WO2005108968A1

WO2005108968A1 - Biosensor, container for biosensor, and biosensor measuring apparatus

Info

Publication number: WO2005108968A1
Application number: PCT/JP2005/007982
Authority: WO
Inventors: Mariko Miyashita; Yuko Taniike; Toshihiko Yoshioka
Original assignee: Matsushita Electric Industrial Co., Ltd.
Priority date: 2004-05-12
Filing date: 2005-04-27
Publication date: 2005-11-17

Abstract

Biosensor (100) comprises basal plate (2) and, disposed thereon, lead wires (3), measuring electrode (4), counter electrode (6), insulating layer (5) and temperature detection part (7) whose color tone changes depending on temperature. Reagent part (8) is provided so as to cover the measuring electrode (4) and counter electrode (6). The reagent part (8) is formed by dropping an aqueous solution containing glucose oxidase as a protein capable of specific reaction with glucose as an analyte and potassium ferricyanide as an electron carrier and drying the same. The temperature detection part (7) consists of a material composed mainly of a thermosensitive material.

Description

Specification

Biosensor, biosensor container, and biosensor measurement device

The present invention relates to a biosensor, a biosensor container, and a biosensor measuring device that can easily, quickly, and accurately measure the concentration of a specific substance contained in a sample.

Background art

[0002] Conventionally, as a method for simply and accurately measuring a specific substance in a sample without performing dilution or stirring, a biosensor as disclosed in Patent Document 1 below has been proposed.

[0003] The biosensor disclosed in Patent Literature 1 below discloses an enzyme reaction comprising a mixture of a hydrophilic polymer, an oxidoreductase, and an electron carrier on an electrode formed on an insulating substrate. A reaction layer is formed. By supplying the sample on the electrode, a reaction between the oxidoreductase, the electron carrier, and the sample occurs. The biosensor is used for electrochemically detecting a change in the concentration of each substance during the reaction and measuring a specific component in the sample.

[0004] Hereinafter, the measurement operation of the biosensor will be described. Here, the case where the biosensor is a glucose sensor will be described as an example.

[0005] When a sample containing glucose is supplied to a glucose sensor, the enzyme reaction layer dissolves, and the sample and the substance in the enzyme reaction layer are mixed. Glucose is oxidized by dalcosoxidase (hereinafter referred to as GOx), which is an oxidoreductase in the enzyme reaction layer, and at the same time, the electron carrier in the enzyme reaction layer is reduced. When a proper voltage is applied between the electrodes after a predetermined time has elapsed, the reduced form of the electron carrier is oxidized. By measuring the oxidation current value at this time, the glucose concentration in the sample is quantified.

[0006] However, the enzymatic reaction and the electrode reaction used in the biosensor are affected by the temperature of the environment in which the measurement is performed.

[0007] Therefore, in order to correct the effect of the environmental temperature by performing the measurement !, a method of measuring a biosensor has been proposed in Japanese Patent Application Laid-Open No. H11-163,098. Measurement of this biosensor The method is to prepare a correction formula that calculates the correlation between the environmental temperature and the sensor response in advance, measure the environmental temperature with the temperature sensor installed in the measuring device, and use that temperature to convert the sensor response into a correction formula. Correct based on

[0008] On the other hand, sensors such as blood glucose meters usually have a guaranteed temperature force of up to 40 ° C, and there are cases where the temperature rises to 50 ° C or more and the sensor or the user exceeds the sensor's guaranteed temperature range during transportation. It was hot.

Patent Document 1: JP-A-3-202764

Patent Document 2: JP-A-61-294356

Disclosure of the invention

Problems to be solved by the invention

[0009] The biosensor described in Patent Document 2 incorporates a thermistor to correct the influence of the environmental temperature. However, in the biosensor described in Patent Document 2, the manufacturing process for incorporating the thermistor into the biosensor is complicated, and the manufacturing cost is high.

[0010] Conventionally, since the temperature history of the sensor was not detected, it was not possible to confirm that the temperature exceeded the guaranteed temperature range when the sensor was stored.

The present invention has been made in view of the above circumstances, and has as its object to provide a biosensor, a neurosensor container, and a biosensor measurement device capable of performing accurate measurement. Means

[0012] The biosensor of the present invention is a biosensor for measuring a substance to be measured contained in a sample, and includes a substrate, a protein provided on the substrate, and specifically reacting with the substance to be measured. And a temperature detection unit formed of a material including a temperature-sensitive material whose color tone changes according to the temperature.

[0013] According to the present invention, it is possible to measure the environmental temperature of the biosensor based on the color tone change of the temperature detection unit when measuring the substance to be measured. Therefore, the influence of the environmental temperature of the biosensor at the time of measuring the substance to be measured can be corrected, so that accurate measurement can be performed. In addition, the biosensor of the present invention includes a conventional thermistor. The manufacturing cost is very low.

[0014] The temperature-sensitive material may contain a dye whose color tone changes irreversibly, or may contain a dye whose color tone changes reversibly.

[0015] When the color tone changes irreversibly, it is possible to know whether or not the biosensor has been subjected to a temperature that is high enough to impair its function, so that accurate measurement can be performed using only good products. .

When the color tone changes reversibly, the measured value can be corrected based on the measured temperature, so that the reliability of the measured result can be improved.

[0017] As the temperature-sensitive material whose color tone changes irreversibly, a material containing at least p-dimethylaminoazobenzene or a derivative thereof and an organic acid and a metal salt of Z or an organic acid is preferable.

[0018] The organic acid is at least one selected from salicylic acid, citric acid, benzoic acid, and maleic acid, and the metal salt thereof is preferably a zinc salt, a sodium salt, or an aluminum salt.

[0019] Further, those containing a conductivity imparting substance are desirable. The conductivity-imparting substance imparts the necessary chargeability to the ink for facilitating printing with an ink-jet printer, and improves the particleization and charge deflection of the ink. Examples include ammonium thiocyanate, sodium thiocyanate, lithium nitrate, and potassium iodide.

C. I. 42595 (IUPAC ^: an oil-soluble dye that has good heat resistance and does not discolor due to heat loss in order to maintain color development after heating.

[4- [4- (Diethylammo) -a- [4- (ethylammo) -1- 1-naphtnyl] benzyliden] cyclohexa-2,5-dien-1-yliden] diethylammoniumchlorid).

[0021] The biosensor container of the present invention includes a substrate, and a reagent unit provided on the substrate and containing a protein specifically reacting with a substance to be measured contained in the sample, and supplied with the sample. A biosensor container for housing a biosensor for measuring the substance to be measured, a housing having a cavity formed therein, and a temperature-sensitive housing provided on an outer surface of the housing. A temperature detecting portion formed of a material including a material.

[0022] By using the biosensor container of the present invention, the temperature of Based on the color change of the part, it is possible to measure the environmental temperature of the reagent part of the biosensor or to detect the history of the temperature experienced by the biosensor. Therefore, it is possible to correct the measured value based on the ambient temperature of the reagent part of the biosensor at the time of measurement of the substance to be measured, and to remove defective products before measurement beforehand. Measurement can be performed. Further, according to the present invention, since it is not necessary to incorporate a thermistor into a biosensor as in the related art, the manufacturing cost of the biosensor can be extremely reduced.

[0023] The biosensor measurement device of the present invention includes a substrate, a reagent unit provided on the substrate, which includes a protein that specifically reacts with an analyte contained in the sample, and to which the sample is supplied, A biosensor measuring device for measuring the above-mentioned substance to be measured using a biosensor having a temperature detecting portion whose color tone changes according to the color tone, wherein the color tone detecting portion for detecting the color tone of the temperature detecting portion; A measuring unit connected to the color tone detecting unit and measuring the temperature of the reagent unit based on the color tone.

[0024] In the biosensor measurement device of the present invention, the influence of the environmental temperature can be automatically corrected based on the change in the color tone of the temperature detection unit of the biosensor when measuring the substance to be measured. Therefore, it is possible for the measurer to automatically perform an accurate measurement without requiring special knowledge. In addition, it is also possible to determine whether the biosensor is defective.

[0025] A configuration may further include a housing having the color tone detection unit and the measurement unit therein, and a temperature sensor for measuring a temperature in the housing.

[0026] With this, measurement can be performed after confirming whether or not the difference between the temperature inside the housing and the temperature near the reagent section of the biosensor is within a preset range. For this reason, with this configuration, only measurement results that are hardly affected by the temperature in the biosensor measurement device can be obtained.

[0027] Another neurosensor measurement device of the present invention includes a substrate, and a reagent unit provided on the substrate, which includes a protein that specifically reacts with a substance to be measured contained in the sample, and to which the sample is supplied. Using the biosensor, a housing having a hollow portion, and a temperature sensor provided on the outer surface of the housing, a container for a biosensor for housing the biosensor, which is used for the measurement, A biosensor measuring device for measuring a substance, A color tone detection unit that detects a color tone of the temperature detection unit; and a measurement unit that is connected to the color tone detection unit and measures the temperature of the reagent unit based on the color tone.

[0028] In the biosensor measurement device of the present invention, the influence of the environmental temperature can be automatically corrected based on the color tone change of the temperature detection unit of the biosensor container when measuring the substance to be measured. . Therefore, it is possible for the measurer to automatically perform accurate measurement without requiring special knowledge. In addition, it is also possible to determine whether the biosensor is defective.

[0029] A configuration may further include a housing having the color tone detection unit and the measurement unit therein, and a temperature sensor for measuring a temperature in the housing.

The invention's effect

According to the present invention, it is possible to provide a biosensor, a biosensor container, and a nanosensor measuring device capable of performing accurate measurement.

Brief Description of Drawings

[FIG. 1] FIG. 1 (a) is a top view of a biosensor, and FIG. 1 (b) is a cross-sectional view taken along line XX shown in FIG. 1 (a).

[FIG. 2] FIG. 2 (a) is a perspective view showing a biosensor measuring device, and FIG. 2 (b) is a diagram in which a biosensor is mounted on a biosensor measuring device, and the biosensor can be measured. FIG. 2C is a diagram illustrating a state, and FIG. 2C is a schematic diagram illustrating a configuration of a biosensor measurement device.

FIG. 3 is a flowchart showing an operation of the biosensor measurement device.

FIG. 4 is a flowchart showing an operation of the biosensor measurement device.

FIG. 5 (a) and FIG. 5 (b) are perspective views showing the appearance of a biosensor container.

[FIG. 6] FIG. 6 (a) is a perspective view showing a biosensor measuring device, and FIG. 6 (b) is a diagram illustrating a biosensor measuring device equipped with a biosensor and a biosensor container. FIG. 6 (c) is a schematic diagram illustrating a configuration of a biosensor measurement device.

Explanation of symbols

[0032] Two substrates

3 Lead wire

4 Measurement pole 5 Insulation layer

6 Counter electrode

7, 207 Temperature detector

8 Reagent section

21, 22 connector

23, 23 'Tone detector

24 Measurement section

25 Data processing section

100, 100, biosensor

101, 301 Biosensor measurement device

101a, 301a housing

102, 302 slots

103, 303 Data display section

200 Biosensor container

202 lid

203 main unit

304 slots

BEST MODE FOR CARRYING OUT THE INVENTION

Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. In this specification,

The term "connection" shall mean "electrical connection" unless otherwise specified.

(Embodiment 1)

In the present embodiment, a biosensor used for quantification of glucose will be described as an example. As will be described later, the present embodiment does not limit the present invention to a Noo sensor in which the substance to be measured is glucose.

[0035] The biosensor of the present embodiment will be described with reference to FIGS. 1 (a) and 1 (b). Figure 1 (a)

FIG. 1B is a top view of the biosensor of the present embodiment, and FIG. 1B is a cross-sectional view taken along line XX shown in FIG. 1A.

[0036] Configuration of Biosensor 1 As shown in FIGS. 1 (a) and 1 (b), a biosensor 100 according to the present embodiment has a lead wire 3 formed by screen printing on a substrate 2 formed of an insulating material, and a lead wire 3 formed by screen printing. A measuring electrode 4 and a counter electrode 6, which are electrodes connected to the sensor, an insulating layer 5, and a temperature detecting section 7 whose color tone changes according to the temperature, are formed. Thus, a reagent section 8 is formed. The reagent section 8 is formed by dropping into an aqueous solution containing glucose oxidase as a protein that specifically reacts with glucose as a substance to be measured and potassium ferricyanide as an electron carrier, followed by drying.

[0037] The reagent section 8 is not particularly limited as long as it is configured to dissolve when the sample is dropped and to come into contact with the measurement electrode 4 and the counter electrode 6 while being mixed with the sample. . However, as described above, it is preferable to provide the measurement electrode 4 and the counter electrode 6 so as to cover them. Further, the reagent section 8 may be provided in a state where the conductive materials constituting the measurement electrode 4 and the counter electrode 6 are further mixed.

It is preferable that the temperature detecting section 7 is provided so as not to contact the reagent section 8 and as close to the reagent section 8 as possible. The specificity of the reaction of the protein contained in the reagent section 8 with the substance to be measured depends on the place where the reaction occurs, that is, the temperature of the reagent section 8 in the present embodiment. Therefore, the closer the temperature detected by the temperature detection unit 7 is to the temperature of the reagent unit 8, the higher the effect of the temperature correction becomes.

The temperature detecting section 7 is formed of a material having a temperature-sensitive material as a main component. Here, the temperature-sensitive material used in the temperature detection unit 7 of the present embodiment is a material that reversibly responds to a temperature change, and in particular, a material whose color tone changes with the temperature change is preferable. As a result, the reliability of the measurement result is improved without making it impossible for the temperature detection unit to measure the temperature. Specifically, a metal complex salt, a cholesteric liquid crystal compound, a mixture of a vinyl alcohol-butyl ester copolymer and an organic solvent, or the like can be used as the temperature-sensitive material.

[0040] Configuration of one biosensor measuring device 1

Next, a measuring device used for measuring the biosensor 100 of the present embodiment will be described with reference to FIG. FIG. 2A is a perspective view showing the biosensor measuring device 101 of the present embodiment, and FIG. 2B is a diagram illustrating the biosensor 100 mounted on the biosensor measuring device 101 of the present embodiment. FIG. 2 is a diagram illustrating a state where measurement by the sensor 100 is possible, and FIG. (c) is a schematic diagram illustrating a configuration of the biosensor measurement device 101 of the present embodiment.

As shown in FIGS. 2 (a) and 2 (b), the biosensor measurement device 101 of the present embodiment can insert a housing 101a and a biosensor 100 provided on the surface of the housing 101a inside. A data display unit 103 for displaying the main slot 102 and the measurement result is provided.

As shown in FIG. 2 (c), a pair of connectors 21 and 22 and a color tone detection unit 23 are connected in the housing 101a, and a pair of connectors 21 and 22 and the color tone detection unit 23 are connected. And a data processing unit 25 connected to the measurement unit 24, and a data display unit 103 connected to the data processing unit 25. In particular, in this embodiment, a pair of connectors 21 and 22 are provided in the slot 102.

Operation and Effect of Biosensor and Biosensor Measurement Device

Next, the operation of the biosensor measurement device 101 when performing measurement using the biosensor 100 and the biosensor measurement device 101 of the present embodiment will be described with reference to FIG. FIG. 3 is a flowchart showing the operation of the biosensor measurement device 101.

As shown in FIG. 3, in step Stl, the biosensor 100 is mounted on the slot 102, and the operation starts. At this time, the pair of connectors 21 and 22 are connected to the lead wires 3 of the biosensor 100, respectively.

Next, as shown in FIG. 3, in step St2, the color tone detection unit 23 confirms that the biosensor 100 has been mounted on the slot 102. At this time, if the biosensor 100 is not mounted, the noise sensor measuring device 101 returns to step Stl and enters a standby state. When the biosensor 100 is mounted, the operation of the biosensor measurement device 101 proceeds to the next step St3.

Next, as shown in FIG. 3, in step St3, the color tone detection unit 23 sets the color tone of the temperature detection unit 7 as an optical characteristic (for example, the wavelength spectrum pattern of incident light or the intensity of light of a specific wavelength). It detects and outputs it to the data processing unit 25 through the measuring unit 24. The color tone detecting section 23 of the present embodiment includes a light source and a light receiving element. The light source emits light to the temperature detecting section 7 of the biosensor 100, and the light reflected from the temperature detecting section 7 enters the light receiving element. It is provided to do. A light emitting diode or a semiconductor laser is used as a light source, and a photodiode or a phototransistor is used as a light receiving element. Receiving The optical element detects the incident light from the temperature detector 7.

Next, as shown in FIG. 3, in step St4, the measurement unit 24 acquires the optical characteristic data from the color tone detection unit 23, and calculates the temperature near the reagent unit 8 of the Noo sensor 100.

Next, as shown in FIG. 3, after supplying the sample to the reagent section 8 of the biosensor 100 in Step St5, the measurement section 24 connects the lead wire 3 to the pair of connectors 21 and 22. Measure the current flowing between them.

Next, as shown in FIG. 3, at step St6, when the optical characteristic data and the current value are input, the data processing unit 25 compares the calculated temperature around the reagent unit 8 of the biosensor 100 with the calculated temperature. Then, the current value is corrected based on the previously created correlation between the temperature and the current value, thereby calculating the glucose concentration. The data display unit 103 displays the density of the dark course calculated by the data processing unit 25.

In particular, in the present embodiment, the temperature detecting section 7 of the biosensor 100 is arranged so as to be located in the biosensor measuring device 101 when the biosensor 100 is mounted on the slot 102. For this reason, when measuring the glucose concentration, the influence of the environmental temperature can be automatically corrected based on the color tone change of the temperature detection unit 7. Therefore, if the biosensor 100 and the biosensor measuring device 101 are used, an accurate measurement can be automatically performed by the measurer without requiring special knowledge.

Further, according to the present embodiment, it is not necessary to incorporate a thermistor into the sensor 100 as in the related art. Therefore, the production cost is very low.

[0052] One modification example

Note that the biosensor measuring device 101 may further include a temperature sensor for measuring the temperature inside the device. The operation of the biosensor measurement device 101 having this configuration will be described with reference to FIG. FIG. 4 is a flowchart showing the operation of the biosensor measurement device 101.

As shown in FIG. 4, even when the biosensor measurement device 101 further includes a temperature sensor, the steps from Step Stl to Step St3 are exactly the same.

Next, as shown in FIG. 4, in step Stl4, the measurement unit 24 acquires the optical characteristic data from the color tone detection unit 23, and calculates the temperature near the reagent unit 8 of the Noo sensor 100. At this time Sometimes, the temperature sensor force receives the temperature inside the device, and determines whether or not the difference between the temperature inside the device and the temperature near the reagent section 8 is within a preset range. If the difference between the temperature in the device and the temperature in the vicinity of the reagent section 8 is within a preset range, the process proceeds to step Stl6, and if the difference is outside the preset range, Proceed to step Stl5.

Next, as shown in FIG. 4, in step St15, the biosensor measurement device 101 stops the measurement.

Next, as shown in FIG. 4, after supplying the sample to the reagent section 8 of the biosensor 100 in Step Stl6, the measuring section 24 connects the lead wire 3 to the pair of connectors 21 and 22. Measure the current flowing between them.

Next, as shown in FIG. 4, when the optical characteristic data and the current value are input in step Stl7, the data processing unit 25 calculates the calculated temperature near the reagent unit 8 of the biosensor 100 and the temperature. Then, the current value is corrected based on the previously created correlation between the temperature and the current value, thereby calculating the glucose concentration. The data display unit 103 displays the density of the dark course calculated by the data processing unit 25.

As described above, in the configuration in which the noise sensor measuring device 101 further includes the temperature sensor for measuring the temperature inside the device, the difference between the ambient temperature (in this case, the temperature inside the device) and the temperature near the reagent section 8 is determined. After confirming whether or not the force is within a preset range, the measurement can be performed. Therefore, in this configuration, only a measurement result that is hardly affected by the temperature in the biosensor measurement device 101 can be obtained. That is, highly accurate measurement can be performed.

[0059] In the present embodiment, a biosensor in which the substance to be measured is glucose is described. However, as described above, the present embodiment does not limit the present invention to a biosensor in which the substance to be measured is glucose. When a substance other than glucose is used as the analyte, an enzyme using the analyte as a substrate may be selected as the enzyme contained in the reagent section 8. In the present embodiment, the enzymes contained in the reagent section 8 are oxidoreductases other than the force GOx using glucose oxidase (GOx), which is an oxidoreductase (eg, phenolectose dehydrogenase, gnorecose dehydrogenase). , Anoleconoreleoxidase, Lactate oxidase, cholesterol oxidase, xanthine oxidase, amino acid oxidase, etc.).

[0060] Examples of the electron mediator include substances such as potassium ferricyanide, p-benzoquinone, phenazine methosulfate, methylene blue, and phenoctene derivatives. Also, a current response can be obtained when oxygen is used as the electron carrier. Note that, instead of using one of the above substances as the electron carrier, two or more substances may be used in combination.

[0061] Further, for example, it is of course possible to use an anti-albumin antibody, an anti-hemoglobin antibody, or the like as a protein that specifically reacts with the substance to be measured, and to form a biosensor using the substance to be measured as albumin, hemoglobin or the like. It is. However, when an antibody is used as a protein that specifically reacts with the above-mentioned substance to be measured, both the biosensor 100 and the biosensor measuring device 101 quantitatively measure the antigen-antibody reaction (for example, optically measure the antigen-antibody reaction). Quantitative means) should be taken.

(Embodiment 2)

In the present embodiment, a biosensor container for storing a biosensor will be described with reference to FIG. 5 (a) and 5 (b) are perspective views showing the appearance of the biosensor container of the present embodiment.

[0063] Configuration of one container

As shown in FIG. 5 (a), the biosensor container 200 of the present embodiment includes a lid 202 and a main body 203, and a temperature detecting section 207 on the bottom surface of the main body 203 whose color tone changes according to the temperature. Having. As shown in FIG. 5 (b), the biosensor container 200 can house the biosensor 100 ′. Here, the biosensor 100 ′ has the same structure as the biosensor 100, but does not include the temperature detection unit 7. Instead, in the present embodiment, the temperature sensor 207 is provided in the biosensor container 200.

[0064] The temperature detecting section 207 is preferably provided so as to be as close as possible to the reagent section 8 in a state where the biosensor 100 'is housed. The specificity of the reaction of the protein contained in the reagent section 8 with the substance to be measured depends on the place where the reaction occurs, that is, the temperature of the reagent section 8 in the present embodiment. Therefore, the effect of the temperature correction increases as the temperature detected by the temperature detection unit 207 approaches the temperature of the reagent unit 8. [0065] The temperature detecting section 207 is formed of a material having a temperature-sensitive material as a main component. Here, the temperature-sensitive material used in the temperature detection unit 207 of the present embodiment is a material that reversibly responds to a temperature change, and in particular, a material whose color tone changes with the temperature change is preferable. As a result, the reliability of the measurement result is improved without making it impossible to measure the temperature with the temperature detection unit. As the temperature-sensitive material, for example, a metal complex salt, a cholesteric liquid crystalline compound, a mixture of a vinyl alcohol-butyl ester copolymer and an organic solvent, and the like can be used.

[0066] Configuration of one measuring device 1

Next, a measuring device for a biosensor used in the present embodiment will be described with reference to FIG. FIG. 6A is a perspective view showing the biosensor measuring device 301 of the present embodiment, and FIG. 6B is a diagram showing the biosensor 100 ′ and the biosensor of the biosensor measuring device 301 of the present embodiment. FIG. 6C is a diagram illustrating a state in which the container 200 is mounted and the biosensor 100 ′ can be measured, and FIG. 6C is a schematic diagram illustrating a configuration of the biosensor measurement device 301 according to the present embodiment. .

As shown in FIGS. 6 (a) and 6 (b), the biosensor measurement device 301 of the present embodiment has a housing 301a and a biosensor 100 ′ provided on the surface of the housing 301a inserted therein. Possible slot 302, data display section 303 provided on the surface of housing 301a for displaying measurement results, and slot capable of inserting biosensor container 200 provided on the surface of housing 301a inside. With 304.

As shown in FIG. 6 (c), inside the housing 301a, a pair of connectors 21 and 22, a color tone detection unit 23 ′, and a pair of connectors 21 and 22 and a color tone detection unit 23 ′ And a data processing unit 25 connected to the measurement unit 24, and a data display unit 303 connected to the data processing unit 25. In particular, in the present embodiment, a pair of connectors 21 and 22 are provided in a slot 302, and a color tone detection unit 23 'is provided in a slot 304.

[0069] Operation and Effect of One Biosensor Measurement Device

Next, the operation of the biosensor measurement device 301 when performing measurement using the biosensor 100, the biosensor container 200, and the biosensor measurement device 301 of the present embodiment will be described. The operation of the biosensor measuring device 301 is substantially the same as that of the biosensor measuring device 301 of the first embodiment. Therefore, here, the same as FIG. This will be described with reference to 3.

[0070] As shown in Fig. 3, the biosensor 100 is mounted in the slot 302 in step Stl, and the operation starts. At this time, each of the pair of connectors 21 and 22 is connected to the lead wire 3 of the biosensor 100 ′.

Next, as shown in FIG. 3, in step St2, the color tone detection unit 23 confirms that the biosensor 100 is mounted on the slot 302. At this time, if the biosensor 100 'is not mounted, the biosensor measuring device 301 returns to Step Stl and enters a standby state. When the biosensor 100 'is mounted, the operation of the biosensor measuring device 301 proceeds to the next step St3.

Next, as shown in FIG. 3, in step St3, the color tone detection unit 23 ′ converts the color tone of the temperature detection unit 207 into optical characteristics (for example, the wavelength spectrum pattern of incident light or the intensity of light of a specific wavelength, etc.). ) And output to the data processing unit 25 through the measuring unit 24. The color tone detection unit 23 'of this embodiment includes a light source and a light receiving element, and the light source emits light to the temperature detection unit 207 of the biosensor 100', and receives light reflected from the temperature detection unit 207. It is provided so as to be incident on the element. A light emitting diode or a semiconductor laser is used as a light source, and a photodiode or a phototransistor is used as a light receiving element. The light receiving element detects the incident light from the temperature detection unit 207.

Next, as shown in FIG. 3, in step St4, the measurement unit 24 acquires the optical characteristic data from the color tone detection unit 23 ′, and obtains the temperature of the biosensor container 200 in which the noosensor 100 ′ is stored. Is calculated.

Next, as shown in FIG. 3, in step St5, the measuring unit 24 measures a current value flowing between the lead wires 3 through the pair of connectors 21 and 22.

Next, as shown in FIG. 3, in step St6, when the optical characteristic data and the current value are input, the data processing unit 25 writes the calculated temperature of the biosensor container 200 and the pre-created temperature. Based on the correlation between the obtained temperature and current value, the current value is corrected to calculate the concentration of dalcos. The data display unit 303 displays the density of the darkos calculated by the data processing unit 25.

In particular, in the present embodiment, when measuring the glucose concentration, the biosensor 100 ′ is switched off. By mounting the biosensor container 200 so that the temperature detection unit 207 of the biosensor container 200 is positioned above the color tone detection unit 23 at the same time as the lot 302, the color change of the temperature detection unit 207 is performed. Therefore, the influence of the environmental temperature can be automatically corrected. Therefore, if the no sensor 100, the biosensor container 200, and the biosensor measuring device 301 are used, an accurate measurement can be automatically performed by the measurer without requiring special knowledge.

Further, according to the present embodiment, it is not necessary to incorporate a thermistor into the biosensor as in the conventional sensor 100 ′. Therefore, the production cost is very low.

[0078] One modification example

Note that the biosensor measurement device 301 may further include a temperature sensor for measuring the temperature inside the device. The operation of the biosensor measurement device 301 having this configuration will be described. The operation of the biosensor measuring device 301 at this time is substantially the same as the operation of the biosensor measuring device 301 of the first embodiment. Therefore, the description will be given here with reference to FIG. 4 as in the first embodiment. FIG. 4 is a flowchart showing the operation of the biosensor measurement device 101.

As shown in FIG. 4, even when the biosensor measurement device 301 further includes a temperature sensor, the steps from Step Stl to Step St3 are exactly the same.

Next, as shown in FIG. 4, in step Stl4, the measuring unit 24 acquires the optical characteristic data from the color tone detecting unit 23, and measures the temperature of the biosensor container 200 in which the noosensor 100 ′ is stored. calculate. At this time, the temperature in the temperature sensor force is simultaneously received in the device, and it is determined whether or not the difference between the temperature in the device and the temperature of the biosensor container 200 is within a predetermined range. If the difference between the temperature in the device and the temperature of the biosensor container 200 is within the preset range, the Noosensor measuring device 301 proceeds to step Stl6, and if the difference is outside the preset range, , Proceed to step St15.

Next, as shown in FIG. 4, in step Stl 5, the biosensor measurement device 301 stops the measurement.

Next, as shown in FIG. 4, in step Stl6, the measuring unit 24 measures a current value flowing between the lead wires 3 through the pair of connectors 21 and 22. Next, as shown in FIG. 4, when the optical characteristic data and the current value are input in step Stl7, the data processing unit 25 compares the calculated temperature of the biosensor container 200 with the previously created temperature. Based on the correlation between the obtained temperature and current value, the current value is corrected to calculate the concentration of dalcos. The data display unit 103 displays the concentration of dalcos calculated by the data processing unit 25.

As described above, in the configuration in which the noise sensor measurement device 301 further includes the temperature sensor for measuring the temperature inside the device, the environmental temperature (in this case, the temperature inside the device) and the biosensor 100 ′ are stored. After confirming whether or not the difference between the temperature of the biosensor container 200 and the temperature is within a preset range, the measurement can be performed. For this reason, in this configuration, the temperature inside the biosensor measuring device 301 is hardly affected, and only the measurement result is obtained. That is, highly accurate measurement can be performed.

[0085] In the present embodiment, a force provided with a temperature detecting section 207 on the bottom surface of the biosensor container 200 The position of the temperature detecting section 207 can be set at any part of the container. However, it must be a position where the temperature can be detected by the color tone detecting section 23 'of the biosensor measuring device 301. In addition, it is desirable to install the temperature detecting unit 207 at a position as close as possible to the reagent unit of the Noo sensor 100, which is stored in the No sensor container 200. This makes it possible to obtain temperature information close to the temperature of the reagent section of the biosensor 100 ', and to perform more accurate temperature correction.

[0086] In the present embodiment, a biosensor that uses glucose as a substance to be measured will be described. However, this embodiment is not intended to limit the present invention to a biosensor in which the substance to be measured is glucose. When a substance other than glucose is used as the substance to be measured, an enzyme using the substance to be measured as a substrate may be selected as the enzyme contained in the reagent section 8. In the present embodiment, glucose oxidase (GOx), which is an oxidative reductase, was used as the enzyme contained in the reagent section 8. However, oxidative reductases other than GOx (for example, fructose dehydrogenase, glucose Dehydrogenase, alcohol oxidase, lactate oxidase, cholesterol oxidase, xanthine oxidase, amino acid oxidase, etc.) may be used.

[0087] Examples of electron carriers include potassium ferricyanide, p-benzoquinone, and phenazine methosal. Examples include substances such as fate, methylene blue, and phenoctene derivatives. Also, a current response can be obtained when oxygen is used as the electron carrier. Note that, instead of using one of the above substances as the electron carrier, two or more substances may be used in combination.

[0088] Also, for example, it is of course possible to use an anti-albumin antibody, an anti-hemoglobin antibody, or the like as a protein that specifically reacts with the substance to be measured, and to form a biosensor using the substance to be measured as albumin, hemoglobin or the like. It is. However, when an antibody is used as a protein that specifically reacts with the substance to be measured, both the Noosensor 100 and the biosensor measuring device 301 measure the antigen-antibody reaction quantitatively (for example, optically measure the antigen-antibody reaction). Quantitative means) should be taken.

(Embodiment 3)

[0090] The biosensor of the present embodiment will be described with reference to FIGS. 1 (a) and 1 (b). FIG. 1A is a top view of the biosensor of the present embodiment, and FIG. 1B is a cross-sectional view taken along line XX shown in FIG. 1A.

[0091] Configuration of one biosensor 1

As shown in FIGS. 1 (a) and 1 (b), a biosensor 100 according to the present embodiment has a lead wire 3 formed by screen printing on a substrate 2 formed of an insulating material, and a lead wire 3 formed by screen printing. A measuring electrode 4 and a counter electrode 6, which are electrodes connected to the sensor, an insulating layer 5, and a temperature detecting section 7 whose color tone changes according to the temperature, are formed. Thus, a reagent section 8 is formed. The reagent section 8 is formed by dropping into an aqueous solution containing glucose oxidase as a protein that specifically reacts with glucose as a substance to be measured and potassium ferricyanide as an electron carrier, followed by drying.

[0092] The reagent section 8 is not particularly limited as long as the reagent section 8 is configured to be dissolved when the sample is dropped and to be brought into contact with the measurement electrode 4 and the counter electrode 6 in a state of being mixed with the sample. . However, as described above, it is preferable to provide the measurement electrode 4 and the counter electrode 6 so as to cover them. In the reagent section 8, a conductive material constituting the measuring electrode 4 and the counter electrode 6 was further mixed. It is provided in a state.

[0093] The temperature detecting section 7 is formed of a material having a temperature-sensitive material as a main component. The temperature-sensitive material used in the temperature detection unit 7 of the present embodiment is a material that irreversibly responds to a temperature change, and is particularly preferably a material whose color tone changes with the temperature change. This makes it possible to visually recognize a sensor exposed to a high temperature due to some environment based on a change in the color tone of the temperature-sensitive material, and easily remove defective products.

[0094] In the case of a glucose sensor, a material that changes color irreversibly in the range of 50 ° C or more and 80 ° C or less is used as a temperature-sensitive material. For example, the temperature-sensitive material contains at least p-dimethylaminoazobenzene or a derivative thereof (Oil Yellow GG (registered trademark) manufactured by Orient Chemical Industries, Ltd.) as a dye, an organic acid and a metal salt of Z or an organic acid. It is preferable to do it.

[0095] The organic acid is composed of at least one selected from the group consisting of salicylic acid, citric acid, benzoic acid, and maleic acid. The metal salt of the organic acid is composed of at least one zinc selected from salicylic acid, citric acid, benzoic acid, and maleic acid. Preference is given to salts, sodium salts or aluminum salts.

[0096] It is preferable that the ink composition further contains a conductivity imparting substance and is printed by an inkjet printer.

[0097] The conductivity-imparting substance imparts the electric charge necessary for facilitating printing with an ink-jet printer to the ink, and improves the particleization and charge deflection of the ink. Examples include ammonium thiocyanate, sodium thiocyanate, lithium nitrate, and lithium iodide.

[0098] In order to maintain color development during heating, CI 42595 (available from Hodogaya Chemical, Aizen Blue—4 (“AIZEN” It is even better to add a registered trademark)).

When this ink is exposed to high-temperature conditions, p-dimethylaminoazobenzene or its derivative in the ink is discolored by the action of an organic acid. Discoloration proceeds depending on the heating time and temperature, so different hues are displayed according to the temperature history. This thermosensitive material has a large change in color tone when heated in a temperature range of 50 to 80 ° C, and is easily visible. [0100] When the discoloration color difference indicated by the indicator before and after heating is measured by an optical measurement device such as a colorimeter, the temperature history is displayed more accurately. Here, the temperature history is a biosensor

100 is the highest temperature experienced.

[0101] According to the temperature history, the composition of the temperature-sensitive material can be adjusted to adjust the discoloration speed and the time required for completing discoloration. For example, in the case of the noise sensor 100 of the present embodiment, the temperature-sensitive material can be adjusted such that it takes about one day for the temperature detector 7 to change color. As described above, the composition of the temperature-sensitive material can be arbitrarily adjusted so that the sensor 100 can be detected only when the sensor is exposed to a high temperature for a time that affects the function of the sensor itself.

[0102] The temperature detector 7 can be manufactured, for example, as follows.

[0103] A weight composition of methyl yellow: salicylic acid: thiocyanic acid: methyl ethyl ketone: methanol: polyamide resin = 1: 3: 2: 40: 34: 20 is prepared. Here, methyl yellow is p-dimethylaminoazobenzene.

[0104] First, a dye, an organic acid, and a conductivity-imparting substance are added to a solvent, and the mixture is sufficiently stirred. Then, a resin is added, and the mixture is stirred and mixed for about 2 hours. Using a 0.7 m pore diameter membrane, the mixed composition is suction-filtered and the insoluble matter is removed to prepare an ink. This ink is applied to the temperature detecting section 7 using an ink jet printer. Note that the ink can be applied to the temperature detection unit 7 without using an ink jet printer. In this case, the conductivity imparting material need not be added to the ink.

[0105] The noise sensor thus manufactured can detect the temperature history as follows.

The color tone of the temperature detecting section 7 did not change during storage of the sample can at room temperature. The biosensor is stored in a thermostat at 40, 50, 60 and 70 ° C for 1 day, and the color change is measured visually and by a color difference meter CR-100 (Minolta Camera Co., Ltd.). It was red before discoloration or at 40 ° C, but turned yellow at 50, 60, and 70 ° C, and the change was easily visible.

In the present embodiment, a biosensor using glucose as a substance to be measured will be described. However, as described above, the present embodiment does not limit the present invention to a biosensor in which the substance to be measured is glucose. Measure substances other than glucose In this case, an enzyme containing the substance to be measured as a substrate may be selected as the enzyme contained in the reagent section 8. In the present embodiment, the enzymes contained in the reagent section 8 are oxidoreductases other than the force GOx using glucose oxidase (GOx), which is an oxidoreductase (eg, phenolectose dehydrogenase, gnorecose dehydrogenase). Anoreconoreoxidase, lactate oxidase, cholesterol oxidase, xanthine oxidase, amino acid oxidase, etc.).

[0108] Examples of the electron carrier include substances such as potassium ferricyanide, p-benzoquinone, phenazine methosulfate, methylene blue, and phenoctene derivatives. Also, a current response can be obtained when oxygen is used as the electron carrier. Note that, instead of using one of the above substances as the electron carrier, two or more substances may be used in combination.

[0109] For example, it is of course possible to use an anti-albumin antibody, an anti-hemoglobin antibody, or the like as a protein that specifically reacts with the substance to be measured to form a biosensor using the substance to be measured as albumin, hemoglobin, or the like. It is. However, when an antibody is used as a protein that specifically reacts with the above-mentioned substance to be measured, both the biosensor 100 and the biosensor measuring device 101 quantitatively measure the antigen-antibody reaction (for example, optically measure the antigen-antibody reaction). Quantitative means) should be taken.

[0110] Furthermore, it is also possible to optically detect the temperature detecting unit 7 with the biosensor measuring device 101.

[0111] The temperature detecting section 7 is divided into two parts, and a temperature-sensitive material that changes color reversibly by heat is applied to one area, and a temperature-sensitive material that changes color irreversibly by heat is applied to the other area. You may. This makes it possible to confirm that the noise sensor is not unusable and at the same time to correct the temperature of the measured value.

(Embodiment 4)

[0113] Configuration of one container

As shown in FIG. 5 (a), the biosensor container 200 of this embodiment It has a body portion 203, and has a temperature detecting portion 207 whose color tone changes according to the temperature on the bottom surface of the main body portion 203. As shown in FIG. 5 (b), the biosensor container 200 can house the biosensor 100 ′. Here, the biosensor 100 ′ has the same structure as the biosensor 100, but does not include the temperature detection unit 7. Instead, in the present embodiment, the temperature sensor 207 is provided in the biosensor container 200.

[0114] Further, temperature detecting section 207 is formed of a material having a temperature-sensitive material as a main component. Here, the temperature-sensitive material used in the temperature detection unit 207 of the present embodiment is a material that responds irreversibly to a temperature change, and in particular, a material whose color tone changes with the temperature change is preferable. This makes it possible to visually recognize a biosensor that has been exposed to a high temperature due to some environment based on a change in the color tone of the temperature-sensitive material, and easily remove defective products in advance.

[0115] The thermosensitive material contains at least p-dimethylaminoazobenzene or a derivative thereof (Oil Yellow GG (registered trademark) manufactured by Orient Chemical Co., Ltd.) as a dye, an organic acid and a metal salt of Z or an organic acid. Do it.

[0116] The organic acid is composed of at least one selected from salicylic acid, citric acid, benzoic acid, and maleic acid, and the metal salt is preferably a zinc salt, a sodium salt, or an aluminum salt.

[0117] The temperature-sensitive material further contains a conductivity-imparting substance, and is preferably printed by an inkjet printer. By using an inkjet printer, the temperature detection unit 207 can be formed easily and at high speed.

[0118] The conductivity-imparting substance imparts the necessary electric charge to the ink for facilitating printing with an ink-jet printer, and improves the particleization and charge deflection of the ink. Examples include ammonium thiocyanate, sodium thiocyanate, lithium nitrate, and lithium iodide.

[0119] In order to maintain the color development during heating, CI 42595 (Aizen Blue—4, manufactured by Hodogaya Chemical Co., Ltd .; “AIZEN” is a registered trademark) is an oil-soluble dye that has good heat resistance and does not discolor due to heat loss. (Trademark)).

When this ink is exposed to high temperature conditions, p-dimethylaminoazobenzene or its derivative in the ink is discolored by the action of an organic acid. Discoloration progresses depending on the heating time and temperature. As a result, different hues are displayed according to the temperature history. This thermosensitive material has a large change in color tone when heated in a temperature range of 50 to 80 ° C, and is easily visible.

[0121] If the discoloration color difference indicated by the indicator before and after heating is measured by an optical measurement device such as a colorimeter, the temperature history is displayed more accurately.

[0122] According to the temperature history, the composition of the thermosensitive material can be adjusted to adjust the discoloration speed and the time required for completing the discoloration.

[0123] The temperature detection unit 207 can be manufactured as follows.

A weight composition of methyl yellow: salicylic acid: thiocyanic acid: methyl ethyl ketone: methanol: polyamide resin = 1: 3: 2: 40: 34: 20 is prepared.

First, a dye, an organic acid, and a conductivity-imparting substance are added to a solvent, and the mixture is sufficiently stirred. Then, a resin is added, and the mixture is stirred and mixed for about 2 hours. Using a 0.7 m pore diameter membrane, the mixed composition is suction-filtered and the insoluble matter is removed to prepare an ink. This ink is applied to the temperature detecting section 7 using an ink jet printer.

[0126] The temperature history can be detected by the sensor manufactured as described above as follows.

[0127] The color tone did not change during storage of the sample can at room temperature. The biosensor container 200 is stored in a thermostat at 40, 50, 60, and 70 ° C for one day, and the change in color tone is visually observed and measured by a colorimeter CR-100 (Minolta Camera Co., Ltd.). The force was red before the discoloration or at 40 ° C. Yellow at 50, 60 and 70 ° C, and the change is easily visible.

Further, in the present embodiment, a biosensor using glucose as a substance to be measured will be described! However, this embodiment is not intended to limit the present invention to a biosensor in which the substance to be measured is glucose. When a substance other than glucose is used as the substance to be measured, an enzyme using the substance to be measured as a substrate may be selected as the enzyme contained in the reagent section 8. In the present embodiment, glucose oxidase (GOx), which is an oxidative reductase, was used as the enzyme contained in the reagent section 8. However, oxidative reductases other than GOx (for example, fructose dehydrogenase, glucose Dehydrogenase, alcohol oxidase, lactate oxidase, cholesterol oxidase, xanthine oxidase, amino acid oxidase, etc.) may be used.

[0129] Examples of electron carriers include potassium ferricyanide, p-benzoquinone, and phenazine methal. Examples include substances such as fate, methylene blue, and phenoctene derivatives. Also, a current response can be obtained when oxygen is used as the electron carrier. Note that, instead of using one of the above substances as the electron carrier, two or more substances may be used in combination.

[0130] Also, for example, a biosensor using an anti-albumin antibody, an anti-hemoglobin antibody, or the like as a protein that specifically reacts with the test substance, and using the test substance as an albumin, hemoglobin, or the like can be used. It is. However, when an antibody is used as a protein that specifically reacts with the substance to be measured, both the Noosensor 100 and the biosensor measuring device 301 measure the antigen-antibody reaction quantitatively (for example, optically measure the antigen-antibody reaction). Quantitative means) should be taken.

Further, the temperature detecting unit 207 can be optically detected by the biosensor measuring device 301.

[0131] In the biosensor container 200 of the present embodiment, the temperature detecting unit 207 may be provided on the lid 202 in addition to the bottom of the container. By providing the temperature detecting section on the lid 202, it is possible to more easily determine defective products visually.

[0132] Further, the biosensor of the first embodiment may be stored in the biosensor container of the present embodiment. In this case, the temperature detection unit 207 provided in the biosensor container can confirm that the biosensor is not unusable, and can perform correction at the time of measurement based on the color tone of the temperature detection unit 7 provided in the biosensor. More accurate measurements can be made.

Industrial applicability

The present invention is useful for analysis that requires simple, precise, and rapid measurement of a specific substance concentration, for example, measurement at the time of medical diagnosis and the like.

Claims

The scope of the claims

[1] A biosensor for measuring an analyte contained in a sample,

Board and

A reagent unit provided on the substrate and containing a protein that specifically reacts with the substance to be measured, to which the sample is supplied;

A biosensor comprising: a temperature detection unit formed of a material including a temperature-sensitive material whose color tone changes according to temperature.

[2] The biosensor according to claim 1,

A biosensor, wherein the temperature-sensitive material contains a dye whose color tone changes irreversibly.

[3] The biosensor according to claim 2,

A biosensor, wherein the temperature-sensitive material contains at least p-dimethylaminoazobenzene or a derivative thereof, and an organic acid and a metal salt of Z or an organic acid.

[4] The biosensor according to claim 3,

The temperature-sensitive material contains an organic acid,

A biosensor, wherein the organic acid is at least one selected from the group consisting of salicylic acid, citric acid, benzoic acid, and maleic acid.

[5] The biosensor according to claim 3,

The temperature-sensitive material contains a metal salt of an organic acid,

A Noo sensor, wherein the metal salt of the organic acid is a zinc salt, a sodium salt, or an aluminum salt.

[6] The biosensor according to claim 2,

A biosensor, wherein the temperature-sensitive material further includes a conductivity-imparting substance.

[7] The biosensor according to claim 6,

A biosensor, wherein the conductivity-imparting substance is at least one selected from the group consisting of ammonium thiocyanate, sodium thiocyanate, lithium nitrate, and potassium iodide.

[8] The biosensor according to claim 2,

A biosensor in which the color of the temperature-sensitive material changes within a range of 50 ° C to 80 ° C.

[9] The biosensor according to claim 1,

A biosensor, wherein the temperature-sensitive material contains a dye whose color tone changes reversibly.

[10] The biosensor according to claim 1,

A biosensor, wherein the protein is an enzyme using the substance to be measured as a substrate.

[11] The biosensor according to claim 1,

A biosensor, wherein the protein is an antibody.

[12] measuring the substance to be measured, comprising: a substrate; and a reagent unit provided on the substrate and containing a protein specifically reacting with the substance to be measured contained in the sample, and supplied with the sample. A biosensor container for housing a Noosensor for

A biosensor container comprising: a temperature detection unit provided on an outer surface of the housing and formed of a material including a temperature-sensitive material.

[13] The container for a neurosensor according to claim 12,

The thermosensitive material contains a dye whose color tone changes irreversibly.

[14] The container for a neurosensor according to claim 13,

A biosensor container, wherein the temperature-sensitive material contains at least p-dimethylaminoazobenzene or a derivative thereof and an organic acid and a metal salt of Z or an organic acid.

[15] The container for a neurosensor according to claim 14,

The temperature-sensitive material contains an organic acid,

A biosensor container, wherein the organic acid is at least one selected from the group consisting of salicylic acid, citric acid, benzoic acid, and maleic acid.

[16] The container for a neurosensor according to claim 14,

The temperature-sensitive material contains a metal salt of an organic acid,

A container for a neurosensor, wherein the metal salt of the organic acid is a zinc salt, a sodium salt, or an aluminum salt.

[17] The container for a neurosensor according to claim 13,

A biosensor container, wherein the temperature-sensitive material further contains a conductivity-imparting substance.

[18] The container for a neurosensor according to claim 17,

A biosensor container, wherein the conductivity-imparting substance is at least one selected from the group consisting of ammonium thiocyanate, sodium thiocyanate, lithium nitrate, and potassium iodide.

[19] The container for a neurosensor according to claim 13,

A valley for a biosensor, in which the color of the temperature-sensitive material changes within the range of 50 ° C to 80 ° C.

[20] A substrate, a reagent portion provided on the substrate and containing a protein that specifically reacts with a substance to be measured contained in the sample, and a reagent portion to which the sample is supplied, and a color tone that changes according to temperature. A biosensor measuring device for measuring the substance to be measured, using a Noosensor having a temperature detecting portion formed from a material including a material,

A color tone detection unit that detects a color tone of the temperature detection unit,

A measurement unit connected to the color tone detection unit and measuring the temperature of the reagent unit based on the color tone;

A biosensor measurement device comprising:

[21] A substrate, a biosensor provided on the substrate and containing a protein that specifically reacts with a substance to be measured contained in a sample, and a reagent part to which the sample is supplied, and a cavity inside the biosensor. A biosensor container for housing the biosensor, comprising: a formed housing; and a temperature detecting unit formed of a material including a temperature-sensitive material provided on an outer surface of the housing. A biosensor measuring device for measuring the substance to be measured using

A biosensor measurement device comprising: