compound selected from the group comprising flavin adenine dinucleotide (FAD), nicotinamide adenine dinucleotide (NAD), and pyrroloquinoline quinone (PQQ).

[0065] For example, when glucose dehydrogenase (GDH) and FAD are used together in the reagent layer (222), the reagent layer (222) may contain FAD-GDH as an enzyme compound.

[0066] For example, when glucose dehydrogenase (GDH) and NAD are used together in the reagent layer (222), the reagent layer (222) may contain NAD-GDH as an enzyme compound.

[0067] For example, when glucose dehydrogenase (GDH) and PQQ are used together in the reagent layer (222), the reagent layer (222) may contain PQQ-GDH as an enzyme compound.

[0068] More specifically, the electron transfer medium is intended to transfer electrons generated through oxidation / reduction reactions between glucose and enzyme compounds in saliva to an electrode. For example, the electron transfer medium may include a metal complex.

[0069] For example, the metal complex may comprise at least one compound selected from the group comprising hexaammineruthenium trichloride, ruthenium(III) hexaamine, ruthenium(II) tris(2,2'-bipyridine), ruthenium(II) tris(4,4'-dicarboxy-2,2'-bipyridine), and ruthenium(III) chlorodi(2,2'-bipyridine). However, it is not limited thereto.

[0070] For example, the metal complex may comprise at least one compound selected from the group comprising ferricyanide, hemin, porphyrin complex, and iron-TPP complex (Iron Tetraphenylporphyrin Complex). However, it is not limited thereto.

[0071] For example, the metal complex may comprise at least one compound selected from the group comprising osmium bipyridine complex, osmium phenanthroline complex, osmium tetraphenylporphyrin complex, and osmium polypyridyl complex. However, it is not limited thereto.

[0072] According to one embodiment of the present invention, the middle plate (220) may comprise at least one material selected from the group comprising polyethylene terephthalate (PET), polypropylene (PP), polytetrafluoroethylene (PTFE), polyethylene (PE), silicone, and polyurethane (PU). However, it is not limited thereto.

[0073] According to one embodiment of the present invention, the middle plate (220) may include an adhesive material on its surface. For example, the adhesive material may include at least one product or material selected from the group comprising acrylic adhesive, hot-melt adhesive, epoxy adhesive, UV-curable adhesive, polyurethane adhesive, silicone adhesive, double-sided adhesive tape, pressure-sensitive adhesive (PSA), and cyanoacrylate adhesive. However, it is not limited thereto.

[0074] According to one embodiment of the present invention, the middle plate (220) can combine the lower plate (210) and the upper plate (230) by means of an adhesive material included on the surface.

[0075] As illustrated in FIG. 2, the lower plate (210) may be placed at the bottom of the middle plate (220) and may include an insulating substrate (210-1) and a plurality of electrodes. Specifically, when the lower plate (210) is inserted into the saliva glucose measuring device (300), it may receive voltage from the saliva glucose measuring device (300) through the plurality of electrodes. Due to the applied voltage, an oxidation / reduction reaction may occur between glucose in the saliva introduced into the saliva inflow channel (221) and the reagent layer (222). The current signal generated through the oxidation / reduction reaction may be transmitted to the saliva glucose measuring device (300) through the plurality of electrodes.

[0076] According to one embodiment of the present invention, the bottom plate (210) may comprise at least one material selected from the group comprising polyethylene terephthalate (PET), polypropylene (PP), polytetrafluoroethylene (PTFE), polyethylene (PE), silicone, and polyurethane (PU). However, it is not limited thereto.

[0077] According to one embodiment of the present invention, the surface of the bottom plate (210) may be coated with a material containing an antistatic material.

[0078] According to one embodiment of the present invention, the biosensor (200) may further include a filter (not shown) for filtering interfering substances in saliva. Interfering substances refer to substances that can affect the oxidation / reduction reaction between the reagent layer (222) and glucose in saliva. For example, interfering substances may include at least one substance selected from the group including proteins and macromolecules such as mucin. However, the present invention is not limited to a biosensor (200) that includes a filter (not shown), and the present invention includes a biosensor (200) that does not include a filter (not shown).

[0079] For example, a filter (not shown) may be placed on the upper part of the top plate (230), but is not limited thereto.

[0080] According to one embodiment of the present invention, a saliva collection device (100) may include a filter (not shown) for filtering interfering substances in saliva. Interfering substances refer to substances that can affect the oxidation / reduction reaction between the reagent layer (222) and glucose in saliva. For example, interfering substances may include at least one substance selected from the group including proteins and macromolecular substances such as mucin. However, the present invention is not limited to a saliva collection device (100) that includes a filter (not shown), and the present invention includes a saliva collection device (100) that does not include a filter (not shown).

[0081] According to one embodiment of the present invention, a biosensor (200) may be manufactured by stacking a bottom plate (210), a middle plate (220), and a top plate (230) in sequence. Specifically, the bottom plate (210) may be placed at the bottom of the biosensor (200). Additionally, the middle plate (220) may be placed on top of the bottom plate (210). Additionally, the top plate (230) may be placed on top of the middle plate (220). Meanwhile, before placing the top plate (230) on top of the middle plate (220), a process of dispensing a reagent layer (222) into a saliva inflow channel (221) formed in the middle plate (220) may be performed prior to the top plate (230).

[0082] Detailed structure of the bottom plate

[0083] FIG. 3 illustrates the electrode structure of a lower plate according to one embodiment of the present invention.

[0084] As illustrated in FIG. 3, the bottom plate (210) may include a working electrode (211), a reference electrode (212), a checking electrode (213), and at least one dummy electrode (214). Additionally, a first region (a), a second region (b), and a third region (c) may be located on the bottom plate (210).

[0085] According to one embodiment of the present invention, the first region (a) may be a portion corresponding to the saliva injection port (231).

[0086] According to one embodiment of the present invention, the second region (b) may be a portion corresponding to the saliva inflow channel (221). Meanwhile, as described below, the second region (b) may be a portion corresponding to the reagent layer (222). That is, the portion corresponding to the saliva inflow channel (221) may coincide with the portion corresponding to the reagent layer (222).

[0087] According to one embodiment of the present invention, the third region (c) may be a portion corresponding to the air outlet (232).

[0088] As illustrated in FIG. 3, the working electrode (211) may include a working electrode body (211-1) and at least one working electrode projection (211-2). Additionally, the reference electrode (212) may include a reference electrode body (212-1) and at least one reference electrode projection (212-2). Additionally, the check electrode (213) may include a check electrode body (213-1) and at least one check electrode projection (213-2).

[0089] According to one embodiment of the present invention, the above-described second region (b) may be a portion where an oxidation / reduction reaction occurs between the reagent layer (222) and glucose in saliva. Specifically, in the second region (b), at least one of the working electrode protrusion (211-2) and the reference electrode protrusion (212-2) may be in contact with at least one of the reagent layer (222) and saliva. Meanwhile, in the second region (b), the check electrode protrusion (231-2) may also be in contact with at least one of the reagent layer (222) and saliva.

[0090] As illustrated in FIG. 3, the working electrode main body (211-1), the reference electrode main body (212-1), and the check electrode main body (213-1) may be spaced apart from each other by a predetermined distance in the transverse direction (X-axis direction) of the second region (b). Additionally, the working electrode main body (211-1), the reference electrode main body (212-1), and the check electrode main body (213-1) may be arranged parallel to each other in the longitudinal direction (Y-axis direction) of the second region (b).

[0091] As shown in FIG. 3, the working electrode protrusion (211-2) and the reference electrode protrusion (212-2) can be arranged perpendicularly to the working electrode main body (211-1) and the reference electrode main body (212-1), respectively. Additionally, the working electrode protrusion (211-2) and the reference electrode protrusion (212-2) can be arranged spaced apart from each other by a predetermined distance in the longitudinal direction (Y-axis direction) of the second region (b).

[0092] According to one embodiment of the present invention, the number of working electrode protrusions (211-2) and reference electrode protrusions (212-2) may be equal to each other. For example, although not shown in FIG. 3, one working electrode protrusion (211-2) and one reference electrode protrusion (212-2) may be disposed in the second region (b). However, it is not limited thereto.

[0093] According to one embodiment of the present invention, the number of working electrode protrusions (211-2) and reference electrode protrusions (212-2) may differ from each other. For example, as shown in FIG. 3, two working electrode protrusions (211-2a, 211-2b) and one reference electrode protrusion (212-2) may be disposed in the second region (b). However, it is not limited thereto.

[0094] According to one embodiment of the present invention, when at least one of the working electrode protrusions (211-2) and the reference electrode protrusions (212-2) is a plurality, the working electrode protrusions (211-2) and the reference electrode protrusions (212-2) may be arranged alternately. For example, as shown in FIG. 3, when the number of working electrode protrusions (211-2) and the reference electrode protrusions (212-2) are two and one, respectively, the working electrode protrusions (211-2) and the reference electrode protrusions (212-2) may be arranged in the order of the first working electrode protrusion (211-2a), the reference electrode protrusion (212-2), and the second working electrode protrusion (211-2b). However, this is not limited thereto.

[0095] According to one embodiment of the present invention, when at least one of the working electrode protrusions (211-2) and the reference electrode protrusions (212-2) is a plurality, the working electrode protrusions (211-2) and the reference electrode protrusions (212-2) may not be arranged alternately. For example, although not shown in FIG. 3, when the number of working electrode protrusions (211-2) and the reference electrode protrusions (212-2) is two and one, respectively, the working electrode protrusions (211-2) and the reference electrode protrusions (212-2) may be arranged in the order of the first working electrode protrusion (211-2a), the second working electrode protrusion (211-2b), and the reference electrode protrusion (212-2). However, this is not limited thereto.

[0096] According to one embodiment of the present invention, when at least one of the working electrode protrusions (211-2) and the reference electrode protrusions (212-2) is a plurality, the working electrode protrusions (211-2) and the reference electrode protrusions (212-2) may be arranged such that both areas that are alternately arranged and areas that are not alternately arranged are formed. However, the invention is not limited thereto.

[0097] As illustrated in FIG. 3, the check electrode projection (213-2) may include a first check electrode projection (213-2a) arranged in a direction perpendicular to the check electrode main body (213-1) and a second check electrode projection (213-2b) arranged in a direction parallel to the check electrode main body (213-1).

[0098] As shown in FIG. 3, at least a portion of each of the working electrode projection (211-2), the reference electrode projection (212-2) and the check electrode projection (213-2) may constitute at least a portion of the second region (b).

[0099] As illustrated in FIG. 3, at least a portion of the check electrode protrusion (213-2) may be placed in the second region (b). Specifically, at least a portion of the check electrode protrusion (213-2) may be placed at one end of the longitudinal direction (Y-axis direction) of the second region (b).

[0100] As illustrated in FIG. 3, the bottom plate (210) may include at least one or more orbital electrodes (214). For example, the orbital electrodes (214) may include a first orbital electrode (214a), a second orbital electrode (214b), and a third orbital electrode (214c). Specifically, the first orbital electrode (214a) may be positioned such that at least a portion thereof is located at the other end of the longitudinal direction (Y-axis direction) of the second region (b). Additionally, the second orbital electrode (214b) and the third orbital electrode (214c) may be positioned such that at least a portion thereof is located at one end of the longitudinal direction (Y-axis direction) of the second region (b), with the second check electrode protrusion (213-2b) in between.

[0101] According to one embodiment of the present invention, the working electrode (211) and the reference electrode (212) are for measuring the concentration of glucose in saliva. The working electrode (211) and the reference electrode (212) can each receive a predetermined voltage from the saliva glucose measuring device (300). At this time, a predetermined potential difference is formed between the working electrode (211) and the reference electrode (212). Due to the formed potential difference, an oxidation / reduction reaction occurs between the glucose in saliva and the reagent layer (222). A current signal is generated due to the oxidation / reduction reaction, and the current signal is transmitted to the saliva glucose measuring device (300) through the working electrode (211) and the reference electrode (212).

[0102] According to one embodiment of the present invention, the check electrode (213) is an electrode for recognizing saliva. The saliva per measuring device (300) can transmit a saliva recognition signal to the check electrode (213). When saliva comes into contact with the check electrode protrusion (213-2) placed within the second region (b), the check electrode (213) can transmit a response signal to the saliva per measuring device (300) in response to the saliva recognition signal. The saliva per measuring device (300) can recognize that saliva has flowed into the saliva inflow channel (221) based on the response signal.

[0103] According to one embodiment of the present invention, the blank electrode (214) is intended to uniformly coat the reagent layer (222) contained in the saliva inflow channel (221). In the presence of the blank electrode (214), the reagent layer (222) may be placed within the saliva inflow channel (221) with an area equal to the area of ​​one cross-section of the saliva inflow channel (221). At this time, as described above, the portion corresponding to the reagent layer (222) on the lower plate (210) may coincide with the portion corresponding to the saliva inflow channel (221). When the blank electrode (214) is present, compared to when the blank electrode (214) is not present, the oxidation / reduction reaction between glucose in the saliva and the reagent layer (222) can occur uniformly. Thus, the saliva glucose measuring device (300) can calculate the concentration of saliva glucose more accurately. Meanwhile, the present invention is not limited to a biosensor (200) including a blank electrode (214), and the present invention also includes a biosensor (200) that does not include a blank electrode (214).

[0104] According to one embodiment of the present invention, the working electrode (211) and the reference electrode (212) may include a metal. For example, the metal may include at least one selected from the group comprising copper (Cu), nickel (Ni), and gold (Au). However, it is not limited thereto.

[0105] According to one embodiment of the present invention, the working electrode (211) and the reference electrode (212) may include carbon. For example, the working electrode (211) and the reference electrode (212) may be at least one electrode selected from the group comprising a glass carbon electrode, a carbon nanotube electrode, a graphene electrode, a carbon fiber electrode, a porous carbon electrode, a conductive polymer carbon composite electrode, a carbon ink electrode, a diamond-like carbon electrode, and an activated carbon electrode. However, they are not limited thereto.

[0106] According to one embodiment of the present invention, the working electrode (211) and the reference electrode (212) may each be composed of a plurality of layers. Each of the plurality of layers may include the metal and / or carbon described above. Each of the plurality of layers may include the same material. Alternatively, each of the plurality of layers may include different materials. However, it is not limited thereto.

[0107] According to one embodiment of the present invention, the working electrode (211) and the reference electrode (212) may each be electrodes comprising the same material. Alternatively, the working electrode (211) and the reference electrode (212) may each be electrodes comprising different materials. However, they are not limited thereto.

[0108] FIG. 4 is a diagram showing another embodiment of the structure of a biosensor and the electrode structure of a bottom plate according to the present invention. Specifically, FIG. 4(a) is a schematic diagram showing the structure of a biosensor. FIG. 4(b) shows the electrode structure of a bottom plate. FIG. 4(c) shows the electrode structure of a top plate.

[0109] According to one embodiment of the present invention, the biosensor (200) may include a bottom plate (210), a middle plate (220), a reagent layer (222), and a top plate (230). Details regarding the bottom plate (210), middle plate (220), reagent layer (222), and top plate (230) are as described above with reference to FIG. 2.

[0110] As illustrated in FIG. 4(a), the lower plate (210) and the upper plate (230) may each include a working electrode (211) and a reference electrode (212). Specifically, the working electrode (211) may be placed on the upper surface of the lower plate (210). Additionally, the reference electrode (212) may be placed on the lower surface of the upper plate (230). That is, unlike as illustrated in FIG. 2 and 3, the working electrode (211) and the reference electrode (212) may be placed on different substrates. This will be explained in detail below with reference to FIG. 4(b) and (c).

[0111] As illustrated in FIG. 4(b), when a reference electrode (212) is placed on the upper plate (230), the lower plate (210) may include a working electrode (211), a check electrode (213), and at least one idle electrode (214). Additionally, a first region (a), a second region (b), and a third region (c) may be located on the lower plate (210). Details regarding the first region (a), the second region (b), and the third region (c) are as described above with reference to FIG. 3.

[0112] As illustrated in FIG. 4(b), when the reference electrode (212) is placed on the upper plate (230), a portion (212') corresponding to the reference electrode (212) may be located on the lower plate (210). Additionally, a portion (212'-1) corresponding to the reference electrode main body portion (212-1) and a portion (212'-2) corresponding to the reference electrode protrusion (212-2) may be located on the lower plate (210).

[0113] As illustrated in FIG. 4(b), the arrangement relationship between the working electrode main body (211-1), the working electrode projection (211-2), the part corresponding to the reference electrode main body (212-1) (212'-1), the part corresponding to the reference electrode projection (212-2) (212'-2), the check electrode main body (213-1), the check electrode projection (213-2), and the idle electrode (214) can be formed in the same way as the arrangement relationship between the working electrode main body (211-1), the working electrode projection (211-2), the reference electrode main body (212-1), the reference electrode projection (212-2), the check electrode main body (213-1), the check electrode projection (213-2), and the idle electrode (214) described above with reference to FIG. 3. However, it is not limited thereto.

[0114] As shown in FIG. 4(a), the middle plate (220) may be additionally perforated to form a connection hole (223). Specifically, the connection hole (223) may be an opening for electrically connecting electrodes included in the upper plate (230) and the lower plate (210).

[0115] As illustrated in FIG. 4(b), the lower plate (210) may further include an extension electrode (215). Specifically, the extension electrode (215) may be an electrode for electrically connecting to a reference electrode (212) included in the upper plate (230) through a connection hole (223) formed in the middle plate (220). More specifically, when the biosensor (200) is inserted into the saliva-percentage measuring device (300), one end of the extension electrode (215) may be electrically connected to the saliva-percentage measuring device (300). Additionally, the other end of the extension electrode (215) may be electrically connected to the reference electrode (212) in a predetermined manner through the connection hole (223). Accordingly, when the biosensor (200) is inserted into the saliva-per-measuring device (300), the reference electrode (212) can be electrically connected to the saliva-per-measuring device (300).

[0116] According to the present invention, the reference electrode (212) and the extension electrode (215) can be electrically connected to each other in various ways through the connection hole (223). For example, the reference electrode (212) and the extension electrode (215) can be electrically connected to each other through at least one method selected from the group including soldering, rivet bonding, bolt and nut connection, welding, and conductive adhesive connection. However, they are not limited thereto.

[0117] Meanwhile, FIG. 4 illustrates an embodiment in which the reference electrode (212) of the upper plate (230) is electrically connected to the saliva-percentage measuring device (300) through a connection hole (223) formed in the middle plate (220) and an extension electrode (215) of the lower plate (210), but the present invention is not limited thereto. The present invention includes all biosensors (200) configured to electrically connect the reference electrode (212) of the upper plate (230) to the saliva-percentage measuring device (300) by a predetermined known method, wherein the connection hole (223) and / or the extension electrode (215) may not be provided.

[0118] As illustrated in FIG. 4(c), the top plate (230) may include a reference electrode (212). Specifically, the reference electrode (212) may include a reference electrode main body (212-1) and a reference electrode protrusion (212-2). Details regarding the reference electrode (212) are as described above with reference to FIG. 2 and 3.

[0119] As illustrated in FIG. 4(c), the top plate (230) may include a fourth region (b'). Specifically, the fourth region (b') may be a portion corresponding to the saliva inlet (221). Alternatively, the fourth region (b) may be a portion corresponding to the reagent layer (222). That is, the portion corresponding to the saliva inlet (221) may coincide with the portion corresponding to the reagent layer (222). More specifically, at least a portion of the fourth region (b') may overlap with the saliva inlet (231) and / or the air outlet (232). However, it is not limited thereto.

[0120] As illustrated in FIG. 4(c), the reference electrode main body (212-1) may be positioned in the longitudinal direction (Y-axis direction) of the fourth region (b'). Additionally, the reference electrode protrusion (212-2) may be positioned in the transverse direction (X-axis direction) of the fourth region (b') so as to be perpendicular to the reference electrode main body (212-1). At this time, at least a portion of the reference electrode protrusion (212-2) may be located in the fourth region (b').

[0121] Meanwhile, the biosensor (200) according to the present invention is not limited to the one described above with reference to FIG. 4, and the biosensor (200) according to the present invention may include any sensor structure in which a working electrode (211) and a reference electrode (212) are formed on the lower plate (210) and the upper plate (230), respectively. At this time, the working electrode protrusion (211-2) may be located in the second region (b) of the lower plate (210). In addition, the reference electrode protrusion (212-2) may be located in the fourth region (b') of the upper plate (230). That is, the working electrode protrusion (211-2) and the reference electrode protrusion (212-2) may be located in the regions of the lower plate (210) and the upper plate (230) corresponding to the saliva inflow channel (221) and / or the reagent layer (222), respectively.

[0122] Unlike what is shown in FIG. 4, the working electrode (211) and the reference electrode (212) may be located on the upper plate (230) and the lower plate (210), respectively. However, this is not limited thereto.

[0123] Meanwhile, it may be preferable for the working electrode (211) to be located on the lower plate (210). However, it is not limited thereto.

[0124] According to one embodiment of the present invention, when the working electrode (211) and the reference electrode (212) are positioned separately on the lower plate (210) or the upper plate (230), it is preferable that the working electrode (211) and the reference electrode (212) be arranged to face each other in the second region (b) or the fourth region (b'). However, this is not limited thereto.

[0125] According to one embodiment of the present invention, in the lower plate (210) or the upper plate (230), the portion corresponding to the saliva inflow channel (221) and the portion corresponding to the reagent layer (222) may not coincide with each other. For example, the portion corresponding to the reagent layer (222) may be included in the portion corresponding to the saliva inflow channel (221) and may be formed narrower than the portion corresponding to the saliva inflow channel (221). However, it is not limited thereto.

[0126] According to one embodiment of the present invention, when both the working electrode protrusion (211-2) and the reference electrode protrusion (212-2) are placed on the lower plate (210), the reagent layer (222) may be placed within the saliva inflow channel (221) so as to be in contact with the working electrode protrusion (211-2) but not with the reference electrode protrusion (212-2).

[0127] According to one embodiment of the present invention, when the working electrode protrusion (211-2) and the reference electrode protrusion (212-2) are respectively placed on the lower plate (210) and the upper plate (230), the reagent layer (222) may be placed within the saliva inflow channel (221) so as to be in contact with the working electrode protrusion (211-2) but not with the reference electrode protrusion (212-2).

[0128] However, the present invention is not limited thereto and may include a biosensor (200) in which a reagent layer (222) contacts both a working electrode protrusion (211-2) and a reference electrode protrusion (212-2).

[0129]

[0130] Area ratio and layout

[0131] FIG. 5 illustrates the slope and Y-intercept of a trend line plotting the measured values ​​of a current signal according to glucose concentration in relation to embodiments of the present invention, according to the area ratio and arrangement between the working electrode protrusion and the reference electrode protrusion. Specifically, FIG. 5(a) shows a table showing the results. Also, FIG. 5(b) shows a second region and the arrangement of the working electrode protrusion and the reference electrode protrusion within the second region.

[0132] As illustrated in FIG. 5(b), the second region (b) on the lower plate (210) is the portion where the working electrode protrusion (211-2) and the reference electrode protrusion (212-2) are placed. Specifically, FIG. 5(a) illustrates the slope and Y-intercept of the trend line according to the area ratio between the working electrode protrusion (211-2) and the reference electrode protrusion (212-2) placed in the second region (b). The trend line refers to a straight line plotting the measured value of the current signal according to the concentration of glucose.

[0133] The table shown in FIG. 5(a) is obtained using a biosensor (200) having a working electrode (211) and a reference electrode (212) containing a metal and a reagent layer (222) containing an oxidoreductase. For example, the metal may include at least one selected from the group including copper (Cu), nickel (Ni), and gold (Au), but is not limited thereto.

[0134] As shown in FIG. 5(a), the results for Examples 1 to 6 are calculated by applying a predetermined voltage (e.g., the voltage may be 0.4V (400mV), but the optimal voltage may change depending on various factors such as the type of substance included in the reagent layer, so it is not limited thereto) to the saliva per measuring device (300) to the biosensor (200).

[0135] Meanwhile, the results for Examples 1 to 6 were calculated under conditions where the sum of the areas of the working electrode protrusion (211-2) and the reference electrode protrusion (212-2) is maintained at a predetermined value.

[0136] The table shown in FIG. 5(a) is calculated using a control solution. The control solution is a solution prepared to have physical, chemical, and biological properties similar to human saliva. The control solution may include a thickener, a preservative, and a colorant. Additionally, the control solution may be prepared to include glucose at a predetermined concentration.

[0137] The table shown in FIG. 5(a) is obtained by performing a process of consistently dropping a control solution having a predetermined glucose concentration into a biosensor (200) having an electrode structure corresponding to Examples 1 to 6 in a predetermined amount, repeating the measurement of the current value for each concentration a predetermined number of times, and then calculating the slope and Y-intercept of a trend line plotting the average of the current values ​​repeatedly measured for each concentration.

[0138] As illustrated in FIG. 5(a), Examples 1 and 2 correspond to the case where the bottom plate (210) has an electrode structure of Structure 1. Structure 1 is an electrode structure in which the area ratio between one of the working electrode protrusions (211-2) or the reference electrode protrusions (212-2) and the other is 3:2, and the working electrode protrusions (211-2) and the reference electrode protrusions (212-2) are arranged alternately. The area ratio of the protrusions refers to the ratio between the total areas of the protrusions located within the second region (b). The total area of ​​the protrusions refers to the area of ​​a single protrusion when there is a single protrusion, and the sum of the areas of multiple protrusions when there are multiple protrusions.

[0139] Specifically, Example 1 corresponds to a case where the area ratio between the working electrode protrusion (211-2) and the reference electrode protrusion (212-2) is 3:2, and one working electrode protrusion (211-2) and two reference electrode protrusions (212-2) are arranged alternately. Additionally, Example 2 corresponds to a case where the area ratio between the working electrode protrusion (211-2) and the reference electrode protrusion (212-2) is 2:3, and two working electrode protrusions (211-2) and one reference electrode protrusion (212-2) are arranged alternately.

[0140] As illustrated in FIG. 5(a), Examples 3 and 4 correspond to the case where the bottom plate (210) has the electrode structure of Structure 2. Structure 2 is an electrode structure in which the area ratio between one of the working electrode protrusions (211-2) or the reference electrode protrusions (212-2) and the other is 5:2, and the working electrode protrusions (211-2) and the reference electrode protrusions (212-2) are arranged alternately. In this case, Structure 2 has an electrode structure in which a plurality of protrusions with a small total area are arranged with a single protrusion with a large total area in between. The area ratio of the protrusions refers to the ratio between the total areas of the protrusions located within the second region (b). The total area of ​​the protrusions refers to the area of ​​a single protrusion when there is a single protrusion, and the sum of the areas of multiple protrusions when there are multiple protrusions.

[0141] Specifically, Example 3 corresponds to a case where the area ratio between the working electrode protrusion (211-2) and the reference electrode protrusion (212-2) is 5:2, and one working electrode protrusion (211-2) and two reference electrode protrusions (212-2) are arranged alternately. Additionally, Example 4 corresponds to a case where the area ratio between the working electrode protrusion (211-2) and the reference electrode protrusion (212-2) is 2:5, and two working electrode protrusions (211-2) and one reference electrode protrusion (212-2) are arranged alternately.

[0142] As illustrated in FIG. 5, Examples 5 and 6 correspond to the case where the bottom plate (210) has the electrode structure of Structure 3. Structure 3 is an electrode structure in which the area ratio between one of the working electrode protrusions (211-2) or the reference electrode protrusions (212-2) and the other is 5:2, and the working electrode protrusions (211-2) and the reference electrode protrusions (212-2) are arranged alternately. In this case, Structure 3 has an electrode structure in which a plurality of protrusions with a large total area are arranged with a single protrusion with a small total area in between. The area ratio of the protrusions refers to the ratio between the total areas of the protrusions located within the second region (b). The total area of ​​the protrusions refers to the area of ​​a single protrusion when there is a single protrusion, and the sum of the areas of multiple protrusions when there are multiple protrusions.

[0143] Specifically, Example 5 corresponds to a case where the area ratio between the working electrode protrusion (211-2) and the reference electrode protrusion (212-2) is 2:5, and one working electrode protrusion (211-2) and two reference electrode protrusions (212-2) are arranged alternately. Additionally, Example 6 corresponds to a case where the area ratio between the working electrode protrusion (211-2) and the reference electrode protrusion (212-2) is 5:2, and two working electrode protrusions (211-2) and one reference electrode protrusion (212-2) are arranged alternately.

[0144] As shown in FIG. 5(a), the slope of the trend line calculated in Example 1 is greater than the slope of the trend line calculated in Example 2. Also, the slope of the trend line calculated in Example 3 is greater than the slope of the trend line calculated in Example 4. Also, the slope of the trend line calculated in Example 6 is greater than the slope of the trend line calculated in Example 5.

[0145] Referring to the result shown in FIG. 5(a), the slope of the trend line increases as the area ratio of the working electrode protrusion (211-2) to the reference electrode protrusion (212-2) increases.

[0146] That is, when the area ratio of the working electrode protrusion (211-2) to the reference electrode protrusion (212-2) increases, the rate of increase of the current signal value according to the glucose concentration increases. When the rate of increase of the current signal value according to the glucose concentration is large, even minute differences in glucose concentration can be detected. Accordingly, the accuracy of salivary glucose and blood glucose measurement is improved.

[0147] Meanwhile, as shown in FIG. 5(a), the slope values ​​calculated in Example 3 and Example 6 were 2.29 and 2.17, respectively, and it was confirmed that there is a slight difference between the corresponding slope values. In addition, the slope values ​​calculated in Example 4 and Example 5 were 1.14 and 1.07, respectively, and it was confirmed that there is likewise a slight difference between the corresponding slope values. That is, the result shown in FIG. 5(a) supports the fact that when the area ratio between the working electrode protrusion (211-2) and the reference electrode protrusion (212-2) is maintained at a predetermined value, the number of each of the working electrode protrusion (211-2) and the reference electrode protrusion (212-2), and the arrangement between the working electrode protrusion (211-2) and the reference electrode protrusion (212-2), do not significantly affect the rate of increase of the current signal value according to glucose concentration.

[0148] According to one embodiment of the present invention, a predetermined process error may occur during the manufacturing process of an electrode. When the electrode has multiple protrusions, the process error may occur for each of the multiple protrusions as substantially the same value, regardless of the area of ​​each of the multiple protrusions. For example, if the process error occurring per protrusion of the electrode regardless of area is denoted as A, then when the number of protrusions is N, the total process error becomes N x A. That is, as the number of protrusions increases, the process error increases proportionally.

[0149] As described above, the process error occurs as the same value for each protrusion, regardless of the area of ​​the electrode protrusion. Therefore, as the area of ​​the protrusion decreases, the ratio of the process error for that protrusion increases. For example, if A is denoted as the process error occurring per electrode protrusion regardless of area, the ratio of the process error when the protrusion area is 10 and when the protrusion area is 100 can be calculated as A / 10 and A / 100, respectively. In other words, the process error when the protrusion area is 10 (A / 10) is greater than the process error when the protrusion area is 100 (A / 100).

[0150] Accordingly, when the total number of protrusions on the electrode is constant, the ratio of the total process error to the total area of ​​the electrode protrusions can be reduced when the number of protrusions with a large area is greater than the number of protrusions with a small area.

[0151] That is, according to one embodiment of the present invention, the total area of ​​the working electrode protrusions (211-2) may be larger than the total area of ​​the reference electrode protrusions (212-2). In this case, the total number of working electrode protrusions (211-2) may be larger than the total number of reference electrode protrusions (212-2). By doing so, the accuracy of salivary glucose and blood glucose measurement can be improved. In addition, the total process error in the manufacturing process can be reduced. However, it is not limited thereto.

[0152] FIG. 6 shows the slope of the trend line and the coefficient of determination (R²) plotting the measured values ​​of the current signal according to the concentration of glucose in relation to embodiments of the present invention. 2The coefficient of variation (CV) for glucose concentration measurement is plotted according to the area ratio between the working electrode protrusions and the reference electrode protrusions arranged in a predetermined manner. Specifically, FIG. 6(a) illustrates Examples 7 to 12, each in which the working electrode protrusions and the reference electrode protrusions are arranged in a predetermined manner. Furthermore, FIG. 6(b), (c), and (d) respectively show the slope of the trend line, the coefficient of variation (CV) for glucose concentration measurement, and the coefficient of determination (R²) of the trend line for Examples 7 to 12. 2 This shows the result value for ).

[0153] As described above with reference to FIG. 5, the working electrode protrusion (211-2) and the reference electrode protrusion (212-2) are placed in the second region (b) on the lower plate (210).

[0154] As shown in FIG. 6(a), Examples 7 to 12 all correspond to cases where the working electrode protrusions (211-2) and the reference electrode protrusions (212-2) are two and one, respectively.

[0155] Specifically, Examples 7 to 12 correspond to cases where the ratio of the total area of ​​the working electrode protrusion (211-2) to the total area of ​​the reference electrode protrusion (212-2) is 1.5 (2:3), 5 (1:5), 6 (1:6), 7 (1:7), 8 (1:8), and 9 (1:9), respectively.

[0156] The table shown in FIGS. 6(b) to (d) is obtained using a biosensor (200) having a working electrode (211) and a reference electrode (212) containing a metal and a reagent layer (222) containing an oxidoreductase. For example, the metal may include at least one selected from the group including copper (Cu), nickel (Ni), and gold (Au), but is not limited thereto.

[0157] Meanwhile, the results for Examples 7 to 12 (see FIG. 6 (b), (c) and (d)) were calculated under conditions where the sum of the areas of the working electrode protrusion (211-2) and the reference electrode protrusion (212-2) is maintained at a predetermined value.

[0158] The tables shown in FIGS. 6(b) to (d) are calculated using a control solution. The control solution is a solution prepared to have physical, chemical, and biological properties similar to human saliva. The control solution may include a thickener, a preservative, and a colorant. Additionally, the control solution may be prepared to include glucose at a predetermined concentration.

[0159] In addition, the table shown in FIG. 6 (b) to (d) is calculated by applying a predetermined voltage (for example, the voltage may be 0.4V (400mV), but the optimal voltage may change depending on various factors such as the type of substance included in the reagent layer, so it is not limited thereto) to the saliva per measuring device (300) to the biosensor (200).

[0160] The tables shown in FIGS. 6(b) and (d) represent the slope of a trend line and the coefficient of determination (R²) of the average of the current values ​​repeatedly measured for each concentration, plotted after a control solution having a predetermined glucose concentration (0μM, 100μM, 250μM, 500μM, 1000μM) is consistently applied in a predetermined amount to a biosensor (200) including the electrode structure shown in FIGS. 6(a), and the current value measurement is repeated 5 times for each concentration. 2 It was obtained by repeating the process of calculating ) 4 to 7 times. In addition, the tables shown in FIGS. 6(b) and (d) respectively represent the mean and standard deviation of the slope and the coefficient of determination (R²) for Examples 7 to 12, respectively. 2 Includes information on the mean and standard deviation of ).

[0161] The table shown in FIG. 6(c) is obtained by repeating the process of measuring the current value at least 20 times by consistently dropping a control solution having a fixed glucose concentration in a predetermined amount onto a biosensor (200) including the electrode structure shown in FIG. 5(a), and then calculating the coefficient of variation (CV) for the glucose concentration measurement based on the average and standard deviation of the at least 20 current values, 4 to 7 times. Additionally, the table shown in FIG. 6(c) includes information on the average and standard deviation of the coefficient of variation (CV) for each of Examples 7 to 12.

[0162] As shown in FIG. 6(b), the slope of the trend line generally tends to increase from Example 7 to Example 12. That is, as the area ratio of the working electrode protrusion (211-2) to the reference electrode protrusion (212-2) increases, the slope of the trend line tends to increase. Meanwhile, although the slope of the trend line increased somewhat significantly from Example 7 to Example 9, it was confirmed that the range of variation decreased from Example 9 to Example 12.

[0163] According to one embodiment of the present invention, when the slope of the trend line is large, the rate of increase of the value of the current signal according to the concentration of glucose is large. When the rate of increase of the value of the current signal according to the concentration of glucose is large, even minute differences in glucose concentration can be detected. Accordingly, the accuracy of salivary glucose and blood glucose measurement is improved. That is, the result shown in FIG. 5(b) supports that as the area ratio of the working electrode protrusion (211-2) to the reference electrode protrusion (212-2) increases, the accuracy of salivary glucose and blood glucose measurement improves.

[0164] As shown in FIG. 6(c), the coefficient of variation (CV) for glucose concentration measurement has a smaller value in Examples 8 to 12 than in Example 7. A lower coefficient of variation (CV) indicates better reproducibility of the measurement. That is, the result shown in FIG. 6(c) supports the fact that when the area ratio of the working electrode protrusion (211-2) to the reference electrode protrusion (212-2) is large, the reproducibility of glucose concentration measurement is superior compared to when the area ratio of the working electrode protrusion (211-2) to the reference electrode protrusion (212-2) is small.

[0165] As shown in FIG. 6(d), the coefficient of determination (R) of the trend line 2 ) has a value of 0.9 or higher in all Examples 7 to 12. That is, in all Examples 7 to 12, it was confirmed that the measured current signal values ​​exhibit excellent linearity with respect to glucose concentration. In particular, in Examples 9, 10, and 12, a high coefficient of determination (R²) was observed compared to other examples. 2 ) was produced.

[0166] FIG. 7 shows the slope, Y-intercept, and coefficient of determination (R²) of a trend line plotting the measured values ​​of a current signal according to glucose concentration in relation to embodiments of the present invention. 2 ) is illustrated according to the area ratio between the working electrode protrusion and the reference electrode protrusion. Specifically, FIG. 7(a) illustrates a table showing the result values. Also, FIG. 7(b) illustrates the second region and the arrangement of the working electrode protrusion and the reference electrode protrusion within the second region.

[0167] As shown in FIG. 7(b), the working electrode protrusion (211-2) and the reference electrode protrusion (212-2) are placed in the second region (b) on the bottom plate (210). Details regarding this are as described above with reference to FIG. 4(b).

[0168] The table shown in FIG. 7(a) is obtained using a biosensor (200) having a working electrode (211) and a reference electrode (212) containing carbon.

[0169] The result values ​​for Examples 13 to 17 illustrated in FIG. 7(a) are calculated by applying a predetermined voltage (e.g., the voltage may be 0.4V (400mV), but the optimal voltage may change depending on various factors such as the type of substance included in the reagent layer, so it is not limited thereto) to the saliva per measuring device (300) to the biosensor (200).

[0170] As shown in FIG. 7, Examples 13 to 17 all correspond to cases where the working electrode protrusions (211-2) and the reference electrode protrusions (212-2) are two and one, respectively.

[0171] Specifically, Examples 13 to 17 correspond to cases where the ratio of the total area of ​​the working electrode protrusion (211-2) to the total area of ​​the reference electrode protrusion (212-2) is 1 (1:1), 3 (1:3), 5 (1:5), 7 (1:7), and 9 (1:9), respectively.

[0172] Meanwhile, the results for Examples 13 to 17 were calculated under conditions where the sum of the areas of the working electrode protrusion (211-2) and the reference electrode protrusion (212-2) is maintained at a predetermined value.

[0173] The table shown in FIG. 7(a) is calculated using a control solution. The control solution is a solution prepared to have physical, chemical, and biological properties similar to human saliva. The control solution may include a thickener, a preservative, and a colorant. Additionally, the control solution may be prepared to include glucose at a predetermined concentration.

[0174] The table shown in FIG. 7(a) shows the slope, Y-intercept, and coefficient of determination (R²) of a trend line plotting the average of the current values ​​repeatedly measured for each concentration, after a control solution having a predetermined glucose concentration is consistently applied in a predetermined amount to a biosensor (200) including an electrode structure corresponding to Examples 13 to 17, and the current value measurement is repeated a predetermined number of times for each concentration. 2 It is obtained by performing the process of producing ).

[0175] As shown in FIG. 7(a), the slope of the trend line tends to increase from Example 13 to Example 17. That is, as the area ratio of the working electrode protrusion (211-2) to the reference electrode protrusion (212-2) increases, the slope of the trend line tends to increase. In particular, it was confirmed that the slope of the trend line in Examples 14 to 17 has a large value compared to Example 13.

[0176] According to one embodiment of the present invention, when the slope of the trend line is large, the rate of increase of the value of the current signal according to the concentration of glucose is large. When the rate of increase of the value of the current signal according to the concentration of glucose is large, even minute differences in glucose concentration can be detected. Accordingly, the accuracy of salivary glucose and blood glucose measurement is improved. That is, the result illustrated in FIG. 7 supports the fact that as the area ratio of the working electrode protrusion (211-2) to the reference electrode protrusion (212-2) increases, the accuracy of salivary glucose and blood glucose measurement improves.

[0177] As shown in FIG. 7(a), the coefficient of determination (R 2 ) has a value of 0.9 or higher in all of Examples 13 to 17. That is, in all of Examples 13 to 17, it was confirmed that the value of the measured current signal shows excellent linearity with respect to the concentration of glucose.

[0178] FIG. 8 shows the slope, Y-intercept, and coefficient of determination (R) of a trend line plotting the measured values ​​of a current signal according to glucose concentration in relation to embodiments of the present invention. 2 ) is illustrated according to the vertical lengths of the working electrode protrusion and the reference electrode protrusion. Specifically, FIG. 8(a) illustrates a table showing result values. Also, FIG. 8(b) illustrates the arrangement of the working electrode protrusion and the reference electrode protrusion within the second region. Also, FIG. 8(c) is a drawing showing the vertical lengths of the working electrode protrusion and the reference electrode protrusion.

[0179] As shown in FIG. 8(b), the working electrode protrusion (211-2) and the reference electrode protrusion (212-2) are placed in the second region (b) on the bottom plate (210). Details regarding this are as described above with reference to FIG. 5(b).

[0180] The table shown in FIG. 8(a) is obtained using a biosensor (200) having a working electrode (211) and a reference electrode (212) containing carbon.

[0181] The result values ​​for Examples 18 to 22 shown in FIG. 8(a) are calculated by applying a predetermined voltage (e.g., the voltage may be 0.4V (400mV), but the optimal voltage may change depending on various factors such as the type of substance included in the reagent layer, so it is not limited thereto) to the saliva per measuring device (300) to the biosensor (200).

[0182] As shown in FIG. 8, Examples 18 to 22 all correspond to cases where the working electrode protrusions (211-2) and the reference electrode protrusions (212-2) are two and one, respectively.

[0183] Specifically, the results for Examples 18 to 22 were all calculated by setting the vertical length of the working electrode protrusion (211-2) to 4.9 mm. Additionally, Examples 18 to 22 correspond to cases where the vertical length of the reference electrode protrusion (212-2) is 0.1 mm, 0.3 mm, 0.5 mm, 0.7 mm, and 0.9 mm, respectively.

[0184] As shown in FIG. 8 (c), the vertical length of the working electrode protrusion (211-2) is the sum (w1+w2) of the vertical lengths (w1, w2) of the two working electrode protrusions (211-2). Also, the vertical length of the reference electrode protrusion (212-2) is the vertical length (r) of the reference electrode protrusion (212-2).

[0185] Meanwhile, in Examples 18 to 22, the ratio between the vertical lengths of the working electrode protrusion (211-2) and the reference electrode protrusion (212-2) may be equal to the ratio between the areas of the working electrode protrusion (211-2) and the reference electrode protrusion (212-2). For example, the horizontal lengths of the working electrode protrusion (211-2) and the reference electrode protrusion (212-2) may be set to be equal to each other. That is, in Examples 18 to 22, the ratio of the total area of ​​the working electrode protrusion (211-2) to the total area of ​​the reference electrode protrusion (212-2) is 49 (=0.1 : 4.9), 16.33 ( 0.3 : 4.9), 9.8(=0.5 : 4.9), 7(=0.7 : 4.9) and 5.4( It can correspond to the case where 0.9 : 4.9).

[0186] Meanwhile, the results for Examples 18 to 22 were calculated under conditions where the sum of the areas of the working electrode protrusion (211-2) and the reference electrode protrusion (212-2) is maintained at a predetermined value.

[0187] The table shown in FIG. 8(a) is calculated using a control solution. The control solution is a solution prepared to have physical, chemical, and biological properties similar to human saliva. The control solution may include a thickener, a preservative, and a colorant. Additionally, the control solution may be prepared to include glucose at a predetermined concentration.

[0188] The table shown in FIG. 8(a) shows the slope, Y-intercept, and coefficient of determination (R²) of a trend line plotting the average of the current values ​​repeatedly measured for each concentration, after a control solution having a predetermined glucose concentration is consistently applied in a predetermined amount to a biosensor (200) including an electrode structure corresponding to Examples 18 to 22, and the current value measurement is repeated a predetermined number of times for each concentration. 2 It is obtained by performing the process of producing ).

[0189] As shown in FIG. 8(a), the slope of the trend line has similar values ​​for Examples 18 to 22. In particular, for all Examples 18 to 22 where the ratio of the total area of ​​the working electrode protrusion (211-2) to the total area of ​​the reference electrode protrusion (212-2) exceeds 5, it was confirmed that the slope of the trend line has a relatively high value (>4.45). This supports the fact that when the ratio of the total area of ​​the working electrode protrusion (211-2) to the total area of ​​the reference electrode protrusion (212-2) exceeds 5, the rate of increase of the current signal value according to the glucose concentration appears relatively large, and accordingly, the accuracy of salivary glucose and blood glucose measurement is improved.

[0190] As shown in FIG. 8(a), the coefficient of determination (R) of the trend line 2 ) has relatively high values ​​in Examples 21 and 22. In particular, the coefficient of determination (R²) of the trend line 2) has the highest value (0.994) in Example 21, which corresponds to the case where the ratio of the total area of ​​the working electrode protrusion (211-2) to the total area of ​​the reference electrode protrusion (212-2) is 7. In addition, the coefficient of determination (R) of the trend line 2 ) has a relatively low value in Examples 18 and 20. That is, when the ratio of the total area of ​​the working electrode protrusion (211-2) to the total area of ​​the reference electrode protrusion (212-2) exceeds 9, the value of the current signal shows somewhat reduced linearity with respect to the concentration of glucose.

[0191] The result illustrated in FIG. 8(a) supports the fact that, under spatial constraints on the biosensor (200) or the bottom plate (210), if the ratio of the total area of ​​the working electrode protrusion (211-1) to the total area of ​​the reference electrode protrusion (212-2) is excessively increased, the linearity of the current signal with respect to glucose concentration decreases.

[0192] Meanwhile, the results illustrated in FIGS. 5 to 8 are derived using a biosensor (200) in which the number of working electrode protrusions (211-2) and reference electrode protrusions (212-2) are each 2 and 1, respectively, and the working electrode protrusions (211-2) and reference electrode protrusions (212-2) are arranged alternately in a second region (b). However, the present invention is not limited thereto, and the present invention may include any biosensor (200) in which the area of ​​the working electrode protrusions (211-2) is larger than the area of ​​the reference electrode protrusions (212-2), regardless of the number of working electrode protrusions (211-2) and reference electrode protrusions (212-2) and the arrangement between the two.

[0193] numerical range

[0194] As described above with reference to FIG. 2, the biosensor (200) may include a bottom plate (210), a middle plate (220), and a top plate (230). Details regarding the bottom plate (210), the middle plate (220), and the top plate (230) are as described above.

[0195] As described above with reference to FIG. 3, the bottom plate (210) may include a working electrode (211), a reference electrode (212), a check electrode (213), and at least one idle electrode (214). Additionally, a first region (a), a second region (b), and a third region (c) may be located on the bottom plate (210). Furthermore, the working electrode (211) may include a working electrode main body (211-1) and at least one working electrode protrusion (211-2). Additionally, the reference electrode (212) may include a reference electrode main body (212-1) and at least one reference electrode protrusion (212-2). Detailed information regarding the working electrode (211), reference electrode (212), check electrode (213), and idle electrode (214), etc., is as described above.

[0196] As described above with reference to FIG. 3, at least a portion of each of the working electrode projection (211-2), the reference electrode projection (212-2), and the check electrode projection (213-2) may constitute at least a portion of the second region (b). Specifically, the working electrode projection (211-2) and the reference electrode projection (212-2) may be spaced apart from each other by a predetermined distance in the longitudinal direction (Y-axis direction) of the second region (b).

[0197] Meanwhile, as described above with reference to FIG. 4, the working electrode (211) and the reference electrode (212) can be placed on the lower plate (210) and the upper plate (230), respectively. At this time, at least a portion of each of the working electrode protrusion (211-2) and the check electrode protrusion (213-2) can form at least a portion of the second region (b) on the lower plate (210). Additionally, at least a portion of the reference electrode protrusion (212-2) can form at least a portion of the fourth region (b') on the upper plate (230).

[0198] According to one embodiment of the present invention, the working electrode protrusion (211-2) and the reference electrode protrusion (212-2) may be configured to improve the accuracy and reproducibility of the biosensor (200) for measuring glucose concentration and to increase the linearity of the value of the current signal for glucose concentration.

[0199] According to one embodiment of the present invention, the total area of ​​the working electrode protrusion (211-2) may be larger than the total area of ​​the reference electrode protrusion (212-2).

[0200] Specifically, the area of ​​the portion of the working electrode protrusion (211-2) that is covered by the saliva inflow channel (221) can be formed to be larger than the area of ​​the portion of the reference electrode protrusion (212-2) that is covered by the saliva inflow channel (221).

[0201] Meanwhile, the working electrode protrusion (211-2) and the reference electrode protrusion (212-2) may come into contact with the reagent layer (222) in the second region (b). At this time, the area of ​​the part of the working electrode protrusion (211-2) that comes into contact with the reagent layer (222) may be formed to be larger than the area of ​​the part of the reference electrode protrusion (212-2) that comes into contact with the reagent layer (222).

[0202] Alternatively, the working electrode protrusion (211-2) may contact the reagent layer (222) in the second region (b), and the reference electrode protrusion (212-2) may contact the reagent layer (222) in the fourth region (b). At this time, the area of ​​the part of the working electrode protrusion (211-2) that contacts the reagent layer (222) may be formed to be larger than the area of ​​the part of the reference electrode protrusion (212-2) that contacts the reagent layer (222).

[0203] According to one embodiment of the present invention, the ratio of the total area of ​​the working electrode protrusion (211-2) to the total area of ​​the reference electrode protrusion (212-2) may be 3 or more and 9 or less. However, it is not limited thereto.

[0204] Specifically, the ratio of the area of ​​the portion of the working electrode protrusion (211-2) covered by the saliva inflow channel (221) to the area of ​​the portion of the reference electrode protrusion (212-2) covered by the saliva inflow channel (221) may be 3 or more and 9 or less. However, it is not limited thereto.

[0205] Additionally, specifically, the area ratio of the area of ​​the working electrode protrusion (211-2) in contact with the reagent layer (222) to the area of ​​the part of the reference electrode protrusion (212-2) in contact with the reagent layer (222) may be 3 or more and 9 or less. However, it is not limited thereto.

[0206] More specifically, when the ratio of the total area of ​​the working electrode protrusion (211-2) to the total area of ​​the reference electrode protrusion (212-2) is 3 or more, compared to when the ratio is less than 3, the rate of increase of the value of the current signal according to the glucose concentration is greater. When the rate of increase of the value of the current signal according to the glucose concentration is large, even minute differences in glucose concentration can be detected. Accordingly, the accuracy of salivary glucose and blood glucose measurement is improved.

[0207] Specifically, when the ratio of the total area of ​​the working electrode protrusion (211-2) to the total area of ​​the reference electrode protrusion (212-2) is 3 or more, the reproducibility of the measurement of glucose concentration is excellent compared to when the ratio is less than 3.

[0208] Specifically, when the ratio of the total area of ​​the working electrode protrusion (211-2) to the total area of ​​the reference electrode protrusion (212-2) is 9 or less, the excellent linearity of the current signal for glucose concentration is maintained compared to when the ratio is greater than 9.

[0209] According to one embodiment of the present invention, the ratio of the total area of ​​the working electrode protrusion (211-2) to the total area of ​​the reference electrode protrusion (212-2) may be 5 or more and 9 or less. However, it is not limited thereto.

[0210] Although the present invention has been described above with reference to the embodiments illustrated in the drawings, this is merely illustrative, and those skilled in the art will understand that various modifications and variations of the embodiments are possible therefrom. However, such modifications should be considered to be within the technical scope of protection of the present invention. Accordingly, the true technical scope of protection of the present invention should be determined by the technical spirit of the appended claims.

[0211] [Explanation of the symbol]

[0212] 10: Saliva glucose measurement system

[0213] 100 : Saliva collection device

[0214] 200 : Biosensor

[0215] 210 : Bottom plate

[0216] 210-1 : Insulating substrate

[0217] 211 : Working electrode

[0218] 211-1 : Working electrode main body

[0219] 211-2 : Working electrode protrusion

[0220] 211-2a : First working electrode projection

[0221] 211-2b : Second working electrode projection

[0222] 212 : Reference electrode

[0223] 212' : Part corresponding to the reference electrode

[0224] 212-1 : Reference electrode main body

[0225] 212'-1 : Part corresponding to the main body of the reference electrode

[0226] 212-2 : Reference electrode protrusion

[0227] 212'-2 : Part corresponding to the reference electrode protrusion

[0228] 213 : Check electrode

[0229] 213-1 : Check electrode main body

[0230] 213-2 : Check electrode protrusion

[0231] 213-2a : First check electrode protrusion

[0232] 213-2b : Second check electrode protrusion

[0233] 214 : Orbital pole

[0234] 214a: First orbital electrode

[0235] 214b : Second orbital electrode

[0236] 214c : Third orbital electrode

[0237] 215 : Extension electrode

[0238] 220 : Middle plate

[0239] 221 : Salivary entry point

[0240] 222 : Reagent layer

[0241] 223 : Connection hole

[0242] 230 : Top plate

[0243] 231 : Saliva inlet

[0244] 232 : Air outlet

[0245] 300 : Saliva per gram measuring device

[0246] a : 1st region

[0247] b : Second area

[0248] b' : 4th area

[0249] c : Third area

Claims

1. A biosensor for detecting glucose in saliva, A lower plate comprising a working electrode for detecting glucose in saliva - said working electrode includes at least one working electrode protrusion - and a reference electrode for detecting glucose in saliva - said reference electrode includes at least one reference electrode protrusion; A middle plate disposed on the upper surface of the lower plate and having a saliva inflow channel perforated therein; An upper plate disposed on the upper surface of the above middle plate; and A reagent layer disposed within the above saliva inflow channel; Includes, The area of ​​the portion of the working electrode protrusion that is covered by the saliva inflow path is formed to be larger than the area of ​​the portion of the reference electrode protrusion that is covered by the saliva inflow path. Biosensor for detecting glucose in saliva.

2. A biosensor for detecting glucose in saliva, A lower plate comprising a working electrode for detecting glucose in saliva - said working electrode includes at least one working electrode protrusion - and a reference electrode for detecting glucose in saliva - said reference electrode includes at least one reference electrode protrusion; A middle plate disposed on the upper surface of the lower plate and having a saliva inflow channel perforated therein; An upper plate disposed on the upper surface of the above middle plate; and A reagent layer disposed within the above saliva inflow channel; Includes, The area of ​​the portion of the working electrode protrusion that contacts the reagent layer is formed to be larger than the area of ​​the portion of the reference electrode protrusion that contacts the reagent layer. Biosensor for detecting glucose in saliva.

3. A biosensor for detecting glucose in saliva, A lower plate comprising a working electrode for detecting glucose in saliva - said working electrode includes at least one working electrode projection; A middle plate disposed on the upper surface of the lower plate and having a saliva inflow channel perforated therein; An upper plate disposed on the upper surface of the middle plate and comprising a reference electrode for detecting glucose in saliva—the reference electrode comprises at least one reference electrode projection—; and A reagent layer disposed within the above saliva inflow channel; Includes, The area of ​​the portion of the working electrode protrusion that is covered by the saliva inflow path is formed to be larger than the area of ​​the portion of the reference electrode protrusion that is covered by the saliva inflow path. Biosensor for detecting glucose in saliva.

4. A biosensor for detecting glucose in saliva, A lower plate comprising a working electrode for detecting glucose in saliva - said working electrode includes at least one working electrode projection; A middle plate disposed on the upper surface of the lower plate and having a saliva inflow channel perforated therein; An upper plate disposed on the upper surface of the middle plate and comprising a reference electrode for detecting glucose in saliva—the reference electrode comprises at least one reference electrode projection—; and A reagent layer disposed within the above saliva inflow channel; Includes, The area of ​​the portion of the working electrode protrusion that contacts the reagent layer is formed to be larger than the area of ​​the portion of the reference electrode protrusion that contacts the reagent layer. Biosensor for detecting glucose in saliva.

5. In Paragraph 1 or Paragraph 3, The area ratio of the portion of the working electrode protrusion covered by the salivary inflow path to the portion of the reference electrode protrusion covered by the salivary inflow path is included in the numerical range of [3, 9]. Biosensor for detecting glucose in saliva.

6. In Paragraph 2 or Paragraph 4, The area ratio of the portion of the reference electrode protrusion in contact with the reagent layer to the area of ​​the portion of the working electrode protrusion in contact with the reagent layer is included in the numerical range of [3, 9]. Biosensor for detecting glucose in saliva.

7. In Paragraph 5, The above area ratio is included in the numerical range of [5, 9], Biosensor for detecting glucose in saliva.

8. In Paragraph 6, The above area ratio is included in the numerical range of [5, 9], Biosensor for detecting glucose in saliva.

9. In Paragraph 5, The above biosensor is inserted into a salivary glucose measuring device for measuring the concentration of glucose in saliva, and is configured to receive voltage from the salivary glucose measuring device through the working electrode and the reference electrode when inserted into the salivary glucose measuring device. Based on the above-mentioned applied voltage, an oxidation / reduction reaction of glucose in the saliva introduced through the reagent layer and the saliva inflow channel occurs, and The current signal generated based on the above oxidation / reduction reaction is proportional to the concentration of glucose in the incoming saliva and is transmitted to the saliva glucose measuring device through the working electrode and the reference electrode, and The above saliva glucose measuring device is configured to measure the concentration of glucose in the incoming saliva based on the transmitted current signal. Biosensor for detecting glucose in saliva.

10. In Paragraph 6, The above biosensor is inserted into a salivary glucose measuring device for measuring the concentration of glucose in saliva, and is configured to receive voltage from the salivary glucose measuring device through the working electrode and the reference electrode when inserted into the salivary glucose measuring device. Based on the above-mentioned applied voltage, an oxidation / reduction reaction of glucose in the saliva introduced through the reagent layer and the saliva inflow channel occurs, and The current signal generated based on the above oxidation / reduction reaction is proportional to the concentration of glucose in the incoming saliva and is transmitted to the saliva glucose measuring device through the working electrode and the reference electrode, and The above saliva glucose measuring device is configured to measure the concentration of glucose in the incoming saliva based on the transmitted current signal. Biosensor for detecting glucose in saliva.

11. In Paragraph 9 or 10, The above numerical range is configured to increase the rate of increase of the measured value of the current signal measured by the salivary glucose measuring device with respect to the concentration of glucose in the incoming saliva, compared to the case where the above area ratio is not included in the above numerical range. Biosensor for detecting glucose in saliva.

12. In Paragraph 9 or 10, The above numerical range is configured to reduce the coefficient of variation for the measured value of the current signal measured by the saliva-per-measuring device compared to the case where the area ratio is not included in the above numerical range. Biosensor for detecting glucose in saliva.

13. In Paragraph 9 or 10, The above numerical range is configured to increase the linear correlation of the measured value of the current signal measured by the salivary glucose measuring device with respect to the concentration of glucose in the incoming saliva, compared to the case where the area ratio is not included in the above numerical range. Biosensor for detecting glucose in saliva.

14. In a system for measuring the concentration of glucose in saliva, A biosensor described in any one of claims 1 to 4; A saliva collection device for collecting saliva and applying the collected saliva to the biosensor; and A salivary glucose measuring device configured to insert the above-mentioned biosensor, applying voltage to the inserted biosensor through the above-mentioned working electrode and the above-mentioned reference electrode, receiving a current signal from the biosensor, and calculating the concentration of glucose in the saliva introduced through the above-mentioned saliva inflow channel based on the received current signal; Includes, Based on the voltage applied by the above saliva glucose measuring device, an oxidation / reduction reaction occurs between the reagent layer and the glucose in the introduced saliva, and The above current signal is generated based on the above oxidation / reduction reaction and is proportional to the concentration of glucose in the incoming saliva, A system for measuring the concentration of glucose in saliva.

15. In Paragraph 14, The area ratio of the portion of the working electrode protrusion covered by the salivary inflow path to the portion of the reference electrode protrusion covered by the salivary inflow path is included in the numerical range of [3, 9]. A system for measuring the concentration of glucose in saliva.

16. In Paragraph 14, The area ratio of the portion of the reference electrode protrusion in contact with the reagent layer to the area of ​​the portion of the working electrode protrusion in contact with the reagent layer is included in the numerical range of [3, 9]. A system for detecting glucose in saliva.

17. In Paragraph 15 or 16, The above area ratio is included in the numerical range of [5, 9], A system for measuring the concentration of glucose in saliva.

18. In Paragraph 15 or 16, The above numerical range is configured to increase the rate of increase of the measured value of the current signal measured by the salivary glucose measuring device with respect to the concentration of glucose in the incoming saliva, compared to the case where the above area ratio is not included in the above numerical range. A system for measuring the concentration of glucose in saliva.

19. In Paragraph 15 or 16, The above numerical range is configured to reduce the coefficient of variation for the measured value of the current signal measured by the saliva-per-measuring device compared to the case where the area ratio is not included in the above numerical range. A system for measuring the concentration of glucose in saliva.

20. In Paragraph 15 or 16, The above numerical range is configured to increase the linear correlation of the measured value of the current signal measured by the salivary glucose measuring device with respect to the concentration of glucose in the incoming saliva, compared to the case where the area ratio is not included in the above numerical range. A system for measuring the concentration of glucose in saliva.

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