Component measurement device and component measurement method

Abstract

This component measurement device measures a component to be measured in blood on the basis of optical characteristics of a color component generated by a reaction between the component to be measured in the blood and a reagent, and is configured so as to correct the measurement value of the component to be measured on the basis of the oxygen saturation of the blood.

Description

Technical Field

[0001] The present disclosure relates to a component measurement device and a component measurement method. Background Art

[0002] Conventionally, in the fields of biochemistry or medicine, as a method for measuring a component to be measured contained in blood (whole blood) as a specimen, a method of separating blood into a part containing the component to be measured and a part not containing the component to be measured, and measuring the amount or concentration of the component to be measured is known. For example, in order to measure the glucose concentration (mg / dL, mmol / L) in plasma, there is a method of measuring the glucose concentration in plasma by performing a step of separating plasma components from blood using a filter or the like.

[0003] However, since it is difficult to completely separate plasma components in blood in a short time, and furthermore, there are variations in the performance of filters or the like used for separation, there is a possibility that a part of blood cell components are contained in the separated plasma components, making it difficult to measure the glucose concentration with high accuracy.

[0004] On the other hand, as a method for measuring a component to be measured in blood without separating the component to be measured from the blood, whole blood measurement using absorptiometry is known. According to this method, compared with the method of performing the separation step of the component to be measured described above, the time required for measuring the component to be measured can be shortened. However, when there are a large number of other components different from the component to be measured in the blood, these other components cause optical phenomena such as light absorption and light scattering, and as a result, they sometimes act as interference factors (noise) in measurement. Therefore, in order to maintain the measurement accuracy of the component to be measured, it is necessary to remove the influence of these interference factors, and thus various methods for removing the influence of interference factors have been proposed.

[0005] For example, Patent Document 1 discloses a component measurement device and a component measurement method for measuring the glucose concentration in plasma components by using multiple types of light sources, estimating the influence amount of interference factors at a measurement wavelength based on measured values in a long wavelength region on the longer wavelength side than the measurement wavelength, correcting the measured value at the measurement wavelength using the estimated influence amount of interference factors, and further correcting the measured value at the measurement wavelength using the predicted hematocrit value.

[0006] Patent Document 1: International Publication No. 2018 / 173609

[0007] However, in whole blood measurement using absorptiometry, it is required to remove the influence of more interference factors and further improve the accuracy of component measurement. Summary of the Invention

[0008] The present disclosure is made in view of the above circumstances, and aims to provide a component measurement device and a component measurement method that improve the measurement accuracy of whole blood measurement using spectrophotometry.

[0009] 〔1〕The component measurement device according to an embodiment of the present disclosure uses a reagent that reacts with a component to be measured in blood, and measures the component to be measured in the blood based on the optical characteristics of a colored component generated by a color reaction between the component to be measured and the reagent. The component measurement device is configured to correct the measured value of the component to be measured based on the oxygen saturation of the blood.

[0010] 〔2〕The component measurement device according to an embodiment of the present disclosure preferably includes, on the basis of the component measurement device described in 〔1〕 above: two correction light sources, including a first correction light source that emits irradiation light having a wavelength at which the absorption coefficient of reduced hemoglobin is equal to the absorption coefficient of oxidized hemoglobin, and a second correction light source that emits irradiation light having a wavelength at which the absorption coefficient of reduced hemoglobin is different from the absorption coefficient of oxidized hemoglobin; and a light receiving unit that receives transmitted light that has passed through the blood among the irradiation lights from the two correction light sources. The component measurement device is configured to estimate the oxygen saturation of the blood based on the transmitted light from the two correction light sources received by the light receiving unit.

[0011] 〔3〕The component measurement device according to an embodiment of the present disclosure preferably determines whether it is before the start of the reaction between the component to be measured and the reagent based on the time series change of the transmitted light from at least one of the two correction light sources received by the light receiving unit. The component measurement device is configured to estimate the oxygen saturation of the blood based on the transmitted light from the two correction light sources received by the light receiving unit before the start of the reaction.

[0012] 〔4〕The component measurement device according to an embodiment of the present disclosure, based on the component measurement device described in the above 〔2〕 or 〔3〕, preferably includes: a first light source that emits irradiation light having a measurement wavelength within a wavelength range corresponding to the full width at half maximum region of the peak wavelength region in the absorption spectrum of the coloring component; a second light source that emits irradiation light having the second wavelength belonging to a long wavelength region compared with the measurement wavelength and the third wavelength, and a third light source that emits irradiation light having the third wavelength; and a fourth light source that emits irradiation light having the fourth wavelength belonging to a short wavelength region compared with the measurement wavelength within the wavelength range corresponding to the full width at half maximum region and the fifth wavelength, and a fifth light source that emits irradiation light having the fifth wavelength. Through the light receiving unit, the transmitted light after passing through the blood in the irradiation light from the first light source to the fifth light source is received. The component measurement device is configured to: use the measured value of the absorbance of the mixture including the blood, the reagent, and the coloring component at the measurement wavelength, and use the measured values of the absorbance of the mixture at the second wavelength to the fifth wavelength to measure the component to be measured in the blood. The first correction light source is the fourth light source, and the second correction light source is the first light source.

[0013] 〔5〕The component measurement device according to an embodiment of the present disclosure, based on the component measurement device described in any one of the above 〔1〕 to 〔4〕, preferably the reagent includes: an oxidoreductase that specifically reacts with the component to be measured, and a coloring reagent that colors according to the amount of reaction between the component to be measured and the oxidoreductase. In addition, it further includes: a hemolytic reagent that hemolyzes the blood, and an oxidizing reagent that oxidizes hemoglobin (Fe 2+ ) in the blood.

[0014] 〔6〕An embodiment of the component measurement method of the present disclosure is a component measurement method for measuring the component to be measured in the blood based on the optical characteristics of the coloring component generated by the coloring reaction between the component to be measured in the blood and the reagent, wherein it includes correcting the measured value of the component to be measured based on the oxygen saturation of the blood.

[0015] According to the present disclosure, a component measurement device and a component measurement method capable of improving the measurement accuracy of whole blood measurement using the absorptiometry can be provided. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 It is a top view of a group of component measurement devices in which a component measurement chip is installed in the component measurement device according to an embodiment of the present disclosure.

[0017] Figure 2 is a view showing a cross-section taken along I-I Figure 1 as shown.

[0018] Figure 3 is a view showing a cross-section taken along II-II Figure 1 as shown.

[0019] Figure 4 is a top view showing the Figure 1 component measurement chip as shown.

[0020] Figure 5 is a cross-sectional view taken along III-III Figure 4 as shown.

[0021] Figure 6 is Figure 1 an electrical block diagram of the component measurement device as shown.

[0022] Figure 7 is Figure 6 a functional block diagram of the arithmetic unit as shown.

[0023] Figure 8 is a view showing Figure 1 the positional relationship of a plurality of light sources in the component measurement device as shown.

[0024] Figure 9 is a view showing Figure 8 the irradiation positions at which a plurality of light sources irradiate a mixture as shown.

[0025] Figure 10 is a view showing the absorption spectra of six mixtures obtained by subjecting six blood specimens to a color reaction with a measurement reagent, respectively.

[0026] Figure 11 is a view showing the absorption spectra of seven blood specimens, respectively.

[0027] Figure 12 is a view showing the absorption coefficients of reduced hemoglobin and oxidized hemoglobin.

[0028] Figure 13 is a view showing the ratio of the absorption coefficient of oxidized hemoglobin to the absorption coefficient of reduced hemoglobin.

[0029] Figure 14 is a graph showing the occupancy rates of the long wavelength region and the short wavelength region in the absorbance caused by interfering factors (noise) other than the colored components at the measurement wavelength estimated by regression analysis.

[0030] Figure 15 is a schematic diagram showing the stage at which blood spreads on the component measurement chip.

[0031] Figure 16 is a schematic diagram showing the change in absorbance as blood spreads in the component measurement chip.

[0032] Figure 17 is a flowchart showing a method for correcting a component to be measured according to an embodiment of the present disclosure.

[0033] Figure 18 is a flowchart showing a component measurement method according to an embodiment of the present disclosure. Detailed Embodiment

[0034] Hereinafter, a component measurement device 1 according to an embodiment of the present disclosure will be described with reference to the accompanying drawings. In the drawings, the same or corresponding parts are denoted by the same reference numerals. However, it should be noted that the drawings are schematic, and the ratios of the respective dimensions and the like may sometimes be different from the actual situation.

[0035] First, the component measurement device 1 of the present embodiment will be described. Figure 1 is a top view of a component measurement device group 100 in which a component measurement chip 2 is installed in the component measurement device 1 of the present embodiment. Figure 2 is shown along Figure 1 a cross-sectional view taken along line I-I. Figure 3 is shown along Figure 1 a cross-sectional view taken along line II-II. In addition, Figure 2 and Figure 3 magnify and show the vicinity of the portion where the component measurement chip 2 is installed.

[0036] As Figures 1 to 3 shown, the component measurement device group 100 includes a component measurement device 1 and a component measurement chip 2. The component measurement device 1 of the present embodiment is a blood glucose measurement device capable of measuring the concentration of glucose in plasma components as components to be measured in blood. In addition, the component measurement chip 2 of the present embodiment is a blood glucose measurement chip that can be installed at the front end of the blood glucose measurement device as the component measurement device 1. In addition, the "blood" mentioned here means whole blood that contains all components without being separated by components.

[0037] The component measurement device 1 includes: a display unit 11, which is composed of a housing 10 made of a resin material, buttons provided on the upper surface of the housing 10, and a liquid crystal or LED (Light Emitting Diode) provided on the upper surface of the housing 10; and a removal lever 12 for operating when removing the component measurement chip 2 installed in the state of the component measurement device 1. In addition, the buttons of the present embodiment may be composed of a power button 13 and an operation button 14.

[0038] AsFigure 1 As shown, the housing 10 includes: a main body 10a having a substantially rectangular shape in plan view and provided with the above-mentioned buttons and display unit 11 on the upper surface, and a chip mounting portion 10b protruding outward from the main body 10a and provided with a removal lever 12 on the upper surface. Figure 2 As shown, a chip mounting space S is divided inside the chip mounting portion 10b, with the front end opening formed on the front end surface of the chip mounting portion 10b as one end. The component measurement chip 2 is inserted into the chip mounting space S from the outside of the chip mounting portion 10b through the front end opening and is pressed into a predetermined position, thereby becoming a state of being locked in the chip mounting portion 10b of the component measurement device 1. Thus, the component measurement chip 2 is mounted on the component measurement device 1. In addition, the locking of the component measurement chip 2 by the component measurement device 1 can be achieved by, for example, providing various structures such as a claw portion that can be engaged with a part of the component measurement chip 2 in the chip mounting portion 10b.

[0039] On the other hand, when the component measurement chip 2 is mounted on the component measurement device 1, the removal lever 12 is operated from the outside of the housing 10, thereby releasing the locking state of the component measurement chip 2 by the chip mounting portion 10b of the component measurement device 1. Then, along with the release of the locking state of the component measurement chip 2, the ejection pin 26 (see FIG. 1 ) in the housing 10 is released. Figure 2 ) can be moved in conjunction with the component measuring device 1 to remove the component measuring chip 2 from the component measuring device 1.

[0040] In addition, if Figure 1 As shown in the figure, although the housing 10 of the present embodiment is a structure including a main body 10a which is substantially rectangular in a plan view and a chip mounting portion 10b which is provided to protrude outward from the main body 10a, the shape of the housing 10 of the present embodiment is not limited as long as the chip mounting portion is provided to mount the component measurement chip 2. Therefore, the component measurement device 1 can adopt any shape other than the shape of the housing 10 of the present embodiment which is easy for the user to hold with one hand.

[0041] The display unit 11 is configured to display information on the measured component measured by the component measuring device 1. In the present embodiment, the display unit 11 can display the glucose concentration measured by the component measuring device 1 as a blood sugar level measuring device. In addition, the display unit 11 can be configured to display various information such as measurement conditions of the component measuring device 1 or instruction information for instructing the user on a predetermined operation in addition to the information on the measured component. The user can operate the power button 13 or the operation button 14 while confirming the content displayed on the display unit 11.

[0042] In addition, if Figure 2 as well as Figure 3As shown, the component measurement device 1 includes a light emitting unit 66 and a light receiving unit 72. The light emitting unit 66 and the light receiving unit 72 are disposed opposite to each other across the chip mounting space S. As Figure 2 and Figure 3 shown, in a state where the component measurement chip 2 is mounted in the chip mounting space S of the component measurement device 1, the irradiation light emitted from the light emitting unit 66 irradiates the component measurement chip 2. The light receiving unit 72 receives the transmitted light that has passed through the component measurement chip 2 from the irradiation light irradiated from the light emitting unit 66 to the component measurement chip 2. The light receiving unit 72 measures the amount of irradiation light irradiated from the light emitting unit 66 as an initial value in a state where the component measurement chip 2 is not mounted, so that the change in the light amount of the light emitting unit can also be corrected.

[0043] In addition, as Figure 2 、 Figure 3 and Figure 6 shown, the light emitting unit 66 includes five light sources. Specifically, the light emitting unit 66 includes a first light source 67, a second light source 68a, a third light source 68b, a fourth light source 68c, and a fifth light source 68d. Here, as Figure 3 shown, the first light source 67, the second light source 68a, and the third light source 68b are arranged at different positions in the flow path width direction B (in Figure 2 it is the left - right direction) orthogonal to the flow direction A (in Figure 3 it is the right - facing direction) of the blood flow in the flow path 23 of the component measurement chip 2 described later. The arrangement of the first light source 67 to the fifth light source 68d will be described in detail later (refer to Figure 8 ).

[0044] Next, the component measurement chip 2 of the present embodiment will be described. Figure 4 is a top view showing the component measurement chip 2. In addition, Figure 5 is a cross - sectional view along Figure 4 III - III. As Figure 4 and Figure 5 shown, the component measurement chip 2 includes: a substrate member 21 having a substantially rectangular plate - like outer shape, a measurement reagent 22 held by the substrate member 21, and a cover member 25 covering the substrate member 21.

[0045] In the thickness direction of the substrate member 21 (in the present embodiment, it is the same as Figure 2 and Figure 3The direction is the same as the thickness direction C of the component measurement chip 2 shown below (hereinafter referred to as the thickness direction C), and a groove is formed on the outer surface on one side. The groove of the base member 21 is covered by the cover member 25, thereby forming a hollow portion extending in a direction orthogonal to the thickness direction C. This hollow portion constitutes the flow path 23 of the component measurement chip 2. A supply portion 24 capable of supplying blood from the outside is formed at one end of the flow path 23. In addition, the measurement reagent 22 is held at the bottom of the groove of the base member 21 on the inner wall of the flow path 23. The measurement reagent 22 of the present embodiment is coated on the bottom of the groove that is the flow path 23, but it is not limited thereto. The blood supplied from the outside to the supply portion 24 moves along the flow path 23 in the flow direction A by capillary action, for example, reaches the holding position where the measurement reagent 22 is held, and contacts the measurement reagent 22. The measurement reagent 22 contains a coloring reagent that develops color by reacting with blood. Therefore, when the measurement reagent 22 contacts the blood, a color reaction occurs in which the coloring reagent contained in the measurement reagent 22 develops color, and a mixture X containing a colored component is generated (refer to Figure 2 etc.). However, although the details will be described later, the measurement reagent 22 may also contain reagents other than the coloring reagent.

[0046] In addition, a gap 23a is formed between the cover member 25 and the measurement reagent 22. The blood moving in the flow path 23 from the supply portion 24 in the flow direction A reaches the other end of the flow path 23 through the gap 23a. Therefore, by bringing the blood into contact with the entire region of the flow direction A of the measurement reagent 22, a color reaction can be generated.

[0047] In Figure 2 for the sake of convenience of explanation, the holding position of the measurement reagent 22 is indicated as "mixture X", but the mixture X is not only located at the holding position of the measurement reagent 22, but also near the holding position of the measurement reagent 22 such as the gap 23a. More specifically, the blood that enters the flow path 23 from the supply portion 24 contacts the measurement reagent 22 at the holding position and reaches the downstream end of the flow path 23 through the gap 23a while being in a state where the flow path 23 is filled with blood. After that, a color reaction between the measurement reagent 22 and the blood occurs, and the mixture X is in a state of being located at the holding position and its vicinity.

[0048] Although the flow path 23 of the present embodiment is constituted by a hollow portion divided by the base member 21 and the cover member 25, the flow path is not limited to this structure. The flow path may also be formed only by a groove formed on the outer surface on one side in the thickness direction of the base member 21.

[0049] The base member 21 and the cover member 25 are preferably made of a transparent material in order to sufficiently measure the signal of the transmitted light amount after the irradiated light passes through. As the materials for the base member 21 and the cover member 25, for example, transparent organic resin materials such as polyethylene terephthalate (PET), polymethyl methacrylate (PMMA), polystyrene (PS), cyclic olefin polymer (COP), cyclic olefin copolymer (COC), and polycarbonate (PC) can be cited; transparent inorganic materials such as glass and quartz.

[0050] The measurement reagent 22 includes: an enzyme that reacts with the component to be measured in the blood, and a color-developing reagent that colors according to the blood concentration of the component to be measured. The measurement reagent 22 of the present embodiment includes: an enzyme that specifically reacts with glucose as the component to be measured in the blood, and a color-developing reagent that quantitatively colors by the electrons generated by the reaction of the enzyme with glucose. As the measurement reagent 22 of the present embodiment, for example, a mixed reagent of (i) glucose oxidase (GOD), (ii) peroxidase (POD), (iii) 1-(4-sulfophenyl)-2,3-dimethyl-4-amino-5-pyrazolone, and (iv) N-ethyl-N-(2-hydroxy-3-sulfopropyl)-3,5-dimethylaniline, sodium salt, monohydrate (MAOS), or a mixed reagent of glucose dehydrogenase (GDH) and a tetrazolium salt, etc. The measurement reagent 22 may also contain an electron mediator, etc. as needed.

[0051] As the enzyme of the present embodiment, oxidoreductase can be cited. The oxidoreductase is not particularly limited and can be appropriately selected according to the type of the biological component to be measured. Specifically, glucose dehydrogenase (GDH), glucose dehydrogenase with pyrroloquinoline quinone (PQQ) as a coenzyme (PQQ-GDH), glucose dehydrogenase with flavin adenine dinucleotide (FAD) as a coenzyme (FAD-GDH), glucose dehydrogenase with nicotinamide adenine dinucleotide (NAD) as a coenzyme (NAD-GDH), and glucose dehydrogenase with nicotinamide adenine dinucleotide phosphate (NADP) as a coenzyme (NADP-GDH) and other glucose dehydrogenases (GDH), glucose oxidase (GOD), lactate dehydrogenase (LDH), cholesterol dehydrogenase, cholesterol oxidase, and uric acid dehydrogenase, etc. Here, the oxidoreductase can be used alone or in combination of two or more. For example, when the measurement object is glucose, the oxidoreductase is preferably glucose dehydrogenase or glucose oxidase. In addition, when measuring cholesterol, the oxidoreductase is preferably cholesterol dehydrogenase or cholesterol oxidase. The content of the oxidoreductase in the measurement reagent 22 when containing the oxidoreductase is not particularly limited and can be appropriately selected according to the amount of the color-developing reagent. As the enzyme of the present embodiment, glucose dehydrogenase is preferred.

[0052] As the color-developing reagent of the present embodiment, a pigment compound is used in which the peak wavelength in the absorption spectrum of the color-developing component generated by the color reaction with glucose in blood is different from the peak wavelength caused by the light absorption characteristics of hemoglobin in blood cells. Although the absorption spectrum of the color-developing component generated by the color reaction of the color-developing reagent of the present embodiment with glucose in blood has a peak wavelength near 650 nm, it is not limited thereto. The details will be described later.

[0053] The color-developing pigment of the present embodiment is preferably a tetrazolium salt, and preferably 2-benzothiazolyl-3-(4-carboxy-2-methoxyphenyl)-5-[4-(2-sulfoethylcarbamoyl)phenyl]-2H-tetrazolium (2-Benzothiazolyl-3-(4-carboxy-2-methoxyphenyl)-5-[4-(2-sulfoethylcarbamoyl)phenyl]-2H-tetrazolium), the tetrazolium salt described in International Publication No. WO2018 / 051822. According to a more preferred embodiment of the present disclosure, the color-developing pigment is selected from 2-benzothiazolyl-3-(4-carboxy-2-methoxyphenyl)-5-[4-(2-sulfoethylcarbamoyl)phenyl]-2H-tetrazolium and at least one selected from the group consisting of tetrazolium salts represented by the following formula (1). According to a particularly preferred embodiment of the present disclosure, the color-developing pigment is a tetrazolium salt represented by the following formula (1).

[0054]

[0055] In the above formula (1), R 1 is any one selected from the group consisting of a hydrogen atom, a hydroxyl group, a methoxy group, and an ethoxy group, and R 2 is any one selected from the group consisting of a nitro group, -OR 4 , and a carboxyl group, R 3 is a hydrogen atom, a methyl group or an ethyl group, and at least one is a methyl group or an ethyl group, R 4 is a methyl group or an ethyl group, m is the number of sulfonyl groups (-SO 3 -) bonded to the phenyl group at the 5-position of the tetrazole skeleton, and is 1 or 2, n is the number of R 2 bonded to the phenyl group at the 3-position of the tetrazole skeleton, and is an integer from 0 to 2, p is the number of sulfonyl groups (-SO 3 -) bonded to the phenyl group at the 3-position of the tetrazole skeleton, and is 0 or 1, n + p is 1 or more, q is 1 or 2, and when q is 2, each OR3 Adjacent configuration, where each OR 3 can also form a ring with each other, and X represents a hydrogen atom or an alkali metal.

[0056] In addition to the enzyme and the chromogenic reagent used for specifically reacting with the component to be measured, the measurement reagent 22 may further contain a hemolytic reagent for hemolyzing blood and an oxidation reagent for oxidizing hemoglobin (Fe 2+ ) in the blood to methemoglobin (Fe 3+ ).

[0057] As the hemolytic reagent of the present embodiment, for example, a nonionic surfactant, an amphoteric surfactant, an anionic surfactant, etc. can be used. From the viewpoint of not hindering the enzyme activity, a nonionic surfactant is preferred. As the nonionic surfactant, from the viewpoints of the destructiveness of the red blood cell membrane or the solubility in water, etc., it preferably has an HLB value of 11 or more and 15 or less (more preferably 12 or more and 14 or less). As such a nonionic surfactant, polyoxyethylene alkyl ethers, nonylphenyl polyethylene glycols, etc. in which the average addition mole number of oxyethylene groups is 1 or more and 150 or less, and the carbon number of the alkyl group is 1 or more and 18 or less can be cited. Such nonionic surfactants can be synthesized or commercially available products can also be used. As commercially available products, polyoxyethylene(9)octylphenyl ether (octylphenoxy poly(ethyleneoxy)ethanol or octylphenyl-polyethylene glycol) (manufactured by Sigma-Aldrich, NonidetTM P-40), Triton (registered trademark) X-100 (polyoxyethylene(10)octylphenyl ether), Triton (registered trademark) X-114 (polyoxyethylene(8)octylphenyl ether) and other polyoxyethylene p-tert-octylphenyl ethers (Triton series surfactants); polyoxyethylene sorbitan fatty acid esters such as Tween (registered trademark) 85; dodecyl-β-D-maltose; octyl-β-D-glucoside; Nonidet (registered trademark) P-40 (octylphenoxy poly(ethyleneoxy)ethanol) and Nonidet (registered trademark) P-40 substitutes; Tergitol (registered trademark) NP-10 Surfactant (nonylphenol ethoxylate); IGEPAL (registered trademark) CA-630 (octylphenoxy poly(ethyleneoxy)ethanol); Emulgen (registered trademark) 108 (polyoxyethylene lauryl ether), Emulgen (registered trademark) 109P; Brij (registered trademark) 96 polyethylene glycol monooleyl ether (n = about 2), etc. can be used. In addition, amphoteric surfactants can be synthesized or commercially available products can also be used. As commercially available products, CHAPS (3-(3-cholamidopropyl)dimethylammonio-1-propane sulfonate), alkyl polyaminoethyl glycine chloride; sodium dodecyl sulfate, etc. can be used. The measurement reagent 22 contains the hemolytic reagent, whereby the hemolytic reagent hemolyzes the blood to eliminate the influence of blood cells, and the measurement accuracy of the component to be measured in the blood (in the present embodiment, the concentration measurement accuracy of glucose) can be improved.

[0058] The composition (content) of the hemolytic reagent in the measurement reagent 22 can be appropriately selected according to the sample volume (total blood volume). The composition (content) of the hemolytic agent in the measurement reagent 22 (in terms of solid component conversion), for example, is 1 to 10% by volume relative to 1.0 μL of the whole blood sample. In addition, when the shape becomes that of the component measurement chip 2, the content of the hemolytic reagent is 10 to 50% by mass, preferably 20 to 40% by mass, relative to the total amount of the measurement reagent (solid component). If it is such an amount, for example, a sensor that can sufficiently hemolyze a whole blood sample with a hematocrit of 20 to 70% can be obtained. In addition, when the measurement reagent 22 contains two or more hemolytic agents, the content of the above hemolytic agent refers to the total amount of the hemolytic reagents incorporated.

[0059] Examples of the oxidation reagent in the present embodiment include nitrite and the like. Since the measurement reagent 22 contains an oxidation reagent, the oxidation reagent oxidizes reduced hemoglobin (especially the reduced hemoglobin that leaks out of red blood cells due to hemolysis), thereby preventing false color development caused by the reaction of hemoglobin with the color-developing reagent. As nitrite, for example, sodium nitrite, potassium nitrite, calcium nitrite, ammonium nitrite, etc. can be used. From the viewpoints of high stability and versatility, sodium nitrite and potassium nitrite are preferred, and sodium nitrite is more preferred. Nitrite can be used alone or in combination of two or more.

[0060] The content of nitrite in the measurement reagent 22 is, for example, 0.8 to 10.0 parts by mass, preferably 1.5 to 7.5 parts by mass, more preferably 2.0 parts by mass or more and less than 5.0 parts by mass, relative to 100 parts by mass of the total amount of the reagent (solid component). In addition, when the measurement reagent 22 contains two or more nitrites, the content of the above nitrite refers to the total amount of the incorporated nitrites.

[0061] In addition, the content of nitrite is preferably 50 moles or less relative to 1 mole of the color-developing reagent.

[0062] In addition, the measurement reagent 22 may also contain a buffer such as a phosphate buffer or various stabilizers. However, it is also possible not to contain a hemolytic reagent, an oxidation reagent, or a buffer in the measurement reagent 22. In addition, the types and components of the reagents contained in the measurement reagent 22 are not limited to these.

[0063] As Figure 2As shown, when measuring the component to be measured by the component measuring device 1, the component measuring chip 2 is installed in the chip mounting portion 10b. Further, when blood is supplied to the supply portion 24 provided at one end of the component measuring chip 2, the blood moves in the flow path 23 due to, for example, capillary action, reaches the holding position of the measurement reagent 22 in the flow path 23, and at this holding position, glucose in the blood reacts with the measurement reagent 22. Then, at the above-described holding position in the flow path 23, a mixture X containing a coloring component is generated. The so-called colorimetric component measuring device 1 irradiates the mixture X containing the coloring component with irradiation light, detects the amount of transmitted light (or the amount of reflected light) thereof, and obtains a detection signal related to the intensity of the color development corresponding to the blood concentration. Then, the component measuring device 1 can measure the component to be measured by referring to a calibration line prepared in advance. In addition, the component measuring device 1 of the present embodiment measures the glucose concentration in the plasma component of the blood as described above.

[0064] Figure 6 is Figures 1 to 3 an electrical block diagram of the component measuring device 1 shown in the figure. For ease of explanation, in Figure 6 the figure, a cross-section of the component measuring chip 2 shown in a state of being installed in the component measuring device 1 is also shown (the same cross-section as Figure 5 the figure). In addition, in Figure 6 the figure, an enlarged portion that magnifies the vicinity of the component measuring chip 2 is also shown in the upper left. Hereinafter, the component measuring device 1 will be described in more detail.

[0065] As Figure 6 shown, in addition to the above-described constituent elements, the component measuring device 1 further includes an arithmetic unit 60, a memory 62, a power supply circuit 63, and a measurement optical system 64.

[0066] The arithmetic unit 60 is composed of an MPU (Micro-Processing Unit) or a CPU (Central Processing Unit), and can realize the control operations of each part by reading out and executing programs stored in the memory 62 and the like. The memory 62 is composed of a volatile or non-volatile non-transitory storage medium, and is configured to be able to read and write various data (including programs) required to execute the component measurement method shown here. The power supply circuit 63 supplies power to each part in the component measuring device 1 including the arithmetic unit 60 or stops the supply according to the operation of the power button 13.

[0067] The measurement optical system 64 is an optical system capable of obtaining the optical characteristics of a mixture X containing a coloring component generated by a coloring reaction between glucose in blood and a coloring reagent contained in the measurement reagent 22. Specifically, the measurement optical system 64 includes a light emitting unit 66, a light emission control circuit 70, a light receiving unit 72, and a light reception control circuit 74.

[0068] The light emitting unit 66 includes a plurality of light sources. Specifically, the light emitting unit 66 of the present embodiment includes five light sources that emit light with different spectral emission characteristics (for example, visible light, infrared light). More specifically, the light emitting unit 66 of the present embodiment includes a first light source 67, a second light source 68a, a third light source 68b, a fourth light source 68c, and a fifth light source 68d. In Figure 6 order to facilitate explanation, a positional relationship in which the five light sources are arranged in a row is shown in the figure to illustrate the five light sources of the first light source 67 to the fifth light source 68d, but this is different from the actual positional relationship of the first light source 67 to the fifth light source 68d. The actual positional relationship of the first light source 67 to the fifth light source 68d is Figure 2 and Figure 3 the positional relationship shown. The details of the actual positional relationship of the first light source 67 to the fifth light source 68d will be described later (see Figure 8 ).

[0069] The peak wavelengths of the light emitted from the first light source 67 to the fifth light source 68d are λ1 to λ5, respectively. As the first light source 67 to the fifth light source 68d, various light emitting elements such as light emitting diode (LED) elements, organic electroluminescence (EL (Electro-Luminescence)) elements, inorganic EL elements, and laser diode (LD (Laser Diode)) elements can be applied. As the first light source 67 to the fifth light source 68d, considering versatility and the like, it is easy to use the above-mentioned LED elements. Hereinafter, the above-mentioned "peak wavelength" will be used as the wavelength of the light emitted from each light source for explanation. For the sake of convenience of explanation, the peak wavelength λ1 of the first light source 67 is recorded as "first specified wavelength λ1", the peak wavelength λ2 of the second light source 68a is recorded as "second specified wavelength λ2", the peak wavelength λ3 of the third light source 68b is recorded as "third specified wavelength λ3", the peak wavelength λ4 of the fourth light source 68c is recorded as "fourth specified wavelength λ4", and then the peak wavelength λ5 of the fifth light source 68d is recorded as "fifth specified wavelength λ5".

[0070] As Figure 2 , Figure 6As shown, the light-receiving unit 72 of the present embodiment is composed of a single light-receiving element in which the various-component measurement chip 2 and the light-emitting unit 66 are arranged opposite to each other. The light-receiving unit 72 receives the transmitted light that irradiates the mixture X generated at the holding position of the measurement reagent 22 on the component measurement chip 2 from the first light source 67 to the fifth light source 68d of the light-emitting unit 66 and passes through the component measurement chip 2. As the light-receiving unit 72, various photoelectric conversion elements including a PD (Photo Diode) element, a photoconductor (photosensitive element), and a phototransistor can be applied.

[0071] The light-emitting control circuit 70 supplies drive power signals to the first light source 67 to the fifth light source 68d respectively, so that the first light source 67 to the fifth light source 68d are turned on or off at a predetermined interval. The light-receiving control circuit 74 obtains a digital signal (hereinafter referred to as a detection signal) by performing logarithmic conversion and A / D conversion on the analog signal output from the light-receiving unit 72.

[0072] Figure 7 is Figure 6 The functional block diagram of the arithmetic unit 60 shown. The arithmetic unit 60 realizes the respective functions of a measurement instruction unit 76 that instructs a measurement operation based on the measurement optical system 64, and a concentration measurement unit 77 that measures the concentration of the component to be measured using various data.

[0073] The concentration measurement unit 77 includes an absorbance acquisition unit 78, an absorbance correction unit 83, and a component-to-be-measured calculation unit 84.

[0074] In Figure 7 it, measured value data 85, correction coefficient data 86, and calibration line data 90 are stored in the memory 62. The measured value data 85 includes the absorbances of the mixture X at the first specified wavelength λ1 to the fifth specified wavelength λ5 measured by the measurement optical system 64, that is, the first measured value D1 to the fifth measured value D5. The correction coefficient data 86 includes a set of correction coefficients related to the absorbance of the mixture X at each of the second specified wavelength λ2 to the fifth specified wavelength λ5. The calibration line data 90 includes a calibration line indicating the relationship between the absorbance of the coloring component in the mixture X obtained by correcting the absorbance of the mixture X measured at the first specified wavelength λ1 using the correction coefficient data 86 and various physical quantities (for example, glucose concentration), or a calibration line indicating the relationship between the absorbance of hemoglobin in the mixture X and the hematocrit value, etc. The "hematocrit value" refers to the value representing the volume ratio of the blood cell components in the blood to the blood (whole blood) as a percentage.

[0075] Details will be described later. However, the component measurement device 1 measures a component to be measured in blood based on the optical characteristics of a mixture X containing a colored component generated by a color reaction between the component to be measured in blood and a reagent. Specifically, the component measurement device 1 uses irradiation light of a second specified wavelength λ2 to a fifth specified wavelength λ5 to estimate the amount of noise other than the colored component included in a first measured value D1 of the absorbance of the mixture X measured by irradiating the mixture X with irradiation light of a first specified wavelength λ1 as a measurement wavelength. More specifically, the component measurement device 1 estimates the above-mentioned amount of noise using second measured values D2 to fifth measured values D5 of the absorbance of the mixture X measured by irradiating the mixture X with irradiation light of the second specified wavelength λ2 to the fifth specified wavelength λ5, measures the absorbance of the colored component, and further measures the component to be measured.

[0076] Here, Figure 8 is a diagram showing the positional relationship of a first light source 67 that emits irradiation light of a first specified wavelength λ1 irradiated to the mixture X, a second light source 68a that emits irradiation light of a second specified wavelength λ2 irradiated to the mixture X, a third light source 68b that emits irradiation light of a third specified wavelength λ3 irradiated to the mixture X, a fourth light source 68c that emits irradiation light of a fourth specified wavelength λ4 irradiated to the mixture X, and a fifth light source 68d that emits irradiation light of a fifth specified wavelength λ5 irradiated to the mixture X. In addition, Figure 8 represents the positional relationship of the first light source 67 to the fifth light source 68d when viewed from the upper surface (refer to Figure 1 ) side of the component measurement device 1. In addition, in Figure 8 , for ease of explanation, the position of a light receiving portion 72 in a flow path 23 of the component measurement chip 2 is indicated by a two-dot chain line. In the present embodiment, the mixture X is generated at the holding position in the flow path 23 and in the vicinity thereof.

[0077] As Figure 2 , Figure 3 , Figure 8 shown, the first light source 67 to the fifth light source 68d are disposed opposite to the mixture X in the flow path 23 of the blood. More specifically, the first light source 67 to the fifth light source 68d in the present embodiment are disposed opposite in a direction orthogonal to both the flow direction A and the flow path width direction B (in the present embodiment, the same direction as the thickness direction C of the component measurement chip 2) at the holding position of the measurement reagent 22 in the flow path 23 of the blood.

[0078] In addition, as Figure 3 , Figure 8As shown, the first light source 67 and the second light source 68a are arranged along the flow path width direction B orthogonal to the blood flow direction A at the position of the mixture X in the blood flow path 23. With such a structure, it is easy to set the first irradiation position SL1 (refer to Figure 9 ) of the irradiation light from the first light source 67 in the mixture X and the second irradiation position SL2 (refer to Figure 9 ) of the irradiation light from the second light source 68a in the mixture X at positions that at least partially overlap in the flow path width direction B.

[0079] Here, Figure 9 is a diagram showing the first irradiation position SL1 to the fifth irradiation position SL5 of the first light source 67 to the fifth light source 68d on the mixture X when viewed from the upper surface (refer to Figure 1 ) side of the component measuring device 1. As Figure 9 shown, in the present embodiment, the first irradiation position SL1 of the irradiation light from the first light source 67 in the mixture X and the second irradiation position SL2 of the irradiation light from the second light source 68a in the mixture X overlap in the flow path width direction B. When such a structure is formed, even if reaction unevenness occurs in the color reaction of the blood due to the influence of the blood flow in the flow path 23 and according to the position of the reagent in the flow direction A, it is possible to suppress the deviation of the measurement result caused by this reaction unevenness. The above-mentioned reaction unevenness is due to the possible gradient of the blood cell amount generated in the flow direction A. The gradient of the blood cell amount generated in the flow direction A may be caused by the dissolution of the measurement reagent 22 when the blood supplied from one end of the flow path 23 moves along the flow direction A and comes into contact with the measurement reagent 22 to cause a color reaction. When the measurement reagent 22 dissolves, mainly the plasma component in the blood components is taken into the measurement reagent 22, and the mixture X is generated. As a result, the ratio of the blood cell component becomes high around the mixture X. The blood enters in the flow direction A. Therefore, in the gap 23a, the blood cell amount is larger on the downstream side than on the upstream side in the flow direction A. That is, a gradient of the blood cell amount is generated in the gap 23a. Due to this gradient of the blood cell amount, the above-mentioned reaction unevenness may occur. It is difficult to generate a gradient of the blood cell amount in the flow path width direction B.

[0080] As Figure 9As shown, in the present embodiment, the regions of the first irradiation position SL1 and the second irradiation position SL2 overlap in the flow path width direction B. That is, in the present embodiment, the first irradiation position SL1 and the second irradiation position SL2 are positions that are substantially equal in the flow direction A. However, the first irradiation position SL1 and the second irradiation position SL2 are not limited to the above position relationship, as long as at least a part of them overlaps in the flow path width direction B. However, as in the present embodiment, if the structure is such that the regions of the irradiation positions of both overlap in the flow path width direction B, compared with the structure where only a part overlaps in the flow path width direction B, the deviation of the measurement result caused by the above reaction unevenness can be further suppressed.

[0081] Moreover, in the present embodiment, the first irradiation position SL1 and the second irradiation position SL2 not only overlap in the flow path width direction B, but also a part of them overlaps in the flow direction A. In this way, the first irradiation position SL1 and the second irradiation position SL2 can be made more consistent, and the deviation of the measurement result due to the difference in the measurement position in the mixture X can be suppressed. More preferably, the first irradiation position SL1 and the second irradiation position SL2 overlap in the region in the flow direction A, that is, the first irradiation position SL1 and the second irradiation position SL2 are positions that are substantially equal in the flow path width direction B.

[0082] In addition, in the present embodiment, as Figure 3 , Figure 8 shown, the first light source 67, the second light source 68a, and the third light source 68b are arranged along the flow path width direction B with the first light source 67 as the center. If such an arrangement is adopted, not only for the two irradiation positions of the first irradiation position SL1 of the first light source 67 and the second irradiation position SL2 of the second light source 68a, but also for the two irradiation positions of the first irradiation position SL1 and the third irradiation position SL3 of the third light source 68b, it is easy to set positions that overlap at least in part in the flow path width direction B.

[0083] Furthermore, as Figure 9 shown, in the present embodiment, the irradiation light from the first light source 67 at the first irradiation position SL1 in the mixture X and the irradiation light from the third light source 68b at the third irradiation position SL3 in the mixture X overlap in the flow path width direction B. When such a structure is formed, similarly to the relationship between the above first irradiation position SL1 and the second irradiation position SL2, even if there is reaction unevenness in the color reaction with the blood due to the influence of the blood flow in the flow path 23 and according to the position of the reagent in the flow direction A, the deviation of the measurement result caused by this reaction unevenness can be suppressed.

[0084] As Figure 9As shown, in the present embodiment, the first irradiation position SL1 and the third irradiation position SL3 overlap in the region in the flow path width direction B. That is, in the present embodiment, the first irradiation position SL1 and the third irradiation position SL3 are positions that are substantially equal in the flow direction A. However, the first irradiation position SL1 and the third irradiation position SL3 are not limited to the above-described positional relationship, and any positional relationship in which at least a part overlaps in the flow path width direction B is acceptable. However, as in the present embodiment, if the structure is such that the regions of the irradiation positions of both overlap in the flow path width direction B, compared with the structure in which only a part overlaps in the flow path width direction B, it is possible to further suppress the deviation of the measurement result caused by the above-described reaction non-uniformity.

[0085] In addition, in the present embodiment, the first irradiation position SL1 and the third irradiation position SL3 not only overlap in the flow path width direction B, but also a part overlaps in the flow direction A. In this way, the first irradiation position SL1 and the third irradiation position SL3 can be made more consistent, and it is possible to suppress the deviation of the measurement result due to the difference in the measurement position in the mixture X. More preferably, the regions of the first irradiation position SL1 and the third irradiation position SL3 overlap in the flow direction A, that is, the first irradiation position SL1 and the third irradiation position SL3 are positions that are substantially equal in the flow path width direction B.

[0086] Here, as Figure 9 shown, the second irradiation position SL2 and the third irradiation position SL3 of the present embodiment overlap in the flow path width direction B. More specifically, the regions of the second irradiation position SL2 and the third irradiation position SL3 of the present embodiment overlap in the flow path width direction B. Or, any structure in which at least a part overlaps in the flow path width direction B is acceptable. However, as in the present embodiment, if the structure is such that the regions of the irradiation positions of both overlap in the flow path width direction B, compared with the structure in which only a part overlaps in the flow path width direction B, it is possible to further suppress the deviation of the measurement result caused by the above-described reaction non-uniformity.

[0087] In addition, in the present embodiment, the regions of the second irradiation position SL2 and the third irradiation position SL3 not only overlap in the flow path width direction B, but also a part overlaps in the flow direction A. In this way, the second irradiation position SL2 and the third irradiation position SL3 can be made more consistent, and it is possible to suppress the deviation of the measurement result due to the difference in the measurement position in the mixture X. More preferably, the regions of the second irradiation position SL2 and the third irradiation position SL3 overlap in the flow direction A, that is, the second irradiation position SL2 and the third irradiation position SL3 are positions that are substantially equal in the flow path width direction B.

[0088] As described above, it is preferable that the first light source 67 to the third light source 68b are arranged along the flow path width direction B, and the regions of the first irradiation position SL1 to the third irradiation position SL3 overlap in the flow path width direction B. More preferably, the regions of the first irradiation position SL1 to the third irradiation position SL3 also overlap in the flow direction A.

[0089] In the present embodiment, the first light source 67 and the second light source 68a are arranged adjacent to each other in the flow path width direction B, and there is no gap between the first light source 67 and the second light source 68a where other light sources can be arranged. In addition, the first light source 67 and the third light source 68b are arranged adjacent to each other in the flow path width direction B, and there is no gap between the first light source 67 and the third light source 68b where other light sources can be arranged. Thus, the first light source 67, the second light source 68a, and the third light source 68b are arranged adjacent to each other in the flow path width direction B without interposing other light sources therebetween. Therefore, it is easy to realize a structure in which the regions of the first irradiation position SL1, the second irradiation position SL2, and the third irradiation position SL3 overlap in the flow direction A.

[0090] Next, the positional relationship between the first light source 67 and the fourth light source 68c and the fifth light source 68d will be described. As Figure 2 , Figure 8 shown, the first light source 67 and the fourth light source 68c of the present embodiment are arranged along the flow direction A. In addition, as Figure 2 , Figure 8 shown, the first light source 67 and the fifth light source 68d of the present embodiment are arranged along the flow direction A. More specifically, the first light source 67, the fourth light source 68c, and the fifth light source 68d are arranged along the flow direction A with the first light source 67 at the center.

[0091] As described above, the second light source 68a and the third light source 68b are arranged adjacent to the first light source 67 in the flow path width direction B. In order to suppress the deviation of the measurement result caused by the flow of blood in the flow path 23, it is also preferable to arrange the fourth light source 68c and the fifth light source 68d along the flow path width direction B with the first light source 67. However, in the case where the fourth light source 68c and the fifth light source 68d are arranged along the flow path width direction B with the first light source 67, due to the presence of the second light source 68a and the third light source 68b, the first light source 67 cannot be arranged adjacent to the fourth light source 68c and the fifth light source 68d respectively. Therefore, the distances between the first light source 67 and the fourth light source 68c and the fifth light source 68d in the flow path width direction B are larger than the distances between the first light source 67 and the second light source 68a and the third light source 68b in the flow path width direction B respectively. If this distance becomes larger, it is difficult to overlap the first irradiation position SL1 of the first light source 67, the fourth irradiation position SL4 of the fourth light source 68c, and the fifth irradiation position SL5 of the fifth light source 68d in the flow direction A. That is, it is likely to be a structure in which the first irradiation position SL1 does not overlap with the fourth irradiation position SL4 and the fifth irradiation position SL5 at all. In the case where the first irradiation position SL1 does not overlap with the fourth irradiation position SL4 and the fifth irradiation position SL5, the measurement parts of the absorbance are different, so the accuracy of the measurement result of the component to be measured may be reduced. The fourth light source 68c and the fifth light source 68d may be tilted or the like to overlap the first irradiation position SL1 of the first light source 67, the fourth irradiation position SL4 of the fourth light source 68c, and the fifth irradiation position SL5 of the fifth light source 68d. However, in this case, the difference in the incident angles of the irradiation light from the first light source 67 to the mixture X and the irradiation lights from the fourth light source 68c and the fifth light source 68d to the mixture X becomes larger. When the difference in the incident angles becomes larger, the difference in the optical path lengths of the irradiation light from the first light source 67 in the mixture X and the irradiation lights from the fourth light source 68c and the fifth light source 68d in the mixture X becomes larger. Also, the interface reflection of the irradiation light from the first light source 67 is different from the interface reflections of the irradiation lights from the fourth light source 68c and the fifth light source 68d. The difference in the optical path lengths and the difference in the interface reflections affect the measured value of the absorbance. That is, the estimation accuracy of the noise amount in the measured value of the absorbance based on the irradiation light of the first light source 67 may be reduced.

[0092] Therefore, in the present embodiment, the first light source 67 and the fourth light source 68c are arranged along the flow direction A such that the first irradiation position SL1 and the fourth irradiation position SL4 overlap in a region when the difference in the incident angles to the mixture X is equal to or less than a specified value. More specifically, there is no gap between the first light source 67 and the fourth light source 68c in the flow direction A where another light source can be arranged, and the first light source 67 and the fourth light source 68c are adjacent to each other in the flow direction A. According to this structure, compared with the structure arranged along the flow path width direction B, it is more susceptible to the influence of the blood flow, but by reducing the difference in the incident angles to overlap the irradiation positions, the estimation accuracy of the noise amount can be improved instead.

[0093] The first light source 67 and the fifth light source 68d are also arranged along the flow direction A such that the first irradiation position SL1 and the fifth irradiation position SL5 can overlap in a region when the difference in the incident angles to the mixture X is equal to or less than a specified value. More specifically, there is no gap between the first light source 67 and the fifth light source 68d in the flow direction A where another light source can be arranged, and the first light source 67 and the fifth light source 68d are adjacent to each other in the flow direction A.

[0094] As described above, the first light source 67 is adjacent to the second light source 68a and the third light source 68b in the flow path width direction B, respectively. Therefore, the first irradiation position SL1 can overlap with the second irradiation position SL2 and the third irradiation position SL3 in a region when the difference in the incident angles to the mixture X is equal to or less than a specified value, respectively. That is, the second light source 68a and the third light source 68b in the present embodiment are less susceptible to the influence of the blood flow in relation to the first light source 67, and the irradiation position regions can overlap with the first light source 67 while reducing the difference in the incident angles.

[0095] Here, in the present embodiment, the second light source 68a and the third light source 68b are arranged along the flow path width direction B with respect to the first light source 67, and the second light source 68a and the third light source 68b emit irradiation light of a second specified wavelength λ2 and a third specified wavelength λ3 that have a large influence on the estimation of the noise amount included in the measured value of the absorbance measured by the irradiation light of the first specified wavelength λ1 that passes through the first light source 67. Moreover, the fourth light source 68c and the fifth light source 68d are arranged along the flow direction A with respect to the first light source 67, and the fourth light source 68c and the fifth light source 68d emit irradiation light of a fourth specified wavelength λ4 and a fifth specified wavelength λ5 that have a relatively small influence on the estimation of the above noise amount compared with the second specified wavelength λ2 and the third specified wavelength λ3. By setting such an arrangement, the estimation accuracy of the above noise amount can be improved. The details of the "influence degree" on the estimation of the noise amount will be described later (refer to Figure 14)。In addition, the details will be described later, but the above-mentioned second specified wavelength λ2 and third specified wavelength λ3 are wavelengths belonging to the infrared region, and the above-mentioned fourth specified wavelength λ4 and fifth specified wavelength λ5 are wavelengths belonging to the visible region.

[0096] In addition, as Figure 2 , Figure 3 shown, the light-receiving unit 72 is opposed to the first light source 67 to the fifth light source 68d across the mixture X located in the flow path 23 of the mounted component measurement chip 2 in the thickness direction C, and as described above, receives the transmitted light of the irradiation light from the first light source 67 to the fifth light source 68d passing through the mixture X. Moreover, as Figure 2 , Figure 3 shown, the component measurement device 1 includes a first aperture unit 69a, and the first aperture unit 69a is located between the mixture X and the light-receiving unit 72 to adjust the amount of light reaching the light-receiving unit 72 among the transmitted light passing through the mixture X. As described above, the difference between the incident angle of the irradiation light from the first light source 67 to the mixture X and the incident angles of the irradiation lights from the second light source 68a to the fifth light source 68d to the mixture X affects the estimation accuracy of the noise amount. Therefore, it is preferable to reduce the difference between the incident angle of the irradiation light from the first light source 67 to the mixture X and the incident angles of the irradiation lights from the second light source 68a to the fifth light source 68d to the mixture X. That is, since the increase in the distance T1 in the opposed direction (in Figure 2 , Figure 3 , the same direction as the thickness direction C of the component measurement chip 2) between the first light source 67 to the fifth light source 68d and the first aperture unit 69a improves the estimation accuracy of the noise amount, it is preferable. On the other hand, by reducing the distance T2 in the opposed direction between the first light source 67 to the fifth light source 68d and the light-receiving unit 72, it is possible to improve the light efficiency and miniaturize the component measurement device 1.

[0097] In addition, if the deviation (hereinafter referred to as "measurement field difference") of the regions of the first irradiation position SL1 of the first light source 67 and the second irradiation position SL2 to the fifth irradiation position SL5 of the second light source 68a to the fifth light source 68d is large, the measurement parts do not match, and thus the accuracy of the measurement result of the component to be measured may be reduced. Therefore, it is preferable to reduce this measurement field difference. Therefore, it is preferable to shorten the distance T3 in the opposed direction (in Figure 2 , Figure 3 , the same direction as the thickness direction C of the component measurement chip 2) between the mixture X and the first aperture unit 69a.

[0098] In addition, as Figure 2 , Figure 3As shown, the component measurement device 1 is provided with a second aperture portion 69b, which is located between the first light source 67 to the fifth light source 68d and the mixture X, and adjusts the amount of light reaching the mixture X from the first light source 67 to the fifth light source 68d. It is particularly preferable that the second aperture portion 69b is designed such that light reflected from the inner wall of the second aperture portion 69b (hereinafter referred to as "stray light") among the light emitted from the first light source 67 to the fifth light source 68d does not enter the first aperture portion 69a. It can be considered that the light emitted from the first light source 67 to the fifth light source 68d is attenuated to 5% by one-time wall reflection and disappears through multiple reflections three or more times. Therefore, in the present embodiment, if the stray light reflected from the inner wall of the second aperture portion 69b does not reach the first aperture portion 69b and is reflected by a wall surface somewhere, it will not enter the first aperture portion 69a due to multiple reflections. In addition, in the present embodiment, it is designed that the optical axes of the respective light sources are specularly reflected by the inner wall of the second aperture portion 69b, but in reality, there is diffuse reflection on the inner wall of the second aperture portion 69b, and there is also a prescribed distribution of stray light. Therefore, in the present embodiment, it is preferable that even when a part of the stray light enters the first aperture portion 69a, the above-described distance T4, etc. is set so that the incident angle thereof and the incident angle of the first light source 67 have a difference below a prescribed value.

[0099] In this way, by adjusting the positions of the first aperture portion 69a and the second aperture portion 69b, etc., the difference in the incident angles of the irradiation light and the difference in the measurement fields of view can be made within a prescribed range. However, no lens such as a condenser lens is used in the optical system of the component measurement device 1. When using a lens, the lens can be brought closer to the light source to improve the condensing efficiency, but it is necessary to accurately maintain the positional relationship between the light source and the lens, which requires high assembly accuracy, or an additional process for adjusting the deviation of the positional relationship between the light source and the lens. Therefore, in the component measurement device 1, a structure for improving the measurement accuracy without requiring high assembly accuracy is realized by setting the positions of the first aperture portion 69a and the second aperture portion 69b without using a lens. However, in the optical system of the component measurement device 1, a lens such as a condenser lens can also be used.

[0100] As described above, in the component measurement device 1, by arranging the first light source 67 to the fifth light source 68d in a prescribed configuration, while reducing the influence of the blood flow direction A in the blood flow path 23, the estimation accuracy of the noise amount is improved.

[0101] The component measurement device 1 of the present embodiment is capable of mounting a component measurement chip 2 that divides a flow path 23 through which blood flows and is provided with a measurement reagent 22 containing a coloring reagent that undergoes a coloring reaction with the component to be measured in the blood in the flow path 23. Moreover, the component measurement device 1 of the present embodiment mounts the component measurement chip 2 and measures the component to be measured in the blood based on the optical characteristics of a mixture containing a coloring component generated by the reaction with the component to be measured in the flow path 23. In addition, the component measurement device 1 includes a first light source 67 and second to fifth light sources 68a to 68d that emit irradiation light of a second specified wavelength λ2 to a fifth specified wavelength λ5. The first light source 67 emits irradiation light of a first specified wavelength λ1 that irradiates the mixture X in the flow path 23 of the component measurement chip 2 in the mounted state. The second to fifth light sources 68a to 68d emit irradiation light of the second specified wavelength λ2 to the fifth specified wavelength λ5, which irradiates the mixture X in the flow path 23 of the component measurement chip 2 in the mounted state and is used to estimate the amount of noise caused by interference factors other than the coloring component included in the measured value of the absorbance of the mixture X measured by the amount of transmitted light of the irradiation light from the first light source 67. Moreover, the first light source 67 to the third light source 68b are arranged and disposed along the flow path width direction B orthogonal to the blood flow direction A at the position of the mixture X in the flow path 23 of the component measurement chip 2 in the mounted state.

[0102] Thus, the component measurement device 1 of the present embodiment measures the absorbance of the mixture X in the detachable component measurement chip 2, but it may also have a structure that does not require the detaching and attaching of the component measurement chip 2. However, considering user convenience, environmental aspects, etc., it is preferably configured such that the disposable component measurement chip 2 can be detached and attached to the reusable component measurement device 1.

[0103] As Figure 8 shown, the first light source 67 to the fifth light sources 68d of the present embodiment are held by a thin plate-shaped support member 80. The support member 80 of the present embodiment has a cross-shaped outer shape in a top view, and holds the first light source 67 at the central portion (the intersection of the cross) of the support member 80 in a top view. Moreover, in the support member 80, the second light source 68a is held at a position on one side of the central portion holding the first light source 67 in the flow path width direction B, and the third light source 68b is held at a position on the other side of the flow path width direction B. In addition, in the support member 80, the fifth light source 68d is held at a position in the flow direction A with respect to the central portion holding the first light source 67, and the fourth light source 68c is held at a position on the side opposite to the flow direction A.

[0104] The following describes a method for measuring components: Instead of separating the plasma component containing glucose from the blood, a color reaction of glucose, which is the component to be measured in the blood, with the color reagent in the measuring reagent 22 is carried out using blood (whole blood) and the color reagent, and based on the absorbances at various wavelengths of the entire mixture X obtained through this color reaction, the absorbance at a specified measuring wavelength of the colored component generated by the color reaction of glucose with the color reagent is estimated, and the component to be measured is measured.

[0105] First, refer to Figure 10 and Figure 11 , and mention the problems when estimating the component to be measured in the blood based on the absorbance measurement using blood (whole blood). In the following examples, as the color reagent, a reagent containing a tetrazolium salt (WST-4) and mixed with glucose dehydrogenase (GDH) and an electron mediator was used as the measuring reagent 22.

[0106] Figure 10 The absorption spectra of six mixtures X obtained by reacting six blood specimens with known hematocrit values and glucose concentrations with the measuring reagent 22 are shown. These six blood specimens are designated as the first to sixth specimens. The hematocrit value of the first specimen is 20%, and the glucose concentration is 0 mg / dL (denoted as "Ht20 bg0" in Figure 10 ). The hematocrit value of the second specimen is 20%, and the glucose concentration is 100 mg / dL (denoted as "Ht20 bg100" in Figure 10 ). The hematocrit value of the third specimen is 20%, and the glucose concentration is 400 mg / dL (denoted as "Ht20 bg400" in Figure 10 ). The hematocrit value of the fourth specimen is 40%, and the glucose concentration is 0 mg / dL (denoted as "Ht40 bg0" in Figure 10 ). The hematocrit value of the fifth specimen is 40%, and the glucose concentration is 100 mg / dL (denoted as "Ht40 bg100" in Figure 10 ). The hematocrit value of the sixth specimen is 40%, and the glucose concentration is 400 mg / dL (denoted as "Ht40bg400" in Figure 10 ).

[0107] In addition, Figure 11 the absorption spectra of seven blood specimens with known hematocrit values and glucose concentrations are shown. These seven blood specimens are designated as the first to seventh specimens. The first to sixth specimens are the same as Figure 10The first to sixth specimens shown are the same. The hematocrit value of the seventh specimen is 70%, and the glucose concentration is 100 mg / dL. In addition, since the absorption spectra of blood specimens with equal hematocrit values are roughly the same, three curves with different hematocrit values are shown only in Figure 11 . Specifically, only the curves with hematocrit values of 20% (denoted as “Ht20” in Figure 11 ), 40% (denoted as “Ht40” in Figure 11 ), and 70% (denoted as “Ht70” in Figure 11 ) are shown.

[0108] Generally, when a sample contains components other than the coloring component that is the object of absorbance measurement, there is a tendency for the measurement result of the concentration of the component to be measured based on the absorbance of the coloring component to be affected by optical phenomena as interference factors (noise). For example, due to “light scattering” caused by blood cell components in blood, the surface of the component measurement chip, or fine particles such as dust adhering to the component measurement chip, or “light absorption” caused by a pigment component (specifically, hemoglobin) different from the coloring component to be measured, there is a tendency to measure an absorbance larger than the true value.

[0109] Specifically, Figure 11 the absorption spectrum of the blood specimen shown has two peaks centered around 540 nm and around 570 nm. These two peaks are mainly caused by the light absorption of oxyhemoglobin in red blood cells. In addition, in the absorption spectrum of the blood specimen shown in Figure 11 , in the wavelength region above 600 nm, as the wavelength becomes longer, the absorbance decreases gently in a roughly linear manner. This roughly linear part is mainly caused by the light scattering of blood cell components.

[0110] In other words, for the absorbance of the blood specimen in the wavelength region on the longer wavelength side compared to around 600 nm, the influence of light scattering caused by blood cell components, etc. is dominant. For the absorbance of the blood specimen in the wavelength region on the shorter wavelength side compared to around 600 nm, the influence of light absorption caused by hemoglobin is greater than the influence of light scattering caused by blood cell components, etc.

[0111] On the other hand, in the absorption spectrum of mixture X shown in Figure 10 , similar to the absorption spectrum of the blood shown in Figure 11 , there is a trend curve in which the absorbance gradually decreases as the wavelength becomes longer. However, Figure 10 the absorption spectrum of mixture X shown in Figure 11Compared with the curve shown in FIG. 1 , the absorbance increases around 600 nm to 700 nm, which is the wavelength region of visible light. The increase in absorbance around 600 nm to 700 nm is mainly caused by the absorption characteristics of the coloring component generated by the coloring reaction between glucose in the blood and the coloring reagent in the measurement reagent 22.

[0112] Thus, in addition to the color-forming component to be measured, a Figure 11 In order to accurately measure the absorbance of the coloring component of a blood mixture X having the absorption characteristics shown, it is necessary to remove interfering factors (noise) such as light scattering caused by blood cell components or light absorption caused by hemoglobin from the actual measured value of the absorbance at a specified measurement wavelength (e.g., 650nm).

[0113] More specifically, it is necessary to estimate the amount of interfering factors (noise) such as light scattering caused by blood cell components or light absorption caused by hemoglobin at a specified measurement wavelength (for example, 650nm) at which the light absorption rate of the color component to be measured is high, and correct the actual measured value of the absorbance at this measurement wavelength.

[0114] Hereinafter, the component measurement method executed by the component measurement device 1 will be described in detail.

[0115] The component measurement device 1 can measure the measured component in the blood based on the optical properties of the mixture X containing the coloring component generated by the coloring reaction between the blood and the measurement reagent 22. Specifically, in this embodiment, the concentration of glucose contained in the plasma component in the blood is measured.

[0116] Furthermore, the component measuring device 1 corrects the measured value of the absorbance of the mixture X at the measuring wavelength based on the blood cell components in the blood, the optical properties caused by the surface of the component measuring chip 2 or the fine particles such as dust attached to the component measuring chip 2, and the ratio of reduced hemoglobin to oxidized hemoglobin in the red blood cells, thereby calculating the glucose concentration in the blood. In other words, the component measuring method performed by the component measuring device 1 includes a step of correcting the measured value of the absorbance of the mixture X at the measuring wavelength based on the blood cell components in the blood, the information of scattered light caused by the surface of the component measuring chip 2 or the fine particles such as dust attached to the component measuring chip 2, and the ratio of reduced hemoglobin to oxidized hemoglobin in the red blood cells.

[0117] Furthermore, the component measuring device 1 is configured to correct the glucose concentration in the blood based on the oxygen saturation of the blood in addition to the above correction. Thus, the component measuring device 1 can correct the measured value of the measured component in consideration of the oxygen saturation that is different for each blood sample, and as a result, can improve the measurement accuracy of the measured component in the blood.

[0118] Figure 12 Shows the absorption coefficient of reduced hemoglobin (denoted as "Hb" in Figure 12 ), and the absorption coefficient of oxyhemoglobin (denoted as "HbO Figure 12 " in 2 ). Hemoglobin in red blood cells mainly contains oxyhemoglobin bound to oxygen and reduced hemoglobin that dissociates oxygen in places with low oxygen partial pressure. Oxyhemoglobin plays the role of binding oxygen with reduced hemoglobin through the lungs and transporting oxygen to the body through arteries, and can be mostly confirmed in arterial blood. For example, when collecting blood from the fingertip, since it is the blood of capillaries, the amount of this oxyhemoglobin is relatively large. On the contrary, reduced hemoglobin can be mostly confirmed in venous blood.

[0119] As the prior art, generally, regardless of the ratio of reduced hemoglobin to oxyhemoglobin, for example, the hematocrit value is used to correct the absorbance obtained at the measurement wavelength corresponding to the coloring component to be measured. However, as Figure 12 shown, the absorption coefficient of reduced hemoglobin is inconsistent with that of oxyhemoglobin, and the absorption amount of reduced hemoglobin and the absorption amount of oxyhemoglobin vary according to the wavelength. Figure 13 Shows the ratio of the absorption coefficient of oxyhemoglobin to the absorption coefficient of reduced hemoglobin. For example, when the measurement wavelength for measuring the absorbance of the coloring component to be measured is 650 nm, the absorption coefficient of reduced hemoglobin is about 0.9, and the absorption coefficient of oxyhemoglobin is about 0.09. That is, the absorption coefficient of oxyhemoglobin is equivalent to about 10% of the absorption coefficient of total hemoglobin. In order to more accurately estimate the absorbance from the coloring component to be measured, it is important to consider the ratio of reduced hemoglobin to oxyhemoglobin.

[0120] Therefore, in the component measurement device 1, the measurement wavelength for measuring the absorbance of the coloring component contained in the mixture X is set to 650 nm, and correction is performed by removing, as interference factors (noise), the influence caused by light scattering of blood cell components, etc., or the influence of light absorption of hemoglobin after further considering the ratio of reduced hemoglobin to oxyhemoglobin, from the measured value of the absorbance of the mixture X measured at this measurement wavelength. Thus, the absorbance of the coloring component contained in the mixture X is estimated, and the glucose concentration is calculated using a calibration line representing the relationship between the estimated absorbance and the glucose concentration.

[0121] Hereinafter, the component measurement method performed by the component measurement device 1 will be described in more detail.

[0122] First, although the absorbance of the colored component generated by the color-developing reagent in the measurement reagent 22 used in the present embodiment has a peak near 600 nm due to the color reaction with glucose in blood, the measurement wavelength for measuring the absorbance of the colored component in the present embodiment is set to 605 nm.

[0123] The measurement wavelength for measuring the absorbance of the colored component to be measured may be a wavelength at which the light absorption rate of the colored component is relatively large and the influence caused by the light absorption of hemoglobin is relatively small. Specifically, it is set to correspond to the full width at half maximum region of the peak wavelength region in the absorption spectrum of the colored component to be measured, and belongs to the wavelength range W3 (see Figure 10 , Figure 11 ) where the ratio of the absorbance based on the light absorption of hemoglobin to the total absorbance is relatively small. The wavelength range "corresponding to the full width at half maximum region of the peak wavelength region" means the range from the wavelength representing the half value on the short wavelength side to the wavelength representing the half value on the long wavelength side when determining the full width at half maximum region of the peak wavelength region in the absorption spectrum. The absorption spectrum of the colored component to be measured in the present embodiment has a peak wavelength near 600 nm, and approximately 500 nm to approximately 700 nm is the wavelength range corresponding to the full width at half maximum region. In addition, the influence caused by the light absorption of hemoglobin in the total absorbance is relatively small in the wavelength region above 600 nm. Therefore, in the present embodiment, the wavelength range W3 corresponding to the full width at half maximum region of the peak wavelength region in the absorption spectrum of the colored component to be measured and where the ratio of the absorbance based on the light absorption of hemoglobin to the total absorbance is relatively small is 600 nm or more and 700 nm or less. Therefore, as the measurement wavelength, it is not limited to 605 nm in the present embodiment, and other wavelengths belonging to the range of 600 nm to 700 nm may be set as the measurement wavelength. Since the signal representing the absorbance of the colored component is strong, and the wavelength range where the ratio of the absorbance based on the light absorption of hemoglobin to the total absorbance can be minimized as much as possible can measure the absorbance from the colored component more accurately, it is preferably to set a wavelength near 650 nm, which is slightly longer than 600 nm, the peak wavelength in the absorption spectrum of the colored component, as the measurement wavelength. More specifically, it is preferably to set the measurement wavelength to a wavelength belonging to the range of 600 nm to 680 nm, and more preferably to a wavelength belonging to the range of 600 nm to 670 nm. As in the present embodiment, it is particularly preferably 605 nm.

[0124] Also, in the present embodiment, a color-developing reagent is used in which the full width at half maximum region in the peak wavelength region of the color-forming component is from about 500 nm to about 700 nm. However, a color-developing reagent having a full width at half maximum region in the peak wavelength region different from this range may also be used. However, as described above, it is preferable to consider the light absorption characteristics of hemoglobin so that the wavelength region (below 600 nm) where the absorbance based on the light absorption of hemoglobin is large does not overlap with the measurement wavelength in the absorption spectrum of the color-forming component.

[0125] Hereinafter, a method for estimating the absorbance of the color-forming component at 605 nm, which is the measurement wavelength in the present embodiment, will be described. The component measurement device 1 actually measures the absorbances of the mixture X at four second specified wavelengths λ2 to fifth specified wavelengths λ5 different from the measurement wavelength (605 nm), and uses these four second measured values D2 to fifth measured values D5 and the correction coefficient data 86 to correct the first measured value D1 of the absorbance of the mixture X at the measurement wavelength, and estimates the absorbance of the color-forming component at the measurement wavelength. The measurement wavelength in the present embodiment refers to the first specified wavelength λ1 described above.

[0126] Specifically, the component measurement device 1 uses two second measured values D2 and third measured values D3 of the absorbances of the mixture X at two second specified wavelengths λ2 and third specified wavelengths λ3 on the longer wavelength side compared to the first specified wavelength λ1, which is the measurement wavelength, and two fourth measured values D4 and fifth measured values D5 of the absorbances of the mixture X at two fourth specified wavelengths λ4 and fifth specified wavelengths λ5 on the shorter wavelength side compared to the first specified wavelength λ1, which is the measurement wavelength, as the above four second measured values D2 to fifth measured values D5.

[0127] More specifically, as the above four second measured values D2 to fifth measured values D5, two second measured values D2 and third measured values D3 of the absorbances of the mixture X at two second specified wavelengths λ2 and third specified wavelengths λ3 on the longer wavelength side compared to the first specified wavelength λ1, which is the measurement wavelength, and which belong to the wavelength region where the influence of light scattering of blood cell components, etc. in the total absorbance is dominant, and two fourth measured values D4 and fifth measured values D5 of the absorbances of the mixture X at two fourth specified wavelengths λ4 and fifth specified wavelengths λ5 on the shorter wavelength side compared to the first specified wavelength λ1, which is the measurement wavelength, and which belong to the wavelength region where the influence of light absorption of hemoglobin in the total absorbance is large.

[0128] In other words, the component measurement device 1 uses the absorbance of the mixture X at the second specified wavelength λ2 and the third specified wavelength λ3, which belong to the long wavelength region compared to the measurement wavelength in the wavelength range (500 to 700 nm in this embodiment) corresponding to the full width at half maximum region of the peak wavelength region in the absorption spectrum of the color-forming component to be measured, as the above-described second measured value D2 and third measured value D3.

[0129] In addition, the component measurement device 1 uses the absorbance of the mixture X at the fourth specified wavelength λ4 and the fifth specified wavelength λ5, which belong to the short wavelength region compared to the measurement wavelength in the wavelength range (500 to 700 nm) corresponding to the full width at half maximum region of the peak wavelength region in the absorption spectrum of the color-forming component to be measured, that is, the fourth measured value D4 and the fifth measured value D5, as the above-described fourth measured value D4 and fifth measured value D5.

[0130] The absorbance acquisition unit 78 of the component measurement device 1 acquires the above-described first measured value D1 to fifth measured value D5. Specifically, irradiation light including the emission wavelengths of the first specified wavelength λ1 to fifth specified wavelength λ5 is irradiated from the first light source 67 to fifth light source 68d of the light emitting unit 66 onto the mixture X. Moreover, the light receiving unit 72 receives the transmitted light that has passed through the mixture X in each irradiation light. Then, the arithmetic unit 60 calculates the absorbance of the mixture X at each wavelength based on the relationship between the irradiation light and the transmitted light, and stores the absorbance of the mixture X at each wavelength, that is, the first measured value D1 to fifth measured value D5, as measured value data 85 in the memory 62. In addition to the absorbance of the mixture X at each wavelength, the arithmetic unit 60 also stores the measured values of the irradiation light amount and the transmitted light amount at each wavelength as measured value data 85 in the memory 62. A series of processes for generating these measured value data 85 can also be repeatedly performed at a specified time interval. The specified time interval is, for example, a 5 millisecond interval, but is not limited thereto. The absorbance acquisition unit 78 of the component measurement device 1 can acquire the measured value data 85 from the memory 62. The method by which the absorbance acquisition unit 78 acquires the first measured value D1 to fifth measured value D5 is not limited to the above method, and can be acquired by various known methods instead of the above method.

[0131] Moreover, the absorbance correction unit 83 of the component measurement device 1 uses the second measured value D2 to fifth measured value D5 to correct the first measured value D1, and estimates the absorbance of the color-forming component at the first specified wavelength λ1 (605 nm in this example) serving as the measurement wavelength.

[0132] In particular, by Figure 10 andFigure 11 It can be seen that in the long-wavelength region W1 where light scattering of blood cell components and the like is dominant, the absorption spectrum of the mixture X is substantially linear. Therefore, if the absorbance at the second specified wavelength λ2, that is, the second measured value D2, and the absorbance at the third specified wavelength λ3, that is, the third measured value D3, can be obtained, then by calculating the slope between the second measured value D2 and the third measured value D3, it is possible to estimate to some extent the absorbance caused by interference factors (noise) other than the absorbance caused by the coloring component at the first specified wavelength λ1 which is the measurement wavelength. In addition to based on the optical characteristics of blood cell components and the like in the blood, the component measuring device 1 calculates the glucose concentration in the blood by considering the ratio of reduced hemoglobin to oxidized hemoglobin in red blood cells. Therefore, in the component measuring device 1, highly accurate correction can be performed by using two wavelengths (the fourth specified wavelength and the fifth specified wavelength) selected according to the ratio of reduced hemoglobin to oxidized hemoglobin.

[0133] Specifically, as the fourth specified wavelength λ4, a wavelength at which the difference in the absorption coefficients of reduced hemoglobin and oxidized hemoglobin becomes equal to or less than a first specified value is used, and as the fifth specified wavelength λ5, a wavelength at which the difference in the absorption coefficients of reduced hemoglobin and oxidized hemoglobin is greater than the above-mentioned first specified value is used. More specifically, as the fourth specified wavelength λ4, a wavelength at which the ratio of the absorption coefficient of oxidized hemoglobin to the absorption coefficient of reduced hemoglobin (refer to Figure 13 ) is equal to or greater than a first threshold which is a specified threshold value is used, and as the fifth specified wavelength λ5, a wavelength at which the ratio of the absorption coefficient of oxidized hemoglobin to the absorption coefficient of reduced hemoglobin is less than the above-mentioned first threshold value is used. In other words, as the fourth specified wavelength λ4 and the fifth specified wavelength λ5, two wavelengths at which the ratio of the absorption coefficient of oxidized hemoglobin to the absorption coefficient of reduced hemoglobin is equal to or greater than the first threshold value and less than the first threshold value are used. Thereby, when the absorbance correction unit 83 corrects the first measured value D1 using the second measured value D2 to the fifth measured value D5, more accurate correction considering the ratio of reduced hemoglobin to oxidized hemoglobin can be performed.

[0134] As two wavelengths selected based on the ratio of reduced hemoglobin to oxidized hemoglobin, it is preferable to use two wavelengths with a large difference in the light absorption of hemoglobin based on the ratio of reduced hemoglobin to oxidized hemoglobin. Therefore, in the present embodiment, as the fourth specified wavelength λ4, a wavelength in which the ratio of the absorption coefficient of oxidized hemoglobin to the absorption coefficient of reduced hemoglobin is 0.8 or more is used, that is, a wavelength belonging to the range of 520 nm to 550 nm or belonging to the range of 565 nm to 585 nm. In addition, as the fifth specified wavelength λ5, it is preferable to use a wavelength in which the ratio of the absorption coefficient of oxidized hemoglobin to the absorption coefficient of reduced hemoglobin is less than 0.8, that is, a wavelength belonging to the range greater than 550 nm and less than 565 nm or belonging to the range greater than 585 nm and less than 600 nm. In the present embodiment, as the fourth specified wavelength λ4, in order to be able to simultaneously estimate the amount of hemoglobin as a whole or the hematocrit value, it is preferable to use a wavelength at which the absorption coefficient of reduced hemoglobin is equal to the absorption coefficient of oxidized hemoglobin, that is, a wavelength around 520 nm, around 545 nm, around 570 nm, or around 580 nm is used in the present embodiment. In addition, as the fifth specified wavelength λ5, it is more preferably around 560 nm where the difference in absorption coefficient is the largest even in the range greater than 550 nm and less than 565 nm, or around 585 to 590 nm where the difference in absorption coefficient is the largest even in the range of 585 nm and 600 nm or less.

[0135] In this way, in the short wavelength region W2 where the light absorption of hemoglobin as a whole varies greatly according to the ratio of reduced hemoglobin to oxidized hemoglobin, by using the fourth specified wavelength λ4 and the fifth specified wavelength λ5 with a large difference in the light absorption of hemoglobin as a whole, it is possible to also take into account the ratio of reduced hemoglobin to oxidized hemoglobin and accurately estimate the absorbance of noise at the first specified wavelength λ1 (605 nm in the present embodiment) as the measurement wavelength. Therefore, according to the component measurement device 1, it is possible to accurately measure the absorbance of the coloring component at the first specified wavelength λ1 as the measurement wavelength, and it is also possible to accurately measure the component to be measured (glucose concentration measurement in the present embodiment).

[0136] In the present embodiment, only the fourth specified wavelength λ4 and the fifth specified wavelength λ5 are set as wavelengths considering the influence of the ratio of reduced hemoglobin to oxidized hemoglobin, but it is not limited thereto. In addition to the fourth specified wavelength λ4 and the fifth specified wavelength λ5, the second specified wavelength λ2 and the third specified wavelength λ3 may also be set as wavelengths considering the influence of the ratio of reduced hemoglobin to oxidized hemoglobin.

[0137] Specifically, as the third specified wavelength λ3 in the long-wavelength region W1 where light scattering of blood cell components and the like is dominant, a wavelength at which the difference between the absorption coefficients of reduced hemoglobin and oxidized hemoglobin is equal to or less than the second specified value is used. Similarly, as the second specified wavelength λ2 in the long-wavelength region W1, a wavelength greater than the second specified value is used. More specifically, as the third specified wavelength λ3, a wavelength at which the ratio of the absorption coefficient of oxidized hemoglobin to the absorption coefficient of reduced hemoglobin is equal to or greater than the above-mentioned first threshold value and equal to or less than the second threshold value is used. Similarly, as the second specified wavelength λ2 in the long-wavelength region W1, a wavelength at which the ratio of the absorption coefficient of oxidized hemoglobin to the absorption coefficient of reduced hemoglobin is preferably less than the above-mentioned first threshold value or greater than the second threshold value is used. Here, the second threshold value refers to another specified threshold value greater than the first threshold value. That is, as the second specified wavelength λ2 and the third specified wavelength λ3, two wavelengths in ranges where the ratio of the absorption coefficient of oxidized hemoglobin to the absorption coefficient of reduced hemoglobin is different are preferably used. Thereby, when the above-mentioned absorbance correction unit 83 corrects the first measured value D1 using the second to fifth measured values D2 to D5, a highly accurate correction that further takes into account the ratio of reduced hemoglobin to oxidized hemoglobin can be performed.

[0138] Particularly in the long-wavelength region W1, the influence brought about by light scattering of blood cell components and the like is dominant, but the influence brought about by light absorption of hemoglobin is also included to the same extent as the measurement wavelength of the component to be measured. Therefore, as the second specified wavelength λ2 and the third specified wavelength λ3, two wavelengths at which the light absorption of hemoglobin varies relatively greatly according to the ratio of reduced hemoglobin to oxidized hemoglobin are preferably used.

[0139] Therefore, in the present embodiment, as the third specified wavelength λ3, it is preferable to use a wavelength in the range of 0.8 or more and 1.56 or less, where the absorption coefficient of reduced hemoglobin and the absorption coefficient of oxidized hemoglobin become a relatively equal ratio, and it is preferable to use a wavelength in the range of 790 nm to 860 nm. Further, as the third specified wavelength λ3, it is also preferable to set 725 to 790 nm, which is in the long wavelength region W1 and where the absorbance of the coloring component included in the total absorbance at the third specified wavelength λ3 is 3% or less, more preferably 1% or less, of the absorbance of the coloring component included in the total absorbance at the measurement wavelength, as the third specified wavelength λ3. In other words, it is particularly preferable to use a wavelength equal to or longer than the wavelength at the end on the long wavelength side of the peak wavelength region of the absorption spectrum of the coloring component. Thereby, the influence of the light absorption of the coloring component can be eliminated, and the noise mainly caused by the light scattering of blood cell components and the like in the long wavelength region W1 can be more accurately estimated. In addition, the "total absorbance" in the "absorbance of the coloring component included in the total absorbance" means the absorbance of the entire mixture. Further, the "absorbance of the coloring component" in the "absorbance of the coloring component included in the total absorbance" means the absorbance of the reactant generated by the color reaction of the component to be measured in the blood and the coloring reagent in the reagent, that is, the absorbance of the coloring component in the mixture.

[0140] Further, as the second specified wavelength λ2, it is preferable to use a wavelength in the range of 725 nm or more and less than 790 nm, where the absorbance of the coloring component included in the total absorbance at the second specified wavelength λ2 is 10% or less, preferably 6% or less, more preferably 1% or less, and further preferably substantially 0%, of the absorbance of the coloring component included in the total absorbance at the measurement wavelength in the long wavelength region W1. That is, as the second specified wavelength λ2, it is more preferable to use a wavelength in the range longer than 860 nm and less than 950 nm, and even within this range, it is particularly preferable to set 940 to 950 nm, where the ratio of reduced hemoglobin to oxidized hemoglobin is larger than that at the third specified wavelength, as the second specified wavelength λ2.

[0141] As described above, the component measuring device 1 can correct the measured value of the absorbance of the mixture X at the measurement wavelength, that is, the first measured value D1, using the measured values of the absorbances of the mixture X at the second specified wavelength λ2 to the fifth specified wavelength λ5, that is, the second measured value D2 to the fifth measured value D5, and can estimate the absorbance of the coloring component at the measurement wavelength.

[0142] Hereinafter, the correction method of the absorbance correction unit 83 of the component measuring device 1 will be described.

[0143] As described above, in the memory 62 of the component measurement device 1, the measured value data 85 of the absorbance of the mixture X at each of the first to fifth specified wavelengths λ1 to λ5 measured by the measurement optical system 64, that is, the first to fifth measured values D1 to D5, a set of correction coefficient data 86 related to the absorbance of the mixture X at each of the second to fifth specified wavelengths λ2 to λ5, and calibration line data 90 indicating the relationship between the absorbance of the coloring component in the mixture X obtained by correcting the absorbance of the mixture X measured at the first specified wavelength λ1 using the correction coefficient data 86 and various physical quantities are stored.

[0144] Based on the measured value data 85 and the correction coefficient data 86 stored in the memory 62, the absorbance correction unit 83 calculates the absorbance of the coloring component at the first specified wavelength λ1 as the measurement wavelength.

[0145] Here, the correction coefficient data 86 is derived by performing regression analysis in advance using the following formula (2).

[0146] B(λ1) = b0 + b1 * B(λ2) + b2 * B(λ3) + b3 * B(λ4) + b4 * B(λ5) (2)

[0147] B(λ) means the absorbance caused by interference factors (noise) other than the absorbance of the coloring component at wavelength λ. By using a variety of blood specimens and performing regression calculations using the above formula (2), the coefficients b0, b1, b2, b3, and b4 are derived. Specifically, in the present embodiment, based on the selection criteria for the above second to fifth specified wavelengths λ2 to λ5, 940 nm is used as the second specified wavelength λ2, 855 nm is used as the third specified wavelength λ3, 520 nm is used as the fourth specified wavelength λ4, and 589 nm is used as the fifth specified wavelength λ5. In addition, this wavelength is the central value of the light source used, and as the actual wavelength width, there is an individual difference of about ±5 to 10 nm with respect to the central value. In addition, based on six blood specimens with different component compositions, blood specimens with hematocrit values adjusted to the range of 10% to 70% are prepared, the absorption spectra of the adjusted blood specimens are measured, and using regression analysis, the coefficients b0, b1, b2, b3, and b4 are derived. In addition, the total number of observations performed this time is 766 times. Moreover, based on these derived coefficients b0 to b4, a set of correction coefficients related to the absorbance of the mixture X at each of the second to fifth specified wavelengths λ2 to λ5 is derived. By using the correction coefficient data 86 including this correction coefficient, it is possible to correct the measured value of the absorbance of the mixture X at 605 nm as the measurement wavelength based on the measured values of the absorbance of the mixture X at 520 nm, 589 nm, 855 nm, and 940 nm, and estimate the absorbance of the coloring component at 605 nm.

[0148] Here, the coefficients b0 to b4 obtained by the above regression calculation can be determined as values inherent to the measurement system, respectively, and are not values that vary according to the hematocrit value. Therefore, the numerical values (measured values) of B(λ2) to B(λ5) used for the regression calculation vary according to the hematocrit value.

[0149] Figure 14 It represents the influence degree (denoted as "W1" in Figure 14 ), of the measured value in the long wavelength region W1, and the influence degree (denoted as "W2" in Figure 14 ), of the measured value in the short wavelength region W2, in the absorbance caused by interference factors (noise) other than the coloring component at the measurement wavelength, that is, the noise amount (hereinafter, also simply referred to as "noise absorbance"). In addition, the "influence degree" mentioned here means the occupancy rate of the data. As Figure 14 shows, when examining the results of the measured data obtained by the above regression calculation, when using the second measured value D2 to the fifth measured value D5 to estimate the noise absorbance at the first specified wavelength λ1 as the measurement wavelength, the second measured value D2 and the third measured value D3 at the second specified wavelength λ2 and the third specified wavelength λ3 in the long wavelength region W1 decrease in influence degree from 92% to 90% as the hematocrit value increases from 10% to 70% (refer to Figure 14 's "W1"). On the other hand, the fourth measured value D4 and the fifth measured value D5 at the fourth specified wavelength λ4 and the fifth specified wavelength λ5 in the short wavelength region W2 increase in influence degree from 8% to 10% as the hematocrit value increases from 10% to 70% (refer to Figure 14 's "W2"). Thus, the influence degrees of the long wavelength region W1 and the short wavelength region W2 used according to the hematocrit value change, and thereby the noise absorbance at the measurement wavelength can be estimated more accurately. As a result, the absorbance of the coloring component at the measurement wavelength can be estimated more accurately. In addition, when the second measured value D2 to the fifth measured value D5 contain the absorption of the coloring component, it is necessary to perform a correction calculation on the second measured value D2 to the fifth measured value D5 to calculate B(λ) as the noise absorbance.

[0150] In addition, in the component measurement device 1, in the short wavelength region W2 where the influence of the light absorption of hemoglobin is overwhelmingly large, and at the wavelength where the absorption coefficient of reduced hemoglobin is equal to the absorption coefficient of oxidized hemoglobin (in Figure 12In the case where the fourth specified wavelength λ4 is 520 nm, 545 nm, 570 nm, or 580 nm, based on the fourth measured value D4, or using the fourth measured value D4 and the long wavelength region W1 where the light scattering of blood cell components and the like has a large influence and the wavelength at which the absorption coefficient of reduced hemoglobin is equal to the absorption coefficient of oxidized hemoglobin (in Figure 12 it is 800 nm), the hematocrit value can be calculated using the second measured value D2. In addition, the hematocrit value can be calculated based on the calibration line of the absorbance of hemoglobin and the hematocrit value stored in the memory 62.

[0151] Refer to Figure 7 , the measured component calculation unit 84 of the component measurement device 1 calculates the measured component (glucose concentration in this embodiment) in the blood based on the first measured value D1 to the fifth measured value D5 obtained by the absorbance acquisition unit 78 and the absorbance of the coloring component at the first specified wavelength λ1 as the measurement wavelength estimated by the absorbance correction unit 83.

[0152] Specifically, the measured component calculation unit 84 calculates the hematocrit value using at least one of the first measured value D1 to the fifth measured value D5 obtained by the absorbance acquisition unit 78. In this embodiment, the measured component calculation unit 84 estimates the absorbance of hemoglobin based on the fourth measured value D4, or based on the fourth measured value D4 and the second measured value D2, and uses the calibration line indicating the relationship between the absorbance of hemoglobin in the mixture X stored in the memory 62 and the hematocrit value to calculate the hematocrit value. Here, when the fourth measured value D4 or the fourth measured value D4 and the second measured value D2 include the absorption of the coloring component, the measured component calculation unit 84 can also perform a correction calculation of subtracting the absorption component of the coloring component from the fourth measured value D4 or the fourth measured value D4 and the second measured value D2, respectively, and calculate the hematocrit value based on the obtained correction value.

[0153] Moreover, the measured component calculation unit 84 calculates the glucose concentration as the measured component based on the absorbance of the coloring component at the first specified wavelength λ1 as the measurement wavelength and the calculated hematocrit value, and uses the calibration line indicating the relationship with the measured component stored in the memory 62.

[0154] And, in this embodiment, the measured component calculation unit 84 is configured to correct the measured value of the measured component calculated as described above based on the absorption information of hemoglobin contained in the blood.

[0155] Hereinafter, a method for correcting the measured component performed by the measured component calculation unit 84 of the component measurement device 1 will be described.

[0156] As described above, in improving the estimation accuracy of the absorbance of the coloring component to be measured, the absorption information of hemoglobin contained in the blood serving as the specimen is important. However, regarding the absorption information of hemoglobin, the oxygen saturation, that is, the ratio of reduced hemoglobin to oxyhemoglobin, is different for each specimen of blood. For example, if it is arterial blood, the oxygen saturation is high, and if it is venous blood, the oxygen saturation is low. When the oxygen saturation varies, the ratio of reduced hemoglobin to oxyhemoglobin changes, and the correction based on the absorption of hemoglobin may be affected by this. Therefore, in the present embodiment, in the measured component calculation unit 84, the measured value of the measured component is corrected in consideration of the influence caused by the difference in oxygen saturation in the blood serving as the specimen. Thus, by performing correction considering the difference in oxygen saturation of each blood serving as the specimen, the measurement accuracy of the measured component in the blood (in the present embodiment, the glucose concentration measurement accuracy) can be further improved.

[0157] Refer to Figure 12 , as described above, taking advantage of the fact that the absorption coefficients of reduced hemoglobin and oxyhemoglobin are different according to the wavelength, in the present embodiment, the measured component calculation unit 84 is configured to estimate the oxygen saturation based on the transmitted light when irradiating the blood with irradiation light having a wavelength at which the absorption coefficients of reduced hemoglobin and oxyhemoglobin are equal and irradiation light having a wavelength at which the absorption coefficients of reduced hemoglobin and oxyhemoglobin are different. In the following description, the wavelength at which the absorption coefficients of reduced hemoglobin and oxyhemoglobin are equal is also referred to as the "equivalent wavelength", and the wavelength at which the absorption coefficients of reduced hemoglobin and oxyhemoglobin are different is also referred to as the "non-equivalent wavelength". The equivalent wavelength is the wavelength at which Figure 12 the absorption coefficient of reduced hemoglobin (Hb) and the absorption coefficient of oxyhemoglobin (HbO 2 ) cross, and examples include 520 nm, 545 nm, 570 nm, or 580 nm, etc. If it is within the range of ±10 nm, preferably ±5 nm, centered on these wavelengths, it can be regarded as the equivalent wavelength.

[0158] In the present embodiment, as the first correction light source that emits the irradiation light of the above equivalent wavelength, the fourth light source 68c is used, and as the second correction light source that emits the irradiation light of a non-equivalent wavelength, the first light source 67 is used. Thus, compared with the case where a first correction light source and a second correction light source are separately provided in the component measurement device 1 in addition to the first light source 67 to the fifth light source 68d, the number of components of the component measurement device 1 can be reduced, and cost reduction and miniaturization can be achieved. For example, the fourth specified wavelength λ4 of the fourth light source 68c may be set to 520 nm, and the first specified wavelength λ1 of the first light source 67 may be set to 605 nm. Alternatively, the fourth specified wavelength λ4 of the fourth light source 68c may be set to 545 nm, and the first specified wavelength λ1 of the first light source 67 may be set to 560 nm. Thus, as the fourth light source 68c and the first light source 67, green LEDs or orange LEDs with high versatility can be used, and the system can be constructed inexpensively. However, the fourth specified wavelength λ4 and the first specified wavelength λ1 may also be a combination of any wavelength that satisfies the above conditions in the present disclosure. In addition, as the first correction light source and the second correction light source, the second light source 68a and the third light source 68b, or the fourth light source 68c and the fifth light source 68d may be used, or a light source different from the first light source 67 to the fifth light source 68d may be provided in the component measurement device 1.

[0159] Refer to Figure 15 , Figure 16 and Figure 17 , the method for correcting the measured component by the measured component calculation unit 84 in the present embodiment will be described in more detail. Figure 15 is a schematic diagram showing the stage where blood spreads on the component measurement chip 2. Figure 16 is a schematic diagram showing the change in absorbance as blood spreads on the component measurement chip 2. Figure 17 is a flowchart showing the method for correcting the measured component in one embodiment of the present disclosure.

[0160] As Figure 15As shown, when the blood as a specimen is supplied from the supply unit 24 of the component measurement chip 2 to the flow path 23, the blood supplied to the flow path 23 of the component measurement chip 2 enters the flow path 23 of the component measurement chip 2 toward the measurement reagent 22. Thereafter, the blood reacts with the enzymes, chromogenic reagents, hemolytic reagents, and oxidation reagents contained in the measurement reagent 22. At this time, it is preferable that the measurement of the oxygen saturation of the blood is performed in a state before the reaction between the blood and the measurement reagent 22 starts after a sufficient amount of blood has reached the measurement reagent 22 after the blood has flowed into the flow path 23 of the component measurement chip 2 (after (B) in the figure, just after the blood spreading ends). Therefore, in the present embodiment, the measured component calculation unit 84 determines whether it is before the reaction between the measured component in the blood and the measurement reagent 22 by using the fact that there is a time lag after the blood flows into the flow path 23 of the component measurement chip 2 and before the measurement reagent 22 starts to react. Thereafter, before the reaction starts, the absorbance required for estimating the oxygen saturation is obtained. At this time, for the light received by the light receiving unit, it is the transmitted light that passes through the unreacted measurement reagent 22 and the unreacted blood.

[0161] Specifically, as Figure 17 shown, in step S101, the measured component calculation unit 84 of the component measurement device 1 performs the determination of the start of blood spreading.

[0162] Any method can be used for the determination of the start of blood spreading. As Figure 16 shown, as the blood is injected into the flow path 23, the amount of transmitted light received by the light receiving unit 72 changes, and the absorbance changes. Therefore, for example, the measured component calculation unit 84 uses the measured value data 85 generated at a prescribed time interval. When there is a prescribed time series change (first time series change) in the transmitted light from at least any one of the first light source 67 to the fifth light source 68d (for example, the fourth light source 68c as the first correction light source), it can also be determined that the blood spreading has started. Specifically, the measured component calculation unit 84 sets the ratio of the amount of transmitted light to the amount of irradiated light at the fourth prescribed wavelength λ4 as the light amount change rate (%). (1) When the light amount change rate increases / decreases continuously twice by more than 5%, the next time point after the period in which (2) the light amount change rate was continuously less than 1.2% before that period is determined as the blood spreading start time point. Thus, as Figure 16 shown, the measured component calculation unit 84 can determine the start time point of blood spreading.

[0163] Referring again to Figure 17 , when it is determined in step S101 that the blood spreading has started, the measured component calculation unit 84 proceeds to step S102 and performs the determination of the end of blood spreading.

[0164] Any method can be adopted to determine the end of blood spreading. For example, when the absorbance at at least any one of the first specified wavelength λ1 to the fifth specified wavelength λ5 (for example, the fourth light source 68c serving as the first correction light source) included in the measured value data 85 has a specified time series change (the second time series change), it can also be determined that the blood spreading has ended. Specifically, the measured component calculation unit 84 can also determine the time point when the difference between the absorbance at the fourth specified wavelength λ4 belonging to the visible region and the average value of the absorbances at the second specified wavelength λ2 and the third specified wavelength λ3 belonging to the infrared region is 0.1 or more, and (2) the time series change amount (for example, moving average three times) of the absorbance at the fourth specified wavelength λ4 is less than 0.005 as the end time point of blood spreading. Thus, as Figure 16 shown, the measured component calculation unit 84 can determine the end time point of blood spreading.

[0165] Referring again to Figure 17 , in step S103, the measured component calculation unit 84 calculates the supplementary absorbance ratio immediately after the blood spreading ends.

[0166] The supplementary absorbance ratio is the ratio of the absorbance at the equivalent wavelength to the absorbance at the non-equivalent wavelength, and is information that has a strong correlation with the oxygen saturation of the blood serving as the specimen. Therefore, in the present embodiment, as the correction based on oxygen saturation, the supplementary absorbance ratio is used to correct the measured component. The supplementary absorbance ratio is calculated using the following formula (3) based on the absorbances at the second specified wavelength λ2 and the third specified wavelength λ3 belonging to the infrared region and the absorbances at the fourth specified wavelength λ4 and the first specified wavelength λ1 belonging to the visible region immediately after the blood spreading ends.

[0167] R = (absorbance at λ1 - average value of absorbances at λ2 and λ3) ÷ (absorbance at λ4 - average value of absorbances at λ2 and λ3) (3)

[0168] Here, R is the supplementary absorbance ratio, the fourth specified wavelength λ4 is the equivalent wavelength, and the first specified wavelength λ1 is the non-equivalent wavelength.

[0169] The calculation of the supplementary absorbance ratio immediately after the completion of blood spreading can be performed by any method. For example, the component to be measured calculation unit 84 calculates the supplementary absorbance ratio based on one or more measured values within a specified period from the time point when the blood spreading is determined to be completed in step S102, which are included in the measured value data 85. The specified period is, for example, the period from when the blood spreads in the flow path 23 of the component measurement chip 2 until the reaction between the blood and the measurement reagent 22 starts, and can be about 150 milliseconds. As an example, the component to be measured calculation unit 84 can calculate the supplementary absorbance ratio for each of the measured values at five consecutive time points at 5 - millisecond intervals from the blood spreading completion time point, and can also set the average value of these as the supplementary absorbance ratio of the blood serving as the specimen. In the calculation of the average value, when there is a value that is not within the specified range (for example, ±0.05 of the average value), the component to be measured calculation unit 84 can also exclude this value as an outlier, and thus calculate the supplementary absorbance ratio of the blood serving as the specimen. Thereby, the calculation accuracy of the supplementary absorbance ratio of the blood serving as the specimen is improved, and furthermore, the measurement accuracy of the component to be measured in the blood is improved. In addition, in the calculation of the average value, when the number of values not within the specified range (for example, ±0.05 of the average value) based on the average value is equal to or more than a specified amount, the component to be measured calculation unit 84 can also not perform the correction of the component to be measured using the supplementary absorbance ratio based on subsequent processing. Thereby, by performing the correction using the supplementary absorbance ratio, it is possible to prevent a decrease in the measurement accuracy of the component to be measured in advance.

[0170] In step S104, the component to be measured calculation unit 84 corrects the component to be measured using the supplementary absorbance ratio.

[0171] The calculation of the supplementary absorbance ratio immediately after the completion of blood spreading can be performed by any method. For example, as a first method, the component to be measured calculation unit 84 can also correct the glucose concentration as the component to be measured by applying the supplementary absorbance ratio calculated in step S103 to the following formula (4).

[0172] Bg = Bg’ - f(R) (4)

[0173] Here, Bg is the corrected glucose concentration, Bg’ is the glucose concentration before correction, R is the supplementary absorbance ratio, f(R) is the correction value, and is a function with the supplementary absorbance ratio R as a parameter.

[0174] In this way, by using the first method, it is possible to improve the measurement accuracy of the component to be measured in the blood measured by the component measurement device 1 (in this embodiment, the glucose concentration measurement accuracy), regardless of the oxygen saturation of the blood serving as the specimen.

[0175] As a second method, when the absorbance at an equivalent wavelength (in this embodiment, the absorbance at the fourth specified wavelength λ4) has a strong correlation with the blood cell volume, the analyte calculation unit 84 can also use the supplementary absorbance x based on the supplementary absorbance ratio and the information related to the absorbance at the equivalent wavelength (the "absorbance at λ4 - the average of the absorbances at λ2 and λ3" in the above formula (3)) to correct the glucose concentration as the analyte. Specifically, the glucose concentration as the analyte can also be corrected using the following formulas (5) and (6).

[0176] x = R × (absorbance at λ4 - the average of the absorbances at λ2 and λ3) = absorbance at λ1 - the average of the absorbances at λ2 and λ3 (5)

[0177] Bg = Bg' - F(x) (6)

[0178] Here, R is the supplementary absorbance ratio, x is the supplementary absorbance, the fourth specified wavelength λ4 is the equivalent wavelength, the first specified wavelength λ1 is a non-equivalent wavelength, Bg is the corrected glucose concentration, Bg' is the glucose concentration before correction, F(x) is the correction value, and it is a function with x as a parameter.

[0179] In this way, by using the second method, it is possible to improve the measurement accuracy of the analyte in the blood measured by the component measurement device 1 (the glucose concentration measurement accuracy in this embodiment), regardless of the oxygen saturation and blood cell volume of the blood used as the specimen. In addition, as shown in formula (5), the supplementary absorbance x that has a correlation with the oxygen saturation and blood cell volume is information related to the absorbance at a non-equivalent wavelength immediately after the blood development (the average of the absorbances at λ1 - the absorbances at λ2 and λ3). Therefore, according to the second method, compared with the first method that uses both the information related to the absorbances at the equivalent wavelength and the non-equivalent wavelength, the correction can be performed with less computational effort.

[0180] In addition, in this embodiment, the functions f(R) and f(x) can also be constructed by statistical methods such as machine learning or deep learning. For example, the functions f(R) and f(x) can use the measured values of absorbance and glucose concentration in experiments using various blood samples as teacher data and be constructed by statistical methods. Thus, through the accumulation of teacher data, the correction accuracy of the glucose concentration can be improved. However, the functions f(R) and f(x) can also include specified arithmetic expressions that do not depend on statistical methods.

[0181] As described above, the component calculation unit 84 can determine whether it is before the start of the reaction between the component to be measured and the reagent based on the time-series change of the transmitted light from at least one of the two correction light sources (the fourth light source 68c as the first correction light source and the fifth light source 68d as the second correction light source) received by the light receiving unit 72 by performing the processes of steps S101 to S104. Based on the transmitted light from the two correction light sources received by the light receiving unit 72 before the start of the reaction, the oxygen saturation of the blood is estimated, and based on this oxygen saturation, the measured value of the component to be measured is corrected.

[0182] Finally, referring to Figure 18 , a summary description of the component measurement method of the above-described component measurement device 1 will be given. Figure 18 It is a flowchart showing the component measurement method executed by the component measurement device 1.

[0183] As Figure 18 shown, the component measurement method of the present disclosure includes: a step S1 of obtaining the absorbance of the mixture X at the first specified wavelength λ1 as the measurement wavelength, that is, the first measured value D1, the absorbance of the mixture X at the second specified wavelength λ2, that is, the second measured value D2, the absorbance of the mixture X at the third specified wavelength λ3, that is, the third measured value D3, the absorbance of the mixture X at the fourth specified wavelength λ4, that is, the fourth measured value D4, and the absorbance of the mixture X at the fifth specified wavelength λ5, that is, the fifth measured value D5; a step S2 of correcting the first measured value D1 using the second measured value D2 to the fifth measured value D5 and the correction of the component to be measured obtained by regression calculation, and obtaining the absorbance of the colored component at the first specified wavelength λ1 as the measurement wavelength; a step S3 of calculating the hematocrit value using at least one of the first measured value D1 to the fifth measured value D5; and a step S4 of calculating the component to be measured in the blood based on the absorbance of the colored component at the first specified wavelength λ1 as the measurement wavelength and the calculated hematocrit value.

[0184] Specifically, in step S1, the absorbance acquisition unit 78 uses the light emitting unit 66 and the light receiving unit 72 of the measurement optical system 64 to acquire the first measured value D1 to the fifth measured value D5. In step S2, the absorbance correction unit 83 uses the second measured value D2 to the fifth measured value D5 and the correction of the component to be measured obtained by regression calculation to correct the first measured value D1, and estimates and acquires the absorbance of the coloring component at the measurement wavelength. In step S3, the component to be measured calculation unit 84 calculates the hematocrit value based on the fourth measured value D4, or based on the fourth measured value D4 and the second measured value D2. Then, in step S4, the component to be measured calculation unit 84 uses a calibration line indicating the relationship between the absorbance of the coloring component at the first specified wavelength λ1 which is the acquired measurement wavelength, the calculated hematocrit value, and the glucose concentration, to calculate the glucose concentration. At this time, the component to be measured calculation unit 84 corrects the glucose concentration based on the oxygen saturation of the blood, and the oxygen saturation of the blood is calculated based on the first measured value D1 to the fourth measured value D4.

[0185] As described above, the component measurement device 1 of the present embodiment is a component measurement device that uses a reagent that reacts with the component to be measured in blood and measures the component to be measured in blood based on the optical characteristics of the coloring component generated by the coloring reaction between the component to be measured and the reagent. The component measurement device 1 is configured to correct the measurement value of the component to be measured based on the oxygen saturation of the blood.

[0186] According to this configuration, the component measurement device 1 can correct the measurement value of the component to be measured in consideration of the fact that the oxygen saturation varies depending on each blood sample, and as a result, can improve the measurement accuracy of the component to be measured in blood. Therefore, according to the component measurement device 1 of the present disclosure, the measurement accuracy of whole blood measurement using the absorbance photometry method can be further improved.

[0187] Although the present disclosure has been described based on the respective drawings and embodiments, it should be noted that those skilled in the art can make various deformations and corrections based on the present disclosure. Therefore, it should be noted that these deformations and corrections are included in the scope of the present disclosure. For example, in order not to be logically contradictory, the structures or functions included in each embodiment can be reconfigured. In addition, the structures or functions included in each embodiment can be used in combination with other embodiments, and multiple results or functions can be combined into one, or divided, or a part can be omitted.

[0188] In addition, for example, although in the above-described embodiments, the glucose concentration as the component to be measured is measured, it is not limited to the concentration, and other physical quantities can also be measured. Further, although in the above-described embodiments, glucose in the plasma component is exemplified as the component to be measured in the blood, it is not limited thereto. For example, cholesterol, sugars, ketone bodies, uric acid, hormones, nucleic acids, antibody-antigens, etc. in the blood can be set as the component to be measured. Therefore, the component measurement device is not limited to a blood glucose measurement device.

[0189] In addition, for example, although in the above-described embodiments, the method of estimating the oxygen saturation of blood based on the transmitted light from two correction light sources received by the light receiving unit 72 before the reaction between the component to be measured and the reagent starts is described, it is not limited thereto. The oxygen saturation of blood can also be estimated based on the transmitted light from two correction light sources received by the light receiving unit 72 after at least part of the reaction between the component to be measured and the reagent starts.

[0190] In addition, for example, in the above-described embodiments, the light receiving unit 72 is configured to receive the transmitted light passing through the component measurement chip 2, but it can also be configured as a light receiving unit that receives the reflected light reflected from the component measurement chip 2.

[0191] In addition, for example, although in the above-described embodiments, there is no step of separating blood, but the blood glucose value in whole blood is measured, it is also possible to filter the blood and use the blood after removing a part such as blood cell components or dust as the measurement object. In the step of separating blood, instead of filtering the blood and using whole blood, it is divided into a measurement area that reacts with the measurement reagent 22 and a correction area for correction, and calculations are performed separately.

[0192] Industrial Applicability

[0193] The present disclosure relates to a component measurement device and a component measurement method.

[0194] Description of Reference Numerals

[0195] 1... Component measurement device; 2... Component measurement chip; 10... Housing; 10a... Main body part; 10b... Chip mounting part; 11... Display part; 12... Removal lever; 13... Power button; 14... Operation button; 21... Substrate component; 22... Measurement reagent (reagent); 23... Flow path; 23a... Gap; 24... Supply part; 25... Cover component; 26... Eject pin; 60... Arithmetic unit; 62... Memory; 63... Power supply circuit; 64... Measurement optical system; 66... Light emitting part; 67... First light source (second correction light source); 68a... Second light source; 68b... Third light source; 68c... Fourth light source (first correction light source); 68d... Fifth light source; 69a... First aperture part; 69b... Second aperture part; 70... Light emission control circuit; 72... Light receiving part; 74... Light receiving control circuit; 76... Measurement indication part; 77... Concentration measurement part; 78... Absorbance acquisition part; 80... Support component; 83... Absorbance correction part; 84... Measured component calculation part; 85... Measured value data; 86... Correction coefficient data; 90... Calibration line data; 100... Component measurement device group; A... Flow direction; B... Flow path width direction; C... Thickness direction; D1... First measured value; D2... Second measured value; D3... Third measured value; D4... Fourth measured value; D5... Fifth measured value; S... Chip mounting space; SL1 to SL5... Irradiation positions of the light source; T1... Distance between the light source and the first aperture part; T2... Distance between the light source and the light receiving part; T3... Distance between the mixture and the first aperture part; T4... Distance between the light source and the second aperture part; W1... Long wavelength region; W2... Short wavelength region; W3... Wavelength range corresponding to the full width at half maximum region; X... Mixture; λ1... First specified wavelength; λ2... Second specified wavelength; λ3... Third specified wavelength; λ4... Fourth specified wavelength; λ5... Fifth specified wavelength; R... Supplementary absorbance ratio; Bg, Bg’... Glucose concentration; x... Supplementary absorbance.

Claims

1. A component measuring device, which uses a reagent that reacts with a component to be measured in blood, and measures the component to be measured in the blood based on the optical properties of a coloring component generated by a coloring reaction between the component to be measured and the reagent, characterized in that: The component measurement device is configured to correct a measurement value of the measured component based on the oxygen saturation of the blood.

2. The component measuring device according to claim 1, characterized in that: have: two correction light sources, including a first correction light source that emits irradiation light of a wavelength whose absorption coefficient of reduced hemoglobin is equal to that of oxidized hemoglobin, and a second correction light source that emits irradiation light of a wavelength whose absorption coefficient of reduced hemoglobin is different from that of oxidized hemoglobin; and a light receiving unit for receiving the transmitted light after passing through the blood among the irradiation lights from the two correction light sources, The component measurement device is configured to estimate the oxygen saturation of the blood based on the transmitted light from the two correction light sources received by the light receiving unit.

3. The component measuring device according to claim 2, characterized in that: Based on the time series change of the transmitted light from at least one of the two correction light sources received by the light receiving unit, it is determined whether the reaction between the component to be measured and the reagent has started. The component measurement device is configured to estimate the oxygen saturation of the blood based on the transmitted light from the two correction light sources received by the light receiving unit before the reaction starts.

4. The component measuring device according to claim 2 or 3, characterized in that: have: a first light source for emitting irradiation light of a measurement wavelength belonging to a wavelength range corresponding to a full width at half maximum region of a peak wavelength region in an absorption spectrum of the coloring component; a second light source emitting irradiation light of a second wavelength and a third wavelength belonging to a longer wavelength region than the measurement wavelength, and a third light source emitting irradiation light of the third wavelength; and a fourth light source for emitting irradiation light of a fourth wavelength and a fifth wavelength belonging to a shorter wavelength region than the measurement wavelength belonging to the wavelength range corresponding to the full width at half maximum region, and a fifth light source for emitting irradiation light of the fifth wavelength, receiving, by the light receiving unit, light transmitted through the blood among the irradiation lights from the first light source to the fifth light source, The component measuring device is configured to measure the measured component in the blood using the measured value of the absorbance of the mixture including the blood, the reagent and the coloring component at the measuring wavelength and using the measured values ​​of the absorbance of the mixture at the second wavelength to the fifth wavelength. The first correcting light source is the fourth light source, and the second correcting light source is the first light source.

5. The component measuring device according to any one of claims 1 to 3, characterized in that: The reagent includes: an oxidoreductase that specifically reacts with the component to be measured, and a color developing reagent that develops color according to the amount of reaction between the component to be measured and the oxidoreductase. In addition, it also includes: a hemolytic reagent that hemolyzes the blood, and an oxidizing reagent that oxidizes hemoglobin in the blood.

6. A component measurement method, using a reagent that reacts with a component to be measured in blood, and measuring the component to be measured in the blood based on the optical properties of a coloring component generated by a coloring reaction between the component to be measured and the reagent, characterized in that: including correcting the measured value of the measured component based on the oxygen saturation of the blood, The oxygen saturation of the blood is estimated based on the transmitted light that has passed through the blood and the reagent.

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