WO2024166622A1 - 照射装置及び測光装置 - Google Patents

照射装置及び測光装置 Download PDF

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Publication number
WO2024166622A1
WO2024166622A1 PCT/JP2024/000972 JP2024000972W WO2024166622A1 WO 2024166622 A1 WO2024166622 A1 WO 2024166622A1 JP 2024000972 W JP2024000972 W JP 2024000972W WO 2024166622 A1 WO2024166622 A1 WO 2024166622A1
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WO
WIPO (PCT)
Prior art keywords
light
emitting element
axis
emitting
chip
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2024/000972
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English (en)
French (fr)
Japanese (ja)
Inventor
雄輝 荒井
由宣 三浦
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Fujifilm Corp
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Fujifilm Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Fujifilm Corp filed Critical Fujifilm Corp
Priority to JP2024576191A priority Critical patent/JPWO2024166622A1/ja
Publication of WO2024166622A1 publication Critical patent/WO2024166622A1/ja
Priority to US19/278,828 priority patent/US20250347628A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/75Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/77Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
    • G01N21/78Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator producing a change of colour
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/314Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry with comparison of measurements at specific and non-specific wavelengths
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N37/00Details not covered by any other group of this subclass
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/314Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry with comparison of measurements at specific and non-specific wavelengths
    • G01N2021/3181Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry with comparison of measurements at specific and non-specific wavelengths using LEDs
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/75Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N2021/757Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated using immobilised reagents

Definitions

  • This disclosure relates to an illumination device and a photometric device.
  • Analytical devices are known that analyze specimen samples by measuring the reaction state between the specimen sample and a reagent (see, for example, JP2008-522160A). Measurement of the reaction state includes, for example, measuring the concentration of a substance to be tested contained in the specimen sample. Specimen samples include, for example, blood and urine. In such analytical devices, an analytical chip (also called a reagent test slide) with a reaction area containing a reagent is used.
  • a specimen is supplied to the reaction area of the analytical chip as described above, and the substance to be tested in the specimen reacts with the reagent in the reaction area to produce a colored reactant.
  • This reaction area is irradiated with measurement light from a light source, which includes light of a wavelength that is absorbed by the colored reactant, and a detection signal corresponding to the output light output from the reaction area in response to the irradiation of the measurement light is obtained, thereby making it possible to measure the concentration of the substance to be tested in the specimen.
  • JP Patent Publication No. 2008-522160 proposes a light source (illumination device) that provides a volume of homogeneous light irradiance on a plane that includes a reaction region when irradiating the reaction region of an analytical chip with light.
  • JP2008-522160A specifically discloses a configuration that includes preferably three or four light-emitting elements of the same wavelength, and that the multiple light-emitting elements are arranged so that their central light-emitting axes are on the normal (corresponding to the Z-axis) of a plane (hereinafter referred to as the measurement reference plane) that includes the reaction area when the analysis chip is properly loaded in the loading position, and intersect at a position shifted from the measurement reference plane.
  • the central light-emitting axis refers to a straight line that extends from the light-emitting center that coincides with the peak of the light intensity distribution in the light-emitting plane in the normal direction to the light-emitting plane. It is also disclosed that with this configuration, substantially the same light irradiance (amount of illumination light) can be obtained even if the reaction area of the analysis chip actually loaded is shifted in the Z-axis direction based on the measurement reference plane.
  • the illumination areas of the multiple light-emitting elements will be roughly the same in a plane perpendicular to the Z axis that includes the intersection of the central light-emitting axes, but as one moves away from the intersection in the Z axis direction, a deviation will occur in the illumination areas of the multiple light-emitting elements in the plane perpendicular to the Z axis. Therefore, there may be a large difference between the amount of illumination light in the reaction area when it is offset from the measurement reference plane along the Z axis toward the intersection and the amount of illumination light in the reaction area when it is offset away from the intersection along the Z axis.
  • the present disclosure aims to provide an illumination device and a photometric device that can homogenize the amount of illumination light within the reaction area of an analysis chip and suppress, more than ever before, fluctuations in the amount of illumination light when the plane containing the reaction area is shifted in the normal direction from the measurement reference plane.
  • the irradiation device of the present disclosure is an irradiation device that uses an analysis chip having a planar reaction area on which a reagent that reacts with a test target substance contained in a sample is fixed, and irradiates light onto the reaction area of the analysis chip when optically analyzing the sample
  • the light emitting device has at least two light emitting elements, a first light emitting element and a second light emitting element, which are light emitting elements that emit light in the same wavelength range,
  • the plane including the reaction area is defined as the XY plane
  • the straight line extending from the light emission center coinciding with the peak of the light intensity distribution in the light emission surface of the light emitting element in the normal direction of the light emission surface is defined as the light emission central axis
  • the relative positional relationship between the first light emitting element and the second light emitting element satisfies the following first and second conditions
  • the second condition is that the intersection point between the first light-emitting central axis of the first light-emitting element and the Z axis is the first intersection point, and the intersection point between the second light-emitting central axis of the second light-emitting element and the Z axis is the second intersection point, and further, when one side on the Z axis is taken as the positive direction and the other as the negative direction with respect to the XY plane, the first intersection point and the second intersection point are located in one positive direction and the other negative direction.
  • the distance of the first intersection from the XY plane is the same as the distance of the second intersection from the XY plane.
  • the central angle is preferably 180°.
  • the angle between the light-emitting surface of the first light-emitting element and the XY plane is equal to the angle between the light-emitting surface of the second light-emitting element and the XY plane, and that the Z coordinates of the first light-emitting element and the second light-emitting element are different.
  • the position of the first light-emitting element is taken as X1, Y1, Z1
  • the position of the second light-emitting element is taken as X2, Y2, Z2, It is preferable that the following is satisfied.
  • a light-emitting element pair may be a set of a first light-emitting element and a second light-emitting element, and may include multiple light-emitting element pairs with different wavelength ranges.
  • the sum of the first inclination angle of the line connecting the center of the first light-emitting element to the origin with respect to the Z axis and the second inclination angle of the line connecting the center of the second light-emitting element to the origin with respect to the Z axis is the same.
  • the first tilt angle and the second tilt angle of one light-emitting element pair are the same as either the first tilt angle or the second tilt angle of the other light-emitting element pair.
  • the light-emitting element is preferably a light-emitting diode.
  • the photometric device of the present disclosure is a photometric device for optically analyzing a specimen sample using an analysis chip having a reaction region to which a reagent that reacts with a test substance is fixed, An irradiation device according to the present disclosure;
  • the analytical chip is provided with a photodetector that detects output light output from the analytical chip when light is irradiated onto the analytical chip, and outputs a detection signal according to the output light.
  • the technology disclosed herein can homogenize the amount of illumination light within the reaction area of an analytical chip, and can suppress fluctuations in the amount of illumination light when the plane containing the reaction area is shifted in the normal direction from the measurement reference plane more than ever before.
  • FIG. 1 is a schematic diagram showing an overall configuration of an analysis device according to an embodiment.
  • FIG. 2 is a plan view of the main part of the analysis device of FIG. 1.
  • 1 is a cross-sectional view of a transport path portion of an analytical chip.
  • FIG. 4A is a perspective view of the analytical chip, and
  • FIG. 4B is a plan view of the back surface of the analytical chip.
  • 1 is a schematic diagram showing the schematic configuration of a photometry unit and the positional relationship of an analysis chip.
  • FIG. 1 is a perspective view showing the positional relationship between an analytical chip, a first light-emitting element group, a second light-emitting element group, and a photodetector.
  • FIG. FIG. 1 is a schematic diagram showing an overall configuration of an analysis device according to an embodiment.
  • FIG. 2 is a plan view of the main part of the analysis device of FIG. 1.
  • 1 is a cross-sectional view of a transport path portion of an analytical chip.
  • FIG. 2 is a plan view of the irradiation device and the photodetector as viewed from the rotating base plate side.
  • 11 is a diagram showing a positional relationship between a measurement reference plane and a first light-emitting element;
  • FIG. 11 is a diagram showing the positional relationship between a measurement reference plane, a first light-emitting element pair, and a second light-emitting element pair.
  • FIG. FIG. 13 is a plan view showing a modified example of the irradiation device.
  • FIG. 13 is a diagram showing an arrangement of light-emitting elements in a configuration example used in a simulation.
  • FIG. 13 is a diagram showing an arrangement of light-emitting elements in a comparative example used in a simulation.
  • FIG. 13 is a diagram showing a variation in illumination light amount with a change in height direction position obtained by simulation.
  • FIG. 1 is a schematic diagram showing the overall configuration of an analysis device 100 equipped with a photometry unit 70, which is one embodiment of a photometry device.
  • FIG. 2 is a plan view of the main parts of the analysis device 100 in FIG. 1
  • FIG. 3 is a cross-sectional view of the transport path portion of the analysis chip
  • FIG. 4A is a perspective view of the analysis chip
  • FIG. 4B is a plan view of the back surface of the analysis chip.
  • the analytical device 100 shown in FIG. 1 is an example of an analytical device that analyzes a specimen sample.
  • An analytical chip 12 is removably mounted on the analytical device 100.
  • the analytical device 100 uses, for example, a dry analytical chip to measure the concentration of a test substance contained in the specimen sample.
  • the analytical device 100 of this example uses blood as the specimen sample and optically measures the concentration of the test substance contained in the blood. More specifically, the concentration of the test substance is measured by colorimetric measurement.
  • the analysis device 100 includes a chip set section 10, a reader 20, a sample application section 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 control device 90.
  • a stocker 14 that stores analytical chips 12 is arranged on a holding stand 11.
  • the stocker 14 stores multiple analytical chips 12 in a stacked manner.
  • the reader 20 is, for example, a code reader that reads the item information attached to the analysis chip 12. This allows the type of analysis chip 12 and/or the lot number, etc. to be identified.
  • the reader 20 is composed of an image sensor such as a CCD (Charge Coupled Device) and a CMOS (Complementary Metal Oxide Semiconductor).
  • the item information read by the reader 20 is output to the control device 90.
  • specimens such as plasma, whole blood, serum or urine are 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 holding stand 11.
  • the chip transport mechanism 40 transports the analytical chip 12 from the chip set section 10 to the specimen application section 30, and then from the specimen application section 30 to the incubator 60.
  • the chip transport mechanism 40 includes a thin plate-shaped chip transport member 42 and a drive mechanism 44 that reciprocates the chip transport member 42 in the direction in which the chip set section 10, the specimen application section 30, and the incubator 60 are aligned.
  • the drive mechanism 44 is, for example, a linear actuator.
  • the chip transport member 42 is supported so as to be freely slidable by a guide rod (not shown), and is reciprocated by the drive mechanism 44.
  • the specimen application mechanism 50 includes a nozzle 52, an aspirating and discharging mechanism (not shown), and a moving 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 to the analysis chip 12 in the specimen application section 30.
  • the incubator 60 is capable of housing multiple analytical chips 12 inside.
  • the incubator 60 has a thermostatic function that keeps the temperature constant in order to promote the reaction between the reagents in the analytical chips 12 and the specimen samples.
  • the set temperature is, for example, 37°C.
  • the incubator 60 is provided with a circular rotating base 62 on which are provided a plurality of cells S in 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 the direction facing the reaction area 12A (see FIG. 4) is provided.
  • the pressing members 64 are provided corresponding to each of the plurality of cells S, and as shown in FIG. 3, in the incubator 60, a slit-shaped space is formed between the pressing surface 64A of the pressing member 64 and the cell S, and the analytical chip 12 is loaded here.
  • a rotating cylinder 66 is provided at the bottom of the rotating substrate 62.
  • the rotating cylinder 66 has a cross-sectional shape of an approximately inverted triangle with an inner diameter that narrows toward the bottom.
  • a bearing 67 is provided at the bottom of the outer periphery of the rotating cylinder 66, and the rotating cylinder 66 is supported by the bearing 67 so that it can rotate freely.
  • the rotating substrate 62 rotates as the rotating cylinder 66 rotates.
  • the holding member 65 rotates integrally with the rotating substrate 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 chips 12 are moved from the state where they are loaded in the cell S toward the center of the annular rotating substrate 62 and are dropped toward the inclined surface of the rotating cylinder 66.
  • the used analytical chips 12 that have fallen into the rotating cylinder 66 slide down the inclined surface and are discarded through the disposal hole 68.
  • the holding member 65 is provided with a heating means such as a heater (not shown), and the analysis chip 12 contained in the cell S is kept at a 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 to expose the rotating base plate 62.
  • a photometric window 62A is formed in the center of the bottom surface of each cell S of the rotating substrate 62, and colorimetric measurement of the analytical chip 12 is performed through this window 62A by a photometric unit 70 disposed below the rotating substrate 62.
  • the photometric unit 70 performs colorimetric measurement, which is a measurement of the optical density of the analytical chip 12 using a colorimetric method.
  • the photometric unit 70 is provided below the rotating substrate 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 analytical chip 12, and outputs it to the control device 90.
  • the photometric unit 70 is one embodiment of the photometric device of the present disclosure. Details of the photometric unit 70 will be described later.
  • the chip disposal mechanism 80 comprises a thin chip transport member 82 and a drive mechanism 84 that reciprocates the chip transport member 82.
  • the chip disposal mechanism 80 inserts the chip 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, and the chip 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.
  • the control device 90 controls the overall operation of the analytical device 100.
  • the control device 90 is realized by a computer including a processor 90A composed of a CPU (Central Processing Unit), NVM (Non-volatile Memory), and RAM (Random Access Memory).
  • the control device 90 derives the concentration of the test substance contained in the specimen sample based on the detection signal obtained from the photometric unit 70.
  • the analytical chip 12 has a planar reaction area 12A to which a reagent is fixed.
  • the reagent reacts with the substance to be tested 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 reactant.
  • a reactant for example, a dry reagent that is in a dry state at least at the time of shipment is used as the reagent.
  • the specimen sample is applied to the reaction area 12A of the analytical chip 12.
  • the analytical chip 12 has a carrier 16 on which a specimen sample is applied, 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 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 applying the specimen sample to the reaction area 12A.
  • the second case 17B has an opening 17D for irradiating the reaction area 12A with light.
  • the carrier 16 is exposed to the opening 17C of the first case 17A that constitutes the front surface of the analytical chip 12.
  • the carrier 16 is also exposed to the opening 17D of the second case 17B that constitutes the back surface of the analytical chip 12.
  • the area of the carrier 16 exposed to the opening 17D constitutes the reaction area 12A to which the reagent is fixed.
  • the second case 17B is provided with an information code 17E that encodes item information related to the measurement item.
  • the information code 17E is, for example, a pattern in which multiple dots are arranged, and the dot arrangement pattern differs for each measurement item.
  • one-dimensional barcodes, two-dimensional barcodes, etc. may also be used as the information code 17E.
  • An analysis chip 12 is prepared for each measurement item, and a carrier 16 that holds a reagent corresponding to the measurement item is fixed to the analysis chip 12.
  • the item information provided for each analysis chip 12 includes identification information (reagent name and identification code, etc.) of the reagent fixed to the carrier 16 of the analysis chip 12, or identification information (item name and identification code, etc.) of the measurement item measured by the reagent.
  • an insertion port 14B through which the chip transport member 42 is inserted is provided on the side wall of the stocker 14.
  • the chip transport member 42 is inserted into the stocker 14 through the insertion port 14B.
  • the stocker 14 has an opening 14A on its bottom surface.
  • the analytical chip 12 is stored in a position with the surface on which the information code 17E is recorded facing the opening 14A of the stocker 14. Therefore, the information code 17E of the analytical chip 12 located at the bottom closest to the opening 14A in the stocker 14 is exposed from the opening 14A.
  • An opening 11A is also formed in the holding table 11 on which the stocker 14 is placed. 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 opening 11A of the holding table 11 and the opening 14A of the stocker 14.
  • the reader 20 is placed below the holding table 11, and reads the information code 17E exposed through the openings 11A and 14A.
  • the chip transport member 42 is pressed against the analytical chip 12 housed in the lowest tier of 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.
  • the analytical chip 12 is loaded into a slit-like space formed between the cell S of the rotating substrate 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 substrate 62 and where colorimetric measurement of the analytical chip 12 is performed.
  • FIG. 5 is a schematic diagram showing the general configuration of the photometric unit 70 and the positional relationship of the analysis chip 12.
  • the photometric unit 70 includes a housing 71, an irradiation device 73 for irradiating the reaction area 12A with measurement light L, and a photodetector 74 for receiving output light L1 from the reaction area 12A and performing photoelectric conversion.
  • the housing 71 includes an optical system (not shown) for collecting output light L1 from the reaction area 12A and guiding it to the photodetector 74.
  • the irradiation device 73 includes two light-emitting element groups 101 and 102 each equipped with a plurality of light-emitting elements, the details of which will be described later.
  • the wavelength range of the measurement light L is determined according to the substance to be tested (i.e., the measurement item). For example, in this example, as described above, a reaction between the substance to be tested 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 or not a reaction substance has been produced, so the wavelength range is determined according to the color produced by the reaction substance.
  • the measurement light L in this example is, for example, light including a wavelength range absorbed by the reaction substance in order to detect the reaction substance.
  • the plurality of light-emitting elements provided in the light-emitting element groups 101 and 102 are a plurality of light-emitting elements that emit measurement light L of mutually different wavelengths, and each light-emitting element is used according to the type of analysis chip 12, i.e., the measurement item.
  • the wavelength range of the measurement light L is preferably limited to a wavelength range that is absorbed by the reactant.
  • Examples of light-emitting elements that emit the measurement light L include light-emitting diodes (LEDs), organic electroluminescence (EL), and semiconductor lasers.
  • the photodetector 74 detects the output light L1 output from the reaction area 12A of the analysis chip 12 when the analysis chip 12 is irradiated with the measurement light L.
  • the photodetector 74 is, for example, a light receiving element such as a photodiode that outputs a detection signal according to the amount of light, or an image sensor such as a CCD camera or CMOS camera.
  • the photodetector 74 outputs the detection signal to the control device 90 (see FIG. 1).
  • Analysis in the analysis device 100 is performed as follows.
  • the analytical chip 12 is removed from the stocker 14 by the chip transport mechanism 40 and then transported to the spotting position on the chip support stand 31. At the spotting position, the sample is spotted onto the analytical chip 12 by the sample spotting unit 30. After the sample has been spotted onto the analytical chip 12, the analytical chip 12 is transported into the incubator 60.
  • the analytical chip 12 After the analytical chip 12 is transported into the incubator 60, the analytical chip 12 is warmed by heat generated by a heating means (not shown) inside the incubator 60.
  • the analytical chip 12 to be measured is transported to a measurement position where a photometric unit 70 is provided by the rotation of the rotating substrate 62. Then, at the measurement position, a colorimetric measurement is performed on the analytical chip 12.
  • the photometric unit 70 irradiates the analytical chip 12 with measurement light L) and receives output light L1 from the analytical chip 12, thereby measuring the optical density in the analytical chip 12 according to the reaction state between the specimen and the reagent, and outputs a detection signal.
  • the control device 90 derives the concentration of the substance to be tested from the detection signal obtained from the photometric unit 70.
  • the specimen sample and the reagent react to produce a reactant that develops a specific color.
  • the production of the reactant changes the color of the reaction area 12A, and this color change appears as a change in the optical density of the reaction area 12A.
  • the output light L1 is light that corresponds to the optical density of the reaction area 12A, and information about the reactant is reflected in the output light L1 due to the absorption of light by the reactant, etc.
  • the optical density of the reaction area 12A changes depending on the amount of reactant, and the amount of reactant represents the concentration of the substance to be tested in the specimen sample. Therefore, the concentration of the substance to be tested can be measured based on the detection signal that represents the output light that contains information about the reactant.
  • the analytical chip 12 is transported by the rotating substrate 62 to the position where the chip disposal mechanism 80 is located.
  • the analytical chip 12 is then transported by the chip disposal mechanism 80 (see FIG. 2) from inside the incubator 60 to a disposal position provided in the center of the rotating substrate 62.
  • the chip transport member 82 pushes out the analytical chip 12, which moves the analytical chip 12 from inside the incubator 60 to the disposal hole 68.
  • the illumination device 73 provided in the photometric unit 70, which is one embodiment of the photometric device of the present disclosure, is described in detail.
  • the illumination device 73 is one embodiment of the illumination device of the present disclosure.
  • the irradiation device 73 includes two light-emitting element groups 101, 102.
  • one of the two light-emitting element groups 101, 102 will be referred to as the first light-emitting element group 101, and the other as the second light-emitting element group 102.
  • FIG. 6 is a perspective view showing the positional relationship between the analysis chip 12, the first light-emitting element group 101, the second light-emitting element group 102, and the photodetector 74 shown in FIG. 5.
  • FIG. 7 is a plan view of the irradiation device 73 and the photodetector 74 viewed from the rotating substrate 62 side.
  • the first light-emitting element group 101 has eight light-emitting elements 1a to 1h on a support substrate 111
  • the second light-emitting element group 102 has eight light-emitting elements 2a to 2h on a support substrate 112.
  • the first light-emitting element group 101 and the second light-emitting element group 102 are arranged opposite each other with the photodetector 74 in between.
  • the first light-emitting element group 101 and the second light-emitting element group 102 are arranged such that the support substrates 111, 112 are inclined with respect to the normal line (Z axis described later) of the analysis chip 12.
  • the inclination angle of the support substrate 111 of the first light-emitting element group 101 with respect to the XY plane is the same as the inclination angle of the support substrate 112 of the second light-emitting element group 102 with respect to the XY plane.
  • the support substrates 111 and 112 are arranged symmetrically with respect to the Z axis.
  • the light-emitting surfaces of the light-emitting elements 1a to 1h, 2a to 2h are approximately parallel to the surfaces of the support substrates 111 and 112 on which the light-emitting elements are installed.
  • eight light-emitting elements 1a to 1h, 2a to 2h are arranged in two rows.
  • 1a, 1b, 1c, and 1d are arranged in this order from the outer periphery of the rotating substrate 62, and in the second row, 1e, 1f, 1g, and 1h are arranged in this order from the inner periphery of the rotating substrate 62.
  • 2e, 2f, 2g, and 2h are arranged in this order from the outer periphery of the rotating substrate 62, and in the second row, 2a, 2b, 2c, and 2d are arranged in this order from the inner periphery of the rotating substrate 62.
  • the eight light-emitting elements 1a to 1h of the first light-emitting element group 101 emit light in different wavelength ranges.
  • the eight light-emitting elements 2a to 2h of the second light-emitting element group 102 emit light in different wavelength ranges.
  • the light-emitting elements of the first light-emitting element group 101 are referred to as first light-emitting elements 1a, 1b, 1c, etc.
  • the light-emitting elements of the second light-emitting element group 102 are referred to as second light-emitting elements 2a, 2b, 2c, etc.
  • the present irradiation device 73 has eight light-emitting element pairs that emit light of the same wavelength. Note that light in the same wavelength range refers to light whose peak wavelengths match within a range of ⁇ 5 nm, and light whose wavelengths match within a range of ⁇ 5 nm is referred to as light of the same wavelength.
  • a pair of light-emitting elements consisting of two light-emitting elements of the same wavelength corresponding to that analytical chip 12 is selectively used from among the light-emitting elements 1a to 1h of the first light-emitting element group 101 and the light-emitting elements 2a to 2h of the second light-emitting element group 102.
  • FIG. 8 is a diagram showing the positional relationship between the measurement reference plane 120 and the first light-emitting element 1a and second light-emitting element 2a.
  • the normal direction of the reaction area 12A of the analytical chip 12 when it is properly loaded in the loading position is the Z axis, and the plane including the reaction area 12A is the XY plane.
  • the center of the reaction area 12A in the XY plane is the origin O.
  • the state in which the analytical chip 12 is properly loaded in the loading position means that the reaction area 12A of the analytical chip 12 is located on the designed measurement surface.
  • This designed measurement surface is called the measurement reference surface 120.
  • the measurement reference surface 120 coincides with the XY plane.
  • the area on the measurement reference surface 120 that corresponds to the reaction area 12A is called the measurement reference area 120A.
  • the surface including the reaction area 12A when the analytical chip 12 is actually loaded is called the measurement surface.
  • the straight line extending from the emission center that coincides with the peak of the light intensity distribution in the emission surface of each light-emitting element 1a to 1h, 2a to 2h in the normal direction of the emission surface is called the emission central axis.
  • the central light-emitting axis of the first light-emitting element 1a is denoted as A1a
  • the central light-emitting axis of the second light-emitting element 2a is denoted as A2a.
  • the relative positional relationship between the first light-emitting element 1a and the second light-emitting element 2a satisfies the following first and second conditions.
  • the first condition concerns the relative positional relationship between the first light-emitting element 1a and the second light-emitting element 2a in the circumferential direction centered on the Z axis.
  • the first condition is that the first light-emitting element 1a and the second light-emitting element 2a are arranged with a central angle ⁇ about the Z axis that is greater than or equal to 90° and less than or equal to 180°. Note that angles such as the central angle include a tolerance of about ⁇ 5°.
  • the central angle ⁇ between the first light-emitting element 1a and the second light-emitting element 2a is slightly smaller than 180°.
  • the first light-emitting element 1a and the second light-emitting element 2a may be arranged so that the central angle ⁇ is 90° or more, but from the viewpoint of averaging the amount of illumination light for the entire reaction area 12A, it is preferable that the central angle ⁇ is closer to 180°, and 180° is most preferable.
  • the second condition relates to a first intersection point P1, which is the intersection point between the first light-emitting central axis A1a of the first light-emitting element 1a and the Z axis, and a second intersection point P2, which is the intersection point between the second light-emitting central axis A2a of the second light-emitting element 2a and the Z axis.
  • the second condition is that, when one side is the positive direction and the other side is the negative direction on the Z axis with respect to the XY plane, one of the first intersection points P1 and the second intersection point P2 is located in the positive direction and the other in the negative direction.
  • the first intersection P1 where the first light-emitting central axis A1a of the first light-emitting element 1a intersects with the Z axis is located in the positive direction of the Z axis from the origin O
  • the second intersection P2 where the second light-emitting central axis A2a of the second light-emitting element 2a intersects with the Z axis is located in the negative direction of the Z axis from the origin O.
  • the first light-emitting element 1a and the second light-emitting element 2a are arranged with a central angle ⁇ of 90° or more and 180° or less about the Z axis. This makes it possible to suppress unevenness in the amount of illumination light in the reaction area 12A when the first light-emitting element 1a and the second light-emitting element 2a irradiate light of the same wavelength.
  • the light-emitting central axis A1a of the first light-emitting element 1a and the light-emitting central axis A2a of the second light-emitting element 2a are arranged to intersect while being shifted in the positive and negative directions along the Z axis from the XY plane, respectively. This makes it possible to suppress fluctuations in the amount of illumination light irradiated to the reaction area 12A even if the actual measurement surface is slightly shifted in the Z direction relative to the measurement reference surface 120.
  • the number of light-emitting elements that emit light of the same wavelength is two, the first light-emitting element 1a and the second light-emitting element 2a, but there may be three or more.
  • three or more light-emitting elements are provided, as long as two of the light-emitting elements satisfy the above relationship as the first light-emitting element 1a and the second light-emitting element 2a, there is no restriction on the arrangement of the other light-emitting elements.
  • two light-emitting elements can suppress unevenness in the amount of illumination light in the measurement surface, and can suppress fluctuations in the amount of illumination light when the measurement surface is shifted in the normal direction relative to the measurement reference surface 120, so two light-emitting elements are most preferable from the viewpoint of cost reduction.
  • the size of the irradiation device 73 can be suppressed and miniaturization can be achieved.
  • the irradiation device 73 can be rectangular with its longitudinal direction aligned with the tangent direction of the circle of the rotating base plate 62.
  • the maximum width of the housing 71 of the photometric unit 70 can be configured to be equal to the longitudinal length of the irradiation device 73.
  • a rotating cylinder 66 with a disposal hole 68 for disposing of the analysis chip 12 in the center is provided at the bottom of the rotating base 62 (see FIG. 1).
  • the irradiation device 73 and photometric unit 70 which are rectangular in plan view and do not protrude toward the inner diameter side of the annular rotating base 62, are suitable for the analysis device 100.
  • the absolute value of the Z coordinate of the first intersection P1 is the same as that of the second intersection P2.
  • the distance of the first intersection P1 from the XY plane is the same as that of the second intersection P2 from the XY plane.
  • the inclination angle of the support substrate 111 of the first light-emitting element group 101 relative to the XY plane is the same as the inclination angle of the support substrate 112 of the second light-emitting element group 102 relative to the XY plane.
  • the light-emitting surfaces of the light-emitting elements 1a to 1h, 2a to 2h are approximately parallel to the surfaces on which the light-emitting elements of the support substrates 111, 112 are installed. That is, the inclination angle of the first light-emitting element 1a relative to the XY plane and the inclination angle of the second light-emitting element 2a relative to the XY plane are equal.
  • the angle ⁇ 1a between the light-emitting central axis A1a perpendicular to the light-emitting surface of the first light-emitting element 1a and the Z axis perpendicular to the XY plane and the angle ⁇ 2a between the light-emitting central axis A2a perpendicular to the light-emitting surface of the second light-emitting element 2a and the Z axis perpendicular to the XY plane are equal.
  • the Z coordinates which are the distances from the XY plane of the first light-emitting element 1a and the second light-emitting element 2a, are different from each other.
  • the Z coordinate Z1a of the first light-emitting element 1a and the Z coordinate Z2a of the second light-emitting element 2a have a relationship of
  • the first intersection point P1 and the second intersection point P2 can be shifted, and a configuration can be easily realized in which one of the first intersection point P1 and the second intersection point P2 is located in the positive direction on the Z axis and the other is located in the negative direction.
  • the coordinates indicating the position of the first light-emitting element 1a are (X1a, Y1a, Z1a) and the coordinates indicating the position of the second light-emitting element 2a are (X2a, Y2a, Z2a)
  • the coordinates of the light emitting element are the coordinates of the center of its light emitting surface.
  • the above formula means that the distance d1a from the first light-emitting element 1a to the origin O and the distance d2a from the second light-emitting element 2a to the origin O are the same.
  • the illumination light amount of the first light-emitting element 1a and the illumination light amount of the second light-emitting element 2a on the measurement reference surface 120 can be made substantially equal, thereby suppressing unevenness in the illumination light amount on the measurement reference surface 120 and making the illumination light amount uniform.
  • the effect of suppressing variations in the illumination light amount when the measurement surface is shifted in the Z-axis direction from the measurement reference surface 120 can be improved.
  • the relationship between the first light-emitting element 1a and the second light-emitting element 2a among the eight light-emitting element pairs in the irradiation device 73 has been described, but it is preferable that the other light-emitting element pairs also satisfy a similar relationship. That is, when the coordinates indicating the position of the first light-emitting element in each light-emitting element pair are (X1, Y1, Z1) and the coordinates indicating the position of the second light-emitting element are (X2, Y2, Z2), it is preferable that the following formula is satisfied.
  • FIG. 9 is a diagram showing the positional relationship between the measurement reference surface 120, the first light-emitting element pair consisting of the first light-emitting element 1a and the second light-emitting element 2a, and the second light-emitting element pair consisting of the first light-emitting element 1h and the second light-emitting element 2h.
  • the first light-emitting element pair consisting of the first light-emitting element 1a and the second light-emitting element 2a
  • the second light-emitting element pair consisting of the first light-emitting element 1h and the second light-emitting element 2h.
  • the center of the light-emitting element is the center of the light-emitting surface of the light-emitting element. Note that in this embodiment, the same relationship exists for light-emitting element pairs other than the first light-emitting element pair and the second light-emitting element pair.
  • the first inclination angle ⁇ 1a of the first light-emitting element 1a of the first light-emitting element pair is equal to the second inclination angle ⁇ 2h of the second light-emitting element 2h of the second light-emitting element pair
  • the first light-emitting elements 1a to 1h are provided on one support substrate 111
  • the second light-emitting elements 2a to 2h are provided on one support substrate 112.
  • the greater the distance of the light-emitting element from the XY plane the greater the absolute value of the Z coordinate
  • the smaller the distance of the light-emitting element from the XY plane the smaller the absolute value of the Z coordinate
  • the illumination light amount in the area where the illumination areas of the two light-emitting elements 1a and 2a of the first light-emitting element pair overlap can be made approximately equal to the illumination light amount in the area where the illumination light amounts of the two light-emitting elements 1h and 2h of the second light-emitting element pair overlap.
  • the lower diagram in Figure 9 shows the irradiation area E1a in the XY plane by the light irradiated from the first light-emitting element 1a, and the irradiation area E2a in the XY plane by the light irradiated from the second light-emitting element 2a.
  • the irradiation areas E1a and E2a overlap over almost the entire area, and since
  • the lower diagram in Figure 9 shows the irradiation area E1h in the XY plane by the light irradiated from the first light-emitting element 1h, and the irradiation area E2h in the XY plane by the light irradiated from the second light-emitting element 2h.
  • the irradiation areas E1h and E2h overlap over almost the entire area, and since
  • the irradiation areas E1a, E2a by the first light-emitting element pair and the irradiation areas E1h, E2h by the second light-emitting element pair are shifted in the XY plane, but each includes the measurement reference surface 120. At least the amount of illumination light on the measurement reference surface 120 by the first light-emitting element pair is approximately equal to the amount of illumination light by the second light-emitting element pair.
  • the irradiation device 73 of this embodiment is configured with eight light-emitting element pairs, but the irradiation device of the present disclosure may be configured with only one light-emitting element pair.
  • the central angle ⁇ between the light-emitting element pairs is slightly smaller than 180°.
  • the light-emitting elements 1a-1d, 2e-2h arranged in the first row of the support substrates 111, 112 are arranged with a gap between them, so that the central angle ⁇ between the light-emitting element pairs can be set to 180°.
  • the central angle ⁇ is 180°, the first and second light-emitting central axes of each light-emitting element pair intersect at a position on the measurement reference surface 120 that is a predetermined distance away from the origin O.
  • FIG. 11 shows the arrangement of the first light emitting element 211 and the second light emitting element 212 with respect to the measurement reference area 120A of the measurement reference surface 120 in the configuration example
  • FIG. 12 shows the arrangement of the first light emitting element 221 and the second light emitting element 222 with respect to the measurement reference area 120A in the comparative example.
  • the measurement reference surface 120 is the XY plane
  • the center of the measurement reference area 120A is the origin O
  • the Z axis passes through the origin O and is taken in the normal direction of the measurement reference surface 120.
  • the first light-emitting element 211 and the second light-emitting element 212 are arranged on the X-axis. That is, the Y coordinates of the first light-emitting element 211 and the second light-emitting element 212 are both 0, and the central angle ⁇ is 180°.
  • the coordinates of the first light-emitting element 211 are (X11, 0, Z11), and the coordinates of the second light-emitting element 212 are (X12, 0, Z12).
  • a first intersection P1 between the light-emitting central axis A11 of the first light-emitting element 211 and the Z-axis is located on the positive side of the Z-axis
  • a second intersection P2 between the light-emitting central axis A12 of the second light-emitting element 212 and the Z-axis is located on the negative side of the Z-axis.
  • the first light-emitting central axis A11 and the second light-emitting central axis A12 intersect at a position that is a distance r away from the origin O on the measurement reference surface 120.
  • the inclination angle ⁇ of the light-emitting central axis A11 of the first light-emitting element 211 with respect to the Z axis and the inclination angle ⁇ of the light-emitting central axis A12 of the second light-emitting element 212 with respect to the Z axis are the same, and are set to 50° here.
  • X11 20.7 mm
  • X12 18.3 mm
  • Z11 13.7 mm
  • Z12 16.8 mm.
  • the first light-emitting element 211 and the second light-emitting element 212 are also arranged on the X-axis. That is, similar to the configuration example, both Y coordinates are 0, and the central angle ⁇ is 180°.
  • the first light-emitting element 221 and the second light-emitting element 222 are arranged symmetrically around the Z-axis. If the coordinates of the first light-emitting element 221 are (X21, 0, Z21) and the coordinates of the second light-emitting element 222 are (X22, 0, Z22), then
  • the light-emitting central axis A21 of the first light-emitting element 221 and the light-emitting central axis A22 of the second light-emitting element 222 intersect at a position P on the positive side of the Z-axis.
  • the inclination angle ⁇ of the light-emitting central axis A21 of the first light-emitting element 221 with respect to the Z-axis and the inclination angle ⁇ of the light-emitting central axis A22 of the second light-emitting element 222 with respect to the Z-axis are the same, and are set to 50° as in the configuration example.
  • the directional characteristics of the LED which is the light-emitting element, is ⁇ 60°, and the size of the measurement surface 121 is 8 mm x 8 mm.
  • a simulation was performed to determine the amount of illumination light on the measurement surface 121 when the positional deviation (height h from the origin) of the measurement surface 121 from the measurement reference surface 120 was changed to -2, -1, 0, 1, and 2 (mm).
  • the amount of illumination light determined by simulation is the total amount of illumination light on the entire measurement surface 121, which is 8 mm x 8 mm in size.
  • Figure 13 is a graph showing the variation in illumination light amount for the configuration example and comparative example, with the height h in Table 1 on the horizontal axis and the illumination light amount ratio on the vertical axis.
  • the comparative example had a variation in illumination light intensity of over 10% within a range of ⁇ 2 mm, whereas the variation in illumination light intensity for the configuration example was 1.5%, showing that the configuration example was able to significantly suppress the variation in illumination light intensity.
  • the results show that by arranging the two light-emitting elements so that one of the intersections P1, P2 between the light-emitting central axis and the Z axis is on the positive side of the Z axis of the reference measurement surface and the other is on the negative side, the variation in illumination light intensity can be significantly improved.
  • An illumination device for irradiating light onto a reaction area of an analytical chip having a planar reaction area on which a reagent that reacts with a test substance contained in a sample is fixed, when optically analyzing the sample comprising:
  • the light emitting device has at least two light emitting elements, a first light emitting element and a second light emitting element, which are light emitting elements that emit light in the same wavelength range,
  • the plane including the reaction area is defined as the XY plane
  • the straight line extending from the light emission center coinciding with the peak of the light intensity distribution in the light emission surface of the light emitting element in the normal direction of the light emission surface is defined as the light emission central axis
  • the relative positional relationship between the first light emitting element and the second light emitting element satisfies the following first and second conditions
  • the second condition is a condition that the intersection point of the first light-emitting central axis of the first light-emitting element and the Z-axis is the first intersection point, and the intersection point of the second light-emitting central axis of the second light-emitting element and the Z-axis is the second intersection point, and further, when one side of the Z-axis is taken as the positive direction and the other side is taken as the negative direction with respect to the XY plane on the Z-axis, one of the first intersection point and the second intersection point is located in the positive direction and the other in the negative direction, in this irradiation device. (Appendix 2) 2.
  • the illumination device of claim 1 wherein the distance of the first intersection from the XY plane is the same as the distance of the second intersection from the XY plane. (Appendix 3) 3.
  • an angle between a light emitting surface of the first light emitting element and the XY plane is equal to an angle between a light emitting surface of the second light emitting element and the XY plane; 4.
  • Appendix 7 A plurality of light-emitting element pairs each including a first light-emitting element and a second light-emitting element, the light-emitting element pairs having different wavelength ranges; An irradiation device described in any one of Appendix 1 to Appendix 5, wherein in at least two of the multiple light-emitting element pairs, the sum of a first inclination angle of a straight line connecting the center of the first light-emitting element to the origin with respect to the Z axis and a second inclination angle of a straight line connecting the center of the second light-emitting element to the origin with respect to the Z axis is identical.
  • Appendix 8 An illumination device as described in Appendix 7, wherein in two light-emitting element pairs, the first inclination angle and the second inclination angle of one light-emitting element pair are the same as either the first inclination angle or the second inclination angle of the other light-emitting element pair.
  • Appendix 9 9. The illumination device according to claim 1, wherein the light-emitting element is a light-emitting diode.
  • a photometric device for optically analyzing a specimen using an analytical chip having a reaction region on which a reagent that reacts with a test substance is fixed comprising: An irradiation device according to any one of claims 1 to 9, A photometric device comprising: a photodetector that detects output light output from the analysis chip when light is irradiated onto the analysis chip, and outputs a detection signal according to the output light.

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005346699A (ja) * 2004-04-24 2005-12-15 Smiths Heimann Biometrics Gmbh 文書上の光学回折構造を検査するための装置および方法
JP2015111132A (ja) * 2009-12-08 2015-06-18 スリーエム イノベイティブ プロパティズ カンパニー 生物学的増殖プレートスキャナーのための照射装置及び方法
WO2017122401A1 (ja) * 2016-01-15 2017-07-20 株式会社Screenホールディングス 撮像装置および撮像方法
JP2019523899A (ja) * 2016-05-31 2019-08-29 モレキュラー デバイシーズ, エルエルシー 傾斜照明を伴う撮像システム

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005346699A (ja) * 2004-04-24 2005-12-15 Smiths Heimann Biometrics Gmbh 文書上の光学回折構造を検査するための装置および方法
JP2015111132A (ja) * 2009-12-08 2015-06-18 スリーエム イノベイティブ プロパティズ カンパニー 生物学的増殖プレートスキャナーのための照射装置及び方法
WO2017122401A1 (ja) * 2016-01-15 2017-07-20 株式会社Screenホールディングス 撮像装置および撮像方法
JP2019523899A (ja) * 2016-05-31 2019-08-29 モレキュラー デバイシーズ, エルエルシー 傾斜照明を伴う撮像システム

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