Analysis device

Abstract

To provide an analyzer capable of performing quantitative analysis with higher accuracy than before.SOLUTION: An analyzer is provided with: a photometric unit which comprises a support unit which is provided with a reaction region for holding a reagent and supports, at a measurement position, an analysis chip to be used for quantitative analysis of a reaction between the reagent and a substance to be detected which reacts with the reagent, a light-emitting element which irradiates the reaction region of the analysis chip with measurement light for measuring the reaction, and an area sensor which photographs an image of a predetermined photographing range including the reaction region irradiated with the measurement light; and a color plate which is arranged in the photographing range and has a region irradiated with the measurement light, has a characteristic that the reflectance changes according to the wavelength of the incident light of the measurement light, and is used for detecting the wavelength fluctuation of the measurement light.SELECTED DRAWING: Figure 4

Description

[Technical Field]

[0001] The present disclosure relates to an analytical device. [Background technology]

[0002] There is known an analytical device that analyzes a specimen sample using an analytical chip onto which the specimen sample is deposited. The analysis of the specimen sample involves measuring the concentration of a detection target substance contained in the specimen sample by measuring the reaction state between the specimen sample and a reagent. The specimen sample is, for example, blood or urine. The analytical chip is generally an analytical chip equipped with a reaction region containing a dry reagent.

[0003] In an analytical device, a measurement light is irradiated onto the reaction area of ​​such an analytical chip, into which a specimen sample has been dropped, and the reflected light is detected to detect the reaction product produced by the reaction between the target substance and the reagent. To this end, the analytical device is equipped with a photometric unit that irradiates the analytical chip with measurement light and detects the reflected light. The analytical device then calculates the optical density of the reflection area from the amount of reflected light, and performs quantitative analysis of the target substance from the optical density.

[0004] Patent Document 1 proposes a method for suppressing a decrease in measurement accuracy due to variations in the central wavelength of a light source in an analyzer. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Japanese Patent Application Laid-Open No. 2004-132706 Summary of the Invention [Problem to be solved by the invention]

[0006] In Patent Document 1, the reaction state between the specimen and the reagent is measured, the measurement wavelength is detected sequentially, and a calibration curve corresponding to the measurement wavelength is used for quantitative analysis. In Patent Document 1, since the reaction state is measured and the measurement wavelength is detected sequentially, if the central wavelength of the light source changes between the two measurements, the analytical accuracy will decrease.

[0007] The technology of the present disclosure has been made in consideration of the above circumstances, and aims to provide an analytical device that can perform quantitative analysis with higher accuracy than conventional devices. [Means for solving the problem]

[0008] The analytical device of the present disclosure includes: a support portion that supports an analytical chip at a measurement position, the analytical chip having a reaction region for holding a reagent and used for quantitative analysis of a detection target substance that reacts with the reagent; a light-emitting element that irradiates a reaction area of ​​the analysis chip with measurement light for measuring a reaction, and a photometric unit that includes an area sensor that captures an image of a predetermined photographing range that includes the reaction area irradiated with the measurement light; The color plate is arranged within the shooting range and has an area onto which measurement light is irradiated, and has a characteristic that the reflectance changes depending on the wavelength of the incident light, and is used to detect wavelength fluctuations of the measurement light.

[0009] It is preferable that the central wavelength of the measurement light is in the wavelength range of 400 nm to 700 nm, and the color plate is used to detect wavelength fluctuations of the measurement light of the light emitting element.

[0010] The color plate preferably has an optical density that changes by 0.6 or more in the wavelength region.

[0011] It is preferable that the optical density of the color plate changes by 0.2 or more in a range of ±40 nm with respect to the central wavelength of the light emitting element.

[0012] The light-emitting element may include a plurality of light-emitting elements that emit measurement light in different wavelength ranges, and the color plate may include a plurality of color plates whose optical density changes according to the wavelength range of each of the plurality of light-emitting elements.

[0013] The color plate may include a color plate whose optical density changes by 0.2 or more in the wavelength region of 400 nm to 450 nm.

[0014] The color plate may include a color plate whose optical density changes by 0.2 or more in the wavelength region of 500 nm to 580 nm.

[0015] The color plate may include a color plate whose optical density changes by 0.2 or more in a wavelength region of 600 nm to 680 nm.

[0016] When the color plate is a first color plate, a second color plate different from the first color plate may be provided, and the second color plate is placed within the shooting range and has an area onto which measurement light from the light-emitting element is irradiated, and further, it is preferable that the change in optical density within the wavelength range of 400 nm to 700 nm is less than 0.2.

[0017] It is preferable that the optical density of the second color plate is 1.5 or less.

[0018] The analytical chip preferably contains a dry reagent as the reagent.

[0019] It is preferable that the apparatus further includes a processor that acquires an image from the photometric unit and performs quantitative analysis of the substance to be detected based on a measurement value corresponding to the photometric area luminance value, which is the luminance value of the reaction area extracted from the acquired image, and that the processor is configured to detect wavelength fluctuations of the measurement light based on the image and perform quantitative analysis according to the detected wavelength fluctuations. [Effects of the Invention]

[0020] According to the analysis device of the present disclosure, quantitative analysis can be performed with high accuracy even when fluctuations occur in the illuminance distribution. [Brief explanation of the drawings]

[0021] [Figure 1] 1 is a schematic diagram illustrating the overall configuration of an analyzer according to an embodiment. [Figure 2] FIG. 2 is a plan view of the main part of the analyzer of FIG. [Figure 3] FIG. 1 is a diagram showing a configuration example of an analytical chip. [Figure 4] FIG. 2 is a schematic diagram showing the schematic configuration of a photometric unit and the positional relationship of an analysis chip. [Figure 5] FIG. 2 is a perspective view showing the positional relationship between the main parts of the photometric unit, the analysis chip, and the color plate. [Figure 6] FIG. 2 is a schematic diagram of the spectral reflectance curve of a color plate. [Figure 7] FIG. 10 is a diagram showing the spectral reflectance curves of specific color plates. [Figure 8] FIG. 10 is a diagram showing an image captured by an area sensor. [Figure 9] FIG. 2 is a perspective view showing the positional relationship between the main parts of the photometric unit, the analysis chip, the first color plate, and the second color plate. [Figure 10] FIG. 10 is a diagram showing an image captured by an area sensor when a second color plate is provided. [Figure 11] 10A and 10B are diagrams showing images P11 to P16 taken when the current values ​​applied to the light-emitting element are 0 mA, 6 mA, 9 mA, 15 mA, 19 mA, and 39 mA. [Figure 12] FIG. 10 is a diagram showing the relationship between the illuminance of a light-emitting element and a pre-correction luminance value. [Figure 13] FIG. 10 is a diagram illustrating the relationship between the illuminance of a light-emitting element and a preliminary photometry region luminance value. [Figure 14] FIG. 10 is a diagram illustrating the correlation between a pre-correction luminance value and a pre-metering region luminance value. DETAILED DESCRIPTION OF THE INVENTION

[0022] Preferred embodiments of the present invention will now be described with reference to the drawings. In each drawing, the same components are designated by the same reference numerals. FIG. 1 is a schematic diagram showing the overall configuration of an analytical device 100 according to one embodiment. FIG. 2 is a plan view of the main parts of the analytical device 100 shown in FIG. 1, and FIG. 3 is a diagram showing an example of the configuration of an analytical chip.

[0023] The analytical device 100 shown in FIG. 1 is an example of an analytical device for analyzing a specimen sample. An analytical chip 12 is detachably mounted on the analytical device 100. The analytical device 100 uses, for example, a dry analytical chip to measure the concentration of a detection target substance contained in the specimen sample. Specifically, the analytical device 100 quantifies the concentration of the detection target substance by colorimetric measurement. The specimen sample may be, for example, plasma, whole blood, serum, or urine.

[0024] As shown in FIG. 3, the analytical chip 12 has a planar reaction area 12A to which a reagent is fixed. The reagent reacts with the detection target substance to produce a substance that develops a specific color. The substance that develops a color as a result of this reaction is hereinafter referred to as a reaction substance. For example, a dry reagent that is in a dry state at least at the time of shipment is used as the reagent. A specimen sample is applied to the reaction area 12A of the analytical chip 12.

[0025] More specifically, the analytical chip 12 has a carrier 16 including a reaction region 12A onto which a specimen sample is deposited, and the carrier 16 is housed in a case 17. The case 17 is composed of a first case 17A and a second case 17B, and the carrier 16 is housed so as to be sandwiched between the first case 17A and the second case 17B. The first case 17A has an opening 17C that functions as a drip port for depositing the specimen sample onto the reaction region 12A. The second case 17B has an opening 17D for irradiating the reaction region 12A with light. The carrier 16 is exposed to the opening 17C of the first case 17A, which constitutes the front surface of the analytical chip 12. The carrier 16 is also exposed to the opening 17D of the second case 17B, which constitutes the back surface of the analytical chip 12. The area of ​​the carrier 16 exposed to the opening 17D constitutes the reaction region 12A to which the reagent is immobilized. Additionally, second case 17B is provided with coded information code 17E containing item information relating to the measurement items. Information code 17E is, for example, a pattern of multiple dots, with the dot arrangement pattern differing for each measurement item. Of course, one-dimensional barcodes, two-dimensional barcodes, etc. may also be used as information code 17E.

[0026] The analyzer 100 comprises a chip set unit 10, a reader 20, a sample application unit 30, a chip transport mechanism 40, a sample application mechanism 50, an incubator 60, a photometric unit 70, a chip disposal mechanism 80, and a processor 90.

[0027] The chip setting unit 10 has a stocker 14 arranged on a holder 11 for accommodating analytical chips 12. The stocker 14 accommodates a plurality of analytical chips 12 stacked on top of one another. The stocker 14 has an opening on its bottom surface. The analytical chips 12 are accommodated with the surface on which the information code 17E is recorded facing the opening of the stocker 14. Therefore, the information code 17E of the analytical chip 12 located at the bottom, closest to the opening, in the stocker 14 is exposed through the opening. In addition, an opening is also formed in the holder 11 on which the stocker 14 is arranged. Therefore, the information code 17E of the analytical chip 12 located at the bottom in the stocker 14 is exposed to the reader 20 through the openings of the holder 11 and the stocker 14. The reader 20 is arranged below the holder 11 and reads the exposed information code 17E.

[0028] The reader 20 is, for example, a code reader that reads the item information attached to the analysis chip 12. The reader 20 is configured with an image sensor such as a CCD (Charge Coupled Device) or a CMOS (Complementary Metal Oxide Semiconductor). The item information read by the reader 20 is output to the processor 90.

[0029] The chip transport mechanism 40 transports the analytical chip 12 from the chip setting unit 10 to the specimen application unit 30, and further from the specimen application unit 30 to the incubator 60. The chip transport mechanism 40 includes a thin chip transport member 42 and a drive mechanism 44 that reciprocates the chip transport member 42 in the direction in which the chip setting unit 10, the specimen application unit 30, and the incubator 60 are aligned. The drive mechanism 44 is, for example, a linear actuator. The chip transport member 42 is slidably supported by a guide rod (not shown) and reciprocates by the drive mechanism 44. The chip transport member 42 is pressed against the analytical chip 12 housed in the lowest row of the analytical chips 12 stacked in the stocker 14. In this state, the chip transport member 42 moves toward the incubator 60, thereby transporting the analytical chip 12 to the incubator 60.

[0030] In the specimen application section 30, a specimen sample such as plasma, whole blood, serum, or urine is applied to the analytical chip 12. A chip support stand 31 is provided in the specimen application section 30, and the specimen sample is applied to the analytical chip 12 transported onto the chip support stand 31 on the chip support stand 31. The specimen sample is applied by a specimen application mechanism 50, which will be described later. The chip support stand 31 is disposed adjacent to the holder stand 11.

[0031] 1, the specimen deposition mechanism 50 includes a nozzle 52, a suction / discharge mechanism (not shown), and a movement mechanism for moving the nozzle 52. The specimen deposition mechanism 50 aspirates a specimen sample from a specimen storage section (not shown), and deposits the specimen sample onto the analysis chip 12 in the specimen deposition section 30.

[0032] The incubator 60 can accommodate multiple analytical chips 12. The incubator 60 has a thermostatic function that keeps the temperature constant to promote the reaction between the reagents in the analytical chip 12 and the specimen sample. The set temperature is, for example, 37°C.

[0033] As shown in FIG. 2, the incubator 60 includes a circular rotating platform 62 on which are provided a plurality of cells S into which analytical chips 12 are loaded. A disk-shaped holding member 65 having a pressing member 64 that presses the analytical chips 12 loaded in the cells S from a direction facing the reaction regions 12A (see FIG. 3) is provided on the upper portion of the rotating platform 62. A pressing member 64 is provided corresponding to each cell S. A slit-shaped space is formed between the pressing surface 64A (see FIG. 4) of the pressing member 64 and the cell S, into which the analytical chip 12 is loaded. By rotating the rotating platform 62, each cell S is sequentially transported to a measurement position where a photometry unit 70 (described later) is disposed. The rotating platform 62 is an example of a support that supports the analytical chip 12 at the measurement position.

[0034] A rotating cylinder 66 is provided below the rotating platform 62. The rotating cylinder 66 has a cross-sectional shape that is roughly an inverted triangle, with the inner diameter tapering downward. A bearing 67 is disposed at the bottom of the outer periphery of the rotating cylinder 66, and the rotating cylinder 66 is rotatably supported by the bearing 67. The rotating platform 62 rotates as the rotating cylinder 66 rotates. The holding member 65 rotates integrally with the rotating platform 62. The rotating cylinder 66 has an opening at the bottom, which is the apex of the inverted triangle, and this opening functions as a disposal hole 68 for disposing of used analytical chips 12. The used analytical chip 12, loaded in the cell S, is moved toward the center of the annular rotating platform 62 and falls toward the inclined surface of the rotating cylinder 66. The used analytical chip 12 that falls into the rotating cylinder 66 slides down the inclined surface and is discarded through the disposal hole 68.

[0035] The holding member 65 is provided with a heating means such as a heater (not shown), and the temperature of the analysis chip 12 housed in the cell S is maintained at a predetermined constant temperature by adjusting the temperature. A heat-retaining cover 69 is provided on the upper surface of the holding member 65. Note that Fig. 2 shows the state in which the holding member 65 and heat-retaining cover 69 have been removed, exposing the rotating platform 62.

[0036] As shown in Figure 2, an opening window 62A for photometry is formed in the center of the bottom surface of each cell S of the rotating substrate 62, and colorimetric measurement of the analysis chip 12 is performed through this opening window 62A by a photometry unit 70 arranged below the rotating substrate 62.

[0037] The photometric unit 70 performs colorimetric measurement, which is measurement of the optical density using a colorimetric method, on the analysis chip 12. The photometric unit 70 is provided below the rotating platform 62 on the outer periphery of the incubator 60. The photometric unit 70 acquires a detection signal representing the optical density of the reaction region 12A of the analysis chip 12 and outputs it to the processor 90.

[0038] 4 is a diagram showing a schematic configuration of the photometry unit 70 and its positional relationship with the analysis chip 12 during measurement. As shown in Fig. 4, the photometry unit 70 includes a housing 71, an irradiation device 73 including light-emitting elements 73a and 73b that irradiate the reaction region 12A with measurement light L, and an area sensor 74 that photographs the reaction region 12A.

[0039] An optical system (not shown) is provided within the housing 71 to collect reflected light L1 from the reaction area 12A and guide it to the area sensor 74. In this example, the light-emitting elements 73a and 73b have approximately the same center wavelength. Here, the center wavelength refers to the central wavelength of the emission spectrum characteristics of the light-emitting elements. When two light-emitting elements 73a and 73b with approximately the same center wavelength are provided as in this example, the emission spectra of these two light-emitting elements are added together, and the central wavelength of the added emission spectrum characteristics is defined as the central wavelength in the present invention.

[0040] The wavelength of the measurement light L is determined according to the detection target substance (i.e., the measurement item). For example, in this example, as described above, a reaction between the detection target substance and the reagent produces a reaction substance that develops a specific color. The light emitted by the irradiation device 73 is measurement light L for detecting whether a reaction substance has been produced, so the wavelength is determined according to the color produced by the reaction substance. The measurement light L in this example is, for example, light that includes a wavelength absorbed by the reaction substance in order to detect the reaction substance. In this example, a configuration is described in which two light-emitting elements with the same center wavelength are provided. However, the irradiation device 73 may also include multiple light-emitting elements with different center wavelengths in order to irradiate measurement light L with different wavelengths depending on the detection target substance. As the light-emitting elements 73a and 73b, for example, light-emitting diodes (LEDs), organic electroluminescence (EL), and semiconductor lasers are used.

[0041] When the analysis chip 12 is irradiated with the measurement light L, the area sensor 74 captures an image of a predetermined imaging range including the reaction region 12A of the analysis chip 12. The area sensor 74 is, for example, an image sensor such as a CCD camera or a CMOS camera. The area sensor 74 outputs the captured image to the processor 90.

[0042] Furthermore, as shown in FIG. 4, a color plate 75 is disposed within the photographing range of the area sensor 74. FIG. 5 is a perspective view showing the positional relationship between the main parts of the photometric unit 70, the color plate 75, and the analysis chip 12 during measurement. The rotatable base 62 is omitted in FIG. 5. The color plate 75 is disposed between the rotatable base 62 and the photometric unit 70. The color plate 75 has an area irradiated with light (measurement light L) emitted from the light-emitting elements 73a and 73b. In this example, the color plate 75 is a rectangular member having a rectangular opening in the center. The measurement light L emitted from the light-emitting elements 73a and 73b passes through the opening of the color plate 75 and enters the reaction area 12A. Note that "the color plate 75 is disposed within the photographing range of the area sensor 74" does not mean that the entire color plate 75 is disposed within the photographing range, but rather that at least a portion of the color plate 75 is within the photographing range. The color plate 75 has the property that its optical density changes depending on the wavelength of the measurement light L and is used to detect wavelength fluctuations of the measurement light L.

[0043] Here, the wavelength of the measurement light L refers to the central wavelength of the measurement light L, that is, the central wavelength of the light emitted from the light emitting elements 73a and 73b. The color plate 75 is sufficient as long as it can detect the deviation of the central wavelength of the measurement light L, and the reflectance R changes before and after the wavelength of the measurement light L. The optical density OD and the reflectance R are expressed by OD=log 10 Since there is a relationship of (1 / R), "change in reflectance" means "change in optical density."

[0044] The central wavelength of the measurement light L is generally preferably in the visible wavelength range of 400 nm to 700 nm, and the color plate 75 is used to detect wavelength fluctuations of the measurement light L emitted from the light-emitting elements 73 a and 73 b. Here, "detection of wavelength fluctuations" may be detection of deviation from the initial central wavelength of the measurement light L, or detection of the central wavelength itself at the time of measurement of the measurement light L. The "initial central wavelength" is, for example, the central wavelength provided by the manufacturer of the light-emitting elements 73 a and 73 b at the time of shipment.

[0045] For example, the color plate 75 has an optical density OD that changes by 0.6 or more in the wavelength region of 400 nm to 700 nm, as shown in Fig. 6. Here, a change in optical density OD of 0.6 or more means that the difference ΔOD between the maximum and minimum optical density values ​​in the wavelength region of 400 nm to 700 nm is 0.6 or more, as shown in Fig. 6.

[0046] The optical density of the color plate 75 preferably changes by 0.2 or more in a range of ±40 nm from the initial central wavelength of the light-emitting elements 73 a and 73 b. It is more preferable that the optical density of the color plate 75 changes by 0.2 or more in a range of ±20 nm from the central wavelength of the light-emitting elements 73 a and 73 b.

[0047] For example, when the measurement light L is blue and has a wavelength of approximately 420 to 430 nm, the color plate 75 preferably has an optical density that changes by 0.2 or more in the wavelength range of 400 to 450 nm. When the measurement light L is green and has a wavelength of approximately 530 to 550 nm, the color plate 75 preferably has an optical density that changes by 0.2 or more in the wavelength range of 500 to 580 nm. Furthermore, when the measurement light L is red and has a wavelength of approximately 630 to 650 nm, the color plate 75 preferably has an optical density that changes by 0.2 or more in the wavelength range of 600 to 680 nm.

[0048] When the irradiation device 73 is equipped with multiple light-emitting elements with different center wavelengths to irradiate measurement light L with different wavelengths depending on the substance to be detected, it is preferable to provide multiple color plates whose optical density changes depending on the wavelength range of each of the multiple light-emitting elements as the color plate 75. For example, when the irradiation device 73 is equipped with a light-emitting element that emits blue light with a wavelength of approximately 420 nm to 430 nm and a light-emitting element that emits red light with a wavelength of approximately 630 nm to 650 nm, the color plate 75 may include a color plate whose optical density changes by 0.2 or more in the wavelength range of 400 nm to 450 nm and a color plate whose optical density changes by 0.2 or more in the wavelength range of 600 nm to 680 nm.

[0049] FIG. 7 shows the spectral reflectance curves for the four color plates (excerpted from the spectral reflectance curves listed on the Evers Corporation website [https: / / evers.c.ooco.jp / ] (search date: July 22, 2024)). The BLUE #3869 color plate is suitable for measurement light L having a central wavelength of 500 nm to 650 nm. The GREEN #4808 color plate is suitable for measurement light L having a central wavelength of 400 nm to 480 nm or 550 nm to 650 nm. The YELLOW #7153 color plate is suitable for measurement light L having a central wavelength of 500 nm to 530 nm. The RED #1900 color plate is suitable for measurement light L having a central wavelength of 600 nm to 620 nm. Color plates 75 may be provided as appropriate depending on the central wavelengths of the light-emitting elements 73a and 73b provided in the irradiation device 73.

[0050] The detection of wavelength fluctuations using the color plate 75 will be described later.

[0051] The tip disposal mechanism 80 comprises a thin plate-shaped tip transport member 82 and a drive mechanism 84 that reciprocates the tip transport member 82. The tip disposal mechanism 80 inserts the tip transport member 82 into the cell S from the outer periphery of the incubator 60, and pushes the used analytical chip 12 after measurement to the center of the incubator 60, causing it to drop into the disposal hole 68. The drive mechanism 84 is, for example, a linear actuator. The tip transport member 82 is slidably supported by a guide rod (not shown), and is reciprocated by the drive mechanism 84. A collection box for collecting used analytical chips 12 is provided below the disposal hole 68.

[0052] In the incubator 60, the analytical chip 12 is loaded into a slit-shaped space formed between the cell S of the rotating base 62 and the pressing member 64. The analytical chip 12 is warmed in the incubator 60 and is transported to a measurement position by the rotation of the incubator 60. The measurement position is a position where a photometric unit 70 is disposed below the rotating base 62 and where colorimetric measurement of the analytical chip 12 is performed. After colorimetric measurement is performed by the photometric unit 70, the analytical chip 12 is dropped into a disposal hole 68 by a chip disposal mechanism 80 and discarded.

[0053] The processor 90 comprehensively controls each part of the analysis device 100. The configuration of the processor 90 is not particularly limited, but for example, the processor 90 is configured by a CPU (Central Processing Unit), NVM (Non-volatile Memory), RAM (Random Access Memory), etc.

[0054] The processor 90 acquires the image captured by the area sensor 74 of the photometry unit 70 from the area sensor 74, and performs quantitative analysis of the detection target substance contained in the specimen sample based on the acquired image.

[0055] The processor 90 performs quantitative analysis of the target substance based on a measurement value corresponding to the photometric region luminance value, which is the luminance value of the reaction region 12A extracted from the image acquired from the photometric unit 70. Specifically, the processor 90 derives the optical density of the reaction region 12A as a measurement value, and derives the concentration of the target substance based on a calibration curve showing the relationship between the optical density and the concentration of the target substance. In this case, the processor 90 detects wavelength fluctuations of the measurement light based on the image, corrects the measurement value according to the detected wavelength fluctuation, and derives the concentration of the target substance using the corrected measurement value. Here, "deriving the concentration of the target substance" means quantifying the target substance.

[0056] The processor 90 corrects the wavelength fluctuation based on the relationship between the wavelength fluctuation and the light intensity fluctuation stored in advance in the memory. Specifically, the correction is performed as follows.

[0057] In the analyzer 100, a memory stores a relationship between the wavelength of incident light and reflectance, which has been acquired in advance on the color plate 75. For example, the relationship shown in FIG. 6 described above is stored in the memory. The reflectance is derived from the luminance value of the image captured by the area sensor 74. The "relationship between the wavelength of incident light and reflectance" does not necessarily mean "reflectance" itself, but may also refer to the relationship between the wavelength of incident light and a parameter related to reflectance, such as the luminance value or optical density of the image, and the wavelength of the incident light. Furthermore, the memory stores multiple calibration curves representing the relationship between the optical density of the reaction area 12A and the analyte concentration when measured at wavelengths within ±3 nm of the wavelength of the measurement light L. That is, if the initial center wavelength of the measurement light L is 500 nm, the memory stores, for example, a calibration curve acquired with light having a center wavelength of 500 nm, as well as calibration curves acquired with light having center wavelengths of 497 nm, 498 nm, 499 nm, 501 nm, 502 nm, and 503 nm.

[0058] When performing colorimetric measurement on the analytical chip 12, that is, when the analytical chip 12 with a specimen sample dropped into the reaction region 12A is subjected to measurement and the detection target substance in the specimen sample is quantitatively analyzed, the processor 90 performs the following process.

[0059] As shown in FIG. 4, the light-emitting elements 73a and 73b are turned on to irradiate the reaction area 12A and the color plate 75 with measurement light L, and an image including the reaction area and the color plate 75 is captured by the area sensor 74. The processor 90 acquires the image from the area sensor 74. FIG. 8 shows a schematic diagram of the image P acquired by the processor 90 from the photometric unit 70. In the image P, the outline of the circular area in the center is the outline of the opening window 62A of the rotating substrate 62. The inside of the circular area is the reaction area 12A of the analysis chip 12 observed through the opening window 62A. The gray components located on both sides of the image P are the color plate 75. In this way, the image P includes at least a partial area of ​​the reaction area 12A and the color plate 75.

[0060] The processor 90 designates a predetermined region within the reaction region 12A, for example, the center of the reaction region 12A shown in FIG. 8, as the region of interest ROI1, and derives the average value A of the luminance data within this range as the photometric region luminance value (hereinafter, referred to as measurement value A). The processor 90 then designates two regions of interest ROI2 and ROI3 on ​​the color plate 75 as regions for extracting luminance data for wavelength fluctuation detection, and derives the average value C of the luminance data within this range as the luminance value for wavelength fluctuation detection. The processor 90 derives reflectance from this luminance value for wavelength fluctuation detection, and identifies the wavelength of the measurement light L from the relationship between the wavelength and reflectance of the incident light (see FIG. 6). This allows the accurate wavelength of the measurement light L during analysis to be identified. The processor 90 selects a calibration curve measured using this identified wavelength, and quantifies the detection target substance from the measurement value A using the selected calibration curve.

[0061] Thus, the analysis device 100 of this embodiment includes a photometric unit 70 including light-emitting elements 73a and 73b that irradiate the reaction area 12A of the analysis chip 12 with measurement light L for measuring the reaction, an area sensor 74 that captures an image of a predetermined imaging range including the reaction area 12A irradiated with the measurement light L, and a color plate 75 that is arranged within the imaging range and has an area irradiated with the measurement light L. The color plate has a characteristic that reflectance changes depending on the wavelength of the incident light and is used to detect wavelength fluctuations of the measurement light L. With this configuration, during analysis, the area sensor 74 can capture an image including the reaction area 12A and the color plate 75, and measurement of the luminance value of the reaction area 12A and measurement of the luminance value of the color plate 75 can be performed simultaneously without time lag. When measurement of the color reaction of the reaction area 12A and detection of wavelength fluctuations of the measurement light L are performed sequentially, the center wavelength of the light-emitting elements 73a and 73b may change between the two measurements. If such a central wavelength fluctuation occurs between measurement of the reaction area 12A and detection of wavelength fluctuations, the analytical accuracy will be reduced. In contrast, in this embodiment, both measurements can be performed simultaneously, so there is no wavelength difference between the measurement of the reaction area and the wavelength detection of the measurement light.Compared to when measurements are performed sequentially, this can suppress a decrease in analytical accuracy, and quantitative analysis can be performed with higher accuracy than conventional methods.

[0062] In colorimetric measurement, if the wavelength of the measurement light L changes, the amount of light reflected from the reaction area 12A, i.e., the brightness of the image, may change. Therefore, if wavelength fluctuations are not taken into consideration, the accuracy of the quantified concentration of the detection target substance will decrease. As in the above embodiment, accurate quantitative analysis can be achieved by identifying the center wavelength of the actual measurement light and using a calibration curve corresponding to that wavelength.

[0063] In the above embodiment, the reflectance is derived from the luminance data of the color plate 75 in the image P during analysis to identify the central wavelength of the measurement light L, and the quantity of the detection target substance is quantified using a calibration curve obtained with light of that central wavelength. However, the method of detecting wavelength fluctuations in the measurement light and performing quantitative analysis based on the detected wavelength fluctuations is not limited to the above. By identifying the central wavelength of the measurement light L using a method similar to the above, it is also possible to derive wavelength fluctuations from the initial central wavelength of the measurement light L, and then correct the measured value based on a previously obtained correlation between the wavelength fluctuation and the fluctuation in the measured value to perform quantification.

[0064] It is preferable that the optical density of the color plate 75 changes by 0.2 or more in a range of ±40 nm from the central wavelength of the light-emitting elements 73 a and 73 b, and more preferably that the optical density changes by 0.2 or more in a range of ±20 nm from the central wavelength. This is because if the optical density of the color plate 75 changes significantly around the central wavelength, fluctuations in the central wavelength can be detected more accurately.

[0065] If the color plate 75 has an optical density that changes by 0.2 or more in the wavelength range of 400 nm to 450 nm, it can accurately detect fluctuations in the center wavelength of blue measurement light L with a wavelength of approximately 420 nm to 430 nm. If the color plate 75 has an optical density that changes by 0.2 or more in the wavelength range of 500 nm to 580 nm, it can accurately detect fluctuations in the center wavelength of green measurement light L with a wavelength of approximately 530 nm to 550 nm. Furthermore, if the color plate 75 has an optical density that changes by 0.2 or more in the wavelength range of 600 nm to 680 nm, it can accurately detect fluctuations in the center wavelength of red measurement light L with a wavelength of approximately 630 nm to 650 nm.

[0066] Furthermore, when the light-emitting elements 73a and 73b are provided with a plurality of light-emitting elements that emit measurement light L in different wavelength ranges, if the color plate 75 is made up of a plurality of color plates whose optical density changes according to the wavelength range of each of the plurality of light-emitting elements, wavelength fluctuations can be accurately detected for each wavelength of measurement light.

[0067] Furthermore, in the analyzer 100, when the color plate 75 is the first color plate (hereinafter referred to as the first color plate 75), a second color plate 76 for correcting illuminance fluctuations may be provided instead of the first color plate 75. The second color plate 76 is disposed within the imaging range and has an area onto which the measurement light L from the light emitting elements 73a and 73b is irradiated. The second color plate 76 is a color plate whose optical density varies less than 0.2 within the wavelength range of 400 nm to 700 nm. The fact that the optical density of the second color plate 76 varies less than 0.2 within the wavelength range of 400 nm to 700 nm means that the difference ΔOD between the maximum and minimum optical density values ​​is less than 0.2, which means that the change in optical density (i.e., reflectance) due to wavelength fluctuations is small. It is preferable that the second color plate 76 be a color plate whose optical density varies less than 0.1 within the wavelength range of 400 nm to 700 nm.

[0068] When the first color plate 75 and the second color plate 76 are provided, for example, instead of the rectangular color plate 75 having a rectangular opening in FIG. 5, a U-shaped first color plate 75 and a U-shaped second color plate 76 are disposed between the photometric unit 70 and the analysis chip 12, as shown in FIG. 9. FIG. 10 is a schematic diagram of an image P1 acquired by the processor 90 from the photometric unit 70 in a configuration including the second color plate 76. In the image P in FIG. 8, color plates 75 are shown on both sides, but in the image P1 in FIG. 10, one of them (the right side in FIG. 10) is the first color plate 75, and the other (the left side in FIG. 10) is the second color plate 76. The second color plate 76 preferably has an optical density of 1.5 or less in the visible range (wavelengths of 400 nm to 700 nm). The color plate 75 is preferably a gray or white plate.

[0069] In this way, in a configuration that includes a second color plate 76 in addition to the first color plate 75, the processor 90 identifies the wavelength of the measurement light L from the luminance value of the first color plate 75 in the image P1, extracts the luminance value of the second color plate 76 as a correction luminance value, corrects the measurement value based on the correction luminance value, and then derives the concentration of the substance to be detected.

[0070] If the light-emitting elements 73a and 73b are, for example, light-emitting diodes (LEDs), the amount of light emitted may change due to temperature changes or the like. If the amount of light emitted by the light-emitting elements 73a and 73b changes, the illuminance of the measurement light L on the reaction area 12A and the first and second color plates 75 and 76 changes as a result. If the illuminance changes, the amount of reflection changes, and the luminance value (i.e., optical density) in the image P1 changes. If the optical density decreases due to a decrease in illuminance, an error will occur in the concentration of the detection substance identified from the optical density.

[0071] Therefore, to suppress errors due to changes in illuminance, in this configuration, the region of interest ROI 22 of the second color plate 76 is used as the extraction region for correction luminance data, and the processor 90 derives the average value B of the luminance data of this region as the correction luminance value (hereinafter referred to as correction luminance value B). Then, the average value A (hereinafter referred to as measurement value A) of the correction luminance data extracted from the region of interest ROI 1 of the response region 12A, which is derived as the photometric region luminance value, is divided by the correction luminance value B to obtain A / B as the correction measurement value. Note that the term "luminance data" here includes the luminance values ​​of multiple pixels contained within a certain region. Therefore, the average value of the luminance data is the sum of the luminance values ​​of each pixel contained in the luminance data divided by the number of pixels. However, instead of the average value of the luminance data, the median or mode of the luminance data may be used as the luminance value.

[0072] Meanwhile, the processor 90 derives the average value C of the luminance data for wavelength fluctuation detection extracted from the region of interest ROI21 on the first color plate 75 as the luminance value for wavelength fluctuation detection. The processor 90 then derives the reflectance from this luminance value for wavelength fluctuation detection and identifies the wavelength of the measurement light L from the relationship between the wavelength of the incident light and the reflectance (see FIG. 6). This allows the accurate wavelength of the measurement light L during analysis to be identified. The processor 90 selects a calibration curve measured using this identified wavelength.

[0073] Then, the processor 90 quantifies the concentration of the detection target substance from the selected calibration curve and the corrected measurement value A / B.

[0074] In this manner, in this embodiment, an image P1 is obtained that simultaneously includes the reaction area 12A and the first and second color plates 75 and 76. From image P1, information about the measurement light L that irradiated the reaction area 12A can be obtained from the first and second color plates 75 and 76. Wavelength fluctuations are detected from the first color plate 75, a calibration curve corresponding to the wavelength of the measurement light L is selected, and the measurement value A is corrected with the correction luminance value B to obtain a corrected measurement value A / B, which is used to quantify the test substance from the calibration curve. This enables quantitative analysis that suppresses errors due to wavelength fluctuations and changes in illuminance, thereby obtaining more accurate analysis results.

[0075] Furthermore, the processor 90 may correct the measurement value A based on the correction luminance value B and the correlation between the pre-measurement area luminance value measured in advance using, for example, a reference plate and the pre-correction luminance value. The pre-measurement area luminance value is the luminance value of the area corresponding to the reaction area 12A in an image captured by the photometry unit 70 with a reference plate placed at the measurement position instead of the analysis chip 12. The pre-correction luminance value is the luminance value of the second color plate 76 obtained from the image from which the pre-measurement area luminance value is obtained. The correlation between the pre-correction luminance value and the pre-measurement area luminance value is obtained by an adjustment operation by the processor 90, for example, between the start of the analysis device 100 and the start of photometry by the photometry unit 70. As the reference plate, for example, a white plate W (see FIG. 2) for luminance calibration provided on the rotating base 62 may be used.

[0076] The adjustment operations performed by processor 90 are as follows. First, the rotatable platform 62 is rotated to place a reference plate (e.g., a white plate W) at the measurement position. With the reference plate positioned at the measurement position, the area sensor 74 acquires an image including the reference plate and at least a portion of the second color plate 776 while changing the current value passed through the light-emitting elements 73a and 73b. In the acquired image, the reference plate is observed through the opening window 62A of the rotatable platform 62. The light-emitting elements 73a and 73b are, for example, LEDs. FIG. 11 shows images P11 to P16 captured when the current values ​​passed through the light-emitting elements 73a and 73b are 0 mA, 6 mA, 9 mA, 15 mA, 19 mA, and 39 mA. As shown in FIG. 11, the larger the current value, the greater the amount of light emitted (irradiation) by the light-emitting elements 73a and 73b, resulting in a brighter (higher brightness) image.

[0077] The correlation between the preliminary photometry region luminance values ​​and the preliminary correction luminance values ​​is determined from a plurality of images P11 to P16 shown in Fig. 11, in which the light-emitting elements 73a and 73b emit different amounts of light. The relationship between the light-emitting element illuminance and the preliminary correction luminance values ​​shown in Fig. 12 and the relationship between the light-emitting element illuminance and the preliminary photometry region luminance values ​​shown in Fig. 13 are derived. The preliminary correction luminance values ​​are derived from luminance data of the region of interest ROI22 on the second color plate 76, from which correction luminance data is extracted during quantitative analysis of image P1, as schematically shown in Fig. 10. Similarly, the preliminary photometry region luminance values ​​are derived from luminance data of a region (i.e., a reference plate) corresponding to the region of interest ROI1 in the response region 12A, from which photometry region luminance data is extracted during quantitative analysis of image P1, as schematically shown in Fig. 10.

[0078] 12 and 13, the correlation between the preliminary photometry area luminance value and the preliminary correction luminance value shown in Fig. 14 is obtained. In the example shown in Fig. 14, the correlation between the preliminary correction luminance value x and the preliminary photometry area luminance value y is y=3.5567x-19.801, and the coefficient of determination R 2= 1 (y = ax + b where a = 3.5567 and b = -19.801). The processor 90 stores in memory the relational expression between the pre-correction luminance value x and the pre-photometric area luminance value y. The processes of deriving the above relational expression and storing the relational expression are performed in advance by the adjustment operation.

[0079] In quantitative analysis, the processor 90 corrects the measured value A, which is the photometric region luminance value, using the above-mentioned relational expression indicating the correlation between the pre-correction luminance value obtained in the above adjustment operation and the pre-photometric region luminance value. Specifically, the processor 90 derives the value A / y, which is the measured value A divided by the relational expression y, as the corrected measured value. If the correlation between the pre-correction luminance value and the pre-photometric region luminance value is approximated by a linear function expressed as y=ax+b, as in the case of Figure 14, the processor 90 derives A / (ax+b) as the corrected measured value. In the example of Figure 14, this is A / (3.5567×B−19.801). Here, B is the correction luminance value obtained from the color plate 75 in the image from which the measured value A was obtained. The processor 90 then derives the optical density from the corrected measured value and, based on the optical density obtained from this corrected measured value, derives the concentration of the detection target substance from the calibration curve.

[0080] Due to factors such as deterioration of the light-emitting elements 73a and 73b, the illuminance distribution may change over repeated measurements, causing a change in the relationship between the illuminance in the reaction area and the illuminance on the second color plate 76. However, as described above, if the processor 90 extracts a correction luminance value, which is the luminance value of the second color plate 76, from the image in addition to the photometric area luminance value, and corrects the measurement value based on the correlation between the correction luminance value and the previously acquired preliminary photometric area luminance value and the preliminary correction luminance value, the measurement value can be corrected with high accuracy even when the illuminance distribution changes due to factors such as deterioration of the light-emitting elements 73a and 73b. As a result, quantitative analysis with extremely high accuracy can be achieved.

[0081] As mentioned above, the optical density of the second color plate 76 is preferably 1.5 or less. The second color plate 76 is preferably gray or white. This is because the greater the amount of reflected light and the higher the luminance value of the second color plate 76 in the image P1 captured by the area sensor 74, the more accurate the correction.

[0082] The photometric unit 70 of the analytical device 100 of the above embodiment is provided with two light-emitting elements 73a and 73b that emit light of the same central wavelength, but the number of light-emitting elements that emit light of the same central wavelength may be three or more, or may be only one.

[0083] In the above embodiment, the hardware structure of the processor 90 may be any of the following various processors: The various processors include a CPU, which is a general-purpose processor that executes software (programs) and functions as various processing units, as well as dedicated electrical circuits such as a PLD (Programmable Logic Device) whose circuit configuration can be changed after manufacture, such as an FPGA (Field-Programmable Gate Array), and an ASIC (Application Specific Integrated Circuit), which is a processor with a circuit configuration designed specifically for executing specific processing.

[0084] The above-described processing may be performed by one of these various processors, or by a combination of two or more processors of the same or different types (for example, a plurality of FPGAs, or a combination of a CPU and an FPGA). Also, a plurality of processing units may be configured by a single processor. An example of configuring a plurality of processing units by a single processor is a form in which a processor is used that realizes the functions of an entire system including a plurality of processing units by a single IC (Integrated Circuit) chip, such as a System on Chip (SOC).

[0085] Furthermore, more specifically, the hardware structure of these processors can be an electric circuit that combines circuit elements such as semiconductor elements.

[0086] In addition to the operating program of the analytical device, the technology of the present disclosure also extends to a computer-readable storage medium (such as a USB memory or a DVD (Digital Versatile Disc)-ROM (Read Only Memory)) that non-temporarily stores the operating program of the analytical device.

[0087] The above-described description and illustrations are a detailed explanation of the parts related to the technology of the present disclosure and are merely an example of the technology of the present disclosure. For example, the above description of the configuration, functions, actions, and effects is an explanation of an example of the configuration, functions, actions, and effects of the parts related to the technology of the present disclosure. Therefore, it goes without saying that unnecessary parts may be deleted, new elements may be added, or replacements may be made to the above-described description and illustrations within the scope of the gist of the technology of the present disclosure. Furthermore, to avoid confusion and facilitate understanding of the parts related to the technology of the present disclosure, the above-described description and illustrations omit explanations of common technical knowledge that do not require particular explanation to enable the implementation of the technology of the present disclosure.

[0088] All publications, patent applications, and technical standards mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent application, or technical standard was specifically and individually indicated to be incorporated by reference.

[0089] The following additional notes are further disclosed regarding the above embodiment.

[0090] <Appendix 1> a support part that supports an analytical chip at a measurement position, the analytical chip having a reaction area for holding a reagent and used for quantitative analysis of a detection target substance that reacts with the reagent; a light-emitting element that irradiates a reaction area of ​​the analysis chip with measurement light for measuring a reaction, and a photometric unit that includes an area sensor that captures an image of a predetermined photographing range that includes the reaction area irradiated with the measurement light; a color plate disposed within the imaging range and having an area onto which measurement light is irradiated, the color plate having a characteristic that reflectance changes depending on the wavelength of incident light, and used to detect wavelength fluctuations of the measurement light; An analytical device comprising: <Appendix 2> The central wavelength of the measurement light is in the wavelength range of 400 nm to 700 nm, The color plate is used to detect the wavelength fluctuation of the measurement light of the light emitting element. 2. The analytical device of claim 1. <Appendix 3> 3. The analytical device of claim 2, wherein the color plate has an optical density that changes by 0.6 or more across a wavelength range. <Appendix 4> 4. An analytical device according to claim 2 or 3, wherein the optical density of the color plate changes by 0.2 or more in a range of ±40 nm relative to the central wavelength of the light-emitting element. <Appendix 5> The light emitting device includes a plurality of light emitting devices that emit measurement light in different wavelength ranges, An analytical device described in any one of appendices 2 to 4, wherein the color plate includes a plurality of color plates whose optical density changes depending on the wavelength region of each of the plurality of light-emitting elements. <Appendix 6> 6. The analytical device according to any one of claims 2 to 5, wherein the color plate includes a color plate whose optical density changes by 0.2 or more in a wavelength region of 400 nm to 450 nm. <Appendix 7> 7. The analytical device according to any one of claims 2 to 6, wherein the color plate includes a color plate whose optical density changes by 0.2 or more in a wavelength region of 500 nm to 580 nm. <Appendix 8> 8. The analyzer according to claim 2, wherein the color plate includes a color plate whose optical density changes by 0.2 or more in a wavelength region of 600 nm to 680 nm. <Appendix 9> When the color plate is a first color plate, a second color plate different from the first color plate is provided, The second color plate is placed within the photographing range, has an area to be irradiated with the measurement light from the light-emitting element, and further, has an optical density change of less than 0.2 within a wavelength range of 400 nm to 700 nm. 9. The analytical device of any one of appendices 2 to 8. <Appendix 10> 10. The analytical device of claim 9, wherein the optical density of the second color plate is 1.5 or less. <Appendix 11> 11. The analytical device according to any one of claims 1 to 10, wherein the analytical chip includes a dry reagent as a reagent. <Appendix 12> The apparatus further includes a processor that acquires an image from the photometric unit and performs quantitative analysis of the detection target substance based on a measurement value corresponding to a photometric region luminance value, which is a luminance value of a reaction region extracted from the acquired image; 12. An analytical device according to any one of claims 1 to 11, wherein the processor detects wavelength fluctuations of the measurement light based on the image and performs quantitative analysis according to the detected wavelength fluctuations. [Explanation of symbols]

[0091] 10: Chipset section 11: Holding stand 12: Analysis chip 12A: Reaction area 14: Stocker 16: Carrier 17: Case 17A: Case 1 17B: Second case 17C: Opening 17D:Aperture 17E: Information code 20: Reader 30: Sample application site 31: Chip support stand 40: Chip transport mechanism 42: Chip transport member 44: Drive mechanism 50: Sample application mechanism 52: Nozzle 60: Incubator 62: Rotating substrate 62A: Opening window 64: Pressing member 64A: Pressing surface 65: Holding member 66: Rotating cylinder 67: Bearing 68: Waste hole 69: Heat insulation cover 70: Photometric unit 71: Housing 73: Irradiation device 73a, 73b: Light-emitting element 74: Area sensor 75: Color board (first color board) 76:Second color plate 80: Chip disposal mechanism 82: Chip transport member 84: Drive mechanism 90: Processor 100: Analyzer L: Measuring light L1:Reflected light P, P1: Image P11~P16: Images ROI1: Region of interest in the reaction area ROI2: Region of interest on color plate 75 ROI3: Region of interest on color plate 75 ROI21: Region of interest on the first color plate 75 ROI22: Region of interest on the second color plate 76 S: Cell

Claims

1. a support part that supports an analytical chip at a measurement position, the analytical chip having a reaction area for holding a reagent and used for quantitative analysis of a detection target substance that reacts with the reagent; A photometric unit including: a light-emitting element that irradiates the reaction area of ​​the analysis chip with measurement light for measuring the reaction; and an area sensor that captures an image of a predetermined imaging range including the reaction area irradiated with the measurement light; a color plate disposed within the imaging range and having an area onto which the measurement light is irradiated, the color plate having a characteristic that reflectance changes depending on the wavelength of incident light, and used to detect wavelength fluctuations of the measurement light; An analytical device comprising:

2. the central wavelength of the measurement light is in a wavelength range of 400 nm to 700 nm, The color plate is used to detect a wavelength variation of the measurement light of the light-emitting element. The analytical device of claim 1 .

3. The analyzer according to claim 2 , wherein the color plate has an optical density that changes by 0.6 or more in the wavelength region.

4. The analyzer according to claim 3 , wherein the optical density of the color plate changes by 0.2 or more in a range of ±40 nm from the center wavelength of the light emitting element.

5. The light-emitting element includes a plurality of light-emitting elements that emit the measurement light in different wavelength regions, The analyzer according to claim 3 , wherein the color plate includes a plurality of color plates whose optical densities change according to the wavelength regions of the plurality of light-emitting elements.

6. 4. The analyzer according to claim 3, wherein the color plate includes a color plate in which the optical density changes by 0.2 or more in a wavelength region of 400 nm to 450 nm.

7. 4. The analyzer according to claim 3, wherein the color plate includes a color plate in which the optical density changes by 0.2 or more in a wavelength region of 500 nm to 580 nm.

8. 4. The analyzer according to claim 3, wherein the color plate includes a color plate in which the optical density changes by 0.2 or more in a wavelength region of 600 nm to 680 nm.

9. When the color plate is a first color plate, a second color plate different from the first color plate is provided, the second color plate is disposed within the imaging range, has an area to which the measurement light from the light-emitting element is irradiated, and further has an optical density change of less than 0.2 within a wavelength range of 400 nm to 700 nm; The analytical device according to claim 3 .

10. The analyzer according to claim 9 , wherein the optical density of the second color plate is 1.5 or less.

11. The analytical device according to claim 1 , wherein the analytical chip includes a dry reagent as the reagent.

12. a processor that acquires the image from the photometric unit and performs the quantitative analysis of the detection target substance based on a measurement value corresponding to a photometric region luminance value, which is a luminance value of the reaction region extracted from the acquired image; The analysis device according to claim 1 , wherein the processor detects a wavelength variation of the measurement light based on the image, and performs the quantitative analysis in accordance with the detected wavelength variation.

Images