WO2013018474A1 - Système d'inspection et procédé associé - Google Patents

Système d'inspection et procédé associé Download PDF

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Publication number
WO2013018474A1
WO2013018474A1 PCT/JP2012/066503 JP2012066503W WO2013018474A1 WO 2013018474 A1 WO2013018474 A1 WO 2013018474A1 JP 2012066503 W JP2012066503 W JP 2012066503W WO 2013018474 A1 WO2013018474 A1 WO 2013018474A1
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WO
WIPO (PCT)
Prior art keywords
measurement
holder
flow path
region
rotation
Prior art date
Application number
PCT/JP2012/066503
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English (en)
Japanese (ja)
Inventor
千里 吉村
由美子 大鹿
千恵 服部
Original Assignee
ブラザー工業株式会社
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Filing date
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Application filed by ブラザー工業株式会社 filed Critical ブラザー工業株式会社
Publication of WO2013018474A1 publication Critical patent/WO2013018474A1/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
    • B01L3/50273—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 or forces applied to move the fluids
    • 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
    • B01L3/502753—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 bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation
    • 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
    • G01N21/07—Centrifugal type cuvettes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00029—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides
    • 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
    • B01L2200/02—Adapting objects or devices to another
    • B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
    • B01L2200/027—Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
    • 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
    • B01L2300/0848—Specific forms of parts of containers
    • B01L2300/0851—Bottom walls
    • 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
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0409—Moving fluids with specific forces or mechanical means specific forces centrifugal forces
    • 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
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0457—Moving fluids with specific forces or mechanical means specific forces passive flow or gravitation
    • 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
    • G01N2021/0325—Cells for testing reactions, e.g. containing reagents
    • G01N2021/0328—Arrangement of two or more cells having different functions for the measurement of reactions

Definitions

  • the present invention relates to an inspection system having a configuration in which a liquid to be inspected can be retained in an absorbance measurement tank by inertia force and optical analysis can be performed, and an inspection method using the inspection system.
  • the microchip corresponding to the inspection object receiver has a substrate surface as a flow path forming surface on which a flow path for the liquid to be inspected is formed, and is housed in a chip holder that can rotate around the main axis of the inspection apparatus.
  • the in the inspection apparatus disclosed in Patent Document 1 the microchip is stored in the chip holder so that the flow path forming surface is perpendicular to the main axis.
  • the inspection apparatus includes a light source for measuring absorbance, a detector as a light receiving unit, a rotational drive source for applying centrifugal force to a liquid in the microchip in a desired direction, and a control unit.
  • the microchip disclosed in Patent Document 2 is used as the microchip.
  • the blood in the microchip of Patent Document 2 is separated into a plasma component and a blood cell component by applying a centrifugal force in an arbitrary direction, and then mixed with a reagent. It is accommodated in a measurement area as an incident detector.
  • the measurement area is shallower than the other areas in the incident direction of the measurement light so that the absorbance can be measured even if the position of the measurement light hits a limited amount of the liquid to be inspected.
  • a wider area is desirable in the plane orthogonal to the direction.
  • the measurement area which is a relatively shallow area, has a small cross-sectional area at the connection portion with the other area, and therefore the air escape path from the measurement area to the other area is limited. For this reason, when the force of flowing the liquid to be inspected to the measurement region is weak compared to other regions, air tends to remain in the measurement region as liquid bubbles.
  • the present invention has been made in view of the above problems, and more liquid to be inspected can be retained in the measurement region of the absorbance measurement tank during measurement, and the absorbance of the liquid can be accurately measured.
  • An object is to provide an inspection system and an inspection method.
  • the inspection system has a flow path forming surface in which a recessed flow path capable of flowing the liquid to be inspected is formed, and the liquid to be inspected.
  • a measurement region having a first depth in a direction perpendicular to the flow path formation surface, and a liquid to be inspected from the flow channel toward the measurement region.
  • An absorbance measurement tank that is a recess having a passage region that passes through and gradually becomes shallower from the second depth deeper than the first depth toward the measurement region in a direction perpendicular to the flow path forming surface.
  • An inspection object receiver a holder for detachably storing the inspection object receiver, a rotation drive source for rotating the holder about a main shaft extending along the direction of gravity, and rotating the holder in the rotation direction.
  • the holder A rotation control unit that controls the rotation drive source to accelerate or decelerate an angular velocity, an angle change source that changes the angle of the holder about an axis that intersects the flow path forming surface, and an angle of the holder
  • An angle setting unit that controls the angle changing source, a light source that causes the measurement light to enter the measurement region of the inspection object receiver housed in the holder, and a measurement light that has passed through the measurement region A mounting position in which the flow path forming surface is along the direction of gravity, and the bottom surface of the measurement region is downstream of the bottom surface of the passage region in the rotation direction.
  • the inspection object receptacle is accommodated, and the angle setting unit reduces the angular velocity of the holder to stop the measurement region in the holder at a position where measurement light emitted from the light source is incident.
  • the measurement region so as to be positioned below the passage area in the direction of gravity, and sets the angle of the holder.
  • the rotation control unit of the inspection system wherein the holder is accelerated at a first angular acceleration from when the rotation is stopped until reaching a predetermined angular velocity in the rotation direction, and from the predetermined angular velocity to the rotation direction.
  • the measurement area in the holder is decelerated at the second angular acceleration until it stops at the position where the measurement light emitted from the light source enters, and the second angular acceleration is equal to or larger than the first angular acceleration.
  • the rotational drive source is controlled as described above.
  • the holder includes first and second holders that respectively accommodate a plurality of inspection object receptacles, and the rotation control unit is accommodated in the first holder.
  • the direction of rotation when guiding the measurement area of the inspection object receiver to the position where the measurement light emitted from the light source enters, and the measurement area of the inspection object receiver housed in the second holder from the light source The direction of rotation when guiding the emitted measurement light to the incident position is the same as the rotation direction.
  • the inspection system according to claim 4 is characterized in that the surface roughness of the bottom surface of the measurement region is an average roughness Ra value of 70 nm or less.
  • the inspection system according to claim 5 is characterized in that the surface roughness of the side wall surface of the measurement region is larger than the surface roughness of the bottom surface of the measurement region.
  • the inspection system according to claim 7 is characterized in that the posture regulating means is a notch provided in the outer wall surface.
  • the inspection method includes a flow path forming surface in which a concave flow path through which a liquid to be inspected can flow is formed, and is used for measuring the absorbance of the liquid to be inspected.
  • a test object receiver comprising an absorbance measurement tank that is a recess having a passage region that gradually becomes shallower from a second depth deeper than the first depth in a direction perpendicular to the first depth to the measurement region;
  • a rotation control unit for controlling the rotation drive source, an angle change source for changing the
  • the rotation control unit In order to guide the measurement light to the incident position, the rotation control unit rotates the rotation drive source so that the bottom surface of the measurement region is downstream of the bottom surface of the passage region in the rotation direction.
  • the rotation control unit decelerates the angular velocity of the holder in order to stop the measurement area in the holder at a position where measurement light emitted from the light source is incident, the measurement area is in the direction of gravity.
  • An angle setting step in which the angle setting unit controls the angle change source so that the angle setting unit is positioned below the passage region, and a measurement light from the light source to the measurement region of the inspection object receiver housed in the holder And a measurement step of receiving measurement light that has been emitted and transmitted through the measurement region.
  • the inspection system according to claim 1 is mounted on the holder in a mounting posture in which the flow path forming surface is along the direction of gravity and the bottom surface of the passage region is downstream of the bottom surface of the measurement region in the rotational direction. It has an outer wall surface that fits into the holder.
  • the liquid to be inspected that has flowed into the passage region of the absorbance measurement tank through the flow path is held in the passage region and does not easily flow into the measurement region. .
  • the inertial force generated by the deceleration acts on the liquid to be inspected in the passage region.
  • the inertial force acts on the liquid to be inspected in the passage region, the liquid to be inspected easily flows from the passage region to the measurement region on the downstream side in the direction in which the inertial force acts.
  • the inertial force acts on the liquid to be inspected, the liquid to be inspected flows vigorously to the measurement area, and the air in the measurement area can be positively moved to the passing area side.
  • the bottom surface of the passage region becomes shallower in the direction perpendicular to the flow path forming surface as it goes downward in the direction of gravity.
  • the inertial force is applied, the liquid in the passage region easily moves to the measurement region along the continuously shallow bottom surface of the passage region. As a result, more liquid to be inspected remains in the measurement region during measurement, and the absorbance of the liquid can be accurately measured.
  • the first angular acceleration of the inspection system according to claim 2 is smaller than the second angular acceleration.
  • the inertial force can be more strongly applied to the liquid to be inspected in the passage region when decelerating at the second angular acceleration.
  • the liquid to be inspected in the passage area can easily enter the measurement area.
  • the inertial force applied to the liquid to be inspected in the measurement region can be further reduced when accelerating at the first angular acceleration.
  • the liquid to be inspected in the measurement region is evenly distributed and is difficult to return to the passage region.
  • more liquid to be inspected remains in the measurement region during measurement, and the absorbance of the liquid can be accurately measured.
  • the rotation direction for the first holder guidance and the rotation direction for the second holder guidance are the same as the rotation direction during deceleration. Since the direction of rotation for rotating the first holder is the same as the direction of rotation, the inertial force is inspected in the direction of rotation in the direction of rotation when the first holder is decelerated for the measurement of the test object receptacle. Applied to the target liquid. As a result, the liquid to be inspected in the passage area easily enters the measurement area. Since the direction of rotation for rotating the second holder is the same as the direction of rotation, the second holder passes through an inertial force on the opposite side of the rotation direction during deceleration for measurement of the receiving object to be inspected. An inertial force is again applied in the rotation direction to the liquid to be inspected returned to the region. As a result, the liquid to be inspected in the passage area easily enters the measurement area.
  • the surface roughness of the bottom surface of the measurement region is an average roughness Ra value of 70 nm or less.
  • the surface roughness of the side wall surface of the measurement region is larger than the surface roughness of the bottom surface of the measurement region. Since the surface roughness of the sidewall surface of the measurement region is large, the liquid to be inspected in the measurement region is supplemented by the sidewall surface of the measurement region. As a result, the liquid to be inspected can be prevented from returning to the passage region due to the influence of the surface tension of the side wall surface of the measurement region.
  • the inspection system according to claim 6 has posture control means.
  • the posture regulation means regulates the mounting posture so that the inertial force acts on the measurement region side, and the liquid to be inspected easily flows into the measurement region. As a result, more liquid to be inspected remains in the measurement region during measurement, and the absorbance of the liquid can be accurately measured.
  • the inspection system according to claim 7 has a notch that fits into the protrusion of the holder. Compared with the case where the inspection object receptacle has a protrusion and the holder has a notch, the volume of the inspection object receptacle can be reduced. As a result, the inspection object receiver can be made compact and the cost can be further reduced.
  • the inspection method wherein a bottom surface of the measurement region is rotated from a bottom surface of the passage region in order to guide the measurement region in the holder to a position where measurement light emitted from the light source is incident.
  • a rotation step that rotates to the downstream side of the direction, and when the angular velocity of the holder is decelerated to stop the measurement region in the holder at a position where measurement light emitted from the light source enters.
  • An angle setting step of setting an angle of the holder so that the measurement region is positioned below the passage region in the direction of gravity. Since the measurement area is located below the passage area in the direction of gravity, when the rotation of the inspection apparatus is stopped, the liquid to be inspected in the passage area easily flows into the measurement area due to gravity.
  • the holder accommodates the test object receiver with the bottom surface of the passing area located downstream of the bottom surface of the measuring area, so that the inertial force is applied to the liquid during deceleration and the liquid is measured from the passing area. It becomes easy to flow into the area. The absorbance of the liquid can be accurately measured by the gravity and inertial force.
  • FIG. 3 is a top view of the inspection apparatus 30.
  • FIG. 3 is a cross-sectional view taken along line AA of the microchip 1 through which measurement light 92 is transmitted.
  • FIG. 2 is a block diagram showing an electrical configuration of a control device 200.
  • inspection apparatus 30 The flowchart which shows the process sequence according to liquid mixing program S20.
  • an inspection system including a microchip 1 according to an embodiment of the present invention, a microchip 101 having the same shape as the microchip 1, and an inspection apparatus 30 to which both the microchips 1 and 101 are detachably mounted. Will be described.
  • the vertical direction, the left-right direction, and the front-back direction in FIG. 5 represent directions in a state where the microchip 1 is mounted on the inspection device 30 and is in a predetermined initial rotation position.
  • the inspection device 30 includes a main shaft 57, a T-shaped plate 48, and holders 47L and 47R.
  • the T-shaped plate 48 has a groove 80.
  • the extending direction of the main shaft 57 parallel to the direction of gravity is defined as the vertical direction.
  • the extending direction of the groove 80 is defined as the left-right direction.
  • a direction perpendicular to the up-down direction and the left-right direction is taken as the front-rear direction. As shown in FIG.
  • the holders 47 ⁇ / b> L and 47 ⁇ / b> R of the inspection apparatus 30 rotate about the main shaft 57 as an axis.
  • centrifugal force CF is applied to both holders 47L and 47R.
  • the holder 47L existing on the left side of FIG. 4 is angle-changed in the first rotation direction LD with the axis 46L extending in the front-rear direction as an axis.
  • the holder 47R present on the right side in FIG. 4 is angle-changed to a second rotation direction RD that is the opposite direction of the first rotation direction LD, with a shaft 46R extending in the front-rear direction as an axis.
  • the microchip 1 shown in FIGS. 1 to 3 is mounted on the holders 47L and 47R of the inspection apparatus 30 and changed to various angles.
  • the directions of the three arrows shown in FIG. Represents the up-down direction, the left-right direction, and the front-rear direction of the inspection apparatus 30 in a state in which is attached and is in the predetermined initial rotation position shown in FIG.
  • the microchip 1 includes a plate member 2 and a cover member 20.
  • the plate member 2 is, for example, a transparent plate that is covered with a plurality of outer wall surfaces and has a substantially square shape when viewed from the front.
  • the thickness which is the dimension of the plate member 2 in the front-rear direction, is about 1 to 10 mm.
  • the plate member 2 is formed from, for example, a synthetic resin.
  • the plate member 2 is manufactured by, for example, injection molding.
  • the plate member 2 has a flow path forming surface 2A.
  • a predetermined flow path having a depth in the front-rear direction which is the thickness direction of the plate member 2 is formed on the flow path forming surface 2A.
  • the predetermined flow path is formed in a concave shape in order to flow a specimen and a reagent that are liquids to be examined.
  • the cover member 20 is, for example, a film having a square flexibility as viewed from the front.
  • the cover member 20 has a thickness of about 0.1 to 0.5 mm.
  • the cover member 20 has an area that can cover a predetermined flow path formed in the plate member 2.
  • the cover member 20 is stuck so as to cover the flow path forming surface 2A.
  • the cover member 20 has a vertical width and a horizontal width of about 10 to 100 mm, respectively.
  • the adhesive layer of the cover member 20 is provided on the surface of the cover member 20 so that it can adhere to the flow path forming surface 2A.
  • the cover member 20 is made of, for example, a synthetic resin.
  • the cover member 20 has a sample insertion port 3H that is an opening for loading a sample, and a reagent loading port 4H that is an opening for loading a reagent.
  • the sample inlet 3H and the reagent inlet 4H are provided in the cover member 20 in advance.
  • the cover member 20 is bonded to the plate member 2 so that the sample insertion port 3H and the reagent insertion port 4H are positioned in the formation region of the sample insertion portion 3 and the reagent insertion portion 4 of the plate member 2 described later. 1, 2, 6, and 14, the flow path of the plate member 2 inside the cover member 20 is represented by a solid line.
  • the microchip 1 has a lower surface 2B.
  • the lower surface 2 ⁇ / b> B is a surface that is parallel to the front-rear direction and the left-right direction and is below the microchip 1.
  • the notch 11 is provided at the right corner of the lower surface 2 ⁇ / b> B of the microchip 1.
  • a predetermined flow path is formed on the flow path forming surface 2A of the plate member 2 shown in FIGS.
  • the predetermined flow path includes a specimen input section 3, a reagent input section 4, a sample supply path 5, a reagent supply path 6, an absorbance measurement tank 7, a centrifuge tank 12, a first flow path 13, and a reservoir.
  • a tank 14 and a second flow path 15 are provided.
  • the sample loading unit 3 is a tank into which a sample is loaded through the sample loading port 3H.
  • the sample insertion unit 3 has a volume capable of accommodating a predetermined amount of sample.
  • the predetermined amount of specimen is about 0.01 to 1 ml of specimen.
  • the specimen is blood, for example.
  • the sample supply path 5 is connected to the lower end of the sample input unit 3.
  • the sample supply path 5 is a flow path that extends downward from the lower end of the sample input section 3, and in this embodiment, the extending direction of the sample supply path 5 is parallel to the vertical direction.
  • the width in the left-right direction of the sample supply path 5 is such that the sample in the sample input unit 3 does not flow out to the centrifuge tank 12 due to downward gravity.
  • the width is set narrower than the width in the left-right direction of the specimen insertion unit 3.
  • the width in the left-right direction of the sample supply path 5 is, for example, about 0.1 mm.
  • the centrifuge tank 12 is provided at the lower end of the sample supply path 5.
  • the centrifuge tank 12 is provided at the lower end of the sample supply path 5.
  • the centrifuge tank 12 extends from the lower end of the sample supply path 5 to the lower right.
  • the centrifuge tank 12 is a tank that is supplied from the sample supply path 5 and separates the specific gravity by applying a centrifugal force to the stored specimen.
  • the first component having a relatively low specific gravity and the second component having a relatively high specific gravity. And a tank that is centrifuged.
  • the first component is, for example, plasma.
  • the second component is, for example, a blood cell.
  • the first flow path 13 is connected to the upper left side of the centrifugal separation tank 12 when viewed from the front.
  • the second flow path 15 is connected to the upper right side of the centrifuge tank 12 as viewed from the front.
  • the first flow path 13 is connected to the upper left end of the storage tank 14.
  • the first flow path 13 is a flow path for introducing the excess liquid flowing out from the centrifugal separation tank 12 into the storage tank 14.
  • the first flow path 13 is provided to extend from the upper left end of the centrifuge tank 12 to the lower left so that the excess liquid from the centrifuge tank 12 can easily flow into the storage tank 14 by centrifugal force.
  • the storage tank 14 has a quadrangular shape.
  • the storage tank 14 is configured to prevent the excess liquid from flowing back from the storage tank 14 to the centrifuge tank 12 when flowing the liquid centrifuged in the centrifuge tank 12 to the second flow path 15. It is arranged on the right side from the lower end and has a volume enough to store the excess liquid flowing in from the first flow path 13.
  • the second flow path 15 is connected to the upper left end of the absorbance measurement tank 7.
  • the second flow path 15 is a flow path for introducing the first component separated in the centrifuge tank 12 into the absorbance measurement tank 7.
  • the upstream side of the second flow path 15 extends to the upper right so that the specimen does not flow into the absorbance measurement tank 7 when centrifugal force is applied to flow from the specimen supply path 5 to the centrifugal separation tank 12.
  • the downstream side of the second flow path 15 is located on the lower right side so that the sample can easily flow into the absorbance measurement tank 7 when a centrifugal force is applied to flow the sample from the centrifuge tank 12 to the absorbance measurement tank 7. It extends.
  • the reagent charging unit 4 is a tank in which a reagent is charged through the reagent charging port 4H.
  • the reagent loading unit 4 has a volume capable of accommodating a predetermined amount of reagent.
  • the predetermined amount of reagent is about 0.01 to 1 ml of reagent.
  • the reagent supply path 6 is a flow path extending downward from the lower end of the reagent charging unit 4.
  • the passage region 8 of the absorbance measurement tank 7 is connected to the lower end of the reagent supply path 6.
  • the width in the left-right direction of the reagent supply path 6 is compared with the width in the left-right direction of the reagent supply unit 4 to the extent that the reagent in the reagent supply unit 4 does not flow out to the passage region 8 of the absorbance measurement tank 7 due to downward gravity. And set narrower.
  • the lateral width of the reagent supply path 6 is, for example, about 0.1 mm.
  • the absorbance measuring tank 7 is a tank for measuring the absorbance of the liquid.
  • the absorbance measurement tank 7 has a rectangular shape that is long in the left-right direction.
  • the absorbance measurement tank 7 has a volume capable of retaining a predetermined amount of the sample supplied from the second flow path 15 and the reagent supplied from the reagent supply path 6.
  • the absorbance measurement tank 7 includes a passage region 8 and a measurement region 10.
  • the measurement region 10 is a region through which measurement light is transmitted in order to measure the absorbance of the specimen and the reagent. As shown in FIG. 3, the measurement region 10 has a first depth D1 in the front-rear direction, which is a direction perpendicular to the flow path forming surface 2A.
  • the first depth D1 is, for example, 1 mm.
  • the measurement region 10 is a region surrounded by the bottom surface 10A, the side wall surfaces 10B, 10C, and 10D and the cover member 20.
  • the bottom surface 10A is a surface in the direction along the flow path forming surface 2A of the measurement region 10.
  • Side wall surface 10B, 10C 10D is a surface perpendicular to the flow path forming surface 2A of the measurement region 10.
  • the bottom surface 10A is formed in a mirror surface to such an extent that the measurement light emitted from the light source of the inspection apparatus is received by the light receiving unit of the inspection apparatus.
  • the mirror surface is, for example, a surface roughness having an average roughness Ra value of 70 nm or less.
  • the surface roughness of the side wall surfaces 10B, 10C, and 10D is rougher than the surface roughness of the bottom surface 10A.
  • the passing area 8 is an area where the specimen is supplied from the second flow path 15 and the reagent is supplied from the reagent supply path 6.
  • the supplied specimen and reagent pass through the passage area 8 and go to the measurement area 10.
  • the passage region 8 is a region surrounded by the bottom surfaces 9 ⁇ / b> A and 9 ⁇ / b> B, the side wall surface, and the cover member 20.
  • the bottom surface 9A of the passage region 8 has a second depth D2 in the front-rear direction, which is a direction perpendicular to the flow path forming surface 2A.
  • the second depth D2 is 3 mm, for example.
  • the second depth D2 is deeper than the first depth D1.
  • the bottom surface 9 ⁇ / b> B is provided so that the depth becomes shallower as it approaches the measurement region 10.
  • the bottom surface 9 ⁇ / b> B connects both regions so that the specimen and the reagent flow from the passage region 8 to the measurement region 10.
  • the bottom surface 9B is provided so that the depth gradually decreases from the predetermined location 8T having the second depth D2 of the passage region 8 to the predetermined location 10T having the first depth D1.
  • the predetermined place 8T is a place located in the middle of the passage area 8.
  • the predetermined location 10T is a location located at the upper end of the measurement region 10.
  • the side wall surface is a surface perpendicular to the flow path forming surface 2 ⁇ / b> A of the passage region 8.
  • the notch portion 11 is formed so that the microchip 1 and the holders 47L and 47R are mounted in a predetermined posture so that an inertial force is applied to the front side during rotation deceleration.
  • the predetermined posture is that the flow path forming surface 2A is along the direction of gravity, the measurement region 10 is positioned below the passage region 8 in the direction of gravity, and the bottom surface 10A of the measurement region 10 is holder 47R from the bottom surface 9B of the passage region 8. It is in the state which exists in the downstream of the rotation direction.
  • the notch portion 11 is formed on the lower surface 2B of the microchip 1 so as to fit into a protruding portion 48R of a bottom surface 47RB of the holder 47R described later.
  • the notch 11 is formed in the lower right corner of the microchip 1 in FIG.
  • the notch 11 is formed in a square shape when viewed from the front.
  • the directions of the three arrows shown in FIG. 4 represent directions corresponding to the up-down direction, the left-right direction, and the front-rear direction shown in FIG.
  • the microchips 1 and 101 configured as described above are mounted with the flow path forming surface 2A along the gravity.
  • the inspection device 30 applies the centrifugal force CF to the microchips 1 and 101 by rotating the turntable 33 with the holders 47L and 47R being held at a predetermined angle under the control of the control device 200.
  • the holder 47R is provided on the right side when viewed from the front.
  • the holder 47R is a box-shaped member that is formed one size larger than the microchip 1 and is surrounded by an upper surface 47RC, a side surface, and a bottom surface 47RB as a lid.
  • the holder 47L is provided on the left side when viewed from the front. Similar to the holder 47R, the holder 47L is a box-shaped member that is formed one size larger than the microchip 101 and is surrounded by a top surface, a side surface, and a bottom surface 47LB as a lid.
  • the holders 47R and 47L hold the microchips 1 and 101 in a state where the flow path forming surface 2A of the microchip 1 and the flow path forming surface 102A of the microchip 101 are orthogonal to the upper surface of the turntable 33.
  • centrifugal force CF is applied in directions parallel to the flow path forming surfaces 2A and 102A of the microchips 1 and 101 in the holders 47R and 47L, respectively.
  • the control device 200 is connected to a spindle motor 35, a stepping motor 51, and the like, which will be described later, via a cable 96.
  • the control device 200 includes a CPU 207, a RAM 206, a ROM 205, and the like which will be described later.
  • the ROM 205 stores an inspection program 205a shown in FIG.
  • the control device 200 controls the rotation of the turntable 33 and the angle change of the holders 47L and 47R to a predetermined angle according to the inspection program 205a.
  • the rotation mechanism of the inspection apparatus 30 shown in FIG. 4 includes a main shaft motor 35, a rotational force transmission mechanism 31, and a turntable 33.
  • the spindle motor 35 is a drive source for rotating the turntable 33 and holders 47L and 47R fixed to the turntable 33 around a spindle 57 extending along the direction of gravity.
  • the spindle motor 35 is fixed inside the frame 52 of the inspection apparatus 30.
  • the main shaft motor 35 includes a rotatable shaft 36.
  • the frame 52 has a rectangular parallelepiped shape.
  • the frame 52 is provided so that driving components for driving the spindle motor 35, the stepping motor 51, and the like can be fixed.
  • the interior of the frame 52 has a volume that can accommodate the drive components.
  • the rotational force transmission mechanism 31 includes a motor pulley 37, a main shaft pulley 38, a belt 39, and a main shaft 57.
  • the rotational force transmission mechanism 31 is fixed and arranged inside the frame 52.
  • the motor pulley 37 is fixed to the shaft 36.
  • the belt 39 is stretched between the motor pulley 37 and the main shaft pulley 38.
  • the main shaft pulley 38 is fixed to the main shaft 57.
  • the main shaft 57 is rotatably supported by the frame 52 of the inspection device 30, extends upward, and is provided so as to penetrate the center portion of the upper plate 32 of the frame 52.
  • the main shaft 57 is connected to the turntable 33.
  • the turntable 33 is provided to be rotatable about the main shaft 57.
  • the angle changing mechanism of the inspection device 30 shown in FIG. 4 includes a stepping motor 51, a first power transmission mechanism 62, a second power transmission mechanism 63, and holders 47L and 47R.
  • the stepping motor 51 is a drive source for changing the angle of the holders 47L and 47R around the shafts 46L and 46R.
  • the stepping motor 51 is fixed to the frame 52.
  • the stepping motor 51 includes a rotatable shaft 58.
  • the first power transmission mechanism 62 includes a cam plate 59, a protrusion 70, a T-shaped plate 48, a guide rail 56, a bearing 41, and a second shaft 40.
  • the first power transmission mechanism 62 is fixed and arranged inside the frame 52.
  • the cam plate 59 has a disk shape when viewed from the front.
  • the cam plate 59 is fixed to the shaft 58.
  • the cam plate 59 includes a protrusion 70 protruding forward.
  • the protrusion 70 has a circular shape when viewed from the front.
  • the guide rail 56 extends in the vertical direction and is fixed to the frame 52.
  • the T-shaped plate 48 is formed to be movable in the vertical direction along the guide rail 56.
  • the T-shaped plate 48 includes a groove 80.
  • the groove part 80 is a groove
  • the state shown in FIG. 4 is a state in which the T-shaped plate 48 is lowered to the bottom.
  • the state shown in FIG. 5 is a state where the T-shaped plate 48 is raised to the top.
  • the bearing 41 is connected to the T-shaped plate 48.
  • the bearing 41 is provided at the lower end of the second shaft 40.
  • the bearing 41 holds the second shaft 40 in a rotatable manner.
  • the inside of the main shaft 57 is hollow.
  • the second shaft 40 is provided inside the main shaft 57 as an inner shaft.
  • the second shaft 40 is connected to the rack gear 43.
  • the second power transmission mechanism 63 includes a rack gear 43, a guide member 42, an upper plate 61, a pinion gear 44, an L-shaped plate 60, a gear 45, and shafts 46L and 46R.
  • the second power transmission mechanism 63 is disposed outside the frame 52.
  • the rack gear 43 is a plate-like member extending in the vertical direction. Gears are respectively carved on the left and right side ends of the rack gear 43. The gears at both end portions of the rack gear 43 mesh with a pair of pinion gears 44.
  • the guide member 42 slidably holds the rack gear 43.
  • the guide member 42 is provided extending in the vertical direction from the central opening of the upper plate 61. Therefore, when the rack gear 43 is raised, the guide member 42 protrudes from the upper plate 61.
  • the pair of L-shaped plates 60 includes a pair of gears 45.
  • the pair of gears 45 includes a pair of shafts 46L and 46R.
  • the pair of shafts 46L and 46R extend in the front-rear direction.
  • the extending direction of the pair of shafts 46L and 46R and the flow path forming surfaces 2A and 102A are orthogonal to each other.
  • the pair of gears 45 mesh with both pinion gears 44, respectively.
  • the pair of gears 45 is provided on the L-shaped plate 60 so that the angle can be changed around a pair of shafts 46L and 46R.
  • the holders 47L and 47R are fixed to the shafts 46L and 46R of the both gears 45, respectively.
  • both pinion gears 44 rotate.
  • both gears 45 rotate.
  • both the gears 45 are rotated, the holders 47L and 47R fixed to the both gears 45 change the angle around the shafts 46L and 46R of the both gears 45.
  • the shaft 46L is orthogonal to the flow path forming surface 102A of the microchip 101 held by the holder 47L.
  • the shaft 46R is orthogonal to the flow path forming surface 2A of the microchip 1 held by the holder 47R.
  • the holders 47L and 47R rotate at the same angle.
  • the bottom surface 47LB of the holder 47L is directed to the left side of the inspection apparatus 30, as shown in FIG.
  • the bottom surface 47RB of the holder 47R is directed to the right side of the inspection apparatus 30 that is opposite to the bottom surface 47LB of the holder 47L.
  • the bottom surface 47LB of the holder 47L and the bottom surface 47RB of the holder 47R are directed to the lower side of the inspection apparatus 30, as shown in FIG.
  • the insertion state of the microchip 1 is a state in which the flow path forming surface 2A faces the front side of the holder 47R and the lower surface 2B of the microchip 1 and the bottom surface 47RB of the holder 47R face each other.
  • the protrusion 48R is provided to extend upward from the bottom surface 47RB in the front-rear direction.
  • the microchip 1 is inserted downward into the holder 47R so that the lower surface 2B of the microchip 1 and the bottom surface 47RB of the holder 47R approach each other, and the notch 11 of the lower surface 2B and the protruding portion 48R of the bottom surface 47RB are fitted. To do. Thereafter, the lid 47RC of the holder 47R is closed. In this way, the microchip 1 is mounted on the holder 47R.
  • the flow path forming surface 102A of the microchip 101 faces the rear side of the holder 47L in FIG. 5, and the lower side of the microchip 101 and the bottom surface 47LB of the holder 47L in FIG. Let the state be Then, the microchip 101 is inserted into the holder 47L in a downward direction in FIG. 5 so that the lower side of the microchip 101 and the bottom surface 47LB of the holder 47L in FIG. 5 approach each other, and the lid of the holder 47L is closed. In this way, the microchip 101 is mounted on the holder 47L.
  • the inspection device 30 includes a light source 90 and a light receiving unit 91.
  • the light source 90 emits measurement light 92 on the optical path 92R.
  • the measurement light 92 is red light having a wavelength of about 650 nm, for example.
  • the light source 90 is, for example, a laser diode.
  • the light receiving unit 91 is provided on the optical path 92R of the measurement light 92 emitted from the light source 90. Specifically, the light source 90 and the light receiving unit 91 are arranged in the front-rear direction in which the incident direction of the measurement light 92 is a direction perpendicular to the flow path forming surface 2A of the microchip 1. The light receiving unit 91 receives the measurement light 92.
  • the light receiving unit 91 is, for example, a photodiode.
  • the turntable 33 rotates in the rotation direction 93.
  • the rotation direction 93 is such that the bottom surface 9B of the microchip 1 is located downstream of the bottom surface 10A in the rotation direction 93.
  • the centrifugal force CF is applied to the microchips 1 and 101 by the rotation.
  • the microchip 1 is restricted to a predetermined mounting posture by fitting the notch 11 and the protrusion 48R.
  • the predetermined mounting posture is that the flow path forming surface 2A is along the direction of gravity GF, the measurement region 10 is positioned below the passage region 8 in the direction of gravity GF, and the bottom surface 10A of the measurement region 10 is the passage region 8 when measuring absorbance.
  • the microchip 1 is arranged in such a manner that it is on the downstream side in the rotation direction 93 of the holder 47R from the bottom surface 9B.
  • the control device 200 shown in FIG. 9 includes, as components, a light source control unit 201, a rotation control unit 203, an angle setting unit 204, a ROM 205, a RAM 206, a CPU 207, an HDD 208, a display unit 209, and an operation unit. 210 and a system bus 211.
  • the system bus 211 is connected to each component of the control device 200.
  • the CPU 207 constitutes a computer together with the ROM 205 and the RAM 206.
  • the control device 200 is a personal computer, for example.
  • the control device 200 is connected to the inspection device 30 via the cable 96.
  • the cable 96 is a USB cable, for example.
  • the light source control unit 201 is connected to the light source 90. In response to a command from the CPU 207, the light source control unit 201 outputs a light emission signal to the light source 90 so that the measurement light 92 is emitted toward the light receiving unit 91.
  • the rotation control unit 203 is connected to the spindle motor 35.
  • the rotation control unit 203 outputs an angular velocity control signal to the spindle motor 35 so that the turntable 33 is rotated in the rotation direction 93 at a predetermined angular velocity in response to a command from the CPU 207 that operates according to the inspection program 205 a stored in the ROM 205. .
  • the angle setting unit 204 is connected to the stepping motor 51.
  • the angle setting unit 204 outputs an angle control signal to the stepping motor 51 so that the holders 47L and 47R are rotated to a predetermined angle ⁇ according to a command from the CPU 207 that operates according to the inspection program 205a stored in the ROM 205.
  • the ROM 205 stores an inspection program 205a for realizing processing according to a flowchart described later.
  • the inspection program 205a is executed by the CPU 207 using the RAM 206.
  • the RAM 206 functions as a temporary storage area for storing various variables to be referred to when the CPU 207 executes a program stored in the ROM 205.
  • the HDD 208 is a hard disk device that stores various data and programs.
  • the various data is, for example, the concentration of the substance to be examined.
  • the display unit 209 displays the concentration of the target substance, which is the inspection result, with reference to various data stored in the HDD 208 in response to a command from the CPU 207 that operates according to the inspection program 205 a stored in the ROM 205.
  • the display unit 209 is a liquid crystal display, for example.
  • the operation unit 210 is a device that supplies an operation signal corresponding to a user operation to the control device 200.
  • the operation unit 210 is, for example, a keyboard.
  • the user operation is, for example, an operation for starting execution of the inspection program 205a.
  • the inspection program 205a executed by the CPU 207 of the inspection apparatus 30 according to the present embodiment will be described with reference to the flowchart shown in FIG.
  • the inspection program 205a includes a liquid mixing program S20 and a measurement program S30 as subroutines.
  • the CPU 207 of the inspection apparatus 30 reads the inspection program 205a stored in the ROM 205 of the inspection apparatus 30 and starts executing it (S10).
  • the CPU 207 executes a liquid mixing program S20 described later. Specifically, the holders 47L and 47R are held at a predetermined angle ⁇ , the turntable 33 is rotated at a predetermined angular velocity, and centrifugal force CF is applied to the holders 47L and 47R (S20). As a result, the mixed liquid in which the specimen and the reagent are mixed is held in the measurement region 10 of the microchip 1.
  • the CPU 207 executes a measurement program S30 described later. Specifically, the holders 47L and 47R are alternately guided onto the optical path 92R over a plurality of times, the measurement light 92 is emitted from the light source 90, and the transmitted light is received by the light receiving unit 91 (S30). From the transmitted light, the concentration of the liquid to be inspected is calculated.
  • the CPU 207 displays the concentration of the target substance of the sample injected into the microchips 1 and 101 on the display unit 209 of the control device 200 (S40).
  • the CPU 207 ends the inspection program 205a (S50).
  • the holder 47R of the inspection apparatus 30 is set to the angle ⁇ 1.
  • the microchip 1 and the inspection apparatus 30 in a state where the angle ⁇ 1 is changed to the angle ⁇ 0 will be described.
  • the stepping motor 51 is driven so that the holder 47R rotates to the angle ⁇ 0 according to the angle control signal (S203).
  • the sample EL input from the sample input unit 3 moves in the sample input unit 3 by gravity GF.
  • the reagent M1 input from the reagent input unit 4 moves in the sample input unit 3 by gravity GF.
  • the microchip 1 and the inspection apparatus 30 in a state where application of the centrifugal force CF is started will be described.
  • the spindle motor 35 is driven to rotate the turntable 33 according to the angular velocity control signal (S204).
  • the specimen EL flows from the specimen supply path 5 to the centrifugal separation tank 12 by the centrifugal force CF.
  • the excess liquid of the sample EL flows and accumulates in the storage tank 14 via the first flow path 13.
  • the specimen EL in the centrifuge tank 12 is separated into the first component EL1 and the second component EL2 as the centrifugal force CF continues to be applied.
  • the reagent M1 flows from the reagent supply path 6 to the absorbance measurement tank 7.
  • the microchip 1 and the inspection apparatus 30 in a state where the angle ⁇ 0 is changed to the angle ⁇ 1 with the centrifugal force CF applied will be described.
  • the angle ⁇ 1 is changed to 90 °.
  • another angle for example, 80 ° is used. Also good.
  • the first component EL1 flows from the centrifugal separation tank 12 via the second flow path 15 to the absorbance measurement tank 7, and is mixed with the reagent M1 accumulated in the absorbance measurement tank 7.
  • the mixed liquid B1 of the first component EL1 of the sample EL and the reagent M1 is drawn in the direction of the centrifugal force CF of the absorbance measurement tank 7 by the centrifugal force CF.
  • the centrifugal separation tank 12 extends to the second flow path 15 side, which is the lower right side when the microchip 1 is viewed from the front, the second component EL2 having a high specific gravity stays in the centrifugal separation tank 12. Since the storage tank 14 has a volume enough to store the excess liquid flowing from the first flow path 13 on the right side from the lower end of the first flow path 13, the excess liquid in the storage tank 14 flows back to the centrifuge tank 12. None do.
  • the microchip 1 and the inspection apparatus 30 in a state where the angular velocity is decelerated will be described.
  • the CPU 207 outputs an angular velocity control signal from the rotation control unit 203 to the spindle motor 35 so as to decelerate the angular velocity of the turntable 33.
  • the spindle motor 35 is driven to reduce the angular velocity of the turntable 33 according to the angular velocity control signal (S206).
  • the liquid mixture B1 on the reagent loading unit 4 side of the absorbance measuring tank 7 is subjected to inertial force 94 on the cover member 20 side (front side) and the measurement region 10 side (rear side) when the angular velocity of the turntable 33 is reduced. Due to the gravity GF toward the lower side, it is drawn toward the measurement region 10 through the bottom surface 9B.
  • the microchip 1 and the inspection apparatus 30 in a state where the application of the centrifugal force CF has been completed will be described.
  • the CPU 207 outputs an angular velocity control signal from the rotation control unit 203 to the spindle motor 35 so as to stop the rotation of the turntable 33.
  • the spindle motor 35 is driven to stop the angular velocity of the turntable 33 according to the angular velocity control signal (S207).
  • the mixed liquid B1 is further drawn to the measurement region 10 through the bottom surface 9B by the inertial force 94 and gravity GF. Soon after the rotation stops, all of the mixed liquid B1 accumulates on the measurement region 10 side as in the state 1406.
  • the CPU 207 ends the execution of the liquid mixing program S20 (S208).
  • FIG. 12 shows a processing procedure according to the measurement program S30 in which the holders 47R and 47L are alternately guided onto the optical path 92R over a plurality of times, the measurement light 92 is emitted from the light source 90, and the transmitted light is received by the light receiving unit 91. It is a flowchart.
  • the measurement program S30 will be described with reference to FIG.
  • CPU207 starts measurement program S30, when liquid mixing program S20 mentioned above is complete
  • the CPU 207 substitutes 1 as an initial value for the algebra N.
  • the algebra N is a value indicating how many times the transmitted light of the microchips 1 and 101 is measured (S302).
  • the algebra N is stored in the RAM 206 of the control device 200.
  • the CPU 207 determines whether or not the algebra N is equal to or less than the required number Nmax of transmitted light measurement (S303).
  • the required number of measurements Nmax is stored in the ROM 205 of the control device 200 in advance.
  • the required number of measurements Nmax is a number of about 1 to 20, for example.
  • the CPU 207 controls the rotation control unit 203 so that the measurement region 10 of the microchip 1 in the holder 47R is positioned on the optical path 92R of the measurement light 92 emitted from the light source 90 of the inspection apparatus 30 according to a guidance program S304 described later.
  • An angular velocity control signal is output to the spindle motor 35.
  • the spindle motor 35 is driven to rotate the turntable 33 in the rotation direction 93 in accordance with the angular velocity control signal (S304).
  • the CPU 207 causes the light source control unit 201 to output a light emission signal to the light source 90 so that the measurement light 92 is emitted from the light source 90 to the mixed liquid B1 in the measurement region 10 of the microchip 1 located on the optical path 92R.
  • the light source 90 emits measurement light 92 according to the light emission signal.
  • the light receiving unit 91 receives the transmitted light that has passed through the measurement region 10.
  • the RAM 206 of the control device 200 stores the intensity of transmitted light received by the light receiving unit 91 (S305).
  • the CPU 207 moves the spindle from the rotation control unit 203 so that the measurement region of the microchip 101 in the holder 47L is positioned on the optical path 92R of the measurement light 92 emitted from the light source 90 of the inspection apparatus 30.
  • An angular velocity control signal is output to the motor 35.
  • the spindle motor 35 is driven so that the turntable 33 rotates by an angle of 180 degrees in the rotation direction 93 according to the angular velocity control signal (S306).
  • the CPU 207 emits light from the light source control unit 201 to the light source 90 so that the measurement light 92 is emitted from the light source 90 to the mixed liquid in the measurement region of the microchip 101 located on the optical path 92R. Output a signal.
  • the light source 90 emits measurement light 92 according to the light emission signal.
  • the light receiving unit 91 receives the transmitted light that has passed through the measurement region.
  • the RAM 206 of the control device 200 stores the intensity of transmitted light received by the light receiving unit 91 (S307).
  • the CPU 207 adds 1 to the algebra N (S308). After S308, the process returns to S303.
  • the CPU 207 calculates the absorbance from the value of the transmitted light stored in the RAM 206 of the control device 200, measures the absorbance of a plurality of test solutions having known concentrations, and uses a calibration curve between the concentration of the target substance and the absorbance. Then, the concentration of the target substance is calculated (S309).
  • the CPU 207 ends the execution of the measurement program S30 (S310).
  • a state 1501 in FIG. 15A is a cross-sectional view showing a state immediately after starting the guidance of the microchip 1 to the optical path 92R according to the process of S304. In the state 1501, since the measurement region 10 is located below the passage region 8 in the direction of gravity GF, the mixed liquid B1 stays in the measurement region 10.
  • the CPU 207 controls the spindle motor 35 from the rotation control unit 203 so that the rotation of the turntable 33 is accelerated in the rotation direction 93 at the angular acceleration ⁇ 1 [rad / s 2 ] until the predetermined maximum angular velocity ⁇ from when the rotation is stopped.
  • An angular velocity control signal is output.
  • the spindle motor 35 is driven to accelerate the rotation of the turntable 33 in the rotation direction 93 with the angular acceleration ⁇ 1 until the maximum angular velocity ⁇ is reached in accordance with the angular velocity control signal (S3042).
  • a state 1502 is a cross-sectional view showing a state of the microchip 1 during acceleration.
  • the mixed liquid B ⁇ b> 1 is drawn toward the bottom surface 9 ⁇ / b> A side of the passage region 8 through the bottom surface 9 ⁇ / b> B by the inertia force 94 a upstream in the rotation direction 93.
  • the CPU 207 outputs an angular velocity control signal from the rotation control unit 203 to the spindle motor 35 so that the turntable 33 is maintained in the state of the maximum angular velocity ⁇ [rad / s].
  • the spindle motor 35 is driven so as to maintain the rotation of the turntable 33 in the rotation direction 93 at the maximum angular velocity ⁇ in accordance with the angular velocity control signal (S3043).
  • a state 1503 is a cross-sectional view showing a state of the microchip 1 rotating at the maximum angular velocity ⁇ . In the state 1503, the mixed liquid B1 is temporarily drawn toward the passing region 8 side.
  • the CPU 207 outputs an angular velocity control signal from the rotation control unit 203 to the spindle motor 35 so that the rotation of the turntable 33 is decelerated in the rotation direction 93 at the angular acceleration ⁇ 2 [rad / s 2 ] from the maximum angular velocity ⁇ to the stop of rotation.
  • the spindle motor 35 is driven to reduce the rotation of the turntable 33 in the rotation direction 93 at the angular acceleration ⁇ 2 from the maximum angular velocity ⁇ to the stoppage of rotation in accordance with the angular velocity control signal (S3044).
  • a state 1504 is a cross-sectional view showing the state of the microchip 1 during deceleration.
  • the mixed liquid B ⁇ b> 1 passes through the bottom surface 9 ⁇ / b> A from the bottom surface 9 ⁇ / b> A of the passage region 8 by the gravity GF from the passage region 8 to the measurement region 10 and the inertia force 94 b downstream in the rotation direction 93. Attracted vigorously.
  • a state 1505 is a cross-sectional view showing the state of S3045 of the microchip 1 that has stopped. In the state 1505, the mixed liquid B1 stays on the bottom surface 9B of the passage region 8 and the measurement region 10 soon after the execution of the guidance program S304 is finished.
  • State 1506 is a cross-sectional view showing the state of the microchip 1 from which the measurement light 92 is emitted.
  • the measurement light 92 is emitted from the light source 90 to the mixed liquid B1 in the measurement region 10 of the microchip 1, and the transmitted light is received by the light receiving unit 91 (S305).
  • the liquid mixture B1 can be stored in the measurement region 10 of the microchip 1 during the measurement of transmitted light by the inertial force 94b downstream in the rotation direction 93. As a result, the absorbance of the mixed liquid B1 can be accurately measured.
  • the sample has been described as blood, but is not limited thereto.
  • the specimen may be a reagent such as serum, plasma, or drug, or a mixed liquid of reagent and blood, and can be appropriately selected by a user according to a desired test.
  • the absorbance measurement tank 7 has a rectangular shape that is long in the left-right direction, but is not limited thereto, and may be a curved shape such as a polygonal shape or a circle.
  • the bottom surface 9 ⁇ / b> B of the passage area 8 is provided from the predetermined place 8 ⁇ / b> T to the predetermined place 10 ⁇ / b> T located in the intermediate portion of the passage area 8.
  • 10T may be provided. That is, the entire depth of the passing region 8 may be provided so as to become shallower as the measuring region 10 is approached. Further, the bottom surface 9B of the passing region 8 linearly becomes shallower in the front-rear direction as it approaches the measurement region 10, that is, the lower side.
  • the present invention is not limited to this, and when the liquid flows from the passage region 8 toward the measurement region 10 by applying an inertial force, the liquid is continuously shallow in the front-rear direction so as not to remain in the passage region 8.
  • Other shapes may be used as long as they are.
  • the surface roughness of each surface of the measurement region 10 is defined, but the surface roughness of each surface of the measurement region 10 may be in a range in which liquid flows into the measurement region 10 due to inertial force. .
  • the measurement region 10 includes the side wall surfaces 10B, 10C, and 10D perpendicular to the flow path forming surface 2A, but may be a surface that intersects instead of a vertical surface.
  • the taper is formed from the bottom surface 10A in the direction along the flow path forming surface 2A of the measurement region 10 toward the flow path forming surface 2A, the surface roughness of the surfaces 10B, 10C, and 10D can be increased during injection molding. Rough and easy to process.
  • the cutout portion 11 is provided at the right corner of the bottom surface 2B of the microchip 1.
  • a posture regulating means capable of regulating the orientation of the microchip 1 to a predetermined posture
  • it is in another form.
  • a protrusion may be provided on the outer wall surface of the microchip
  • a notch may be provided on the inner wall surface on the holder side.
  • there may be two or more notches.
  • the notch part may be extended and provided upward from the lower end of one side surface among the side surfaces perpendicular to the flow path forming surface 2A of the microchip.
  • the reagent supply path 6 and the passage area 8 are directly connected, but a measuring unit and a surplus tank are provided between the reagent supply path 6 and the passage area 8. May be.
  • the measuring unit is a tank for measuring a predetermined amount of reagent.
  • the measuring unit has a volume capable of measuring a predetermined amount of the reagent.
  • the surplus tank is a tank for storing the surplus liquid measured by the measuring unit.
  • the surplus tank has a volume capable of storing a predetermined amount of surplus liquid flowing out by measuring a predetermined amount by the measuring unit.
  • the second flow path 15 and the reagent supply path 6 are connected to the upper end of the passage area 8.
  • the second flow path and the reagent supply path need only be connected to one of the end portions of the passage region.
  • the sample loading unit 3 is provided on the left side and the reagent loading unit 4 is provided on the right side as viewed from the front, but the sample loading unit 3 on the right side and the reagent loading unit 4 on the left side, You may arrange
  • the thicknesses of the sample loading unit 3 and the reagent loading unit 4 are constant, but the sample loading unit 3 and the reagent loading unit 4 are close to the sample supply path 5 and the reagent supply path 6. Accordingly, it may be formed in a shape in which the thickness in the front-rear direction is reduced. By reducing the thickness of the sample supply path 5 and the reagent supply path 6 in the front-rear direction, it is possible to accurately measure a smaller amount of sample and reagent.
  • both the microchips 1 and 101 have one sample EL input portion, but there may be two or more sample input portions in each of the microchips 1 and 101.
  • the specimen EL of the microchip 101 is mixed with one reagent M1, but may be mixed with a plurality of reagents.
  • the material of the plate member 2 and the cover member 20 is not particularly limited, and polyethylene terephthalate (PET), polybutylene terephthalate (PBT), polymethyl methacrylate (PMMA), polycarbonate (PC), polystyrene (PS) , Polypropylene (PP), polyethylene (PE), polyethylene naphthalate (PEN), polyarylate resin (PAR), acrylonitrile / butadiene / styrene resin (ABS), vinyl chloride resin (PVC), polymethylpentene resin (PMP), Organic materials such as polybutadiene resin (PBD), biodegradable polymer (BP), cycloolefin polymer (COP), and polydimethylsiloxane (PDMS) can be used.
  • an inorganic material such as silicon, glass, or quartz may be used.
  • the plate member 2 was a substantially square transparent plate, but if it has an area that can form a flow path on the flow path forming surface, a polygon such as an octagon, Alternatively, the shape may be chamfered such as a circle or an ellipse.
  • the holders 47L and 47R may be formed so as to be accommodated in accordance with the shapes of the various plate members.
  • the plate member 2 may not be transparent as long as it is a member that can transmit measurement light.
  • the cover member 20 may be not only a flexible film but also a sheet-like substance having higher rigidity than the film.
  • substrate which has the hardness comparable as the board member 2 and consists of a homogeneous material may be sufficient.
  • the substrate is known, for example, described in JP-A-2006-234600.
  • the plate member 2 is manufactured by injection molding, but may be manufactured by other various resin molding methods such as vacuum molding, or mechanical cutting.
  • step S304 for guiding the holder 47R onto the optical path 92R in the rotation direction 93 is performed.
  • a motor that can control the rotation stop position which is different from the spindle motor 35, is used.
  • the holder 47R may be controlled to stop on the optical path 92R.
  • it is desirable that the angular acceleration at the start of the liquid mixing program S20 is smaller than the angular acceleration at the end of the liquid mixing program S20. Thereby, inertia force can be given comparatively strongly downstream in the direction of rotation.
  • the light source 90 is a laser diode, but any light source capable of emitting directional light such as an LED may be used.
  • control device 200 is provided as a separate configuration connected to the drive mechanism of the inspection device 30 via the cable 96, but is incorporated into the drive mechanism and provided integrally therewith. Also good.
  • the holder 47 includes the holder 47L and the holder 47R, but there may be one holder 47 or three or more holders 47.
  • the angular acceleration ⁇ 1 is smaller than the angular acceleration ⁇ 2.
  • the angular acceleration ⁇ 1 is It may be larger than the angular acceleration ⁇ 2.
  • the measurement light emitted from the light source is arranged so that the incident direction of the measurement light is perpendicular to the flow path forming surface, but the flow path forming surface is limited to the arrangement perpendicular to the incident direction. Absent. For example, if the light source enters measurement liquid into the liquid mixture in the measurement region and the light receiving unit can receive transmitted light, the angle formed between the flow path forming surface and the incident direction is an acute angle or an obtuse angle. May be.
  • the turntable 33 has a disk shape, but may have various shapes such as a polygonal shape as long as the turntable 33 is provided to be rotatable about the vertical direction.
  • the extending direction of the pair of shafts 46L and 46R and the flow path forming surfaces 2A and 102A are orthogonal to each other, but the flow path forming surface is limited to an arrangement orthogonal to the rotation axis. There is no.
  • the direction of the centrifugal force CF can be switched to a desired direction when the angle is changed to a predetermined angle around the pair of shafts 46L, 46R, the flow path forming surfaces 2A, 102A and the pair of shafts 46L,
  • the angle formed by the extending direction of 46R may be an acute angle or an obtuse angle.
  • the centrifugal force CF is applied in a direction parallel to the flow path forming surfaces 2A and 102A of the microchips 1 and 101 in the holders 47L and 47R, but the flow path forming surface is in the direction of the centrifugal force CF. It is not limited to arrangement
  • the centrifugal acceleration of the inspection apparatus 30 is 500 G [m / s 2 ], but may be any centrifugal acceleration that allows the specimen or the mixed liquid to move through a predetermined flow path or tank. Further, the centrifugal acceleration of the centrifugal force CF may be a value of about 100 G to 5000 G [m / s 2 ], for example.
  • the flow path forming surfaces 2A and 102A in the present embodiment are examples of the flow path forming surfaces in the present invention.
  • the predetermined channel in the present embodiment is an example of the channel in the present invention.
  • the microchips 1 and 101 in the present embodiment are an example of a test object receptacle in the present invention.
  • the specimen EL, the reagent M1, or the mixed liquid B1 in the present embodiment is an example of a liquid to be inspected in the present invention.
  • the absorbance measurement tank 7 in the present embodiment is an example of the absorbance measurement tank in the present invention.
  • the first depth D1 and the second depth D2 in the present embodiment are examples of the first depth and the second depth in the present invention in order.
  • the passage region 8 and the measurement region 10 in this embodiment are examples of the passage region and the measurement region in the present invention in order.
  • the rotation direction 93 in the present embodiment is an example of the rotation direction in the present invention.
  • the front-rear direction in the present embodiment is an example of a direction perpendicular to the flow path forming surface in the present invention.
  • the optical path 92R in the present embodiment is an example of the position where the measurement light in the present invention is incident.
  • the main shaft 57 in the present embodiment is an example of the main shaft in the present invention.
  • the notch 11 in the present embodiment is an example of the notch and the posture regulating means in the present invention.
  • the side wall surfaces 10B, 10C, and 10D of the measurement region 10 in the present embodiment are examples of the side wall surfaces of the measurement region in the present invention.
  • the bottom surface 9 ⁇ / b> B and the bottom surface 10 ⁇ / b> A in this embodiment are examples of the bottom surface of the passing region and the bottom surface of the measurement region in the present invention in order.
  • the measurement light 92, the light source 90, the light receiving unit 91, and the inspection device 30 in this embodiment are examples of the measurement light, the light source, the light receiving unit, and the inspection device in the present invention in order.
  • the holders 47L and 47R in the present embodiment are examples of the holder in the present invention.
  • the spindle motor 35, the rotation control unit 203, the stepping motor 51, and the angle setting unit 204 in the present embodiment are examples of the rotation drive source, the rotation control unit, the angle change source, and the angle setting unit in the present invention in order.
  • the angle ⁇ in the present embodiment is an example of the angle in the present invention.
  • the axes of the shafts 46L and 46R in the present embodiment are examples of the axes in the present invention.
  • the angular acceleration ⁇ 1, the maximum angular velocity ⁇ , and the angular acceleration ⁇ 2 in this embodiment are examples of the first angular acceleration, the predetermined angular velocity, and the second angular acceleration in the present invention in order.
  • the holder 47R and the holder 47L in the present embodiment are examples of the first holder and the second holder in the present invention in order.
  • S3042 in the present embodiment is an example of a rotation step in the present invention.
  • S3044 in this embodiment is an example of an angle setting step in the present invention.
  • S305 in the present embodiment is an example of a measurement step in the present invention.

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  • Analytical Chemistry (AREA)
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  • Life Sciences & Earth Sciences (AREA)
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Abstract

Cette invention permet à un liquide qui doit être inspecté d'être stocké dans une région de mesure d'une cuve de mesure d'absorbance pendant la mesure et permet de mesurer avec précision l'absorbance du liquide. Un accepteur d'objets à inspecter (1) selon l'invention comprend une cuve de mesure d'absorbance (7), ladite cuve de mesure d'absorbance (7) comprenant une région de passage (8) qui a une seconde profondeur (D2) dans un sens perpendiculaire à une surface formant voie d'écoulement et par laquelle passe le liquide qui doit être inspecté (EL), une région de mesure (10) qui a une première profondeur (D1), moins profonde que la seconde profondeur dans le sens perpendiculaire et par laquelle passe la lumière de mesure destinée à mesurer l'absorbance du liquide qui doit être inspecté (EL), et une surface inférieure (9B) qui relie les deux régions (8, 10) de façon que le liquide qui doit être inspecté (EL) s'écoule depuis la région de passage (8) jusqu'à la région de mesure (10). La surface formant voie d'écoulement (2A) est parallèle au sens de la force de gravité (GF), la surface inférieure (9B) de la région de passage (8) se trouve côté aval dans le sens de rotation (93) par rapport à la surface inférieure (10A) de la région de mesure (10), et l'accepteur d'objets à inspecter a une surface de paroi extérieure (2B) qui lui permet de se loger dans un support (47R) du dispositif d'inspection (30) de façon à pouvoir être monté dans ledit support (47R).
PCT/JP2012/066503 2011-07-29 2012-06-28 Système d'inspection et procédé associé WO2013018474A1 (fr)

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JP2011-166436 2011-07-29

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JP2017090236A (ja) * 2015-11-10 2017-05-25 ブラザー工業株式会社 検査方法、検査システム、及び検査装置
CN111122893A (zh) * 2018-10-31 2020-05-08 天亮医疗器材股份有限公司 检测卡匣、检测方法及检测装置

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JP2015031643A (ja) * 2013-08-06 2015-02-16 ブラザー工業株式会社 検査チップ
JP6164186B2 (ja) * 2014-09-30 2017-07-19 ブラザー工業株式会社 検査装置、検査プログラム、検査方法
JP6994113B2 (ja) * 2018-07-02 2022-01-14 Ｐｈｃホールディングス株式会社 試料分析用基板および試料分析方法

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JP2010066195A (ja) * 2008-09-12 2010-03-25 Seiko Epson Corp 生体試料反応用チップ、生体試料反応用チップに反応液を充填する遠心装置、および生体試料反応用チップに反応液を充填する方法

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JP2006337221A (ja) * 2005-06-03 2006-12-14 Sharp Corp 電気化学検出装置
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JP2017090236A (ja) * 2015-11-10 2017-05-25 ブラザー工業株式会社 検査方法、検査システム、及び検査装置
CN111122893A (zh) * 2018-10-31 2020-05-08 天亮医疗器材股份有限公司 检测卡匣、检测方法及检测装置
CN111122893B (zh) * 2018-10-31 2024-04-12 天亮医疗器材股份有限公司 检测卡匣、检测方法及检测装置

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