WO2014038399A1 - Instrument de mesure et appareil de mesure - Google Patents

Instrument de mesure et appareil de mesure Download PDF

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Publication number
WO2014038399A1
WO2014038399A1 PCT/JP2013/072544 JP2013072544W WO2014038399A1 WO 2014038399 A1 WO2014038399 A1 WO 2014038399A1 JP 2013072544 W JP2013072544 W JP 2013072544W WO 2014038399 A1 WO2014038399 A1 WO 2014038399A1
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WIPO (PCT)
Prior art keywords
reagent
measurement
measuring
component
particles
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PCT/JP2013/072544
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English (en)
Japanese (ja)
Inventor
克佳 高橋
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シャープ株式会社
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Publication of WO2014038399A1 publication Critical patent/WO2014038399A1/fr

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502746—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means for controlling flow resistance, e.g. flow controllers, baffles
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/14—Optical investigation techniques, e.g. flow cytometry
    • G01N15/1484—Optical investigation techniques, e.g. flow cytometry microstructural devices
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483—Physical analysis of biological material
    • G01N33/487—Physical analysis of biological material of liquid biological material
    • G01N33/49—Blood
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483—Physical analysis of biological material
    • G01N33/487—Physical analysis of biological material of liquid biological material
    • G01N33/493—Physical analysis of biological material of liquid biological material urine
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/16—Reagents, handling or storing thereof
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0867—Multiple inlets and one sample wells, e.g. mixing, dilution
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0688—Valves, specific forms thereof surface tension valves, capillary stop, capillary break
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/08—Regulating or influencing the flow resistance
    • B01L2400/084—Passive control of flow resistance
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502715—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N2015/1006—Investigating individual particles for cytology
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/14—Optical investigation techniques, e.g. flow cytometry
    • G01N2015/1486—Counting the particles
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01—Arrangements or apparatus for facilitating the optical investigation
    • G01N21/03—Cuvette constructions
    • G01N2021/0378—Shapes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01—Arrangements or apparatus for facilitating the optical investigation
    • G01N21/03—Cuvette constructions

Definitions

  • the present invention relates to a measuring instrument provided with a measuring unit for measuring a component contained in a reagent, and a measuring apparatus that performs measurement using the measuring instrument. More specifically, the present invention relates to a measurement instrument including measurement units having different depths, and a measurement apparatus that performs measurement using the measurement instrument.
  • various measuring instruments and measuring devices are used to measure components contained in blood, urine, saliva and the like, for example.
  • components in various reagents are measured for inspection of contamination of pharmaceuticals and foods, monitoring of tap water, industrial wastewater, and the like.
  • Examples of the measuring instrument used for measuring the components in the reagent include a hemocytometer for measuring red blood cells, white blood cells, platelets and the like contained in blood.
  • Patent Document 1 describes a counting board having a main body having a counting unit for calculating the number of observation objects and a cover by means of a scale provided in a grid pattern.
  • the counting board has a locking member for positioning and fixing the cover with respect to the main body.
  • Patent Document 2 describes a blood cell calculation plate comprising a calculation plate main body having a blood cell counting scale, and an observation plate fixed to the calculation plate main body with an adhesive. Yes.
  • a spacer is mixed in the adhesive in order to maintain the calculation plate main body and the observation plate in a close arrangement and in a parallel arrangement with a certain interval.
  • Patent Document 3 describes an apparatus for counting specific elements in a biological fluid sample, which includes two planar members separated from each other at a substantially uniform height. In the apparatus, the height is such that when the biological fluid sample is introduced, the specific elements are unevenly distributed.
  • Patent Document 4 describes an analysis container in which a well having a flat bottom surface is formed on a plate surface.
  • the bottom and side surfaces of the well are made of the same material and have heat resistance.
  • Patent Document 5 describes a sample cell having two cell parts that can be manually adjusted.
  • the sample cell can assume a first position suitable for analyte measurement and a second position suitable for washing the sample path by sliding the cell portions relative to each other.
  • the measurement signal of the component is not a signal that can be measured by the measurement system unless the reagent is diluted or concentrated. There is a problem that the component measurement cannot be performed quantitatively because it does not fall within the range.
  • the component contained in the reagent is measured, for example, in a measurement system (for example, transmitted light measurement) in which the measurement signal of the component increases in proportion to the depth of the measurement unit.
  • a measurement system for example, transmitted light measurement
  • the measurement signal of the component may fall within the measurable signal range of the measurement system depending on the concentration of the component. Absent. That is, when a large amount of reagent containing a high concentration component is introduced into the measurement unit, the measurement signal of the component may exceed the upper limit of the signal range measurable by the measurement system.
  • the measurement signal of the component may fall below the lower limit of the measurable signal range of the measurement system.
  • some conventional instrument for measuring particles has two measuring units, but the measuring units have the same depth (for example, 0.1 mm).
  • the concentration ratio of red blood cells and white blood cells in blood is 1000: 1
  • blood is diluted with a large amount of diluent (for example, 200 times volume ratio), and white blood cells are measured.
  • a diluent for example, 200 times volume ratio
  • a diluent staining solution
  • a part of each dilution is collected, introduced into two measuring parts (for example, 10 ⁇ L in volume), and measured.
  • the number of red blood cells in the dilution is large, counting accuracy can be maintained by converting the concentration after measuring one region in the measurement part.
  • the number of white blood cells in the blood is smaller than the number of red blood cells, and therefore the number of white blood cells in the diluted solution is also small. Therefore, in order to maintain the counting accuracy, it is necessary to measure a wide area in the measurement unit.
  • Patent Documents 1 to 5 have a configuration in which the measurement signals of the components contained in the reagent can be kept within the measurable signal range of the measurement system without diluting or concentrating the reagent as described above. No suggestion has been made.
  • the present invention has been made in view of the above problems, and its purpose is to include measurement signals of components contained in a reagent within a signal that can be measured by a measurement system without diluting or concentrating the reagent. It is an object of the present invention to provide a measuring instrument and a measuring apparatus that can be stored and can quantitatively measure components.
  • a measuring instrument is a measuring instrument for measuring a component in a reagent in order to solve the above-described problem, and stores the reagent and includes the component in the stored reagent.
  • a measurement unit that measures components in the reagent by irradiating light is provided, and the depth of the measurement unit in the light transmission direction is different.
  • the measuring instrument includes a measuring unit that stores a reagent and measures a component in the reagent by irradiating light to the component in the stored reagent.
  • the depth of the measurement part in the light transmission direction is different.
  • the concentration of the component is unknown, it is measured in the shallow area of the measurement unit when the concentration of the component is high, and conversely, when the concentration of the component is low, measurement is performed in the deep area of the measurement unit.
  • the measurement signal of the component can be stored within the measurable signal range, and the components in the reagent can be measured quantitatively.
  • FIG. (A) is a top view of the measuring instrument according to the first embodiment, and (b) to (f) are cross-sectional views taken along the dotted line AA ′ in (a), showing a modification of the measuring unit.
  • FIG. (G) is sectional drawing which shows the instrument for a measurement with the same depth of a measurement part.
  • (A) is a top view of the measuring instrument according to the first embodiment, and (b) to (d) are cross-sectional views taken along the dotted line AA ′ in (a), showing a modification of the measuring unit.
  • FIG. It is a top view which shows the modification of the measurement part of the instrument for a measurement which concerns on 1st Embodiment.
  • FIG. (A) is the schematic which shows the example which introduce
  • FIG. (B) is the schematic which shows the example which introduce
  • (A) And (c) is the schematic which shows the measuring method using the instrument for a measurement which concerns on 1st Embodiment, (b) is a figure which shows the measurement result in (a), (d) is It is a figure which shows the measurement result in (c).
  • (A) And (c) is the schematic which shows the measuring method using the instrument for a measurement which concerns on 1st Embodiment, (b) is a figure which shows the measurement result in (a), (d) is It is a figure which shows the measurement result in (c).
  • FIG. 1A is a plan view showing a measuring instrument 10 according to the present invention.
  • the measuring instrument 10 is a measuring instrument for measuring the components in the reagent, and includes a measuring unit 1 as shown in FIG.
  • reagent means a substance containing a component to be measured.
  • the reagent is preferably a fluid, and more preferably a liquid. According to the said structure, a reagent can be easily introduce
  • the “component” is a substance that is contained in the reagent and is the object of measurement. Although it does not specifically limit as an example of the component used as a measuring object, For example, a biomolecule is mentioned. According to the said structure, the measuring instrument of this invention can be used for the measurement of the biomolecule in a reagent. Examples of biomolecules include nucleic acids, proteins, and sugars.
  • the component may be a particle. According to the said structure, the measuring instrument of this invention can be used for the measurement of the particle
  • the components in the reagent may be at least two or more components, and the concentration of any two of the two or more components may be different.
  • the at least two or more types of components may be particles, and the concentration of any two types of the two or more types of particles may be different.
  • the measuring instrument of this invention can be used for the measurement of the reagent containing 2 or more types of particle
  • the measuring unit 1 stores the reagent and measures the components in the reagent by irradiating light to the components in the stored reagent.
  • the measurement unit 1 has different depths in the light transmission direction. According to the above configuration, even if the concentration of the component is unknown, the component is relatively shallow when the concentration of the component is high, and conversely when the concentration of the component is low, the component is relatively By measuring in a deep region, the measurement signal of the component can be contained within the range of signals that can be measured by the measurement system, and the component in the reagent can be quantitatively measured. Therefore, there is no need to dilute or concentrate the reagent so as to match the detection range of the measurement system, and quantitative measurement of the components becomes possible simply by introducing the reagent into the measurement unit. Details of the measuring method using the measuring instrument 10 will be described later.
  • the depth are different the depth of the shallowest portion T s of the measuring unit, when the depth of the deepest portion of the measuring portion was T d, and T s It means that Td is clearly different.
  • T d 5 ⁇ T d / T s ⁇ 5000 It is preferable that the relationship is satisfied.
  • the depth of a measurement part will be changed greatly (in other words, it will become a measurement part which has both a very shallow area
  • FIG. 1B to 1F are cross-sectional views taken along the dotted line A-A ′ in FIG. 1A, showing a modification of the measuring unit 1.
  • the measurement unit 1 is formed by bonding the substrates 101 and 102 together.
  • the measurement unit 1 is irradiated with light from the substrate 101 side or the substrate 102 side for measurement.
  • the measurement unit 1 may have one region having a relatively shallow depth and one deep region in the light transmission direction.
  • the depth in the light transmission direction, the region where the depth in the light transmission direction is relatively shallow, and the region where the depth in the light transmission direction is relatively deep are simply referred to as “depth”. ”,“ Shallow region ”, and“ deep region ”.
  • the measuring unit 1 may have three or more regions having different depths. That is, for example, as shown in FIG. 1 (c), at least one of the wall surfaces surrounding the space for storing the reagent of the measuring unit 1 may be stepped. Further, for example, as shown in FIG. 1 (d), the depth of the measurement unit 1 may change smoothly.
  • At least one of the wall surfaces surrounding the space for storing the reagent of the measurement unit 1 may be formed on substantially the same plane. According to the above configuration, since the components in the reagent can be arranged on substantially the same plane, the position of the observation point in the depth direction of the measurement unit when performing measurement in part of the depth direction of the measurement unit It is possible to measure with high accuracy without causing an error due to the difference.
  • the “wall surface surrounding the space for storing the reagent” of the measurement unit may be simply referred to as “wall surface” of the measurement unit.
  • the “at least one of the wall surfaces” is preferably a surface perpendicular to the depth direction.
  • the depth direction and the gravity direction are parallel, one surface perpendicular to the depth direction of the wall surface and one surface below the gravity direction is referred to as a “bottom surface”.
  • the upper surface may be referred to as the “upper surface”.
  • the bottom surface is formed on substantially the same plane as shown in FIG. 1 (e)
  • the components in the reagent are allowed to settle according to gravity after introduction of the measurement unit, and are arranged on the substantially same plane (measurement unit bottom surface). Therefore, an error due to the difference in the position of the observation point in the depth direction of the measurement unit does not occur, and highly accurate measurement can be performed.
  • the phrase “at least one of the wall surfaces surrounding the space for storing the reagent is formed on substantially the same plane” of the measuring unit 1 means that any one point on the at least one surface. between a plane A including a and perpendicular to the depth direction and a plane B including any one point b different from a on the at least one plane and perpendicular to the depth direction It means that the distance L is 1 nm or more and 1 mm or less.
  • at least one of the wall surfaces surrounding the space for storing the reagent of the measuring unit 1 is formed on the same plane.
  • the distance L is preferably 1 nm or more and the distance d or less, where d is the particle diameter.
  • the distance d takes a value of several to several tens of ⁇ m.
  • the upper limit value of the distance L is preferably equal to or less than the depth of field C calculated from the focal depth c and the particle diameter d of the condensing element.
  • the upper limit value of the distance L is preferably not more than the depth of focus c of the light collecting element.
  • the measurement unit 1 may have a deep region around a shallow region.
  • a shallow region may be provided at the center of the deep region, or the deep region and the shallow region may be alternately provided in a row.
  • FIG. 1G is a cross-sectional view showing a measuring instrument that is the same depth as the measuring unit 1 and is not included in the present invention.
  • the difference in the depth of the measurement unit 1 is caused by, for example, variations during molding of the measurement unit 1.
  • (g) in FIG. 1 clearly not different from the depth T d of the deepest portion of the depth T s and the measuring section 1 of the shallowest part of the measuring unit 1, for example, T d / T s ⁇ 1 .1.
  • the measurement unit 1 includes a plurality of reagents stored in measurement units having different depths in a direction substantially parallel to the depth direction of the measurement unit 1, respectively.
  • the measurement part is divided
  • substantially parallel to the depth direction means that the smaller one of the angles formed by the intersection of the depth direction of the measurement unit 1 and the partition wall is 0 ° or more and less than 45 °.
  • the smaller angle is more preferably 0 ° (that is, the depth direction of the measurement unit 1 and the partition wall are parallel).
  • a plurality of reagents stored in measurement units having different depths may be different reagents or the same reagent. That is, the same reagent may be introduced into the measurement parts with different depths separated by the partition walls 2. According to the said structure, even if it is the same kind of reagent, it can prevent mixing.
  • FIG. 2 is a top view of the measuring instrument 10 provided with the partition wall 2.
  • the shallow region 1 s and the deep region 1 d of the measurement unit of the measurement instrument 10 are separated by the partition wall 2.
  • FIGS. 2B to 2D are cross-sectional views taken along the dotted line A-A ′ in FIG. 2A, and show modifications of the shallow region 1s and the deep region 1d.
  • At least one of the wall surfaces of the measurement unit may be on substantially the same plane.
  • the bottom surfaces of the shallow region 1s and the deep region 1d may be on substantially the same plane.
  • the component in the reagent can be settled according to gravity after introduction of the measurement unit, and the component can be arranged on the same plane (measurement unit bottom surface), so the position of the observation point in the depth direction of the measurement unit It is possible to measure with high accuracy without causing an error due to the difference.
  • the upper surfaces of the shallow region 1s and the deep region 1d may be substantially on the same plane.
  • each of the shallow region 1s and the deep region 1d may further include regions having different depths. According to the above configuration, since the measuring instrument has a measurement unit with various depths, even if the concentration of the component in the reagent is unknown, the component having a wide range of concentrations that can exist in the reagent, Two components having a large concentration difference can be reliably measured with one measuring instrument.
  • FIG. 3 is a top view showing a modification of the measurement unit of the measurement instrument according to the present embodiment.
  • the shape seen from the upper surface of the measuring unit 1 is not particularly limited, and for example, a rhombus as shown in FIG. 3A, a circle as shown in FIG. 3B, or as shown in FIG. It may be oval.
  • the measuring instrument 10 may include two or more partition walls.
  • FIG. 3D shows, as an example, a measuring instrument 10 in which a shallow region 1s, a deep region 1d, and a deeper region 1da are separated by two partition walls.
  • the method for producing the measurement instrument 10 is not particularly limited, and examples thereof include the method shown in FIGS.
  • 4 (a) and 4 (b) are schematic diagrams showing a method for producing the measuring instrument 10 that does not include a partition wall.
  • the measurement instrument 10 is manufactured by bonding the substrate 102 and the substrate 101 on which grooves corresponding to the shallow region 1s and the deep region 1d are formed.
  • the substrate 101 having the groove 1d ′ having the same depth, the substrate 103 having the through hole 1h, and the substrate 102 are bonded together in this order. 10 is manufactured.
  • a part of the through hole 1h overlaps the groove 1d '.
  • the measuring instrument 10 shown in FIG. 1 (b) can be produced. That is, in FIG. 4A, the measurement unit 1 is formed by grooves corresponding to the shallow region 1s and the deep region 1d. In FIG. 4B, the measurement unit 1 is formed by the through hole 1h and the groove 1d '. 4A and 4B, the substrate 102 may not have a groove, or may have a groove corresponding to the shallow region 1s and / or the deep region 1d.
  • 5 (a) to 5 (c) are schematic views showing a method for producing the measuring instrument 10 having a partition wall.
  • the measurement instrument 10 is manufactured by bonding the substrate 103 and the substrate 102 in this order.
  • the substrate 104, the substrate 101 in which the through hole 1sh and the through hole 1dh ′ are formed, the substrate 103 in which the through hole 1dh is formed at a position overlapping the through hole 1dh ′, the substrate 102, Are bonded together in this order to produce the measuring instrument 10.
  • the measurement instrument 10 is manufactured by bonding the substrate 102 and the substrate 101 on which grooves corresponding to the shallow region 1s and the deep region 1d are formed.
  • the measuring instrument 10 shown in FIG. 2B can be manufactured. That is, in FIG. 5A, the shallow region 1s is formed by the groove 1s, and the deep region 1d is formed by the through hole 1dh and the groove 1d '. In FIG. 5B, a shallow region 1s is formed by the through hole 1sh, and a deep region 1d is formed by the through holes 1dh and 1dh '. In FIG. 5C, a shallow region 1s is formed by the groove 1s, and a deep region 1d is formed by the groove 1d. 5 (a) to 5 (c), the substrate 102 and the substrate 104 may not have grooves, or may have grooves corresponding to the shallow region 1s and / or the deep region 1d. .
  • the method for forming the groove and the through hole is not particularly limited.
  • a method for excavating a substrate by machining or laser processing, or injection using a mold having irregularities corresponding to the groove and / or the through hole examples include molding, press molding, and casting.
  • the material of the substrates 101 to 104 is not particularly limited, but for example, glass, silicon, plastic, or the like can be used.
  • the measurement instrument according to this embodiment is connected to the measurement unit 1, is connected to the reagent introduction unit 3 for introducing the reagent into the measurement unit 1, and the measurement unit 1, and derives the reagent from the measurement unit 1. And a reagent derivation unit 4.
  • a reagent can be efficiently introduce
  • the reagent can be continuously or repeatedly supplied to the measuring unit 1 and the measurement accuracy can be increased.
  • another structure it is the same as that of the instrument for a measurement which concerns on 1st Embodiment, The description regarding these structures is abbreviate
  • 6A to 6C are top views showing modifications of the reagent introduction unit 3 and the reagent derivation unit 4 of the measuring instrument 10 according to this embodiment.
  • the reagent introduction unit 3 may be configured to be able to introduce the reagent into the measurement unit 1
  • the reagent derivation unit 4 may be configured to be able to derive the reagent from the measurement unit 1.
  • FIG. 6A when the measurement unit 1 has a rectangular cross section when viewed from the top surface of the measurement instrument 10 according to this embodiment, the measurement unit is arranged along one side of the rectangular cross section.
  • a through hole that connects the inside of 1 and the outside of the measuring instrument 10 may be formed in the measuring instrument 10, and the through hole may be used as the reagent introduction part 3.
  • a through hole that connects the inside of the measuring unit 1 and the outside of the measuring instrument 10 along the opposite side of the one side may be formed in the measuring instrument 10, and the through hole may be used as the reagent deriving unit 4.
  • the reagent introduction part may be composed of a reagent introduction hole 5 for introducing a reagent into the measurement part 1 and a reagent introduction path 6 for connecting the reagent introduction hole 5 and the measurement part 1.
  • a reagent can be introduce
  • the reagent deriving unit may be configured by a reagent deriving hole 7 for deriving a reagent from the measuring unit 1 and a reagent deriving path 8 that connects the reagent deriving hole 7 and the measuring unit 1.
  • the positions of the reagent introduction hole 5 and the reagent introduction path 6 are not particularly limited as long as the reagent can be introduced into the measuring section 1, and the positions of the reagent outlet hole 7 and the reagent outlet path 8 are not particularly limited as long as the reagent can be derived from the measuring section 1.
  • the reagent introduction path 6 and the reagent lead-out path 8 may be arranged at positions that are line-symmetric with respect to the measurement unit 1 as shown in FIG. As shown in (c) of FIG. 6, it may be arranged at a position that is point-symmetric with respect to the measurement unit 1.
  • FIG. 7A to 7D are top views showing modified examples of the reagent introduction part and the reagent lead-out part when the measuring instrument 10 according to this embodiment includes a partition wall.
  • the measuring instrument 10 may be provided with a reagent introduction unit for introducing a reagent into each of the shallow region 1s and the deep region 1d, or a common reagent introduction unit 3 as shown in FIG. You may have.
  • the measuring instrument 10 is separately provided with reagent deriving portions 4a and 4b for deriving a reagent from each of the shallow region 1s and the deep region 1d, but the shallow region 1s and the deep region 1d are provided.
  • a common reagent deriving unit may be provided.
  • the reagent introduction path 6 has a branch structure, and each of the branched reagent introduction paths 6 is connected to each of the regions having different depths of the measurement unit. It may be. According to the said structure, the same reagent can be introduce
  • the reagent introduction hole may be connected to an external mechanism for injecting the reagent, it needs to have a certain size (a size that can be connected to the external mechanism) and is formed as a through hole. Therefore, the volume is larger than the reagent introduction path. Therefore, the amount of reagent necessary for measurement can be reduced by the amount of the reagent introduction hole decreased. Furthermore, the reagent of the same composition (concentration) can be surely introduced into two or more measurement parts. That is, in the measurement, there is no error caused by connecting an external mechanism for injecting the reagent to the plurality of reagent introduction holes.
  • the reagent outlet hole 7a and the reagent outlet path 8a for leading the reagent from each of the shallow region 1s and the deep region 1d, and the reagent A lead-out hole 7b and a reagent lead-out path 8b may be provided.
  • the reagent outlet path 8 has a branched structure, and each of the branched reagent outlet paths 8 is connected to each of the shallow region 1s and the deep region 1d. Good.
  • the measurement instrument 10 may be provided with a reagent introduction hole and a reagent introduction path corresponding to each of the measurement units having different depths, and a reagent lead-out hole and a reagent lead-out path. That is, for example, as shown in FIG. 7D, the reagent introduction hole 5a and the shallow region 1s are connected by the reagent introduction path 6a, and the reagent lead-out hole 7a and the shallow region 1s are connected by the reagent lead-out path 8a.
  • the reagent introduction hole 5b and the deep region 1d may be connected by the reagent introduction path 6b, and the reagent lead-out hole 7b and the deep region 1d may be connected by the reagent lead-out path 8b. According to the above configuration, different reagents can be introduced into each of the shallow region 1s and the deep region 1d.
  • the wall surface surrounding the space for storing the reagent of the measurement unit 1 is lyophilic with respect to the reagent in contact with the wall surface ( That is, the contact angle is 0 ° or more and less than 90 °, and at least a part of the reagent deriving unit 4 that is in contact with the reagent is liquid repellent with respect to the reagent (that is, the contact angle is 90 ° or more and 180 °). Or less).
  • the reagent can be introduced into the measuring unit by capillary force, and the reagent is stopped by the surface tension at the reagent deriving unit, so that a mechanism such as a pump is not required, and the reagent is simply and reliably introduced into the measuring unit. can do.
  • the volume of the reagent used for the measurement can be reliably made equal to the volume of the measurement unit, and the measurement accuracy (concentration measurement) can be increased.
  • known methods can be used as a method for imparting lyophilicity to the wall surface of the measurement unit 1 and a method for imparting liquid repellency to at least a partial region of the reagent deriving unit 4.
  • FIG. 8 shows a top view of the measuring instrument 10 in which the wall surface of the measuring unit 1 is lyophilic and a partial region of the reagent deriving unit 4 is liquid repellent.
  • FIGS. 8B to 8D are schematic views showing a method for introducing the reagent 200 using the measuring instrument 10 according to FIG.
  • a method for introducing the reagent 200 will be described with reference to (b) to (d) of FIG.
  • the reagent 200 is introduced into the reagent introduction unit 3.
  • the reagent 200 proceeds inside the measurement unit 1 whose wall surface is lyophilic.
  • the reagent 200 stops immediately before the reagent deriving unit 4 due to the surface tension of the reagent deriving unit 4 whose partial region is liquid repellent.
  • the reagent introduction part 3 (or the reagent introduction path 6) may have any shape that can introduce the reagent into the measurement part 1, and the reagent derivation part 4 (or the reagent delivery path 8) may have any shape that can derive the reagent from the measurement part 1.
  • FIG. 9A shows a top view of the measuring instrument 10 according to this embodiment.
  • FIGS. 9B to 9D are cross-sectional views taken along the dotted line BB ′ in FIG. 9A, and show modified examples of the reagent introduction part 3 and the reagent derivation part 4a (and 4b). .
  • FIG. 9 shows an example in which the measurement instrument 10 includes a partition wall, and includes a common reagent introduction unit 3 and separate reagent extraction units 4a and 4b for the shallow region 1s and the deep region 1d.
  • the same shapes as in (b) to (d) of FIG. 9 can be taken.
  • the reagent introduction unit 3 includes the reagent introduction path 6 and when the reagent derivation unit 4 includes the reagent extraction path 8, the same configuration as described above can be taken.
  • the reagent introducing unit 3 and the reagent deriving unit 4a (and 4b) may be configured to intersect perpendicularly with the measuring unit (the shallow region 1s and the deep region 1d) as shown in FIG. 9B.
  • the shape of the cross-section of the channel 6) is from the end of the reagent introduction part 3 opened to the atmosphere (or the connection end between the reagent introduction path 6 and the reagent introduction hole 5), and the reagent introduction part 3 (or the reagent introduction path 6). It is preferable to have a reverse taper shape toward the connection end of the measurement portion (shallow region 1s and deep region 1d).
  • reverse taper shape means a cross section of the reagent introduction part 3 (or reagent introduction path 6) in a direction orthogonal to the direction of transfer of the reagent in the reagent introduction part 3 (or reagent introduction path 6). From the end of the reagent introduction part 3 opened to the atmosphere (or the connection end between the reagent introduction path 6 and the reagent introduction hole 5), the area viewed from the upper surface of the reagent introduction part 3 (or the reagent introduction path 6) This means that it is larger toward the connection end with the measurement unit 1 (the shallow region 1s and the deep region 1d).
  • the reagent introduction part or the reagent introduction path has a reverse taper shape”.
  • the area seen from the upper surface of the cross section of the reagent introduction part 3 (or reagent introduction path 6) in the direction orthogonal to the transfer direction in the reagent introduction part 3 (or reagent introduction path 6) of the reagent is the reagent introduction.
  • the reagent introduction unit 3 (or the reagent introduction channel 6) and the measurement unit 1 may increase smoothly toward the connection end with 1d), or as shown in FIG. 9 (d), the reagent introduction part 3 (or the reagent introduction path 6).
  • the wall surface with may be stepped.
  • a reagent introduction part (or reagent introduction
  • released by the atmosphere of a reagent introduction part Is formed smoothly between the connection end of the channel and the measuring unit, so that the concentration of the components in the reagent is introduced without the reagent staying at the connecting end of the reagent introducing unit (or the reagent introducing channel) and the measuring unit. Since it can prevent changing with a part (or reagent introduction path) and a measurement part, a highly accurate measuring instrument can be provided.
  • a pretreatment path 9 for introducing a pretreatment agent for bringing the components in the reagent into a state that can be measured by the measurement unit is connected to the reagent introduction path 6. Yes.
  • the pre-processing operation for making the component in a reagent measurable in a measurement part is required, it is a measurement instrument, without using external instruments other than a measurement instrument Alone, the components in the reagent can be measured.
  • the instrument for a measurement which concerns on 1st and 2nd embodiment The description regarding these structures is abbreviate
  • FIGS. 11A to 11D are top views of the measuring instrument 10 according to the present embodiment, showing a modification of the pretreatment path 9.
  • a partition is provided, the reagent introduction path 6 is branched, and the regions 1 s and 1 d having different depths of the measurement unit are respectively connected to the reagent outlet paths 8 a and 8 b and the reagent outlet holes 7 a and 7 b.
  • 1 shows a measuring instrument 10 comprising:
  • the pretreatment path 9 may connect one end of the reagent introduction path 6 and the pretreatment agent introduction hole 11.
  • the pretreatment path 9a for connecting one of the reagent introduction paths 6 and the pretreatment agent introduction hole 11a, and the other branch of the reagent introduction path 6 A pretreatment path 9b for connecting the pretreatment agent introduction hole 11b may be provided.
  • a plurality of pretreatment paths may be connected to one side where the reagent introduction path 6 is branched.
  • the pretreatment path 9a ′ for connecting the branched one of the reagent introduction paths 6 connected to the pretreatment path 9a and the pretreatment agent introduction hole 11a ′.
  • a pretreatment path 9b ′ for connecting the other branched branch of the reagent introduction path 6 to which the pretreatment path 9b is connected to the pretreatment agent introduction hole 11b ′ may be provided.
  • the pretreatment path 9a and the pretreatment path 9a ′ may be connected to the opposite side across the branched reagent introduction path 6, for example, FIG.
  • the branched reagent supply path 6 may be connected in the same direction.
  • the positional relationship between the preprocessing path 9b and the preprocessing path 9b ' is the same as described above.
  • the pretreatment agent when red blood cells are contained in the reagent, the pretreatment agent preferably contains a hemolytic agent that hemolyzes red blood cells.
  • erythrocytes are removed only by introduce
  • the measuring instrument is used for measuring the components in the reagent by irradiating the components in the reagent stored in the measuring unit with light.
  • the reagent is irradiated with incident light such as ultraviolet light or visible light, and the absorbance of the component in the reagent (including the case where the absorbing dye is labeled on the component in the reagent) or in the reagent
  • incident light such as ultraviolet light or visible light
  • the absorbance of the component in the reagent including the case where the absorbing dye is labeled on the component in the reagent
  • a method of measuring scattered light (or attenuation of incident light due to scattering) by a component a method of labeling a component in a reagent with a fluorescent dye, irradiating the component with excitation light, and measuring a fluorescence amount, etc. Can be mentioned.
  • FIGS. 12-14 the depth of the shallow region as T 1, and the depth of the deep region to the T 2.
  • FIG. 12 shows a measurement method in the case of using the measurement instrument 10 (measurement instrument 10 corresponding to (b) of FIG. 1) not provided with a partition wall.
  • FIG. 12A shows the measuring instrument 10 into which a reagent containing a relatively high concentration component is introduced
  • FIG. 12B shows the measurement result in the case of FIG. Is shown.
  • 12 (c) shows the measuring instrument 10 in which a reagent containing a relatively low concentration component is introduced
  • FIG. 12 (d) shows the case of FIG. 12 (c). The measurement results are shown.
  • the true value of the component signal value is the upper limit of the measurable signal range (measurement). Exceeding the detection limit of the device). However, in the shallow region, the true value of the signal value of the component can be kept within the signal range measurable by the measuring device.
  • the signal value of a component represents the light absorbency, scattered light, fluorescence amount, etc. which were mentioned above, for example, and is also called a measurement signal.
  • the true value of the component signal value is the lower limit of the measurable signal range of the measuring device in the shallow region. (Lower detection limit of the measuring device). However, in the deep region, the true value of the signal value of the component can be kept within the signal range measurable by the measuring device.
  • FIG. 13 shows a measurement method in the case of using the measurement instrument 10 having a partition wall (measurement instrument 10 corresponding to FIG. 2B).
  • FIG. 13A shows the measuring instrument 10 into which a reagent containing a relatively high concentration component is introduced
  • FIG. 13B shows the measurement result in the case of FIG. Is shown.
  • FIG. 13 (c) shows the measuring instrument 10 into which a reagent containing a relatively low concentration component is introduced
  • FIG. 13 (d) shows the case of FIG. 13 (c). The measurement results are shown.
  • the true value of the signal value of the component is deep in the deep region.
  • the true value of the component signal value can be kept within the measurable signal range of the measuring device (FIG. 13B).
  • the true value of the component signal value is below the lower limit of the measurable signal range of the measuring device in the shallow region, but in the deep region, The true value of the signal value can be within the range of the signal that can be measured by the measuring apparatus ((d) in FIG. 13).
  • the relatively shallow region of the measurement unit is a region for measuring a component having a relatively high concentration
  • the relatively deep region of the measurement unit is for measuring a component having a relatively low concentration.
  • a region is preferred.
  • the concentration of the relatively high concentration particle is C 1
  • the maximum diameter of the particle is D 1
  • the concentration of the relatively low concentration particle is C 2
  • the maximum diameter of the particles and D 2 T 1 the depth of the relatively shallow region of the measuring section, when the depth relatively deep region of the measuring portion was T 2, T 1 ⁇ D 1 and T 2 ⁇ D 2 and 0.01 ⁇ (T 2 / T 1 ) / (C 1 / C 2 ) ⁇ 10 It is preferable to satisfy the relationship.
  • the particles can be reliably introduced into the measurement unit, and even if the concentration ratio is large, a certain number of particles necessary for maintaining measurement accuracy can be obtained according to the depth of the measurement unit.
  • a measuring instrument that can be held in the measuring section and has high accuracy can be provided. That is, by holding particles having a relatively high concentration in a shallow region, the number of particles can be suppressed to such an extent that the signal value of the component does not exceed the upper limit of the signal range measurable by the measuring device. In addition, by holding particles having a relatively low concentration in a deep region, it is possible to secure the number of particles so that the signal value of the component does not fall below the lower limit of the signal range measurable by the measuring device.
  • the relatively low concentration particles may be white blood cells, and the relatively high concentration particles may be red blood cells or platelets.
  • the measuring instrument of this invention can be utilized for the measurement of the white blood cell, the red blood cell, and the platelet in a blood reagent.
  • FIG. 14A corresponds to the measuring instrument 10 shown in FIG.
  • the measurement may be performed with the particles dispersed in the measurement unit as shown in FIG.
  • the particle 30a having a relatively high concentration is measured in the shallow region 1s
  • the particle 30b having a relatively low concentration is preferably measured in the deep region 1d.
  • the particles 30a having a relatively high concentration can be held in a range where the signal value of the component does not exceed the upper limit of the signal range measurable by the measuring device, and at a relatively low concentration. Since a certain particle 30b has a sufficient number of particles in the depth direction, the signal value of the component can be held in a range that does not fall below the lower limit of the signal range measurable by the measuring device.
  • the reagent contains the particles and a solvent, and the specific gravity of the particles with respect to the solvent is greater than 1. According to the said structure, after introduce
  • the measurement may be performed in a state where the particles have settled on the bottom surface of the measurement unit.
  • a concentration effect according to the depth of the measurement part can be exerted in the measurement. That is, even with a relatively low concentration of particles 30b, there is a sufficient number of particles in the depth direction, so that a sufficient number of particles can be settled on the bottom surface of the deep region 1d. That is, the particles can be concentrated on the bottom surface. Therefore, it is possible to perform particle measurement with high measurement accuracy while maintaining the downsizing of the measurement instrument without increasing the measurement area.
  • the measuring apparatus 20 is a measuring apparatus for optically measuring a component in a reagent, which includes a light source 12 and a detecting element 13.
  • the measuring apparatus which measures the presence or absence or density
  • Other configurations are the same as those of the measurement instrument according to the first to third embodiments, and a description thereof will be omitted.
  • FIGS. 15A to 15D are schematic views showing a modification of the measuring apparatus according to the present embodiment.
  • the light source 12 is for irradiating light to the components in the reagent stored in the measuring unit 1 of the measuring instrument 10 according to the present invention.
  • Examples of the light source 12 include lasers, LEDs, and lamps.
  • the detection element 13 is for detecting the light emitted from the component or the change before and after the irradiation of the light applied to the component.
  • a fluorescence detector, an absorbance detector, or the like may be used according to the measurement method. For example, a multi-pixel detector described later may be used.
  • the light source 12 only needs to be at a position where light can be emitted to the component in the reagent, and the detection element 13 can detect light emitted from the component or change before and after irradiation of the light emitted to the component. If it is in.
  • the light source 12 and the detection element 13 are preferably located on the opposite side with the measuring instrument 10 in between. Further, it is preferable that the straight line connecting the light source 12 and the detection element 13 is parallel to the depth direction.
  • the measuring apparatus 20 may include a light source 12a and a detection element 13a corresponding to a shallow area of the measurement unit 1, and a light source 12b and a detection element 13b corresponding to a deep area. Good. According to the said structure, it can measure about each of the area
  • the measuring device 20 may include a scanning mechanism 14 for measuring part or all of the measuring unit 1.
  • the scanning mechanism 14 is represented by an arrow in FIG. 15B, and moves the light source 12 and the detection element 13 or the measuring instrument 10 in the direction of the arrow. According to the said structure, since most or all of the components in the reagent introduced into the measurement part can be measured, a highly accurate component measurement is attained.
  • the light source 12a and the detection element 13a corresponding to the shallow region 1s, and the light source 12b and the detection element corresponding to the deep region 1d. 13b may be provided, or a scan mechanism 14 may be provided as shown in FIG.
  • FIGS. 15A to 15D the positional relationship between the light source and the detection element may be reversed.
  • the detection element When detecting fluorescence or scattered light, since the fluorescence or scattered light is emitted in all directions with respect to the incident light direction, the detection element may be disposed at a position where it can receive the emitted light.
  • the detection elements 13a and 13b are not parallel to the depth direction as shown in FIG. You may arrange
  • the reflection element 17a such as a reflection mirror provided on the opposite side to the light sources 12a and 12b with the measurement instrument 10 interposed therebetween. And 17b may be used to receive the incident light after passing through the components by the detection elements 13a and 13b.
  • the light source and the detection element may be arranged on the same side with respect to the measuring instrument.
  • the components in the reagent can be measured by reflection measurement.
  • reflection measurement in the case of absorbance detection, the optical path length is almost doubled, and measurement with high sensitivity is possible.
  • a reflection film such as a metal may be provided on the bottom surface of the measurement unit, and the reflection film may reflect the light.
  • FIG. 17 shows a schematic diagram of the measuring apparatus 20 in which the light source and the detecting element are arranged on the same side with respect to the measuring instrument.
  • the light emitted from the light sources 12a and 12b is reflected by the reflective film on the bottom surface of the measuring unit 1, and the reflected light is received by the detection elements 13a and 13b.
  • the light emitted from the light sources 12a and 12b is reflected by the reflecting elements 17a and 17b provided on the opposite side of the light source 12a and 12b with the measuring instrument 10 interposed therebetween, and the reflected light is reflected. Light is received by the detection elements 13a and 13b.
  • a fifth embodiment of the present invention will be described with reference to FIGS.
  • a first condensing element for condensing light on the measuring unit which is provided at a position between the light source and the measuring unit, and the measurement
  • at least one of a second light condensing element for condensing light on the detection element provided at a position between the unit and the detection element.
  • the irradiation light from a light source or the detection light from the component in the reagent stored in the measurement part can be condensed with high precision, and a highly accurate measuring apparatus can be provided.
  • the first condensing element and the second condensing element include a lens.
  • Other configurations are the same as those of the measurement instrument according to the first to third embodiments and the measurement apparatus according to the fourth embodiment, and a description thereof will be omitted.
  • FIGS. 18A and 18B are schematic views of the measuring apparatus 20 including the first light collecting element 15a.
  • FIG. 18A shows an example in which the light source 12 is provided on the upper surface side of the measurement unit and the detection element 13 is provided on the lower surface side of the measurement unit.
  • FIG. 18B shows an example in which the light source 12 is provided on the measurement unit bottom surface side and the detection element 13 is provided on the measurement unit top surface side.
  • FIG. 19A shows an example in which the light source 12 is provided on the upper surface side of the measurement unit and the detection element 13 is provided on the lower surface side of the measurement unit.
  • FIG. 19B shows an example in which the light source 12 is provided on the measurement unit bottom surface side and the detection element 13 is provided on the measurement unit top surface side.
  • FIG. 20A and FIG. 20B show schematic views of the measuring apparatus 20 including both the first light collecting element 15a and the second light collecting element 15b.
  • FIG. 20A shows an example in which the light source 12 is provided on the upper surface side of the measurement unit and the detection element 13 is provided on the lower surface side of the measurement unit.
  • FIG. 20B shows an example in which the light source 12 is provided on the measurement unit bottom surface side and the detection element 13 is provided on the measurement unit top surface side.
  • the component in the reagent is a particle
  • at least one of the focal position of the first condensing element and the focal position of the second condensing element is a space for storing the reagent of the measuring unit. It is preferable that the distance from at least one of the surrounding wall surfaces to the direction of the particles stored in the measurement unit is a position not more than the maximum diameter of the particles.
  • the detection element is a multi-pixel detector.
  • the component in the reagent introduced into the measurement part can be collectively measured in the area form using a multi-pixel detector (that is, a highly accurate scanning mechanism according to particle diameter etc. becomes unnecessary, and measurement is possible.
  • the device 20 can be provided at a low cost.
  • Other configurations are the same as those of the measurement instrument according to the first to third embodiments and the measurement apparatus according to the fourth or fifth embodiment, and a description thereof will be omitted.
  • Multi-pixel detector 16 Examples of the multi-pixel detector 16 include a CCD and a CMOS sensor.
  • FIG. 21 is a schematic diagram of the measuring apparatus 20 including the multi-pixel detector 16.
  • the measuring apparatus 20 shown in FIG. 21A light is emitted from the light source 12 to the components in the reagent stored in each of the shallow region 1s and the deep region 1d, and the light is emitted to the second light collecting element.
  • the light is focused on the multi-pixel detector 16 by 15b. According to the said structure, it can measure collectively with respect to the component in the reagent stored in each of the shallow area
  • the measuring apparatus 20 may include a scanning mechanism 14 as shown in FIG.
  • the scanning mechanism at this time does not need to be a micrometer-order high-accuracy mechanism corresponding to the particle diameter, and may be a millimeter-order mechanism that allows the measurement unit 1 (the shallow region 1s and the deep region 1d) to enter the detection range. . According to the said structure, it can measure by moving the light source 12, the condensing element 15b, the multi-pixel detector 16, or the instrument 10 for a measurement.
  • the measuring apparatus includes an arithmetic element.
  • the other configurations are the same as those of the measurement instrument according to the first to third embodiments and the measurement apparatus according to the fourth to sixth embodiments, and a description thereof will be omitted.
  • the measurement signal of the component in a plurality of regions having different depths of the measurement unit is compared with a range of signals that can be measured by the measurement device that has been acquired in advance, and is acquired in advance. It is preferable to include a first arithmetic element that calculates the measurement signal within the range of the signal as the measurement value of the component. According to the said structure, since the measurement signal of the component in the reagent which fits in the detection range of a measuring apparatus can be obtained reliably, the measurement of the component in a reagent with high precision is attained.
  • the concentration of the particle contained in the reagent is determined from the number of particles measured by the detection element and the volume of the region measured by the detection element. It is preferable to include a second arithmetic element that calculates. According to the said structure, the density
  • the “volume of the region measured by the detection element” is calculated by multiplying the area of the region measured by the detection element and the depth of the measurement unit, not the position where the detection element is in focus.
  • a measuring instrument is a measuring instrument for measuring a component in a reagent in order to solve the above-described problem, and stores the reagent and includes the component in the stored reagent.
  • a measurement unit that measures components in the reagent by irradiating light is provided, and the depth of the measurement unit in the light transmission direction is different.
  • the measurement unit since the depth of the measurement unit in the light transmission direction is different, even if the concentration of the component is unknown, if the concentration of the component is high, the measurement unit is relatively shallow.
  • the concentration of the component is low, the measurement signal of the component can be stored within the measurable signal range of the measurement system by measuring in a relatively deep region of the measurement unit, and the component in the reagent is quantified. Can be measured automatically. Therefore, there is no need to dilute or concentrate the reagent so as to fit the measurable range of the measurement system, and the component can be quantitatively measured simply by introducing the reagent into the measuring section.
  • the measurement unit includes a partition wall in which a plurality of reagents stored in the measurement units having different depths are not mixed in a direction substantially parallel to the depth direction of the measurement unit. It is preferable to provide.
  • the measurement unit is divided into a plurality of spaces by the partition walls. Therefore, when the concentration range of the component is known before the measurement, the reagent only needs to be introduced into the measurement part having a predetermined depth, and thereby the amount of the reagent used for the measurement can be reduced. Moreover, when measuring two or more types of reagents, it is possible to prevent the reagents from interfering with each other (for example, mixing) at the time of measurement.
  • the depth of the shallowest part of the measurement part is T s and the depth of the deepest part of the measurement part is T d , 5 ⁇ T d / T s ⁇ 5000 It is preferable that the relationship is satisfied.
  • the depth of the measurement unit is greatly changed (in other words, the measurement unit has both a very shallow region and a very deep region). Therefore, even when the concentration range of the components contained in the reagent is wide, or even when two components with a large concentration difference are contained in the reagent, it is ensured with one measuring instrument. Can be measured.
  • At least one of the wall surfaces surrounding the space for storing the reagent of the measuring unit is formed on substantially the same plane.
  • the components in the reagent can be arranged on substantially the same plane. Therefore, when measurement is performed in a part in the depth direction of the measurement unit, an error due to a difference in the position of the observation point in the depth direction of the measurement unit does not occur, and high-precision measurement can be performed. For example, after introducing the reagent into the measurement part, even if the component in the reagent settles, the component in the reagent can be arranged on substantially the same plane (for example, the bottom of the measurement part) When measurement is performed in a part in the depth direction of the measurement unit, an error due to the difference in the position of the observation point in the depth direction of the measurement unit does not occur, and highly accurate measurement can be performed.
  • At least one substrate having a groove or a through-hole having the same depth and a through-hole formed at a position overlapping at least a part of the groove or the through-hole is provided. It is preferable that the measurement part is formed by the groove and the through hole.
  • the measurement instrument by forming the measurement instrument using at least two or more substrates, it is possible to form a measurement unit having a greatly different depth on a single measurement instrument.
  • a reagent introducing unit for introducing the reagent into the measuring unit, and connected to the measuring unit, for deriving the reagent from the measuring unit
  • a reagent deriving unit for deriving the reagent from the measuring unit
  • the reagent can be efficiently introduced into the measurement unit.
  • the reagent can be continuously or repeatedly supplied to the measurement unit, and the measurement accuracy can be increased.
  • the reagent is a liquid
  • a wall surface surrounding a space for storing the reagent of the measurement unit is lyophilic with respect to the reagent in contact with the wall surface, It is preferable that at least a part of the reagent deriving portion in contact with the reagent is liquid repellent with respect to the reagent.
  • the reagent can be introduced into the measuring unit by capillary force, and the reagent is stopped by the surface tension at the reagent deriving unit. can do.
  • the volume of the reagent used for the measurement can be reliably made equal to the volume of the measurement unit, and the measurement accuracy (concentration measurement) can be increased.
  • the reagent introduction part comprises a reagent introduction hole for introducing a reagent into the measurement part, and a reagent introduction path connecting the reagent introduction hole and the measurement part,
  • the shape of the cross section of the reagent introduction path in the direction orthogonal to the direction of transfer of the reagent in the reagent introduction path is determined from the connection end of the reagent introduction path and the reagent introduction hole, and the reagent introduction path and the measurement. It is preferable that it is a reverse taper shape toward the connection end with a part.
  • the flow line when introducing the reagent is smoothly formed from the reagent introduction hole to the connection end of the reagent introduction path and the measurement part. Since it is possible to prevent the concentration of the components in the reagent from changing between the reagent introduction path and the measurement part without the reagent staying at the connection end between the measurement part and the measurement part, it is possible to provide a highly accurate measurement instrument.
  • the measurement unit is a partition wall for preventing a plurality of reagents stored in the measurement units having different depths from mixing with each other in a direction substantially parallel to the depth direction of the measurement unit.
  • the reagent introduction part comprises a reagent introduction hole for introducing a reagent into the measurement part, and a reagent introduction path connecting the reagent introduction hole and the measurement part, and the reagent introduction path Preferably has a branched structure, and each of the branched reagent introduction paths is connected to each of the measurement units having different depths.
  • the same reagent can be introduced from one reagent introduction hole into two or more measurement parts having different depths. That is, the process of introducing the reagent into the measuring unit can be simplified. Further, since “volume of reagent introduction hole> volume of reagent introduction path”, the amount of reagent necessary for measurement can be reduced. Furthermore, the reagent of the same composition (concentration) can be surely introduced into two or more measurement parts.
  • the reagent introduction part comprises a reagent introduction hole for introducing a reagent into the measurement part, and a reagent introduction path connecting the reagent introduction hole and the measurement part, It is preferable that a pretreatment path for introducing a pretreatment agent for bringing the components in the reagent into a state that can be measured by the measurement unit is connected to the reagent introduction path.
  • the pre-processing operation for making the component in a reagent measurable in a measurement part is required, it is a measurement instrument, without using external instruments other than a measurement instrument Alone, the components in the reagent can be measured.
  • the component in the reagent is preferably a biomolecule.
  • the measuring instrument of the present invention can be used for measuring biomolecules in the reagent.
  • the component in the reagent is preferably a particle.
  • the measuring instrument of the present invention can be used for measuring particles in the reagent.
  • the component in the reagent is at least two kinds of particles and the concentration of any two kinds of the two or more kinds of particles is different.
  • the measuring instrument of the present invention can be used for measuring a reagent containing two or more kinds of particles having greatly different concentrations, such as red blood cells and white blood cells in blood.
  • the relatively shallow region of the measurement unit is a region for measuring particles having a relatively high concentration among the particles, and the relatively deep region of the measurement unit. Is preferably a region for measuring particles having a relatively low concentration among the particles.
  • the measuring unit can hold a certain number of particles necessary for maintaining the measurement accuracy for both high-concentration particles and low-concentration particles. it can.
  • the ratio of dilution volume ratio of reagent to diluent
  • the ratio of dilution can be made substantially the same for low-concentration particles and high-concentration particles, thus simplifying pretreatment operations. Can be realized.
  • the concentration of the relatively high concentration particle is C 1
  • the maximum diameter of the particle is D 1
  • the concentration of the relatively low concentration particle is C 2
  • the maximum diameter and D 2 T 1 the depth of the relatively shallow region of the measuring section, when the depth of the relatively deep region of the measuring portion was T 2, T 1 ⁇ D 1 and T 2 ⁇ D 2 and 0.01 ⁇ (T 2 / T 1 ) / (C 1 / C 2 ) ⁇ 10 It is preferable to satisfy the relationship.
  • the particles can be reliably introduced into the measurement unit, and even if the concentration ratio is large, a certain number of particles necessary for maintaining measurement accuracy can be obtained according to the depth of the measurement unit.
  • a measuring instrument that can be held in the measuring section and has high accuracy can be provided.
  • the reagent includes the particles and a solvent, and the specific gravity of the particles with respect to the solvent is greater than 1.
  • the particles settle on the bottom surface of the measurement unit, so that a concentration effect according to the depth of the measurement unit can be exerted in the measurement. That is, the particles can be concentrated on the bottom surface of the measurement unit. And even if it is a low concentration particle
  • the particles are preferably cells.
  • the measurement instrument of the present invention can be used for cell measurement.
  • the cell is preferably a blood cell.
  • the measuring instrument of the present invention can be used for measuring blood cells in a blood reagent.
  • the relatively low concentration particles are white blood cells, and the relatively high concentration particles are red blood cells or platelets.
  • the measuring instrument of the present invention can be used for measuring white blood cells, red blood cells and platelets in a blood reagent.
  • red blood cells are contained in the reagent, and the pretreatment agent contains a hemolytic agent that hemolyzes red blood cells.
  • red blood cells are removed simply by introducing a blood reagent into the measurement instrument of the present invention, and components other than red blood cells (white blood cells and the like) can be measured in the measurement unit.
  • a measuring apparatus includes a light source for irradiating a component in the reagent stored in the measuring unit of the measuring instrument according to the present invention, and the component.
  • a detection element for detecting emitted light or a change before and after irradiation of the light applied to the component.
  • a first condensing element for condensing light on the measuring unit which is provided at a position between the light source and the measuring unit, and the measuring unit It is preferable that at least one of a second condensing element for condensing light with respect to the detection element, provided at a position between the detection element and the detection element.
  • the irradiation light from the light source or the detection light from the components in the reagent stored in the measurement unit can be condensed with high accuracy, and a highly accurate measurement device can be provided.
  • the component in the reagent is particles
  • at least one of the focal position of the first light condensing element and the focal position of the second light condensing element is the reagent of the measuring unit. It is preferable that the distance from at least one of the wall surfaces surrounding the space for storing the particle to the direction of the particle stored in the measurement unit is a position equal to or smaller than the maximum diameter of the particle.
  • the particles in the reagent introduced into the measuring unit settle on the bottom surface of the measuring unit, and the focal position of the light collecting element for optically measuring the particles is arranged at the position of the settled particles. Therefore, particles can be measured with high accuracy without a complicated focus alignment mechanism.
  • the detection element is preferably a multi-pixel detector.
  • the components in the reagent introduced into the measurement unit can be collectively measured in an area using the multi-pixel detector.
  • the measuring apparatus preferably includes a scanning mechanism for measuring part or all of the measuring unit.
  • the measurement signal of the component in a plurality of regions where the depth of the measurement unit is different from the range of signals that can be measured by the measurement apparatus that has been acquired in advance It is preferable to include a first arithmetic element that calculates the measurement signal within a range of signals acquired in advance as a measurement value of the component.
  • the component in the reagent can be measured with high accuracy.
  • the component in the reagent is a particle, and the concentration of particles contained in the reagent is determined from the number of particles measured by the detection element and the volume of the region measured by the detection element. It is preferable to include a second arithmetic element that calculates.
  • the concentration of particles contained in the reagent can be accurately calculated.
  • the present invention can be used for measurement of specific components such as enzymes and substrates in blood, counting of cells such as blood cells, and the like.
  • Measuring instruments 11, 11a, 11b, 11a ', 11b' Pretreatment agent introduction hole 12, 12a, 12b ... Light source 13, 13a, 13b ... Detection element 14 ... Scanning mechanism 15a ... First condensing element 15b ... Second Light condensing element 16 ... multi-pixel detector 17a, 17b ... reflective element 20 ... Measuring device 30 ... Particles 30a ... Particles with relatively high concentration 30b ... Particles with relatively low concentration 101, 102, 103, 104 ... Substrate 200 ... Reagent

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  • Physics & Mathematics (AREA)
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Abstract

L'invention concerne un instrument de mesure doté d'une unité de mesure pour stocker un agent et mesurer un composant dans l'agent stocké en irradiant le composant de l'agent avec de la lumière, et caractérisé en ce que l'unité de mesure présente différentes profondeurs dans la direction de la transmission de la lumière. Une valeur de mesure d'un composant contenu dans un agent est placée dans une portée de détection d'un système de mesure sans dilution ni concentration de l'agent, et la mesure du composant est effectuée de manière quantitative.
PCT/JP2013/072544 2012-09-07 2013-08-23 Instrument de mesure et appareil de mesure WO2014038399A1 (fr)

Applications Claiming Priority (2)

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JP2012197788A JP2015215164A (ja) 2012-09-07 2012-09-07 測定用器具および測定装置
JP2012-197788 2012-09-07

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JP2016070658A (ja) * 2014-09-26 2016-05-09 シスメックス株式会社 血液分析装置および血液分析方法
EP3199937A1 (fr) * 2016-01-28 2017-08-02 Minitüb GmbH Compartiment de comptage et un procédé pour l'analyse d'échantillons
CN110595971A (zh) * 2019-10-16 2019-12-20 恒天益科技（深圳）有限公司 一种超低粉尘仪
EP3502661B1 (fr) * 2017-12-22 2021-01-20 Minitüb GmbH Procédé et dispositifs d'analyse d'échantillons de sperme

Families Citing this family (1)

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JP7475050B2 (ja) 2018-11-14 2024-04-26 国立大学法人 東京大学 アッセイ用カートリッジデバイス

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JP2006234549A (ja) * 2005-02-24 2006-09-07 Mitsubishi Heavy Ind Ltd 吸光光度分析装置および吸光光度分析方法
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JP2016070658A (ja) * 2014-09-26 2016-05-09 シスメックス株式会社 血液分析装置および血液分析方法
EP3199937A1 (fr) * 2016-01-28 2017-08-02 Minitüb GmbH Compartiment de comptage et un procédé pour l'analyse d'échantillons
WO2017129819A1 (fr) * 2016-01-28 2017-08-03 Minitüb GmbH Compartiment de comptage et procédé d'analyse d'échantillons
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US11971341B2 (en) 2017-12-22 2024-04-30 Minitüb GmbH Method and devices for analyzing sperm samples
CN110595971A (zh) * 2019-10-16 2019-12-20 恒天益科技（深圳）有限公司 一种超低粉尘仪

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