Analysis device
By using a dual-wavelength light-emitting element configuration and correction processing, the analytical device stabilizes light emission for precise quantitative analysis, addressing emission instability issues.
Patent Information
- Application Number
- JP2024117841
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2024-07-23
- Publication Date
- 2026-02-04
AI Technical Summary
The instability in light emission due to heat generation when LEDs are repeatedly turned on and off for detecting color reactions and obtaining correction values leads to variations in photometric values, affecting the accuracy of quantitative analysis in analytical devices.
The analytical device employs a configuration with a first and second light-emitting element emitting different wavelengths, positioned to minimize overlap and fluctuation, and a processor for correcting brightness values, stabilizing light emission and enabling accurate quantitative analysis.
Stabilizes light emission, allowing for highly accurate quantitative analysis by correcting brightness values, thereby improving measurement precision.
Smart Images

Figure 2026017151000001_ABST
Abstract
Description
[Technical Field]
[0001] The present disclosure relates to an analytical device. [Background technology]
[0002] Analytical devices are known that analyze specimen samples, such as blood, using analytical chips onto which the specimen samples are deposited. One such analytical device is a device that quantitatively analyzes a target substance contained in the specimen sample by reacting the specimen sample with a reagent and optically detecting the resulting coloration. The specimen sample is, for example, blood or urine. The analytical chip is generally provided with a reagent layer containing a dry reagent.
[0003] On the other hand, the analytical device may be configured to flow a specimen sample, react it with a reagent in the flow path, and optically detect the coloration state in the flow path. Patent Document 1 proposes a measurement chip for detecting the coloration state in such a flow path. In Patent Document 1, the analytical device includes a first light-emitting element and a second light-emitting element that irradiate an irradiation source with light of different wavelengths. The first light-emitting element and the second light-emitting element are arranged side by side in the irradiation source. A light-receiving element is disposed opposite the irradiation source and is configured to receive light transmitted through the analytical chip. Here, the first light-emitting element is used to detect the coloration reaction, and the second light-emitting element is used to determine a correction value for correcting the measured value of the coloration reaction. [Prior art documents] [Patent documents]
[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2015-179038 Summary of the Invention [Problem to be solved by the invention]
[0005] When detecting a color reaction using a first light-emitting element and obtaining a correction value using a second light-emitting element are performed sequentially, and these light-emitting elements are LEDs (Light Emitting Diodes), if they are repeatedly turned on and off in a short period of time, the amount of light emitted may become unstable due to heat generation, which may result in variations in the photometric values.
[0006] The present disclosure aims to provide an analytical device that stabilizes the light emission amounts of two light-emitting elements, one for detecting a color reaction and one for obtaining a correction value, and that is capable of performing quantitative analysis with higher accuracy. [Means for solving the problem]
[0007] The analytical device of the present disclosure includes: a support base for supporting a wet analytical chip having a flow path for holding a mixture of a specimen sample and a reagent; a wet-type light source unit that irradiates transmitted measurement light that passes through a flow channel of the wet analytical chip; an area sensor disposed opposite the wet-type light source unit across the support base, and receiving the transmitted measurement light to capture an image showing the reaction state between the specimen and the reagent in the flow path; The wet light source unit includes a first light-emitting element and a second light-emitting element that respectively emit first and second measurement lights having different wavelengths as transmitted measurement lights, and within the flow path, the irradiation area of the first measurement light and the irradiation area of the second measurement light exist within the shooting range of the area sensor and have at least different center positions.
[0008] The first light-emitting element and the second light-emitting element are preferably arranged with an interval therebetween in the direction along the flow path.
[0009] When the irradiation areas of the first measurement light and the second measurement light partially overlap, it is preferable that the first light-emitting element and the second light-emitting element are positioned so that the fluctuation in brightness value caused by the overlap of the irradiation areas when both are turned on is 10% or less based on the brightness value of one of the irradiation areas when only one is turned on.
[0010] Preferably, the first measurement light is light of a wavelength whose transmittance when passing through the specimen sample changes depending on the reaction state, and the second measurement light is light of a wavelength whose transmittance when passing through the specimen sample does not change even when the reaction state changes. It is preferable that the device further includes a processor that performs quantitative analysis of the substance to be detected based on the reaction state, and the processor acquires an image from the area sensor, which includes an area irradiated with the first measurement light and an area irradiated with the second measurement light, and which is captured with the first light-emitting element and the second light-emitting element turned on, and corrects the first brightness value acquired from the area irradiated with the first measurement light in the image with the second brightness value acquired from the area irradiated with the second measurement light in the image.
[0011] The support stand may be capable of supporting a dry analytical chip having a reaction area for holding a dry reagent, and preferably further includes a dry light source unit that is arranged on the area sensor side of the support stand and irradiates reflected measurement light onto the reaction area of the dry analytical chip supported by the support stand.
[0012] It is preferable that the wet analysis chip and the dry analysis chip are flat and have the same planar shape, and the support base has a plurality of cells on which either the wet analysis chip or the dry analysis chip is placed, and further has a plurality of chip pressing units each arranged opposite each of the plurality of cells on the support base and having a pressing surface for pressing the analysis chip placed on the cell, and it is preferable that the plurality of chip pressing units have the same external shape, and a wet light source unit is arranged in at least one chip pressing unit, and the first measurement light and the second measurement light are irradiated from the pressing surface.
[0013] It is preferable to have a processor that controls the wet light source unit, the dry light source unit, and the area sensor, and the processor is preferably configured to execute control such that, for wet analysis chips, the wet light source unit is turned on and an image is taken using the area sensor, and for dry analysis chips, the dry light source unit is turned on and an image is taken using the area sensor.
[0014] It is preferable that the first measurement light is light of a wavelength whose transmittance changes when passing through the specimen sample due to a reaction in the flow path, and the second measurement light is light of a wavelength whose transmittance does not change when passing through the specimen sample due to a reaction in the flow path, and the processor is configured to acquire an image from the area sensor, including an area irradiated with the first measurement light and an area irradiated with the second measurement light, taken with the first light-emitting element and the second light-emitting element turned on for the wet analysis chip, and correct the first brightness value acquired from the area irradiated with the first measurement light in the image with the second brightness value acquired from the area irradiated with the second measurement light in the image, to perform quantitative analysis of the target substance. [Effects of the Invention]
[0015] According to the analysis device of the present disclosure, the amounts of light emitted by the two light-emitting elements can be stabilized, enabling quantitative analysis with higher accuracy. [Brief explanation of the drawings]
[0016] [Figure 1] FIG. 1 is a schematic configuration diagram of an analysis device according to a first embodiment. [Figure 2] FIG. 1 is a diagram illustrating the configuration of a wet analytical chip. [Figure 3] 3A and 3B are explanatory diagrams of the first irradiation area and the second irradiation area, respectively. [Figure 4] 1 is a schematic diagram of an image P captured by an area sensor. [Figure 5] FIG. 10 is a schematic configuration diagram of an analysis device according to a second embodiment. [Figure 6] FIG. 6 is a plan view of the main part of the analyzer shown in FIG. 5. [Figure 7] FIG. 1 is a diagram illustrating the configuration of a dry analytical chip. [Figure 8] FIG. 10 is a diagram showing the positional relationship between the dry analysis chip and the photometry unit at the photometry position. [Figure 9] FIG. 10 is a diagram showing the positional relationship between the wet analytical chip and the photometry unit at the photometry position. DETAILED DESCRIPTION OF THE INVENTION
[0017] DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Preferred embodiments of the present invention will now be described with reference to the accompanying drawings, in which the same components are designated by the same reference numerals.
[0018] (First embodiment) FIG. 1 is a diagram showing the schematic configuration of an analyzer 1 according to a first embodiment. The analyzer 1 quantifies a detection target substance contained in a specimen sample using a wet analytical chip 20. The analyzer 1 measures the concentration of the detection target substance by colorimetric measurement. The specimen sample may be, for example, plasma, whole blood, serum, or urine.
[0019] The wet analysis chip 20 has a flow path that holds the reaction product of the specimen and the reagent. Unlike the dry analysis chip described in the second embodiment below, the "wet analysis chip" does not have a carrier for holding a dry reagent. Instead, it refers to an analysis chip that mixes the specimen with a liquid reagent and analyzes the specimen as a solution. The wet analysis chip 20 is supplied with a mixture of the specimen and the reagent that has been mixed in a separate vial. The reagent may be supplied before, after, or together with the specimen supplied to the flow path 22. Alternatively, the reagent may be pre-stored in the flow path 22 of the wet analysis chip 20, and the specimen may be injected into the flow path 22. The reagent reacts with the target substance in the specimen sample to produce a substance that develops a specific color, or becomes cloudy due to aggregation. The substance that develops color or aggregates as a result of these reactions is referred to below as the reaction product. The reagent used in wet analysis is, for example, a latex reagent containing latex particles that undergo aggregation upon reaction with the target substance.
[0020] FIG. 2 is an exploded perspective view of the wet analysis chip 20. In the wet analysis chip 20, a flow path 22 is enclosed in a case 27. The case 27 is composed of a case body 27A in which a recess 23 is formed, and a lid 27B that is joined to the case body 27A so as to cover the recess 23. The recess 23 of the case body 27A and the lid 27B that covers the recess 23 form the flow path 22. The lid 27B is provided with two openings 24 and 25 that communicate with the flow path 22. A mixture of a specimen sample and a reagent is dispensed into the flow path 22 from the opening 24 or the opening 25.
[0021] The analysis device 1 includes a support base 2, a wet-use light source unit 4, an area sensor 6, and a processor 8. The support base 2 supports a wet analysis chip 20. The wet-use light source unit 4 irradiates a flow path 22 of the wet analysis chip 20 with transmitted measurement light that passes through the flow path 22. The area sensor 6 is disposed opposite the wet-use light source unit 4 across the support base 2. The area sensor 6 receives the transmitted measurement light that has passed through the wet analysis chip 20, thereby capturing an image that shows the reaction state between the specimen sample and the reagent in the flow path 22. The area sensor 6 is, for example, an image sensor such as a CCD (Charge Coupled Device) camera or a CMOS (Complementary Metal Oxide Semiconductor) camera.
[0022] The wet light source unit 4 includes a first light-emitting element 4a and a second light-emitting element 4b that respectively emit a first measurement light L1 and a second measurement light L2 having different wavelengths as transmitted measurement light. The first light-emitting element 4a and the second light-emitting element 4b are disposed at positions facing the flow path 22 of the wet analysis chip 20 placed on the support base 2. When the first light-emitting element 4a and the second light-emitting element 4b are turned on, an irradiation area E1 of the first measurement light L1 and an irradiation area E2 of the second measurement light L2 are present within the imaging range of the area sensor 6 in the flow path 22, and at least their center positions are different. Examples of the light-emitting elements 4a and 4b include light-emitting diodes (LEDs), organic electroluminescence (EL), and semiconductor lasers.
[0023] 3A and 3B are diagrams schematically illustrating an irradiation area E1 (hereinafter referred to as the first irradiation area E1) of the first measurement light L1 and an irradiation area E2 (hereinafter referred to as the second irradiation area E2) of the second measurement light L2 in the flow path 22. As shown in FIGS. 3A and 3B, the center position of the first irradiation area E1 and the center position of the second irradiation area E2 are different. In this example, the first irradiation area E1 and the second irradiation area E2 are arranged with a distance D between them in a direction along the flow path 22, i.e., in the extension direction of the flow path 22.
[0024] As shown in FIG. 3A, the first and second illumination regions E1 and E2 preferably do not overlap, but they may partially overlap as shown in FIG. 3B. When the first and second illumination regions E1 and E2 partially overlap as shown in FIG. 3B, the first and second light-emitting elements 4a and 4b are positioned so that the fluctuation in luminance caused by the overlap between the first and second illumination regions E1 and E2 when both are lit is 10% or less, preferably 5% or less, of the luminance value of one of the illumination regions when only one of the illumination regions is lit. Specifically, the first and second light-emitting elements 4a and 4b are positioned at an interval such that the luminance value of the first illumination region E1 when only the second light-emitting element 4b is lit is 10% or less, preferably 5% or less, of the luminance value of the second illumination region E2. Here, the luminance value of the illumination region is the average value of the luminance data within the illumination region.
[0025] The first measurement light L1 is light of a wavelength whose transmittance when passing through the sample varies depending on the reaction state between the sample and the reagent. That is, the first measurement light L1 is light of a wavelength whose transmittance when passing through a mixture of the sample and the reagent varies depending on the presence and amount of a reaction product produced by the reaction between the sample and the reagent. The first measurement light L1 is, for example, light including a wavelength that is absorbed by the reaction product. On the other hand, the second measurement light L2 is light of a wavelength whose transmittance when passing through the sample does not change even when a reaction occurs between the sample and the reagent. That is, the second measurement light L2 is light of a wavelength whose transmittance when passing through a mixture of the sample and the reagent does not change depending on the presence and amount of a reaction product produced by the reaction between the sample and the reagent. In the analyzer 1, the first measurement light L1 is used to perform colorimetric measurement of the sample, and the second measurement light L2 is used to measure a correction value.
[0026] The processor 8 comprehensively controls each part of the analyzer 1. The processor 8 is composed of, for example, a CPU (Central Processing Unit), and executes a program to perform measurement processing in the analyzer 1. The processor 8 performs quantitative analysis of the detection target substance based on the reaction state between the specimen and the reagent. The processor 8 optically detects the reaction state by colorimetric measurement, and derives the concentration of the detection target substance based on a calibration curve that shows the relationship between optical density and the concentration of the detection target substance.
[0027] The quantitative analysis process in the analysis device 1 will now be described.
[0028] First, the wet analytical chip 20, in which a mixture of a specimen sample and a reagent, which have been mixed in advance in a vial, is injected into the flow path 22, is placed on the support base 2. The mixture, in which the specimen sample contains a detection target substance that reacts with the reagent, contains a reaction product, which causes a color reaction.
[0029] With the wet analysis chip 20 placed on the support base 2, the processor 8 controls the wet-use light source unit 4 and the area sensor 6 to capture an image of the flow path 22. Specifically, the processor 8 turns on the first light-emitting element 4a and the second light-emitting element 4b of the wet-use light source unit 4 to irradiate the flow path 22 with the first measurement light L1 and the second measurement light L2. The processor 8 then controls the area sensor 6 to capture an image P (see FIG. 4 ) including the first irradiation area E1 of the flow path 22 irradiated with the first measurement light L1 and the second irradiation area E2 of the flow path 22 irradiated with the second measurement light L2. The image P captured by the area sensor 6 is sent to the processor 8.
[0030] The processor 8 derives, as the first luminance value, the average value of the luminance data of the first illumination region E1 of the image P acquired from the area sensor 6. The luminance data may be data of the entire first illumination region E1, or may be extracted luminance data of a part of the first illumination region E1, for example, a region of interest such as the center. The processor 8 also derives, as the second luminance value, the average value of the luminance data of the second illumination region E2 of the image P acquired from the area sensor 6. In this case, the luminance data may be data of the entire second illumination region E2, or may be extracted luminance data of a part of the second illumination region E2, for example, a region of interest such as the center.
[0031] The first brightness value reflects the reaction state between the specimen and the reagent, while the second brightness value is a corrected value reflecting a background unrelated to the reaction state between the specimen and the reagent.
[0032] Processor 8 derives a corrected measurement value by correcting the first luminance value with the second luminance value. For example, the corrected measurement value is derived as corrected measurement value = first luminance value / second luminance value. Processor 8 derives the optical density from the corrected measurement value, and derives the concentration of the detection target substance based on a calibration curve that shows the relationship between optical density and the concentration of the detection target substance, which is stored in advance in a memory (not shown). Here, "deriving the concentration of the detection target substance" means quantifying the detection target substance.
[0033] In this manner, quantitative analysis of the detection target substance is carried out.
[0034] As described above, the analyzer 1 of this embodiment includes a support base 2 supporting a wet analysis chip 20 having a flow path 22 for holding a mixture of a specimen sample and a reagent, a wet-type light source unit 4 for irradiating a transmitted measurement light that transmits through the flow path 22 of the wet analysis chip 20, and an area sensor 6 disposed opposite the wet-type light source unit 4 across the support base 2 and for receiving the transmitted measurement light to capture an image P representing a reaction state between the specimen sample and the reagent in the flow path 22. The wet-type light source unit 4 includes a first light-emitting element 4a and a second light-emitting element 4b that respectively emit a first measurement light L1 and a second measurement light L2 having different wavelengths as transmitted measurement light. In addition, within the flow path 22, an irradiation area E1 of the first measurement light L1 (here, the first irradiation area E1) and an irradiation area E2 of the second measurement light L2 (here, the second irradiation area E2) are present within an imaging range of the area sensor 6, and at least their center positions are different. With this configuration, the area sensor 6 can capture transmitted light images while irradiating the two irradiation areas E1 and E2 on the flow path 22 of the wet analytical chip 20 with measurement light L1 and L2 of different wavelengths, and the two irradiation areas E1 and E2 can be captured simultaneously. When the two light-emitting elements 4a and 4b are sequentially turned on and off to capture an image using the first measurement light L1 and an image using the second measurement light L2 at different times, the amount of light emitted by the light-emitting elements 4a and 4b may become unstable due to heat generation, etc., and the measured values (brightness values) may vary. In contrast, in this embodiment, both the first and second light-emitting elements 4a and 4b are turned on, and the amount of light emitted is stabilized, and measurement values and correction values based on the color reaction can be acquired, enabling highly accurate quantitative analysis.
[0035] The color reaction is measured using the first measurement light L1, and the correction value is measured using the second measurement light L2. Correcting the first luminance value derived from the luminance data of the first irradiation area E1 with the second luminance value derived from the luminance data of the second irradiation area E2 allows for a measurement value that is not affected by background light. If the specimen itself contains color or turbidity components, the measurement of the color reaction using the first measurement light L1 will contain background components such as the color or turbidity components of the specimen, resulting in a falsely high optical density. As in this embodiment, measuring the correction value, which is the background, using the second measurement light L2 allows for a luminance value (optical density) that is substantially based on the color reaction and is not affected by the color or turbidity components of the specimen, enabling highly accurate quantitative analysis. Specifically, "when the specimen itself contains color or turbidity components" refers to a hemolyzed specimen or a chylic specimen.
[0036] (Second embodiment) Fig. 5 shows a schematic configuration of an analytical device 100 of the second embodiment. Fig. 6 is a plan view of the main parts of the analytical device 100 of Fig. 5. The analytical device 1 of the first embodiment described above is an apparatus that performs measurements using a wet analytical chip 20, but the analytical device 100 of the second embodiment is an apparatus that can selectively measure the wet analytical chip 20 and the dry analytical chip 12. The wet analytical chip 20 used in the analysis of this analytical device 100 is the same as in the analytical device 100 of the first embodiment described above, and therefore a detailed description thereof will be omitted (see Fig. 2).
[0037] FIG. 7 shows an example of the configuration of the dry analysis chip 12. The dry analysis chip 12 is flat like the wet analysis chip 20 described above, and has the same planar shape as the wet analysis chip 20. The dry analysis 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 color as a result of this reaction is hereinafter referred to as a reaction product. 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 is deposited in the reaction area 12A of the dry analysis chip 12. Note that the planar shapes of the wet analysis chip 20 and the dry analysis chip 12 being the same do not mean that they are completely identical, but rather that they are essentially the same. Note that the external shapes of the dry analysis chip 12 and the wet analysis chip 20 are not limited to those of this embodiment, as long as they can be loaded into an incubator 60 (described later) and used for measurement.
[0038] More specifically, the dry 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 dry 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 dry 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.
[0039] The analyzer 100 includes a chip setting section 10, a sample application section 30, a chip transport mechanism 40, a sample application mechanism 50, an incubator 60, a photometry unit 70, a chip disposal mechanism 80, and a processor 90.
[0040] In the chip setting section 10, a stocker 14 for storing dry analytical chips 12 is arranged on a holder 11. In the stocker 14, a plurality of dry analytical chips 12 are stored in a stacked state.
[0041] The chip transport mechanism 40 transports the dry analysis chip 12 from the chip setting unit 10 to the specimen application unit 30, and then 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 dry analysis chip 12 stored in the lowest row of the dry analysis chips 12 stacked in the stocker 14. In this state, the chip transport member 42 moves toward the incubator 60, thereby transporting the dry analysis chip 12 to the incubator 60.
[0042] In the specimen application section 30, a specimen sample such as plasma, whole blood, serum, or urine is applied to the dry analysis chip 12. A chip support stand 31 is provided in the specimen application section 30, and the specimen sample is applied to the dry analysis 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.
[0043] 5, the specimen application mechanism 50 includes a nozzle 52, a suction / discharge mechanism (not shown), and a movement mechanism for moving the nozzle 52. The specimen application mechanism 50 aspirates a specimen sample from a specimen storage section (not shown), and applies the specimen sample to the dry analysis chip 12 in the specimen application section 30.
[0044] As in the case of the analyzer 1, the wet analytical chip 20 is placed on the chip support base 31 of the sample application unit 30 with a mixture of a specimen sample and a reagent mixed externally injected into the flow path 22, and is transported to the incubator 60 by the chip transport member 42. Note that the analyzer 100 may be separately provided with a stocker for the wet analytical chip 20, a mixed liquid dispensing mechanism, and the like.
[0045] The incubator 60 can accommodate multiple dry analysis chips 12 and wet analysis chips 20. The incubator 60 has a thermostatic function that maintains a constant temperature to promote the reaction between the reagent and the specimen sample. The set temperature is, for example, 37°C.
[0046] As shown in FIG. 6, the incubator 60 includes a circular rotating platform 62 having a plurality of cells S in which dry analysis chips 12 or wet analysis chips 20 are loaded. A disk-shaped holding member 65 is provided on the upper portion of the rotating platform 62. The holding member 65 has a first chip pressing portion 64 that presses the dry analysis chip 12 loaded in the cell S toward the rotating platform 62 from a direction facing the reaction region 12A. The holding member 65 also has a second chip pressing portion 164 that presses the wet analysis chip 20 loaded in the cell S toward the rotating platform 62 from a direction facing the reaction region 12A or the flow path 22. One of the first chip pressing portion 64 and the second chip pressing portion 164 is disposed facing each of the plurality of cells S. As shown in FIG. 8, a slit-shaped space is formed between the pressing surface 64A of the first chip pressing portion 64 and the cell S, and the dry analysis chip 12 is loaded therein. 9, a slit-shaped space is formed between the pressing surface 164A of the second chip pressing part 164 and the cell S, and the wet analysis chip 20 is loaded into this space. The rotating substrate 62 is an example of the "support base" of the present disclosure that can support the wet analysis chip 20 and the dry analysis chip 12.
[0047] The first tip pressing section 64 and the second tip pressing section 164 have the same outer shape. However, the second tip pressing section 164 is provided with a wet-use light source section 4 inside. The transmitted measurement light emitted from the wet-use light source section 4 embedded inside the second tip pressing section 164 is irradiated from the pressing surface 164A of the second tip pressing section 164 toward the flow path of the wet analysis chip 20. The portion of the second tip pressing section 164 through which the transmitted measurement light passes is transparent to the transmitted measurement light (at least 50% transmittance). The wet-use light source section 4 is the same as that of the analysis device 1 of the first embodiment, and the relationship between the wet-use light source section 4 and the wet analysis chip 20 is also the same as that of the analysis device 1, so a detailed description will be omitted. Here, the first tip pressing section 64 and the second tip pressing section 164 having the same outer shape means that they are interchangeable, and differences in parts other than those essential for interchange are permitted.
[0048] A rotating cylinder 66 is provided below the rotating platform 62. The rotating cylinder 66 has a cross-sectional shape that is approximately 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. This opening functions as a disposal hole 68 for disposing of used dry analysis chips 12 or wet analysis chips 20. The used dry analysis chips 12 or wet analysis chips 20 loaded in the cell S are moved toward the center of the annular rotating platform 62 and dropped toward the inclined surface of the rotating cylinder 66. The used dry analysis chips 12 or wet analysis chips 20 that have fallen into the rotating cylinder 66 slide down the inclined surface and are discarded through the disposal hole 68.
[0049] The holding member 65 is provided with a heating means such as a heater (not shown), and by adjusting the temperature, the dry analysis chip 12 and the wet analysis chip 20 housed in the cell S are maintained at a predetermined constant temperature. A heat-retaining cover 69 is provided on the upper surface of the holding member 65. Note that Fig. 6 shows the state in which the holding member 65 and the heat-retaining cover 69 have been removed, exposing the rotating base plate 62.
[0050] 6, 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 dry analytical chip 12 and the wet analytical chip 20 is performed through this opening window 62A by a photometry unit 70 disposed below the rotating substrate 62. The position where colorimetric measurement is performed by the photometry unit 70 is called the photometry position.
[0051] The photometric unit 70 performs colorimetric measurement, which is measurement of optical density using colorimetry, on the dry analytical chip 12. The photometric unit 70 is provided below the rotating platform 62 on the outer periphery of the incubator 60.
[0052] As shown in Fig. 8, photometric unit 70 includes housing 71, dry-type light source unit 73 that irradiates reaction area 12A with reflected measurement light LB, and area sensor 74 that captures the reaction area 12A. In this example, dry-type light source unit 73 includes light-emitting elements 73a and 73b. In this example, light-emitting elements 73a and 73b have approximately the same center wavelength. Here, "approximately the same" means that the wavelengths match within a range of ±5 nm.
[0053] The wavelength of the reflected measurement light LB is determined according to the substance to be detected. In the reaction area 12A where the specimen sample is dropped, a reaction between the substance to be detected and the reagent generates a reaction product that develops a specific color. The reflected measurement light LB is light of a wavelength whose reflection amount changes depending on the presence and amount of the reaction product. The reflected measurement light LB is, for example, light including a wavelength absorbed by the reaction product. In this example, a configuration including two light-emitting elements with approximately the same center wavelength is described, but the dry light source unit 73 may also include multiple light-emitting elements with different center wavelengths to irradiate reflected measurement light LB with different wavelengths depending on the substance to be detected. As the light-emitting elements 73a and 73b, for example, light-emitting diodes (LEDs), organic electroluminescence (EL), and semiconductor lasers are used.
[0054] The area sensor 74 captures an image of a predetermined imaging range. When the dry analysis chip 12 is positioned at the photometric position due to the rotation of the rotating substrate 62, the area sensor 74 captures an image of the reaction region 12A irradiated with the reflected measurement light LB from the light-emitting elements 73a and 73b. In this case, the area sensor 74 acquires an image based on the reflected light Lr of the reflected measurement light LB. When the wet analysis chip 20 is positioned at the photometric position due to the rotation of the rotating substrate 62, the area sensor 74 captures an image of the region including the first irradiation region E1 and the second irradiation region E2 (see FIG. 4) irradiated with the transmitted measurement light from the wet light source unit 4. In this case, the area sensor 74 acquires an image based on the transmitted light of the transmitted measurement light. The area sensor 74 is, for example, an image sensor such as a CCD (Charge Coupled Device) camera or a CMOS (Complementary Metal Oxide Semiconductor) camera. In this way, the area sensor 74 also has the same function as the area sensor 6 in the analysis device 1. The area sensor 74 then outputs the captured image to the processor 90.
[0055] In addition, an optical system (not shown) is provided within the housing 71 to collect reflected light Lr from the reaction area 12A or collect the first measurement light L1 and second measurement light L2 that have passed through the flow path 22 and guide them to the area sensor 74.
[0056] The processor 90 comprehensively controls each part of the analytical device 100. The photometric unit 70 and the wet-use light source unit 4 are also controlled by the processor 90. The processor 90 is composed of, for example, a CPU (Central Processing Unit), and executes a program to perform measurement processing in the analytical device 100. The processor 90 performs quantitative analysis of the detection target substance based on the reaction state between the specimen and the reagent. The processor 90 optically detects the reaction state by colorimetric measurement of the reaction region 12A of the dry analytical chip 12 and the flow path 22 of the wet analytical chip 20, and derives the concentration of the detection target substance based on a calibration curve showing the relationship between optical density and the concentration of the detection target substance.
[0057] Quantitative analysis using the dry analytical chip 12 is performed with the dry analytical chip 12 positioned at the photometric position by rotating the rotary base 62. With the dry analytical chip 12 positioned at the photometric position, the processor 90 turns on the light-emitting elements 73a and 73b of the dry analytical light source unit 73. The processor 90 then turns on the light-emitting elements 73a and 73b to irradiate the reaction area 12A with reflected measurement light LB, and then performs an image capture using the area sensor 74. The processor 90 derives an average luminance value as a measurement value from the luminance data of the region of interest in the reaction area 12A in the image acquired from the area sensor 74. The processor 90 corrects the measurement value as necessary and then derives the optical density. The processor 90 then derives the concentration of the target substance based on a calibration curve indicating the relationship between optical density and the concentration of the target substance, which has been stored in advance in a memory (not shown).
[0058] Quantitative analysis using the wet analysis chip 20 is performed with the wet analysis chip 20 positioned at the photometric position by rotating the rotating substrate 62. With the wet analysis chip 20 positioned at the photometric position, the processor 90 turns on the light-emitting elements 4a and 4b of the wet-use light source unit 4. The processor 90 then turns on the light-emitting elements 4a and 4b to irradiate the flow path 22 with the first measurement light L1 and the second measurement light L2, which are transmitted measurement light, and performs imaging using the area sensor 74. The quantitative analysis process using the wet analysis chip 20 is the same as in the first embodiment, and similar effects can be obtained.
[0059] The memory stores a calibration curve for the dry analytical chip and a calibration curve for the wet analytical chip, and the processor 90 selects the calibration curve appropriate for the analytical chip to perform quantitative analysis of the substance to be detected.
[0060] As described above, the analysis device 100 of the second embodiment is capable of quantitative analysis using the dry analysis chip 12 and the wet analysis chip 20.
[0061] In the analysis device 100, of the multiple cells S, a first tip pressing unit 64 is installed on the cell S for measuring the dry analysis chip 12, and a second tip pressing unit 164 equipped with a wet-use light source unit 4 inside is installed on the cell S for measuring the wet analysis chip 20. However, the second tip pressing units 164 may be installed on all of the cells S. When the second tip pressing units 164 are installed on all of the cells S, when the dry analysis chip 12 is loaded into the cell S, the wet-use light source unit 4 is not used, and photometry is simply performed by the photometry unit 70. On the other hand, if the cell S for the wet analysis chip 20 is set in advance, it is only necessary to provide the second tip pressing unit 164 equipped with the wet-use light source unit 4 on the cell S for the wet analysis chip 20, which reduces costs compared to when the second tip pressing units 164 are provided on all of the cells S.
[0062] The first tip pressing unit 64 and the second tip pressing unit 164 have the same external shape and are therefore interchangeable as needed. Therefore, the number of first tip pressing units 64 and second tip pressing units 164 can be freely set depending on how the user of the analytical device 100 uses it. For example, in the case of a device having 13 cells S as shown in FIG. 6, the ratio of the first tip pressing units 64 to the second tip pressing units 164 can be 12:1 for users who perform measurements on the wet analytical chip 20 infrequently, and the ratio of the first tip pressing units 64 to the second tip pressing units 164 can be 10:3 for users who perform measurements on the wet analytical chip 20 relatively frequently.
[0063] In the first and second embodiments, the hardware structure of the processors 8 and 90 can be any of the various processors listed below. 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.
[0064] 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).
[0065] Furthermore, more specifically, the hardware structure of these processors can be an electric circuit that combines circuit elements such as semiconductor elements.
[0066] 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.
[0067] 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.
[0068] 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.
[0069] The following additional notes are further disclosed regarding the above embodiment.
[0070] <Appendix 1> a support base for supporting a wet analytical chip having a flow path for holding a mixture of a specimen sample and a reagent; a wet-type light source unit that irradiates transmitted measurement light that passes through a flow channel of the wet analytical chip; an area sensor disposed opposite the wet-type light source unit across the support base, and receiving the transmitted measurement light to capture an image showing the reaction state between the specimen and the reagent in the flow path; The wet light source unit includes a first light-emitting element and a second light-emitting element that respectively emit first and second measurement lights having different wavelengths as transmitted measurement lights, and within the flow path, the irradiation area of the first measurement light and the irradiation area of the second measurement light exist within the shooting range of the area sensor and have at least different center positions. <Appendix 2> 2. The analytical device according to claim 1, wherein the first light-emitting element and the second light-emitting element are arranged at an interval in a direction along the flow path. <Appendix 3> When the irradiation areas of the first measurement light and the second measurement light partially overlap each other, The first light-emitting element and the second light-emitting element are arranged at positions where a fluctuation in luminance value caused by overlapping of the irradiation areas when both are turned on is 10% or less based on the luminance value of one of the irradiation areas when only one is turned on. 2. The analytical device of claim 1. <Appendix 4> the first measurement light is light of a wavelength whose transmittance when passing through the specimen sample changes depending on the reaction state; the second measurement light is light of a wavelength whose transmittance when passing through the specimen sample does not change even if the reaction state changes, Further comprising a processor that performs quantitative analysis of the detection target substance based on the reaction state; The processor acquires, as an image from the area sensor, an image including an irradiation area of the first measurement light and an irradiation area of the second measurement light, the image being captured in a state in which the first light-emitting element and the second light-emitting element are turned on; correcting a first luminance value acquired from an area in the image irradiated with the first measurement light with a second luminance value acquired from an area in the image irradiated with the second measurement light; 4. The analytical device according to any one of claims 1 to 3. <Appendix 5> the support base is capable of supporting a dry analytical chip having a reaction area for holding a dry reagent; An analytical device described in any one of Appendix 1 to Appendix 4, further comprising a dry-type light source unit that is arranged on the area sensor side of the support base and irradiates reflected measurement light onto the reaction area of the dry analysis chip supported on the support base. <Appendix 6> The wet analytical chip and the dry analytical chip are flat and have the same shape in plan view, the support base includes a plurality of cells on which either a wet analytical chip or a dry analytical chip is placed; a plurality of chip pressing units each disposed opposite to a corresponding one of the plurality of cells on the support base and having a pressing surface for pressing an analytical chip placed on the cell; An analytical device as described in Appendix 5, wherein the multiple chip pressing units have the same external shape, and a wet-type light source unit is arranged in at least one chip pressing unit, and the first measurement light and the second measurement light are irradiated from the pressing surface. <Appendix 7> a processor for controlling a wet light source unit, a dry light source unit, and an area sensor; The analytical device described in Appendix 5 or Appendix 6, wherein the processor controls the wet analysis chip by turning on the wet light source unit and taking an image using an area sensor, and the dry analysis chip by turning on the dry light source unit and taking an image using an area sensor. <Appendix 8> the first measurement light is light of a wavelength whose transmittance changes when passing through the specimen sample due to a reaction in the flow channel; the second measurement light is light of a wavelength whose transmittance does not change when passing through the specimen sample due to a reaction in the flow channel; The processor An image including an irradiation area of the first measurement light and an irradiation area of the second measurement light is acquired from the area sensor as an image, the image being captured with the first light-emitting element and the second light-emitting element turned on for the wet analysis chip; correcting a first luminance value acquired from an area in the image irradiated with the first measurement light with a second luminance value acquired from an area in the image irradiated with the second measurement light; Conduct quantitative analysis of target substances, 8. The analytical device of claim 7. [Explanation of symbols]
[0071] 1:Analyzer 2: Support stand 4: Wet light source section 4a: First light-emitting element 4b: Second light-emitting element 6: Area sensor 8: Processor 10: Chipset section 11: Holding stand 12: Dry analytical chip 12A: Reaction area 14: Stocker 16: Carrier 17: Case 17A: Case 1 17B: Second case 17C: Opening 17D:Aperture 20: Wet analysis chip 22: Flow path 23: Recess 24 :Aperture 25 :Aperture 27: Case 27A: Case body 27B: Lid body 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: First tip pressing part 64A: Pressing surface 65: Holding member 66: Rotating cylinder 67: Bearing 68: Waste hole 69: Heat insulation cover 70: Photometric unit 71: Housing 73:Dry type light source section 73a: Light emitting element 73b: Light emitting element 74: Area sensor 80: Chip disposal mechanism 90: Processor 100: Analyzer 164: Second tip pressing part 164A: Pressing surface E1: 1st irradiation area E2: 2nd irradiation area L1: 1st measurement light L2: 2nd measurement light LB: Measuring light for reflection P: Image S: Cell
Claims
1. a support base for supporting a wet analytical chip having a flow path for holding a mixture of a specimen sample and a reagent; a wet-type light source unit that irradiates transmitted measurement light that passes through the flow channel of the wet analytical chip; an area sensor disposed opposite the wet-type light source unit across the support base, and configured to receive the transmitted measurement light and capture an image representing a reaction state between the specimen sample and the reagent in the flow path; The wet light source unit includes a first light-emitting element and a second light-emitting element that respectively emit first and second measurement light having different wavelengths as the transmitted measurement light, and within the flow path, the irradiation area of the first measurement light and the irradiation area of the second measurement light are located within the shooting range of the area sensor and have at least different center positions.
2. The analyzer according to claim 1 , wherein the first light-emitting element and the second light-emitting element are arranged at an interval in a direction along the flow channel.
3. When the irradiation areas of the first measurement light and the second measurement light partially overlap each other, The first light-emitting element and the second light-emitting element are arranged at positions such that a fluctuation in luminance value caused by the overlap of the irradiation areas when both are turned on is 10% or less based on a luminance value of one of the irradiation areas when only one of the first light-emitting elements is turned on. The analytical device of claim 1 .
4. the first measurement light is light of a wavelength whose transmittance when passing through the specimen sample changes depending on the reaction state, the second measurement light is light of a wavelength whose transmittance when passing through the specimen sample does not change even if the reaction state changes, a processor that performs quantitative analysis of the detection target substance based on the reaction state; The processor acquires, as the image from the area sensor, an image including an irradiation area of the first measurement light and an irradiation area of the second measurement light, the image being captured in a state in which the first light-emitting element and the second light-emitting element are turned on; correcting a first luminance value acquired from an area irradiated with the first measurement light in the image with a second luminance value acquired from an area irradiated with the second measurement light in the image; The analytical device according to any one of claims 1 to 3.
5. the support base is capable of supporting a dry analytical chip having a reaction region for holding a dry reagent; The analytical device according to claim 1, further comprising a dry-type light source unit that is arranged on the area sensor side of the support base and irradiates the reaction area of the dry analytical chip supported by the support base with reflected measurement light.
6. the wet analytical chip and the dry analytical chip are flat and have the same shape in plan view; the support base includes a plurality of cells on which either the wet analytical chip or the dry analytical chip is placed, a plurality of chip pressing units each disposed opposite to each of the plurality of cells of the support base and having a pressing surface for pressing the analytical chip placed on the cell; The analytical device according to claim 5, wherein the plurality of chip pressing portions have the same outer shape, the wet-type light source portion is disposed in at least one of the chip pressing portions, and the first measurement light and the second measurement light are irradiated from the pressing surface.
7. a processor that controls the wet-use light source unit, the dry-use light source unit, and the area sensor; The processor controls the wet analytical chip to turn on the wet light source unit and perform an image capture using the area sensor, and the dry analytical chip to turn on the dry light source unit and perform an image capture using the area sensor. The analytical device according to claim 5 or 6.
8. the first measurement light is light of a wavelength whose transmittance when passing through the specimen sample changes depending on the reaction state in the flow channel; the second measurement light is light of a wavelength whose transmittance does not change when passing through the specimen sample due to the reaction state in the flow channel, The processor: Acquire, as the image from the area sensor, an image including an irradiation area of the first measurement light and an irradiation area of the second measurement light, which is photographed with the first light-emitting element and the second light-emitting element turned on for the wet analytical chip; correcting a first luminance value acquired from an area irradiated with the first measurement light in the image with a second luminance value acquired from an area irradiated with the second measurement light in the image; Conduct quantitative analysis of target substances, The analytical device according to claim 7 .
Citation Information
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Chip for measurement
JP2015179038A