WO2016093332A1 - 試料分析用基板、試料分析装置、試料分析システムおよび試料分析システム用プログラム - Google Patents
試料分析用基板、試料分析装置、試料分析システムおよび試料分析システム用プログラム Download PDFInfo
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- WO2016093332A1 WO2016093332A1 PCT/JP2015/084738 JP2015084738W WO2016093332A1 WO 2016093332 A1 WO2016093332 A1 WO 2016093332A1 JP 2015084738 W JP2015084738 W JP 2015084738W WO 2016093332 A1 WO2016093332 A1 WO 2016093332A1
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- 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
- G01N35/00069—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 whereby the sample substrate is of the bio-disk type, i.e. having the format of an optical disk
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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
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- 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
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- 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
- G01N35/00584—Control arrangements for automatic analysers
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- 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
- G01N35/0098—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation
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- 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
- G01N35/08—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
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- 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
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
- G01N35/1016—Control of the volume dispensed or introduced
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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
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/06—Fluid handling related problems
- B01L2200/0621—Control of the sequence of chambers filled or emptied
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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
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/06—Fluid handling related problems
- B01L2200/0647—Handling flowable solids, e.g. microscopic beads, cells, particles
- B01L2200/0668—Trapping microscopic beads
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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
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0803—Disc shape
- B01L2300/0806—Standardised forms, e.g. compact disc [CD] format
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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
- 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
- B01L2300/0864—Configuration of multiple channels and/or chambers in a single devices comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
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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
- 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
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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
- 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
- B01L2400/0406—Moving fluids with specific forces or mechanical means specific forces capillary forces
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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
- 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
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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
- 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
- B01L2400/043—Moving fluids with specific forces or mechanical means specific forces magnetic forces
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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
- 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
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- 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
- G01N2035/00465—Separating and mixing arrangements
- G01N2035/00495—Centrifuges
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N37/00—Details not covered by any other group of this subclass
Definitions
- the present application relates to a sample analysis substrate, a sample analysis device, a sample analysis system, and a sample analysis system program.
- Patent Document 1 uses a disk-shaped sample analysis substrate on which a channel, a chamber, and the like are formed, and rotates the sample analysis substrate to transfer, distribute, and mix the components in the sample solution. The technology which performs analysis etc. of this is disclosed.
- Analysis of specific components in a sample includes an analysis method using complicated reaction steps using enzyme reaction, immune reaction, and the like. There has been a demand for a technique capable of performing an analysis method through such a complicated reaction step in a sample analysis substrate.
- Non-limiting exemplary embodiments of the present application provide a sample analysis substrate, a sample analysis apparatus, a sample analysis system, and a sample analysis that can be applied to an analysis method in which components in a specimen are analyzed through more complicated reaction steps. Provide system programs.
- a sample analysis substrate is a sample analysis substrate that transfers a liquid by a rotational motion, and includes a substrate having a rotation axis and a first space that is located in the substrate and holds a liquid.
- the first space is connected to the first opening, and includes a first region including a portion extending from the first opening toward a side farther from the rotation axis.
- the first space of the first chamber includes the first space. It is larger than the volume of the flow path.
- the sample analysis substrate According to the sample analysis substrate, the sample analysis apparatus, the sample analysis system, and the sample analysis system program according to one aspect of the present application, it is possible to cope with an analysis method in which components in a specimen are analyzed through complicated reaction steps.
- FIG. 1 is an example of a schematic diagram illustrating a sandwich immunoassay method using magnetic particles.
- FIG. 2A is a schematic diagram illustrating an example of a configuration of the sample analysis system of the embodiment. It is a schematic diagram which shows an example of the structure for detecting the origin of the board
- FIG. 3A is an exploded perspective view showing an example of a sample analysis substrate.
- FIG. 3B is a plan view showing an example of a sample analysis substrate.
- FIG. 3C shows an example of the thickness of each chamber and channel in the cross section of the thick broken line part in FIG. 3B.
- FIG. 3D shows an example of an arrangement relationship from the rotation axis on the sample analysis substrate in the reaction chamber, the second chamber, the third chamber, the second path, and the fourth path.
- FIG. 3E is a diagram schematically illustrating an example of another structure of the sample analysis substrate.
- FIG. 4 is a flowchart showing an example of the operation of the sample analysis system.
- FIG. 5 is a diagram schematically illustrating an example of the stop angle of the sample analysis substrate and the position of the liquid during the operation of the sample analysis system.
- FIG. 6 is a diagram schematically illustrating an example of the stop angle of the sample analysis substrate and the position of the liquid during the operation of the sample analysis system.
- FIG. 7 is a diagram schematically illustrating an example of the stop angle of the sample analysis substrate and the position of the liquid during the operation of the sample analysis system.
- FIG. 8 is a diagram schematically illustrating an example of the stop angle of the sample analysis substrate and the position of the liquid during the operation of the sample analysis system.
- FIG. 9 is a diagram schematically illustrating an example of the stop angle of the sample analysis substrate and the position of the liquid during the operation of the sample analysis system.
- FIG. 10 is a diagram schematically illustrating an example of the stop angle of the sample analysis substrate and the position of the liquid during the operation of the sample analysis system.
- FIG. 11 is a diagram schematically illustrating an example of the stop angle of the sample analysis substrate and the position of the liquid during the operation of the sample analysis system.
- FIG. 12 is a diagram schematically illustrating an example of the stop angle of the sample analysis substrate and the position of the liquid during the operation of the sample analysis system.
- FIG. 13 is a diagram schematically illustrating an example of the stop angle of the sample analysis substrate and the position of the liquid during the operation of the sample analysis system.
- FIG. 14 is a diagram schematically illustrating an example of the stop angle of the sample analysis substrate and the position of the liquid during the operation of the sample analysis system.
- FIG. 15 is a diagram schematically illustrating an example of the stop angle of the sample analysis substrate and the position of the liquid during the operation of the sample analysis system.
- FIG. 16 is a plan view showing another example of the sample analysis substrate.
- FIG. 17A is a plan view showing another example of the sample analysis substrate.
- FIG. 17B is an enlarged plan view showing the vicinity of the connection portion between the first flow path and the first chamber of the sample analysis substrate shown in FIG. 17A.
- FIG. 18 is a plan view showing an example of a sample analysis substrate used in the second embodiment.
- FIG. 19 is a flowchart showing an example of the operation of the sample analysis system according to the second embodiment using the sample analysis substrate shown in FIG. 18A.
- FIG. 20 is a diagram schematically illustrating an example of the stop angle of the sample analysis substrate and the position of the liquid during the operation of the sample analysis system according to the second embodiment.
- FIG. 21 is a diagram schematically illustrating an example of the stop angle of the sample analysis substrate and the position of the liquid during the operation of the sample analysis system according to the second embodiment.
- FIG. 22 is a diagram schematically illustrating an example of the stop angle of the sample analysis substrate and the position of the liquid during the operation of the sample analysis system according to the second embodiment.
- FIG. 23 is a diagram schematically illustrating an example of the stop angle of the sample analysis substrate and the position of the liquid during the operation of the sample analysis system according to the second embodiment.
- FIG. 24 is a diagram schematically illustrating an example of the stop angle of the sample analysis substrate and the position of the liquid during the operation of the sample analysis system according to the second embodiment.
- FIG. 25 is a diagram schematically illustrating an example of the stop angle of the sample analysis substrate and the position of the liquid during the operation of the sample analysis system according to the second embodiment.
- FIG. 26 is a diagram schematically illustrating an example of the stop angle of the sample analysis substrate and the position of the liquid during the operation of the sample analysis system according to the second embodiment.
- FIG. 27 is a diagram schematically illustrating an example of the stop angle of the sample analysis substrate and the position of the liquid during the operation of the sample analysis system according to the second embodiment.
- FIG. 28 is a diagram schematically illustrating an example of the stop angle of the sample analysis substrate and the position of the liquid during the operation of the sample analysis system according to the second embodiment.
- FIG. 29 is a diagram schematically illustrating an example of the stop angle of the sample analysis substrate and the position of the liquid during the operation of the sample analysis system according to the second embodiment.
- FIG. 30 is a diagram schematically illustrating an example of the stop angle of the sample analysis substrate and the position of the liquid during the operation of the sample analysis system according to the second embodiment.
- FIG. 31 is a diagram schematically illustrating an example of the stop angle of the sample analysis substrate and the position of the liquid during the operation of the sample analysis system according to the second embodiment.
- FIG. 32 is a diagram schematically illustrating an example of the stop angle of the sample analysis substrate and the position of the liquid during the operation of the sample analysis system according to the second embodiment.
- FIG. 33 is a diagram schematically illustrating an example of the stop angle of the sample analysis substrate and the position of the liquid during the operation of the sample analysis system according to the second embodiment.
- FIG. 34 is a plan view showing another example of the sample analysis substrate.
- FIG. 35 is a plan view showing another example of the sample analysis substrate.
- a binding reaction between an analyte as an analysis target and a ligand that specifically binds to the analyte may be used.
- analysis methods include immunoassay methods and genetic diagnosis methods.
- immunoassay methods include competitive methods and non-competitive methods (sandwich immunoassay methods).
- An example of a gene diagnosis method is a gene detection method by hybridization.
- magnetic particles sometimes referred to as “magnetic beads”, “magnetic particles” or “magnetic beads”.
- a sandwich immunoassay method using magnetic particles will be specifically described.
- an antigen-antibody reaction between a primary antibody 304 immobilized on the surface of a magnetic particle 302 (hereinafter referred to as “magnetic particle-immobilized antibody 305”) and an antigen 306 as a measurement object.
- the secondary antibody to which the labeling substance 307 is bound (hereinafter referred to as “labeled antibody 308”) and the antigen 306 are bound by an antigen-antibody reaction.
- labeled antibody 308 the secondary antibody to which the labeling substance 307 is bound
- a complex 310 in which the magnetic particle-immobilized antibody 305 and the labeled antibody 308 are bound to the antigen 306 is obtained.
- the signal based on the labeled substance 307 of the labeled antibody 308 bound to the complex 310 is detected, and the antigen concentration is measured according to the amount of the detected signal.
- the labeling substance 307 include enzymes (for example, peroxidase, alkaline phosphatase, luciferase, etc.), chemiluminescent substances, electrochemiluminescent substances, fluorescent substances, etc., and dyes corresponding to the respective labeling substances 307, Signals such as luminescence and fluorescence are detected.
- the sandwich immunoassay method using magnetic particles has been described as an example, but B / F separation is performed by immunoassay or hybridization using competitive or non-competitive methods, regardless of the presence or absence of magnetic particles. Necessary for gene detection.
- magnetic particles for example, a ligand immobilized on a solid phase composed of a material such as polystyrene or polycarbonate by physical adsorption, a ligand immobilized on a solid phase by chemical bonding, a metal composed of gold, etc.
- SAM self-assembled monolayer
- the magnetic particles including the composite 310 In order to sufficiently perform the B / F separation, it is preferable to wash the magnetic particles including the composite 310 with a washing solution a plurality of times. Specifically, first, in the reaction solution containing the complex 310, the unreacted antigen 306, the labeled antibody 308, and the like, only the reaction solution is removed while the complex 310 containing the magnetic particles is captured by the magnet. . Thereafter, a cleaning liquid is added to clean the composite 310, and the cleaning liquid is removed. By repeating this washing a plurality of times, B / F separation in which unreacted substances and non-specifically adsorbed substances are sufficiently removed can be achieved. This point is also described in an example using magnetic particles, but this is true for sandwich-type assays in general, regardless of whether magnetic particles are used.
- a sample analysis substrate, a sample analysis device, a sample analysis system, and a sample analysis system program according to an aspect of the present application are as follows.
- a sample analysis substrate that transfers liquid by a rotational motion, A substrate having a rotation axis; A first chamber located within the substrate and having a first space for holding a liquid; A second chamber located within the substrate and having a second space for holding the liquid discharged from the first chamber; A first flow path located in the substrate, having a path connecting the first chamber and the second chamber, and capable of being filled with a liquid held in the first space by capillary action; , With The first flow path has a first opening and a second opening, and the first opening and the second opening are connected to the first chamber and the second chamber, respectively, and the first opening is connected to the second opening.
- the first space has a first region connected to the first opening and including a portion extending from the first opening toward a side farther from the rotation axis,
- the sample analysis substrate wherein the first space of the first chamber is larger than a volume of the first flow path.
- the first space further includes a second region connected to the extending portion of the first region at a position farther from the rotation axis than the first opening.
- a part of the first chamber and a part of the first flow path are located in a radial direction centering on the rotation axis with the first opening interposed therebetween.
- the first flow path includes a first portion having the first opening and a second portion having the second opening, 3.
- [Item 5] 5.
- the first flow path further includes a space that is adjacent to the first portion and located closer to the rotating shaft than the first portion, and an opening that communicates with the space. 6.
- the first region of the first space includes a connection portion connected to the first opening, and the connection portion is capable of sucking the liquid held in the first space by capillary action, 7.
- Item 8 Item 8.
- Item 9 Item 3.
- the sample analysis substrate according to Item 2 wherein the extending portion of the first region can suck the liquid held in the second region by capillary action.
- 10 10.
- the sample analysis substrate according to any one of items 1 to 9, wherein the first space of the first chamber is at least twice the volume of the first flow path.
- a third chamber in the substrate which is located farther from the rotation axis than the second chamber and has a third space for holding the liquid discharged from the second chamber;
- a second flow path located in the substrate having a path connecting the second chamber and the third chamber, and capable of being filled with a liquid held in the second space by capillary action;
- the substrate for sample analysis according to any one of items 1 to 10 further comprising: [Item 12] A fourth chamber located within the substrate and having a fourth space for holding a liquid; Another flow path located in the substrate, having a path connecting the fourth chamber and the second chamber, and capable of being filled with a liquid held in the fourth space by capillary action; , Item 12.
- the sample analysis substrate according to Item 11 further comprising: [Item 13] The sample analysis according to item 12, wherein the first chamber and the fourth chamber are respectively disposed in two regions divided by a straight line connecting the vicinity of the center of the second chamber and the rotation axis in the substrate. Substrate. [Item 14] Item 13. The item 12, wherein both the first chamber and the fourth chamber are disposed in one of two regions separated by a straight line connecting the vicinity of the center of the second chamber and the rotation axis in the substrate. Sample analysis substrate. [Item 15] 15. The sample analysis substrate according to any one of items 1 to 14, further comprising a magnet positioned in proximity to the second chamber.
- a sample analysis substrate according to any one of items 1 to 15, A motor that rotates the sample analysis substrate around the rotation axis in a state where the rotation axis is at an angle greater than 0 ° and less than or equal to 90 ° with respect to the direction of gravity; A rotation angle detection circuit for detecting a rotation angle of the rotation shaft of the motor; Based on the detection result of the rotation angle detection circuit, the drive circuit that controls the rotation angle of the motor when rotating and stopping, and the arithmetic unit, the memory, and the memory are configured to be executable by the arithmetic unit
- a sample analyzer including a program and having a control circuit for controlling operations of the motor, the rotation angle detection circuit, and the drive circuit based on the program;
- a sample analysis system comprising: The program is When the sample analysis substrate in which the liquid in the first chamber is filled is loaded in the sample analysis device, (A) by stopping the sample analysis substrate at a predetermined first angle, the first flow path is filled with a part of the liquid in the first chamber by capillary
- the sample analysis substrate is the sample analysis substrate according to item 11,
- the program after the step (b), (C) by stopping the sample analysis substrate at a predetermined second angle, the second flow path is filled with a portion of the liquid transferred to the second chamber by capillary action; (D) by rotating the sample analysis substrate, the liquid transferred to the second chamber is moved to the third chamber through the second flow path by centrifugal force; Item 17.
- the sample analyzer further includes an optical measurement unit, The program, after the step (j), (K) causing the optical measurement unit to perform optical measurement of the part of the liquid transferred to the second chamber; Item 21.
- Item 22 Item 17.
- a rotation angle detection circuit for detecting a rotation angle of the rotation shaft of the motor; Based on the detection result of the rotation angle detection circuit, the drive circuit that controls the rotation angle of the motor when rotating and stopping, and the arithmetic unit, the memory, and the memory are configured to be executable by the arithmetic unit
- a sample analyzer including a program and having a control circuit for controlling operations of the motor, the rotation angle detection circuit, and the drive circuit based on the program; With The program is When the sample analysis substrate in which the liquid in the first chamber is filled is loaded in the sample analysis device, (A) by stopping the sample analysis substrate at a predetermined first angle, the first flow path is filled with a part of the liquid in the first chamber by capillary action; (B) The sample liquid in the first flow path is transferred to the second chamber by rotating the sample analysis substrate.
- Sample analyzer [Item 24] The sample analysis substrate according to any one of items 1 to 15, A motor that rotates the sample analysis substrate around the rotation axis in a state where the rotation axis is at an angle greater than 0 ° and less than or equal to 90 ° with respect to the direction of gravity; A rotation angle detection circuit for detecting a rotation angle of the rotation shaft of the motor; Based on the detection result of the rotation angle detection circuit, the drive circuit that controls the rotation angle of the motor when rotating and stopping, and the arithmetic unit, the memory, and the memory are configured to be executable by the arithmetic unit
- a sample analyzer including a program and having a control circuit for controlling operations of the motor, the rotation angle detection circuit, and the drive circuit based on the program;
- a sample analysis system program comprising: The program is When the sample analysis substrate in which the liquid in the first chamber is filled is loaded in the sample analysis device, (A) by stopping the sample analysis substrate at a predetermined first angle, the first flow path is filled with a part of the
- sample analysis substrate a sample analysis substrate, a sample analysis device, a sample analysis system, and a sample analysis system program according to the present embodiment will be described in detail with reference to the drawings.
- the sample analysis substrate, sample analysis apparatus, sample analysis system, and sample analysis system program of this embodiment weigh a certain amount of liquid held in one chamber, divide it into multiple chambers, and transfer it to another chamber. Can be transported.
- the liquid is a cleaning liquid, but the liquid is not limited to the cleaning liquid, and may be various liquids used for sample analysis.
- FIG. 2A is a schematic diagram showing the overall configuration of the sample analysis system 501.
- the sample analysis system 501 includes a sample analysis substrate 100 and a sample analysis device 200.
- the sample analyzer 200 includes a motor 201, an origin detector 203, a rotation angle detection circuit 204, a control circuit 205, a drive circuit 206, and an optical measurement unit 207.
- the motor 201 has a rotation axis A inclined from the gravity (vertical) direction G at an angle ⁇ greater than 0 ° and not more than 90 ° with respect to the turntable 201a and the gravity direction, and the sample analysis placed on the turntable 201a
- the substrate 100 is rotated around the rotation axis A. Since the rotation axis A is inclined, in addition to the centrifugal force due to the rotation, the movement due to the gravity can be used for the transfer of the liquid in the sample analysis substrate 100.
- the inclination angle of the rotation axis A with respect to the gravity direction G is preferably 5 ° or more, more preferably 10 ° or more and 45 ° or less, and further preferably 20 ° or more and 30 ° or less.
- the motor 201 may be, for example, a direct current motor, a brushless motor, an ultrasonic motor, or the like.
- the origin detector 203 detects the origin of the sample analysis substrate 100 attached to the motor 201.
- the origin detector 203 includes a light source 203a, a light receiving element 203b, and an origin detection circuit 203c, and is arranged such that the sample analysis substrate 100 is positioned between the light source 203a and the light receiving element 203b. Is done.
- the light source 203a is a light emitting diode
- the light receiving element 203b is a photodiode.
- the sample analysis substrate 100 has a marker 210 provided at a specific position.
- the marker 210 has a light shielding property of shielding at least a part of light emitted from the light source 203a.
- the area of the marker 210 has a low transmittance (for example, 10% or less), and the area other than the marker 210 has a high transmittance (for example, 60% or more).
- the light receiving element 203b When the sample analysis substrate 100 is rotated by the motor 201, the light receiving element 203b outputs a detection signal corresponding to the amount of incident light to the origin detection circuit 203c. Depending on the direction of rotation, the detection signal increases or decreases at the edges 210a and 210b of the marker 210. For example, when the sample analysis substrate 100 is rotating clockwise as indicated by the arrow in FIG. 2B, the origin detection circuit 203c detects a decrease in the detected light amount and outputs it as an origin signal. In the present specification, the position of the edge 210a of the marker 210 is treated as the origin position of the sample analysis substrate 100 (the angular position serving as the reference of the sample analysis substrate 100).
- the position of a specific angle arbitrarily determined from the position of the edge 210a of the marker 210 may be determined as the origin.
- the marker 210 has a sector shape and the central angle thereof is smaller than the angle detection accuracy necessary for sample analysis, the marker 210 itself may be determined as the origin position.
- the origin position is used for the sample analyzer 200 to acquire information on the rotation angle of the sample analysis substrate 100.
- the origin detector 203 may have other configurations.
- the sample analysis substrate 100 may include an origin detection magnet, and the origin detector 203 may be a magnetic detection element that detects the magnetism of the magnet. Moreover, you may use the magnet for catching the magnetic particle mentioned later for origin detection.
- the origin detector 203 may not be provided.
- the rotation angle detection circuit 204 detects the angle of the rotation axis A of the motor 201.
- the rotation angle detection circuit 204 may be a rotary encoder attached to the rotation axis A.
- the rotation angle detection circuit 204 includes a hall element provided in the brushless motor and a detection circuit that receives an output signal of the hall element and outputs an angle of the rotation axis A. Also good.
- the drive circuit 206 rotates the motor 201. Specifically, based on a command from the control circuit 205, the sample analysis substrate 100 is rotated clockwise or counterclockwise. Further, based on a command from the control circuit 205, the detection result of the rotation angle detection circuit 204 and the origin detector 203 and the swing and rotation of the sample analysis substrate 100 are stopped.
- the optical measurement unit 207 detects a signal (for example, dye, luminescence, fluorescence, etc.) corresponding to the labeling substance 307 of the labeled antibody 308 bound to the complex 310 (FIG. 1) held on the sample analysis substrate 100.
- a signal for example, dye, luminescence, fluorescence, etc.
- the control circuit 205 includes a CPU provided in the sample analyzer 200, for example.
- the control circuit 205 executes a computer program read into a RAM (Random Access Memory; not shown), and sends instructions to other circuits according to the procedure of the computer program.
- Each circuit that receives the instruction operates as described in this specification to realize the function of each circuit.
- the command from the control circuit 205 is sent to the drive circuit 206, the rotation angle detection circuit 204, the optical measurement unit 207, etc., as shown in FIG. 2A, for example.
- the procedure of the computer program is shown by the flowchart in the accompanying drawings.
- the RAM into which the computer program is read in other words, the RAM that stores the computer program may be volatile or non-volatile.
- Volatile RAM is RAM that cannot store stored information unless power is supplied.
- dynamic random access memory DRAM
- the nonvolatile RAM is a RAM that can hold information without supplying power.
- magnetoresistive RAM (MRAM), resistance change memory (ReRAM), and ferroelectric memory (FeRAM) are examples of nonvolatile RAM. In the present embodiment, it is preferable to employ a nonvolatile RAM.
- Both volatile RAM and non-volatile RAM are non-transitory examples of computer-readable recording media.
- a magnetic recording medium such as a hard disk or an optical recording medium such as an optical disk is an example of a computer-readable recording medium that is not temporary. That is, the computer program according to the present disclosure can be recorded on various non-transitory computer-readable media other than a medium such as the atmosphere (temporary medium) that propagates the computer program as a radio wave signal.
- control circuit 205 is described as a separate component from the rotation angle detection circuit 204 and the origin detection circuit 203c of the origin detector 203.
- these may be realized by common hardware.
- a CPU computer
- a CPU provided in the sample analyzer 200 functions as a computer program that functions as the control circuit 205, a computer program that functions as the rotation angle detection circuit 204, and a computer program that functions as the origin detection circuit 203 c of the origin detector 203. May be executed serially or in parallel. Thereby, the CPU can be apparently operated as a different component.
- FIG. 3A is an exploded perspective view of the sample analysis substrate 100.
- the sample analysis substrate 100 includes a rotating shaft 110 and a plate-shaped substrate 100 ′ having a predetermined thickness in a direction parallel to the rotating shaft 110.
- the substrate 100 ′ of the sample analysis substrate 100 is composed of a base substrate 100a and a cover substrate 100b.
- the substrate 100 ′ of the sample analysis substrate 100 has a circular shape, but may have, for example, a polygonal shape, an elliptical shape, a sector shape, or the like.
- the substrate 100 ′ has two main surfaces 100c and 100d.
- the main surface 100c and the main surface 100d are parallel to each other, and the thickness of the substrate 100 ′ (the distance between the two main surfaces) defined by the distance between the main surface 100c and the main surface 100d is the substrate.
- the main surfaces 100c and 100d need not be parallel.
- a part of two main surfaces may be non-parallel or parallel, or may be totally non-parallel.
- FIG. 3B is a plan view of the base substrate 100a.
- the sample analysis substrate 100 includes a first chamber 101, a second chamber 102, and a third chamber 103 (first sub-chamber 103A and second sub-chamber 103B, respectively) located in the substrate 100 ′. ), A storage chamber 104, and a reaction chamber 105.
- the shape of each chamber is not limited as long as it is not specifically mentioned below, and may have any shape.
- Each chamber generally has a space defined by upper and lower surfaces parallel to the two major surfaces 100c, 100d of the substrate 100 'and four side surfaces located between them. Two adjacent surfaces of the upper surface, the lower surface, and the side surface may not be separated by a clear ridge line.
- the shape of each chamber may be a flat sphere or a spheroid.
- the sample analysis substrate 100 further includes a first flow path 111, a second flow path 112, a third flow path 113, a fourth flow path 114, and a fifth flow path 115 that are located in the substrate 100 ′. And have.
- the first flow path 111 connects the first chamber 101 and the second chamber 102.
- the second flow path 112 connects the second chamber 102 and the third chamber 103 (first sub chamber 103A).
- the third flow path 113 connects the storage chamber 104 and the first chamber 101.
- the fourth flow path 114 connects the reaction chamber 105 and the second chamber 102.
- the fifth flow path 115 connects the first sub chamber 103A and the second sub chamber 103B.
- the liquid transfer between the chambers through the flow path can be realized by various methods. For example, transfer by gravity and transfer by capillary force and centrifugal force by rotation can be used. The two transfer methods will be generally described below.
- the sample analysis substrate 100 is supported with the rotating shaft 110 tilted with respect to the gravity direction G in a range of greater than 0 degrees and less than 90 degrees. Then, by changing the rotation angle position of the sample analysis substrate 100, the transfer source chamber in which the liquid exists is arranged at a higher position than the transfer destination chamber. “High” means being higher in the direction of gravity G. Thereby, a liquid can be transferred to another chamber using gravity.
- the channel connecting the chambers is not a capillary channel.
- “Capillary channel” refers to a channel having a narrow space in which at least a portion of the inside can be filled with a liquid by capillary action.
- the liquid can be transferred to another chamber using a capillary channel.
- the transfer of the liquid in the capillary channel will be described by taking as an example a configuration having chambers A and B that are not capillary spaces, and a capillary channel that connects the chamber A and the chamber B.
- the chamber A side that is, the inlet side of the capillary channel from the relationship between the pressure in each chamber and the channel.
- the chamber B is arrange
- the sample analysis substrate 100 having a diameter of 60 mm can be rotated in the range of 100 rpm to 8000 rpm.
- the rotation speed is determined according to the shape of each chamber and flow path, the physical properties of the liquid, the timing of liquid transfer and processing, and the like.
- the first chamber 101, the second chamber 102, the third chamber 103 (the first sub chamber 103A and the second sub chamber 103B), the storage chamber 104, and the reaction chamber 105 are formed in the base substrate 100a.
- the upper and lower portions of each space are formed by covering the base substrate 100a with the cover substrate 100b. That is, these spaces are defined by the inner surface of the substrate 100 '.
- the first flow path 111, the second flow path 112, the third flow path 113, the fourth flow path 114, and the fifth flow path 115 are also formed in the base substrate 100a, and the base substrate 100a is covered with the cover substrate 100b.
- the upper and lower portions of the space of these flow paths are formed.
- the base substrate 100a and the cover substrate 100b define an upper surface and a lower surface, respectively.
- the substrate 100 ′ can be made of a resin such as acrylic, polycarbonate, or polystyrene.
- the reaction chamber 105 is a reaction field in which a magnetic particle-immobilized antibody 305, a specimen containing an antigen 306, and a labeled antibody 308 are reacted to form a complex 310.
- a magnetic particle-immobilized antibody 305 a specimen containing an antigen 306, and a labeled antibody 308 are reacted to form a complex 310.
- the reaction chamber 105 is provided as a reaction field for forming the complex 310.
- Various methods can be used for transferring the magnetic particle-immobilized antibody 305, the specimen containing the antigen 306, and the labeled antibody 308 to the reaction chamber 105.
- a mixed solution in which the specimen containing the magnetic particle-immobilized antibody 305 and the antigen 306 and the labeled antibody 308 are mixed in advance is weighed, the mixed solution is injected into the sample analysis substrate 100, and the complex is formed in the reaction chamber 105. It may be formed.
- the sample analysis substrate 100 includes, for example, a chamber holding each of the magnetic particle-immobilized antibody 305, the specimen containing the antigen 306, and the labeled antibody 308, and a flow path (for example, a capillary tube) connecting each chamber and the reaction chamber 105. Road).
- a flow path for example, a capillary tube connecting each chamber and the reaction chamber 105. Road.
- the magnetic particle-immobilized antibody 305, the specimen containing the antigen 306 and the labeled antibody 308 are weighed into the respective chambers, and the magnetic particle-immobilized antibody 305, the specimen containing the antigen 306 and the labeled antibody 308 injected into each chamber.
- the composite 310 may be formed by transferring to the reaction chamber 105 and mixing in the reaction chamber 105.
- the magnetic particle-immobilized antibody 305 and the labeled antibody 308 may be dried (hereinafter referred to as “drying reagent”).
- drying reagent may be formed by holding the drying reagent in the reaction chamber 105 and dissolving the drying reagent in a liquid containing the sample solution containing the antigen 306.
- the complex 310 may be formed by dissolving a drying reagent held in a chamber at the time of measurement with a predetermined solution and mixing a specimen solution containing the antigen 306 in the reaction chamber 105.
- the solution containing the complex 310 is transferred to the second chamber 102 via the fourth channel 114.
- the storage chamber 104 stores a cleaning liquid used for cleaning at the time of B / F separation.
- the complex 310 can be washed multiple times during the B / F separation. Therefore, the storage chamber 104 can hold a total volume of cleaning liquid corresponding to the number of cleanings.
- the first chamber 101 holds the entire cleaning liquid stored in the storage chamber 104. Thereafter, in order to clean the composite 310 in the second chamber 102, a part of the cleaning liquid is transferred to the second chamber 102 and the rest is retained. The amount of the cleaning liquid used for one cleaning is weighed by the first flow path 111 as described below. For this reason, the first chamber 101 has a volume equal to or larger than the first flow path 111 and has a volume equal to or larger than the total amount of cleaning liquid corresponding to the number of times of cleaning (for example, if the cleaning is performed twice, the first flow path 111 If the cleaning is performed three times, the volume is twice or more than that of the first flow path 111).
- the space (first space) of the first chamber 101 includes a first region 101a and a second region 101b.
- the first region 101a is connected to a first opening 111c of the first flow path 111 described below.
- the first region 101a includes a portion extending from the first opening 111c toward the side farther from the rotation shaft 110.
- the second region 101b is connected to the first region 101a at a position farther from the rotation shaft 110 than the first opening 111c.
- the second region 101b includes a portion that is located farther from the rotation axis 110 than the first region 101a, and the portion of the second region 101b that is connected to the first region 101a is more than the rotation axis 110 than the first region 101a. Located far from. Moreover, it is possible to hold the cleaning liquid in excess in the amount used for one cleaning in the second region 101b. In order to transfer the cleaning liquid from the storage chamber 104 to the first chamber 101, at least a part of the second region 101 b is located farther from the rotation shaft 110 than the storage chamber 104.
- the first region 101a includes a connection portion 101c connected to the first opening 111c in order to smoothly move the cleaning liquid to the first flow path 111.
- the connecting portion 101c is at least a part of the first region 101a and extends from the first opening 111c to the side farther from the rotating shaft 110.
- the connecting part 101c can suck the cleaning liquid held in the first chamber 101 and hold it in the connecting part 101c by capillary action. This makes it possible to move the cleaning liquid to the first flow path 111 more reliably.
- the first chamber 101 excluding the connection portion 101c is not a space filled with liquid by capillary action, but a space in which the liquid can move between the first chambers 101 by gravity.
- the first chamber 101 includes the first region 101a and the second region 101b.
- the second region 101 b is located farther from the rotation shaft 110 than the storage chamber 104, and the second region 101 b and the storage chamber 104 are connected via a third flow path 113.
- a part of the cleaning liquid stored in the storage chamber 104 in the third flow path 113 is filled by capillary action. Then, by rotating the sample analysis substrate 100 in a state where the third flow path 113 is filled with the cleaning liquid, the cleaning liquid in the storage chamber 104 is moved to the second region 101b via the third flow path by the centrifugal force. Be transported. That is, since the first chamber 101 includes the second region 101b located farther from the rotation shaft 110 than the storage chamber 104, the cleaning liquid can be transferred by centrifugal force.
- the first chamber 101 includes the first region 101a and the second region 101b.
- the first chamber 101 may include the first region 101a. That is, the first chamber 101 may include a portion farther from the rotation shaft 110 than the first opening 111c.
- the connection portion between the first chamber 101 and the third flow path 113 is preferably configured to be located farther from the rotating shaft 110 than the connection portion between the storage chamber 104 and the third flow path 113.
- the second chamber 102 is a place where B / F separation of the solution containing the complex 310 is performed.
- the sample analysis substrate 100 includes a magnet 126 disposed in the substrate 100 ′.
- the magnet 126 is located close to the space of the second chamber 102 in the sample analysis substrate 100. More specifically, the magnet 126 is disposed in proximity to the side surface 102 s farthest from the rotation shaft 110 among the plurality of side surfaces of the second chamber 102. However, the magnet 126 in the sample analysis substrate 100 may be disposed at a position close to the upper surface or the lower surface other than the side surface 102 s of the second chamber 102. That is, the position is not particularly limited as long as the magnetic particles can be captured on the wall surface of the second chamber 102 by the magnet 126.
- the magnet 126 may be configured to be removable according to B / F separation, may be attached to the substrate 100 ′ in a non-detachable manner, or may be configured to be provided on the sample analyzer 200 side. .
- the substrate 100 ′ includes a storage chamber in which the magnet 126 can be stored.
- the substrate 100 ′ may include a concave storage chamber 120 having an opening 120 a on the main surface 100 c.
- the storage chamber 120 has a space in which the magnet 126 can be stored. By inserting the magnet 126 into the storage chamber 120 through the opening 120a, the magnet 126 can be loaded on the substrate 100 '.
- the opening 120a of the storage chamber 120 may be provided on the main surface 100d, or may be provided on a side surface located between the two main surfaces 100c and 100d.
- the turntable 201a of the sample analyzer 200 may include a magnet unit including the magnet 126.
- the magnet 126 when the user arranges the sample analysis substrate 100 at a predetermined position of the turntable 201 a (magnet unit), the magnet 126 is arranged at a position where the magnetic particles can be captured on the wall surface of the second chamber 102.
- the sample analyzer 200 may include a magnet 126 and a drive mechanism that moves the magnet 126.
- the sample analysis substrate 100 includes a storage chamber for holding the magnet 126, and the drive mechanism inserts the magnet 126 into the storage chamber of the sample analysis substrate 100 according to B / F separation, and the magnet 126 in the storage chamber. May be taken out.
- the complex 310 in the reaction solution and the unreacted magnetic particle-immobilized antibody 305 (hereinafter, when referring to both, The magnetic particles 311) are captured on the side surface 102s side by the attractive force (magnetic force) of the magnet 126 disposed close to the side surface 102s.
- the reaction liquid excluding the magnetic particles 311 is transferred to the third chamber 103 via the second flow path 112.
- a certain amount of cleaning liquid is transferred from the first flow path 111 to the second chamber 102, and the captured magnetic particles 311 are cleaned in the second chamber 102.
- the cleaning liquid is transferred to the third chamber 103 via the second flow path 112.
- the space (second space) of the second chamber 102 includes a first region 102a and a second region 102b, and the second region 102b is formed in the second chamber 102 by capillary action.
- the held reaction liquid or cleaning liquid can be sucked and held in the second region 102b.
- the side surface 102s is located in the second region 102b and is connected to the second flow path 112.
- the third chamber 103 stores a reaction liquid other than the magnetic particles 311 transferred from the second chamber 102 via the second flow path 112 and a used cleaning liquid.
- the third chamber 103 is the first sub-chamber 103A and A second sub chamber 103B is included.
- the first sub chamber 103 ⁇ / b> A and the second sub chamber 103 ⁇ / b> B are each constituted by another independent space, and are connected by a fifth flow path 115. That is, the space (third space) of the third chamber 103 includes the space of the first sub chamber 103A and the space of the second sub chamber 103B.
- the second sub chamber 103B is located farther from the rotation shaft 110 than the first sub chamber 103A.
- the first sub chamber 103 ⁇ / b> A is located farther from the rotation shaft 110 than the second chamber 102. That is, the third chamber 103 is located farther from the rotation shaft 110 than the second chamber 102 as a whole.
- the space of the first sub chamber 103A has a larger capacity than the larger amount of the reaction liquid and the amount of the cleaning liquid for one time.
- the second sub chamber 103B has a capacity larger than the sum of the reaction liquid and the cleaning liquid for a plurality of times.
- the third chamber 103 has the first sub chamber 103A and the second sub chamber 103B.
- the second sub chamber 103B (and the fifth flow path 115) is not provided.
- the shape of the third chamber 103 is not particularly limited.
- the first flow path 111 transfers the cleaning liquid stored in the first chamber 101 to the second chamber 102. At this time, instead of the total amount of the cleaning liquid in the first chamber 101, a single cleaning liquid is weighed according to the volume of the space defined by the first flow path 111, and the weighed cleaning liquid is transferred to the second chamber 102.
- the first flow path 111 includes a first opening 111c and a second opening 111d.
- the first opening 111c is connected to the first chamber 101, and the second opening 111d is connected to the second chamber 102. More specifically, the first flow path 111 includes a first portion 111a having a first opening 111c and a second portion 111b having a second opening 111d.
- the first portion 111a and the second portion 111b are respectively connected at one end where the first opening 111c and the second opening 111d are not located.
- the first opening 111c is located closer to the rotation shaft 110 than the second opening 111d.
- each part of the first flow path 111 is located at the same position as the first opening 111 c from the rotation shaft 110 or from the rotation shaft 110. It is preferable to be located farther than the first opening 111c. Accordingly, when a centrifugal force stronger than the capillary force applied to the liquid in the first flow path 111 is applied to the cleaning liquid in a state where the first flow path 111 is filled with the cleaning liquid, all the cleaning liquid in the first flow path 111 is discharged. It is transferred to the second chamber 102 without returning to the first chamber 101.
- the second opening 111d is an inner peripheral side surface located on the side closer to the rotation shaft 110 than the space of the second chamber 102 among the side surfaces of the second chamber 102, or a side surface adjacent to the inner peripheral side surface. It is preferable to be provided in the vicinity of the connection position with the peripheral side surface. This is to prevent the cleaning liquid transferred to the second chamber 102 from coming into contact with the second opening 111 d and backflowing into the first flow path 111.
- the total capacity of the first portion 111a and the second portion 111b corresponds to the amount of the cleaning liquid for one time, and the space between the first opening 111c and the second opening 111d of the first flow path 111 is seen by the cleaning liquid. Thus, the washing liquid for one time is weighed. Both the first portion 111a and the second portion 111b of the first flow path 111 can be filled with the cleaning liquid held in the first chamber 101 by capillary action.
- a space 111ab having two air holes 108 is provided along the rotation axis side of the first portion 111a.
- the space 111ab is a space for securing the air hole 108, and is not a space that can be filled with liquid by capillary action.
- the thickness of the space 111ab is larger than the thickness of the first portion 111a, and when the first portion 111a is filled with a liquid due to capillary action, a capillary force does not substantially act on the space 111ab, and the space 111ab Not filled with liquid.
- the space 111ab By providing the space 111ab, when bubbles are generated in the liquid held in the first portion 111a for some reason, the bubbles move to the space 111ab and the bubbles in the liquid are easily removed. Thereby, when the sample analysis substrate 100 is rotated, in particular, it is possible to suppress the bubbles from entering the second portion 111b and hindering the movement of the liquid.
- FIG. 3C shows the first portion 111a, the second portion 111b, the first region 102a of the second chamber 102, the second region 102a, and the second portion from the first region 101a of the first chamber 101, which are indicated by thick broken lines in FIG. 3B.
- the thickness (depth) in the direction parallel to the thickness of the substrate 100 ′ of the space in the path connected to the second flow path 112 via the region 102b is shown.
- the horizontal axis indicates the distance from one end of the first region 101a
- the vertical axis indicates the thickness.
- the horizontal axis is an example for explanation, and is not shown accurately.
- the vertical axis shows the relative thickness relationship between adjacent regions, but the thickness values are not accurately shown.
- the thickness of the second portion 111b is smaller than the thickness of the first portion 111a, and the second portion 111b has a greater capillary force than the first portion 111a. Is provided. For this reason, when the cleaning liquid retained in the first region 101a of the first chamber is sucked into the first portion 111a of the first flow path 111 from the first opening 111c to the second portion 111b where a greater capillary force works. The cleaning solution spreads. As a result, the entire first flow path 111 is filled with the cleaning liquid.
- the thickness of the connecting portion 101c is smaller than the thickness of the other part of the first region 101a. Further, the thickness of the connecting portion 101c is the same as the thickness of the first portion 111a. Thereby, it is possible to make capillary force act on the connection part 101c. As shown in FIG. 3B, the connecting portion 101c has an opening 101d (shown by a thick line) larger than the first opening 111c, and contacts the remaining portion of the first region 101a through the opening 101d.
- connection part 101c can be filled with the cleaning liquid.
- the thickness of the connecting portion 101c may be different from that of the first portion 111a. Further, the entire first region 101a of the first chamber 101 may be the connection part 101c, or may not have the connection part 101c.
- the capillary force of the 1st part 111a of the 1st flow path 111 is larger than the capillary force of the connection part 101c. Therefore, the cleaning liquid held in the connection portion 101c can be sucked and moved by the first portion 111a of the first flow path 111.
- the opening 101d of the connection portion 101c is larger than the first opening 111c of the first flow path 111, the connection portion 101c functions as a funnel, and a large amount of cleaning liquid flows smoothly through the connection portion 101c to the first flow. It can be sucked into the path 111.
- the second flow path 112 includes a third opening 112c and a fourth opening 112d, the third opening 112c is connected to the second chamber 102, and the fourth opening 112d is connected to the first sub chamber 103A of the third chamber 103. ing.
- the third opening 112c of the second flow path 112 is a side surface (the outermost peripheral side surface) located on the side farthest from the rotating shaft 110 among the side surfaces of the second chamber 102, or a side surface adjacent to the outermost peripheral side surface. Thus, it is preferably provided at a position including a connection portion with the outermost peripheral side surface. This is because when the liquid in the second chamber 102 is transferred to the first sub chamber 103 ⁇ / b> A of the third chamber 103, it is possible to suppress the occurrence of liquid residue in the second chamber 102.
- FIG. 3B shows a configuration in which the third opening 112c is provided on a part of the outermost peripheral side surface.
- the fourth opening 112d of the second flow path 112 is located on the side farther from the rotation shaft 110 than the third opening 112c.
- the fourth opening 112d is a side surface (innermost peripheral side surface) located on the side closest to the rotation shaft 110 among the side surfaces of the first sub chamber 103A, or a side surface adjacent to the innermost peripheral side surface. It is desirable to be provided at a position close to the innermost side surface.
- FIG. 3B shows a configuration in which the fourth opening 112d is provided in a part of the innermost peripheral side surface of the first sub chamber 103A.
- the second channel 112 can also suck the liquid held in the second chamber 102 by capillary action.
- the thickness of the second flow path 112 is smaller than the thickness of the second region 102 b of the second chamber 102.
- the second region 102 b has a thickness smaller than that of the first region 102 a and larger than that of the second channel 112. Therefore, it is possible to apply a capillary force to the second region 102b, and the cleaning liquid transferred from the first flow path 111 is sucked into the second region 102b of the second chamber 102 by a capillary phenomenon.
- the second flow path 112 is connected to the second region 102b of the second chamber 102, a part of the cleaning liquid is removed from the second chamber 102 by a capillary force larger than that of the second region 102b of the second chamber 102. It is sucked into the second flow path 112.
- the third flow path 113 and the fourth flow path 114 can also be filled with a liquid by capillary action. Specifically, the third flow path 113 and the fourth flow path 114 can each fill the inside with a liquid filled in the storage chamber 104 and the reaction chamber 105 by capillary action.
- the fourth flow path 114 includes a fifth opening 114c and a sixth opening 114d, the fifth opening 114c is connected to the reaction chamber 105, and the sixth opening 114d is connected to the second chamber 102.
- the fifth opening 114c of the fourth channel 114 is a side surface (the outermost peripheral side surface) located on the side farthest from the rotation shaft 110 among the side surfaces of the reaction chamber 105, or a side surface adjacent to the outermost peripheral side surface. It is preferable to be provided at a position including a connection portion with the outermost peripheral side surface. This is because when the reaction solution in the reaction chamber 105 is transferred to the second chamber 102, it is possible to suppress the occurrence of liquid residue in the reaction chamber 105.
- FIG. 3B shows a configuration in which the fifth opening 114c is provided in a part of the outermost peripheral side surface.
- the sixth opening 114d is an inner peripheral side surface located closer to the rotation shaft 110 than the space of the second chamber 102 among the side surfaces of the second chamber 102, or a side surface adjacent to the inner peripheral side surface. It is preferable to be provided in the vicinity of the connection position with the peripheral side surface. This is to prevent the reaction liquid transferred to the second chamber 102 from coming into contact with the sixth opening 114 d and backflowing into the fourth flow path 114.
- Hydrophilic treatment may be performed. Capillary force works greatly by hydrophilic treatment.
- the hydrophilic treatment is performed by, for example, applying a nonionic, cationic, anionic or zwitterionic surfactant to the inner surface described above, performing a corona discharge treatment, or providing physical fine irregularities. (For example, refer to JP 2007-3361 A).
- the second flow path 112, the third flow path 113, and the fourth flow path 114 are spaces that can be filled with a liquid by capillary action, these flow paths may be similarly subjected to hydrophilic treatment.
- the second flow path 112 and the fourth flow path 114 can further control the movement of the liquid by the siphon principle. For this reason, as the siphon structure, the second flow path 112 and the fourth flow path 114 have a first bent portion and a second bent portion, respectively.
- the second flow path 112 has a first bent portion 112a and a second bent portion 112b.
- the first bent portion 112a has a convex shape on the side opposite to the rotary shaft 110
- the second bent portion 112b has a convex shape on the rotary shaft 110 side.
- the first bent portion 112a is located between the second chamber 102 and the second bent portion 112b, which are located on the side closer to the rotation shaft 110, of the second chamber 102 and the third chamber 103 to which the flow path is connected.
- the fourth flow path 114 has a first bent portion 114a and a second bent portion 114b.
- the first bent portion 114a has a convex shape on the side opposite to the rotary shaft 110
- the second bent portion 114b has a convex shape on the rotary shaft 110 side.
- the first bent portion 114a is located between the reaction chamber 105 and the second bent portion 114b, which are located on the side close to the rotation shaft 110, of the reaction chamber 105 and the second chamber 102 to which the flow path is connected. .
- the principle of the siphon is that liquid feeding is controlled by the balance between the centrifugal force applied to the liquid by the rotation of the sample analysis substrate 100 and the capillary force of the flow path. Specifically, an example in which a liquid is transferred from the reaction chamber 105 to the second chamber 102 and further transferred to the third chamber 103 will be described.
- the second channel 112 is a capillary channel without a siphon structure
- it is transferred from the reaction chamber 105 to the second chamber 102 via the fourth channel 114 by the centrifugal force generated by the rotation of the sample analysis substrate 100.
- the liquid transferred to the second chamber 102 fills the second channel 112 by the capillary force of the second channel 112. If the rotation of the sample analysis substrate 100 continues in this state, the liquid is not held in the second chamber 102 and is transferred to the third chamber 103 via the second flow path 112.
- the rotation of the sample analysis substrate 100 here is a rotation speed at which a centrifugal force stronger than the capillary force of the second flow path 112 can be applied.
- the liquid transferred from the reaction chamber 105 to the second chamber 102 is liquid in the second channel 112 due to the capillary force of the second channel 112. Is drawn. However, if the sample analysis substrate 100 continues to rotate and rotates at a rotational speed at which a centrifugal force stronger than the capillary force of the second flow path 112 can be applied, the centrifugal force is higher than the capillary force applied to the liquid. Since this is stronger, the entire second flow path 112 is not filled with the liquid. That is, the second flow path 112 is filled with the liquid only to the same height as the distance of the liquid surface of the liquid existing in the second chamber 102 with respect to the rotation shaft 110.
- the second channel 112 has a capillary force. Is filled with liquid, and no further movement of the liquid by capillary force.
- the sample analysis substrate 100 When it is desired to transfer the liquid in the second chamber 102 to the third chamber 103, the sample analysis substrate 100 is rotated at a rotation speed (rotation stop) at which a centrifugal force equal to or less than the capillary force of the second channel 112 can be applied. The liquid is filled in the second flow path 112 by capillary force. Thereafter, when the sample analysis substrate 100 is rotated at a rotation speed at which a centrifugal force stronger than the capillary force of the second flow path 112 can be applied, the liquid in the second chamber 102 is transferred to the third chamber 103. Can do.
- the two flow paths 112 are preferably configured with a siphon structure.
- a capillary channel having a siphon structure may be adopted even when the above-described liquid control is unnecessary.
- the distance between the rotating shaft 110 and the side surface of the chamber located farthest from the rotating shaft 110 closest to the rotating shaft 110 is R1, and from the rotating shaft 110 to the most rotating shaft of the first bent portion.
- R1> R2 condition 1 is satisfied.
- the sample analysis substrate 100 is centrifuged from another chamber (not shown) stronger than the capillary force applied to the liquid in the fourth flow path 114.
- the complex 310 can be formed, and the reaction liquid can be prevented from being transferred to the second chamber 102.
- each flow path or chamber has a thickness of 50 ⁇ m to 300 ⁇ m, for example.
- different thicknesses can be realized by changing the depths of the spaces provided in the base substrate 100a.
- the depth of the space provided in the base substrate 100a is made constant, and convex portions having different heights are provided at positions corresponding to the respective chambers and flow paths of the cover substrate 100b, so that the thicknesses of the respective flow paths and chambers are different. It may be allowed.
- Each of the first chamber 101, the second chamber 102, the third chamber 103, the storage chamber 104, and the reaction chamber 105 is provided with at least one air hole 108.
- the inside of each chamber is maintained at atmospheric pressure, and each flow path can be moved by the capillary phenomenon and siphon principle.
- the reaction chamber 105 and the storage chamber 104 may be provided with an opening 109 for injecting a liquid such as a sample solution, a reaction solution, or a cleaning solution.
- the air hole 108 may also serve as the opening 109.
- the air hole 108 and the opening 109 are arranged on the upper surface in each chamber and on the side surface close to the rotating shaft 110.
- the air hole 108 and the opening 109 are in contact with the liquid, and the liquid is supplied from the air hole 108 and the opening 109 to the sample analysis substrate 100. Can be prevented from moving to the outside.
- the air hole 108 and the opening 109 may be provided in a side surface portion of each chamber.
- the space of each chamber has, for example, a convex portion protruding toward the rotating shaft 110 indicated by 105p, and the air hole 108 and the opening 109 are located in the convex portion.
- the position of the air hole 108 and the opening 109 in each chamber can be as close as possible to the rotation shaft 110 in the radial direction. Therefore, in a state where the sample analysis substrate 100 is rotated, the amount of liquid that can be held in each chamber can be increased without being in contact with the air hole 108 and the opening 109. Dead space that cannot be used for holding can be reduced.
- FIG. 4 is a flowchart showing the operation of the sample analysis system 501.
- a program that defines the procedure for controlling each part of the sample analysis system 501 for operating the sample analysis system 501 is stored in, for example, the memory of the control circuit 205.
- the execution of the program by the arithmetic unit causes the following operations. Realize. Prior to the following steps, the sample analysis substrate 100 is loaded into the sample analysis apparatus 200, and the origin of the sample analysis substrate 100 is detected.
- the cleaning liquid is introduced into the storage chamber 104 of the sample analysis substrate 100.
- the magnetic particle-immobilized antibody 305, the specimen containing the antigen 306, and the labeled antibody 308 are introduced into the reaction chamber 105.
- a liquid containing the magnetic particle-immobilized antibody 305 is held in the reaction chamber 105, and a chamber (not shown) provided on the sample analysis substrate 100 holds the liquid containing the antigen 306 and the labeled antibody 308 separately. These may be transferred to the reaction chamber 105 by a centrifugal force generated by the rotation of the sample analysis substrate 100.
- the magnetic particle-immobilized antibody 305, the specimen containing the antigen 306, and the labeled antibody 308 are simultaneously reacted by an antigen-antibody reaction to form a complex 310.
- the third flow path 113 and the fourth flow path 114 are filled with the reaction liquid containing the cleaning liquid and the complex 310, respectively, by capillary action.
- Step S2 After the complex 310 is generated, the sample analysis substrate 100 is rotated, and the reaction solution containing the complex 310 is moved to the second chamber 102. At this time, the fourth flow path 114 is filled with the reaction solution by capillary action. For this reason, when a centrifugal force stronger than the capillary force applied to the reaction solution in the fourth flow path 114 due to the rotation of the sample analysis substrate 100 acts on the reaction solution containing the complex 310 of the reaction chamber 105, the reaction solution becomes the first solution. It is transferred to the two chamber 102. The reaction solution transferred to the second chamber 102 is not subsequently transferred to the third chamber 103 while the sample analysis substrate 100 is rotating.
- the second flow path 112 forms a siphon as described above, so that the liquid does not move in the direction toward the rotation shaft 110 against the centrifugal force against the centrifugal force.
- the reaction liquid containing the complex 310 transferred to the second chamber 102 most of the magnetic particles 311 are captured by the side surface 102 s by the attractive force of the magnet 126.
- the rotation speed of the sample analysis substrate 100 is set to a speed at which a liquid such as a reaction liquid does not move due to gravity and a centrifugal force stronger than the capillary force of each capillary channel can be applied due to the centrifugal force generated by the rotation. Is done.
- this rotation speed is set for rotation using centrifugal force.
- the cleaning solution is transferred from the storage chamber 104 through the third flow path 113 to the second region 101b of the first chamber 101.
- the cleaning liquid may fill a part of the first region 101a.
- the sample analysis substrate 100 is stopped at a predetermined angle.
- the predetermined first angle means that the cleaning liquid transferred to the first chamber 101 in the sample analysis substrate 100 does not come into contact with the connection portion 101c of the first chamber 101, and This is an angle at which the reaction solution transferred to the two chambers 102 can come into contact with the opening of the second flow path 112.
- This angle depends on the shape of the first chamber 101 and the second chamber 102, the position in the substrate 100 ', the amounts of the cleaning liquid and the reaction liquid, the inclination angle ⁇ of the sample analysis substrate 100, and the like. For example, in the example shown in FIG. 6, if the direction of gravity (indicated by an arrow) in the sample analysis system 501 projected onto a plane parallel to the sample analysis substrate 100 is within the angle range indicated by ⁇ 1 of the sample analysis substrate 100. Good.
- reaction liquid in the second chamber 102 fills the second flow path 112 by capillary action by contacting the opening of the second flow path 112.
- Step S3 The sample analysis substrate 100 is rotated. A centrifugal force is generated with the rotation, and acts on the reaction solution and the magnetic particles 311 (complex 310 and unreacted magnetic particle-immobilized antibody 305) in the second chamber 102. This centrifugal force acts so that the liquid and the complex move toward the side surface 102 s of the second chamber 102. For this reason, as shown in FIG. 7, the magnetic particles 311 are pressed against the side surface 102s.
- the reaction solution that has received the centrifugal force is discharged from the second flow path 112 and transferred to the first sub chamber 103 ⁇ / b> A of the third chamber 103. Further, the reaction solution is transferred to the second sub chamber 103B through the fifth flow path 115. Due to the sum of the centrifugal force and the attractive force of the magnet 126, the magnetic particles 311 are strongly pressed against the side surface 102s and captured.
- the reaction solution is discharged from the second flow path 112, and the magnetic particles 311 remain in the second chamber 102.
- the cleaning liquid in the first chamber 101 receives a centrifugal force due to rotation and moves to the second region 101b. After the transfer of the reaction liquid to the second sub chamber 103B is completed, the rotation of the sample analysis substrate 100 is stopped.
- the reaction solution and the magnetic particles 311 are separated. Specifically, the reaction liquid moves to the second sub chamber 103 ⁇ / b> B of the third chamber 103, and the magnetic particles 311 remain in the second chamber 102. Even if the rotation of the sample analysis substrate 100 stops, the magnetic particles 311 can remain in the state of being collected on the side surface 102s by the attractive force received from the magnet 126.
- the stop angle at this time may be the first angle, the second angle of the next step, or another angle.
- Step S4 Process (a)
- the sample analysis substrate 100 is slightly rotated and stopped at a predetermined second angle.
- the second angle is an angle at which the cleaning liquid transferred to the first chamber 101 comes into contact with the connection portion 101 c of the first chamber 101.
- the gravity direction is an angle within the angle range indicated by ⁇ ⁇ b> 2 of the sample analysis substrate 100.
- the cleaning liquid is sucked from the first chamber 101 by the capillary force in the connection portion 101c, the first portion 111a and the second portion 111b of the first flow path 111, and the first portion 111a and the second portion 111b of the first flow path 111 are cleaned. Filled with. Thereby, the washing
- the first flow path 111 In order to ensure that the first flow path 111 is filled with the cleaning liquid, it may be rotated about several degrees alternately around the second angle in the clockwise direction and counterclockwise, that is, may be swung. Since capillary force acts on the first flow path 111, the cleaning liquid does not move from the second portion 111 b of the first flow path 111 to the second chamber 102 at this time.
- Step S5 (Steps (b) and (c))
- the sample analysis substrate 100 is rotated.
- the centrifugal force due to rotation acts on the cleaning liquid in the first flow path 111 and the first chamber 101.
- the cleaning liquid in the first flow path 111 is transferred to the second chamber 102 by centrifugal force.
- excess cleaning liquid located in the first region 101a in the first chamber 101 moves to the second region 101b in the first chamber 101 by centrifugal force. Therefore, only the cleaning liquid weighed by the first flow path 111 is transferred to the second chamber 102.
- the centrifugal force also acts on the cleaning liquid transferred to the second chamber 102, the cleaning liquid does not move in the direction of the rotation axis 110 in the second flow path 112, and the cleaning liquid substantially remains in the second chamber 102. As a result, the magnetic particles 311 in the second chamber 102 come into contact with the cleaning liquid, and the first cleaning is performed.
- the sample analysis substrate 100 is stopped at a predetermined third angle.
- the third angle is an angle at which the cleaning liquid in the first chamber 101 does not come into contact with the connection portion 101 c and the cleaning liquid transferred to the second chamber 102 can come into contact with the opening of the second flow path 112.
- the gravity direction in the sample analysis system 501 projected onto a plane parallel to the sample analysis substrate 100 may be within the angle range indicated by ⁇ 3 on the sample analysis substrate 100.
- the cleaning liquid in the second chamber 102 is in contact with the opening of the second channel 112 and fills the second channel 112 by capillary action.
- Step S6 (Step (d))
- the sample analysis substrate 100 is rotated.
- a centrifugal force is generated with the rotation and acts on the cleaning liquid and the magnetic particles 311 in the second chamber 102.
- This centrifugal force works so that the cleaning liquid and the magnetic particles 311 move to the side surface 102 s of the second chamber 102, and the magnetic particles 311 are captured on the side surface 102 s by the centrifugal force and the attractive force by the magnet 126.
- the cleaning liquid that has received the centrifugal force is discharged from the second flow path 112 and transferred to the first sub chamber 103 ⁇ / b> A of the third chamber 103. Further, the cleaning liquid is transferred to the second sub chamber 103B through the fifth flow path 115.
- the stop angle at this time may be the third angle or the fourth angle of the next step.
- Step S7 Process (e))
- the sample analysis substrate 100 is slightly rotated and stopped at a predetermined fourth angle.
- the fourth angle is an angle at which the cleaning liquid transferred to the first chamber 101 comes into contact with the connection portion 101 c of the first chamber 101.
- the gravity direction is an angle within the angle range indicated by ⁇ 4 of the sample analysis substrate 100. Since the amount of the cleaning liquid remaining in the first chamber 101 is different from that in step S4, the angle range ⁇ 4 may be different from the angle range ⁇ 2.
- the cleaning liquid is sucked from the first chamber 101 by the capillary force in the connection portion 101c, the first portion 111a and the second portion 111b of the first flow path 111, and the first portion 111a and the second portion 111b of the first flow path 111 are cleaned. Filled with. Thereby, the cleaning liquid for one time is weighed again.
- the sample analysis substrate 100 may be swung around the fourth angle so that the first flow path 111 is surely filled with the cleaning liquid. Since capillary force acts on the first flow path 111, the cleaning liquid does not move from the second portion 111 b of the first flow path 111 to the second chamber 102 at this time.
- Step S8 Subsequently, the sample analysis substrate 100 is rotated.
- the centrifugal force due to rotation acts on the cleaning liquid in the first flow path 111 and the first chamber 101.
- the cleaning liquid in the first flow path 111 is transferred to the second chamber 102 by centrifugal force.
- excess cleaning liquid located in the first region 101a in the first chamber 101 moves to the second region 101b in the first chamber 101 by centrifugal force. Therefore, only the cleaning liquid weighed by the first flow path 111 is transferred to the second chamber 102.
- the centrifugal force also acts on the cleaning liquid transferred to the second chamber 102, the cleaning liquid does not move in the direction of the rotation axis 110 in the second flow path 112, and the cleaning liquid substantially remains in the second chamber 102. As a result, the magnetic particles 311 in the second chamber 102 come into contact with the cleaning liquid, and the second cleaning is performed.
- the sample analysis substrate 100 is stopped at a predetermined fifth angle as shown in FIG.
- the fifth angle is an angle at which the cleaning liquid in the first chamber 101 does not come into contact with the connection portion 101 c and the cleaning liquid transferred to the second chamber 102 can come into contact with the opening of the second flow path 112.
- the gravity direction in the sample analysis system 501 projected onto a plane parallel to the sample analysis substrate 100 may be within the angle range indicated by ⁇ 5 on the sample analysis substrate 100.
- the cleaning liquid in the second chamber 102 is in contact with the opening of the second channel 112 and fills the second channel 112 by capillary action.
- Step S9 Process (f)
- the sample analysis substrate 100 is rotated.
- a centrifugal force is generated with the rotation and acts on the cleaning liquid and the magnetic particles 311 in the second chamber 102.
- This centrifugal force works so that the cleaning liquid and the magnetic particles 311 move to the side surface 102 s of the second chamber 102, and the magnetic particles 311 are captured on the side surface 102 s by the centrifugal force and the attractive force by the magnet 126.
- the cleaning liquid that has received the centrifugal force is discharged from the second flow path 112 and transferred to the first sub chamber 103 ⁇ / b> A of the third chamber 103. Further, the cleaning liquid is transferred to the second sub chamber 103B through the fifth flow path 115.
- the cleaning liquid in the first chamber 101 receives a centrifugal force due to rotation and moves to the second region 101b.
- the rotation of the sample analysis substrate 100 is stopped.
- the cleaning liquid and the magnetic particles 311 are separated.
- the cleaning liquid moves to the second sub chamber 103 ⁇ / b> B of the third chamber 103, and the magnetic particles 311 remain in the second chamber 102.
- the magnetic particles 311 can remain in the state of being collected on the side surface 102s by the attractive force received from the magnet 126.
- B / F separation specifically, magnetic particles 311 and various unreacted substances and cleaning liquid are separated.
- a signal such as a dye, light emission, or fluorescence corresponding to the labeling substance 307 of the labeled antibody 308 bound to the complex 310 included in the magnetic particle 311 is detected.
- detection of the antigen 306, quantification of the concentration of the antigen 306, and the like can be performed.
- the liquid can be introduced into the same chamber in a plurality of times. For this reason, when performing B / F separation using the sample analysis substrate, sufficient cleaning can be performed.
- a flow path that develops a capillary force is used, so that each weighing can be performed more reliably and accurately.
- This operation can be realized by controlling the rotation and stop of the sample analysis substrate and controlling the angle at the time of stop. For this reason, it can be suitably applied to analysis methods in which components in a sample are analyzed through complex reaction steps including B / F separation without using a large analytical instrument or manually operated by an operator. It is.
- the sample analysis substrate 150 shown in FIG. 16 has a first chamber 101 'including a first region 101a' and a second region 101b.
- the first region 101a ′ does not have the connection portion 101c and extends from the first opening 111c in the first region toward the side farther from the rotation shaft 110. Contains only part.
- the entire first region 101a ' can suck the liquid held in the second region 101b by capillary action.
- the cleaning liquid held in the first chamber 101 ′ can be sucked and held by the capillary action as a whole.
- the sample analysis substrate 150 can also weigh the cleaning liquid for one time through the first flow path 111. According to the sample analysis substrate 150, if the portion connected to the second region 101b of the first region 101a ′ is in contact with the cleaning liquid, the first region 101a ′ and the first flow path 111 are filled with the cleaning liquid by capillary force. be able to.
- sample analysis substrate 160 shown in FIG. 17A is another example of the sample analysis substrate 100 shown in FIG. 3B.
- the sample analysis substrate 160 will be described in comparison with the sample analysis substrate 100 shown in FIG. 3B.
- the first chamber 101 includes only the first region 101a. Specifically, the first chamber 101 has a first region 101a including a portion extending from the first opening 111c toward the side farther from the rotation axis, and does not have the second region 101b. The cleaning liquid transferred from the storage chamber 104 via the third flow path is held in the first region 101a located farther from the rotation shaft 110 than the first opening 111c. Unlike the sample analysis substrate 100 shown in FIG. 3B, the first chamber 101 does not have the connection portion 101c.
- the second chamber 102 includes a first region 102a and a second region 102b as in FIG. 3B. Further, the magnet 126 is also disposed in the vicinity of the side surface 102 s located farthest from the rotation shaft 110 of the second chamber 102.
- the third chamber 103 is not composed of the first sub chamber 103A and the second sub chamber 103B, but is composed of one chamber.
- the first flow path 111 includes a first portion 111a and a second portion 111b, similar to the sample analysis substrate 100 shown in FIG. 3B.
- the first portion 111a includes a first opening 111c and is connected to the first chamber 101.
- the second portion 111 b has a second opening 111 d and is connected to the second chamber 102.
- a part of the first chamber 101 and a part of the first flow path 111 are positioned in the circumferential direction around the rotation shaft 110 with the first opening 111c interposed therebetween. It was.
- the sample analysis substrate 160 as shown in FIG. 17A, a part of the first chamber 101 and a part of the first flow path 111 are approximately centered on the rotation shaft 110 with the first opening 111c interposed therebetween. It is located in the radial direction.
- the first flow path 111 is further provided with a space 111ab having one air hole 108 along the first portion 111a. Similar to the sample analysis substrate 100, the space 111ab is a space for securing the air holes 108, and is not a capillary passage that can be filled with liquid by capillary action. For example, the thickness of the space 111ab is larger than the thickness of the 111a, and when the first portion 111a is filled with the liquid due to capillary action, the space 111ab is not filled with the liquid.
- the space 111ab By providing the space 111ab, when bubbles are generated in the liquid held in the first portion 111a for some reason, the bubbles move to the space 111ab and the bubbles in the liquid are easily removed. Thereby, when the sample analysis substrate 100 is rotated, in particular, it is possible to suppress the bubbles from entering the second portion 111b and hindering the movement of the liquid.
- the rotation angle of the sample analysis substrate 160 is changed to a position where the cleaning liquid contacts the first opening 111c while the cleaning liquid is held in the first chamber 101, the first excluding the space 111ab.
- the channel 111 is filled with the cleaning liquid by capillary action.
- the sample analysis substrate 160 is rotated at a rotation speed at which a centrifugal force stronger than the capillary force applied to the cleaning liquid in the first channel 111 is applied.
- the cleaning liquid transferred to the first chamber 101 on the plane perpendicular to the rotation shaft 110 and the first flow path, with reference to the straight line db connecting the rotation shaft 110 and the position z, The cleaning liquid returns to 111.
- the reference position z is two side surfaces s1 and s2 that are located farther from the rotation axis 110 than the space of the first chamber 101 or the space of the first flow path 111, It is defined by the boundary position between the surface s1 inclined toward the first chamber 101 and the surface s2 inclined toward the second chamber from the tangential direction dt of the arc ar centered on the rotation axis 110.
- the liquid filled in the first flow path 111 is transferred to the second chamber 102, but not limited to this, a part is transferred. It may be a configuration. Also in the example of FIG. 17A, the weighed liquid can be transferred to the second chamber 102 if the first flow path 111 is filled with the cleaning liquid.
- the second flow path 112 is a capillary path similar to the sample analysis substrate 100 shown in FIG. 3B and has a siphon structure.
- the fourth channel 114 is a capillary channel as in the sample analysis substrate 100, but does not have a siphon structure.
- the sample analysis system according to the second embodiment includes a sample analysis substrate 162 and a sample analysis apparatus 200.
- the configuration of the sample analyzer 200 is the same as that of the sample analyzer 200 in the sample analysis system 501 of the first embodiment.
- the sample analysis substrate 162 of this embodiment has a storage chamber 106, a fourth chamber 107, a sixth flow path 116, and a first flow path. 7 flow paths 117.
- the storage chamber 106 is located closer to the rotation shaft 110 than the fourth chamber 107 in the radial direction.
- the storage chamber 106 stores the substrate solution at the start of analysis using the sample analysis system.
- the fourth chamber 107 holds the substrate solution while washing the complex 310 after the start of the analysis using the sample analysis system.
- the sixth flow path 116 connects the storage chamber 106 and the fourth chamber 107.
- the sixth flow path 116 extends in the radial direction around the rotation shaft 110 and is configured by a capillary path.
- the sixth flow path 116 has a seventh opening 116 c and an eighth opening 116 d, and the seventh opening 116 c is located between the storage chamber 106 and the sixth flow path 116.
- the eighth opening 116 d is located between the sixth flow path 116 and the fourth chamber 107.
- the seventh opening 116c is a side surface (the outermost peripheral side surface) that is located farthest from the rotation shaft 110 among the side surfaces of the storage chamber 106, or a side surface that is adjacent to the outermost peripheral side surface and is close to the outermost peripheral side surface. It is preferable to be provided at a position where
- the eighth opening 116d is a side surface (innermost peripheral side surface) located closest to the rotation shaft 110 among the side surfaces of the fourth chamber 107, or a side surface adjacent to the innermost peripheral side surface. It is preferable to be provided at a position close to the inner peripheral side surface.
- the seventh flow path 117 has a first portion 117a and a second portion 117b, a ninth opening 117c, and a tenth opening 117d.
- a ninth opening 117c is located between the fourth chamber 107 and the first portion 117a of the seventh flow path 117.
- the first portion 117a of the seventh channel 117 is a capillary channel, and can fill the inside with a liquid by capillary action.
- the first portion 117a extends substantially in the circumferential direction.
- the tenth opening 117d is located between the second part 117b and the second chamber 102, and the first part 117a and the second part 117b are one ends where the ninth opening 117c and the tenth opening 117d are not located. Are connected to each other.
- the ninth opening 117c is located closer to the rotating shaft 110 than the tenth opening 117d.
- each part of the seventh flow path 117 is located at the same position as the ninth opening 117c from the rotation shaft 110 or from the rotation shaft 110. It is preferable to be located farther than the ninth opening 117c. Accordingly, when a centrifugal force stronger than the capillary force applied to the substrate solution in the seventh flow path 117 is applied to the substrate solution in a state where the seventh flow path 117 is filled with the substrate solution, all of the seventh flow paths 117 are The substrate solution is transferred to the second chamber 102 without returning to the fourth chamber 107.
- the total volume of the first portion 117a and the second portion 117b corresponds to the amount of the substrate solution used for the analysis, and the space between the ninth opening 117c and the tenth opening 117d of the seventh channel 117 is filled with the substrate solution. As a result, the substrate solution is weighed. As described above, the first portion 117a and the second portion 117b of the seventh flow path 117 can be filled with the substrate solution held in the fourth chamber 107 by capillary action.
- a space 117ab having one air hole 108 may be provided along the rotation axis side of the first portion 117a.
- the thickness of the space 117ab is larger than the thickness of the first portion 117a.
- sample analysis substrate 162 are the same as those of the sample analysis substrate 100 shown in FIG. 3B and the sample analysis substrate 160 shown in FIG. 17A.
- FIG. 19 is a flowchart showing the operation of the sample analysis system 502.
- a program that defines the procedure for controlling each part of the sample analysis system 502 for operating the sample analysis system 502 is stored, for example, in the memory of the control circuit 205, and the following operations are performed by executing the program by the arithmetic unit. Realize.
- the sample analysis substrate 162 is loaded into the sample analysis device 200, and the origin of the sample analysis substrate 162 is detected.
- the cleaning liquid is introduced into the storage chamber 104 of the sample analysis substrate 162, and the substrate solution is introduced into the storage chamber 106.
- the substrate solution contains a substrate that generates a change in light emission, fluorescence, or absorption wavelength due to reaction with the labeling substance 307 or catalysis by the labeling substance 307.
- a specimen containing magnetic particle-immobilized antibody 305, antigen 306, and labeled antibody 308 is introduced into reaction chamber 105.
- a liquid containing the magnetic particle-immobilized antibody 305 is held in the reaction chamber 105, a chamber (not shown) provided on the sample analysis substrate 162 holds a liquid containing the antigen 306 and the labeled antibody 308, and the sample These may be transferred to the reaction chamber 105 by centrifugal force generated by the rotation of the analysis substrate 162.
- the magnetic particle-immobilized antibody 305, the antigen 306 in the specimen, and the labeled antibody 308 are combined by an antigen-antibody reaction to form a complex 310.
- the third flow path 113 and the fourth flow path 114 are filled with the reaction liquid containing the cleaning liquid and the complex 310, respectively, by capillary action.
- the sixth channel 116 is not filled with the substrate solution. However, the sixth channel 116 may be filled with the substrate solution.
- Step S22 After the complex 310 is generated, the sample analysis substrate 162 is rotated, and the reaction solution containing the complex 310 is moved to the second chamber 102. At this time, the fourth flow path 114 is filled with the reaction solution by capillary action. For this reason, when a centrifugal force stronger than the capillary force applied to the reaction liquid in the fourth flow path 114 due to the rotation of the sample analysis substrate 162 acts on the reaction liquid containing the complex 310 of the reaction chamber 105, the reaction liquid It is transferred to the two chamber 102. The reaction solution transferred to the second chamber 102 is not subsequently transferred to the third chamber 103 while the sample analysis substrate 162 is rotating.
- the second flow path 112 forms a siphon as described above, so that the liquid does not move in the direction toward the rotation shaft 110 against the centrifugal force against the centrifugal force.
- the reaction liquid containing the complex 310 transferred to the second chamber 102 most of the magnetic particles 311 are captured by the side surface 102 s by the attractive force of the magnet 126.
- the rotation speed of the sample analysis substrate 162 is set such that a centrifugal force is generated by the rotation, so that a liquid such as a reaction solution does not move by gravity and a centrifugal force stronger than the capillary force of each capillary passage can be applied. Is done.
- this rotation speed is set for rotation using centrifugal force.
- the rotation direction of the sample analysis substrate 162 may be clockwise or counterclockwise.
- the cleaning solution is transferred from the storage chamber 104 to the first chamber 101 through the third flow path 113.
- the sample analysis substrate 162 is stopped at a predetermined first angle.
- the predetermined first angle means that the cleaning liquid transferred to the first chamber 101 in the sample analysis substrate 162 exceeds the first opening 111 c of the first flow path 111 and is first
- the substrate solution in the storage chamber 106 is not in contact with the portion 111 a and can come into contact with the seventh opening 116 c of the sixth flow path 116, and the reaction solution in the second chamber 102 is in contact with the third opening of the second flow path 112. It is an angle at which it can contact 112c.
- This angle depends on the shape of the first chamber 101, the second chamber 102, and the storage chamber 106, the position in the substrate 162, the amounts of the cleaning solution, the substrate solution, and the reaction solution, the inclination angle ⁇ of the sample analysis substrate 162, and the like.
- the gravity direction (indicated by an arrow) in the sample analysis system 501 projected onto a plane parallel to the sample analysis substrate 162 may be within the angle range indicated by ⁇ 1 of the sample analysis substrate 162. .
- the substrate solution in the storage chamber 106 is in contact with the seventh opening 116c of the sixth channel 116, thereby filling the sixth channel 116 by capillary action.
- the reaction liquid in the second chamber 102 fills the second flow path 112 by capillary action by contacting the third opening 112 c of the second flow path 112.
- Step S23 The sample analysis substrate 162 is rotated. A centrifugal force is generated with the rotation, and acts on the reaction liquid and the magnetic particles 311 (complex 310 and unreacted magnetic particles) in the second chamber 102. This centrifugal force acts so that the liquid and the complex 310 move to the side surface 102 s side of the second chamber 102. For this reason, the magnetic particles 311 are pressed against the side surface 102s.
- the reaction liquid that has received the centrifugal force is discharged from the second flow path 112 and transferred to the third chamber 103. Due to the sum of the centrifugal force and the attractive force of the magnet 126, the magnetic particles 311 are strongly pressed against the side surface 102s and captured.
- the reaction solution is discharged from the second flow path 112 to the third chamber 103, and the magnetic particles 311 remain in the second chamber 102.
- the cleaning liquid in the first chamber 101 receives centrifugal force due to rotation, but remains in the first chamber 101 because it is pressed against the side surface farthest from the rotation axis 110 of the first chamber 101.
- the substrate solution in the storage chamber 106 and the sixth flow path receives the centrifugal force of rotation and moves to the fourth chamber 107.
- the substrate solution that has moved to the fourth chamber 107 is pressed against the side surface farthest from the rotating shaft 110 of the fourth chamber 107 by centrifugal force. For this reason, the substrate solution remains in the fourth chamber 107.
- the reaction solution and the magnetic particles 311 are separated. Specifically, the reaction liquid moves to the third chamber 103, and the magnetic particles 311 remain in the second chamber 102. Even if the rotation of the sample analysis substrate 162 stops, the magnetic particles 311 can remain in the state of being collected on the side surface 102s by the attractive force received from the magnet 126.
- the stop angle at this time may be the first angle, the second angle of the next step, or another angle.
- Step S24 Process (a)
- the sample analysis substrate 162 is slightly rotated counterclockwise and stopped at the predetermined second angle.
- the second angle is an angle at which the cleaning liquid transferred to the first chamber 101 comes into contact with the first opening 111 c of the first flow path 111.
- the gravity direction is an angle within the angle range indicated by ⁇ 2 of the sample analysis substrate 162.
- the cleaning liquid comes into contact with the first portion 111a of the first channel 111 through the first opening 111c, the cleaning liquid is sucked into the entire first portion 111a by the capillary force, and the first portion 111a and the second portion of the first channel 111 are sucked. Portion 111b is filled with the cleaning liquid. Thereby, the washing
- the first flow path 111 In order to ensure that the first flow path 111 is filled with the cleaning liquid, it may be rotated about several degrees alternately around the second angle in the clockwise direction and counterclockwise, that is, may be swung. Since capillary force acts on the first flow path 111, the cleaning liquid does not move from the second portion 111 b of the first flow path 111 to the second chamber 102 at this time.
- Step S25 (Steps (b) and (c))] Subsequently, the sample analysis substrate 162 is rotated. The centrifugal force due to rotation acts on the cleaning liquid in the first flow path 111 and the first chamber 101. As described with reference to FIG. 17A, the cleaning liquid located on the first flow path 111 side moves to the second chamber 102 via the first flow path 111 with reference to the straight line db shown in FIG. Further, the cleaning liquid positioned on the first chamber 101 side with respect to the straight line db is returned to the first chamber 101 by centrifugal force. Therefore, as shown in FIG. 24, only the cleaning liquid weighed by the first flow path 111 is transferred to the second chamber 102.
- the centrifugal force also acts on the cleaning liquid transferred to the second chamber 102, the cleaning liquid does not move in the direction of the rotation axis 110 in the second flow path 112, and the cleaning liquid substantially remains in the second chamber 102. As a result, the magnetic particles 311 in the second chamber 102 come into contact with the cleaning liquid, and the first cleaning is performed.
- the substrate solution is pressed against the side surface farthest from the rotation shaft 110 in the fourth chamber 107 by centrifugal force. For this reason, the substrate solution remains in the fourth chamber 107.
- the sample analysis substrate 162 is stopped at a predetermined third angle.
- the third angle is that the cleaning liquid in the first chamber 101 is not in contact with the first opening 111c, and the cleaning liquid transferred to the second chamber 102 is in contact with the third opening 112c in the second flow path 112. It is an angle that can be done.
- the gravity direction in the sample analysis system 501 projected onto a plane parallel to the sample analysis substrate 162 may be within the angle range indicated by ⁇ 3 on the sample analysis substrate 162.
- the cleaning liquid in the second chamber 102 is in contact with the third opening 112c of the second flow path 112, thereby filling the second flow path 112 by capillary action.
- Step S26 (Process (d))
- the sample analysis substrate 162 is rotated.
- a centrifugal force is generated with the rotation and acts on the cleaning liquid and the magnetic particles 311 in the second chamber 102.
- This centrifugal force works so that the cleaning liquid and the magnetic particles 311 move to the side surface 102 s of the second chamber 102, and the magnetic particles 311 are captured on the side surface 102 s by the centrifugal force and the attractive force by the magnet 126.
- the cleaning liquid that has received the centrifugal force is discharged from the second flow path 112 and transferred to the third chamber 103.
- the rotation of the sample analysis substrate 162 is stopped. As a result, the cleaning liquid and the magnetic particles 311 are separated. Specifically, the cleaning liquid moves to the third chamber 103 and the magnetic particles 311 remain in the second chamber 102. Even if the rotation of the sample analysis substrate 162 stops, the magnetic particles 311 can remain in the state of being collected on the side surface 102s by the attractive force received from the magnet 126.
- the stop angle at this time may be the third angle or the fourth angle of the next step.
- Step S27 (Process (e))
- the sample analysis substrate 162 is slightly rotated counterclockwise and stopped at the predetermined fourth angle.
- the fourth angle is an angle at which the cleaning liquid transferred to the first chamber 101 comes into contact with the first opening 111 c of the first flow path 111.
- the gravity direction is an angle within the angle range indicated by ⁇ 4 of the sample analysis substrate 162. Since the amount of the cleaning liquid remaining in the first chamber 101 is different from that in step S4, the angle range ⁇ 4 may be different from the angle range ⁇ 2.
- the cleaning liquid is sucked into the first flow path 111 from the first chamber 101 by the capillary force in the first portion 111a of the first flow path 111, and the first portion 111a and the second portion 111b of the first flow path 111 are filled with the cleaning liquid. It is. Thereby, the cleaning liquid for one time is weighed again.
- the sample analysis substrate 162 may be swung around the fourth angle so that the first flow path 111 is surely filled with the cleaning liquid. Since capillary force acts on the first flow path 111, the cleaning liquid does not move from the first flow path 111 to the second chamber 102 at this time.
- Step S28 (Steps (f) and (g))] Subsequently, the sample analysis substrate 162 is rotated. The centrifugal force due to rotation acts on the cleaning liquid in the first flow path 111 and the first chamber 101. As in the first cleaning, the cleaning liquid positioned on the first flow path 111 side moves to the second chamber 102 via the first flow path 111 with reference to the straight line db shown in FIG. Further, the cleaning liquid positioned on the first chamber 101 side with respect to the straight line db is returned to the first chamber 101 by centrifugal force. Therefore, as shown in FIG. 28, only the cleaning liquid weighed by the first flow path 111 is transferred to the second chamber 102.
- the centrifugal force also acts on the cleaning liquid transferred to the second chamber 102, the cleaning liquid does not move in the direction of the rotation axis 110 in the second flow path 112, and the cleaning liquid substantially remains in the second chamber 102. As a result, the magnetic particles 311 in the second chamber 102 come into contact with the cleaning liquid, and the second cleaning is performed.
- the substrate solution is pressed against the side surface farthest from the rotation shaft 110 in the fourth chamber 107 by centrifugal force. For this reason, the substrate solution remains in the fourth chamber 107.
- the sample analysis substrate 162 is stopped at a predetermined fifth angle.
- the fifth angle is that the cleaning liquid in the first chamber 101 does not come into contact with the first opening 111c, and the cleaning liquid transferred to the second chamber 102 comes into contact with the third opening 112c in the second flow path 112. It is an angle that can be done.
- the gravity direction in the sample analysis system 501 projected onto a plane parallel to the sample analysis substrate 162 may be within the angle range indicated by ⁇ 5 on the sample analysis substrate 162.
- the cleaning liquid in the second chamber 102 is in contact with the third opening 112c of the second flow path 112, thereby filling the second flow path 112 by capillary action.
- Step S29 (Process (h))
- the sample analysis substrate 162 is rotated.
- a centrifugal force is generated with the rotation and acts on the cleaning liquid and the magnetic particles 311 in the second chamber 102.
- This centrifugal force works so that the cleaning liquid and the magnetic particles 311 move to the side surface 102 s of the second chamber 102, and the magnetic particles 311 are captured on the side surface 102 s by the centrifugal force and the attractive force by the magnet 126.
- the cleaning liquid that has received the centrifugal force is discharged from the second flow path 112 and transferred to the third chamber 103.
- the rotation of the sample analysis substrate 162 is stopped. Thereby, as shown in FIG. 31, the cleaning liquid and the magnetic particles 311 are separated. Specifically, the cleaning liquid moves to the third chamber 103 and the magnetic particles 311 remain in the second chamber 102. Even if the rotation of the sample analysis substrate 162 stops, the magnetic particles 311 can remain in the state of being collected on the side surface 102s by the attractive force received from the magnet 126.
- the stop angle at this time may be the fifth angle or the sixth angle of the next step.
- Step S30 (Process (i))
- the sample analysis substrate 162 is slightly rotated and stopped at the predetermined sixth angle. Unlike the procedure so far, at this time, the sample analysis substrate 162 is rotated clockwise.
- the sixth angle is an angle at which the substrate solution transferred to the fourth chamber 107 comes into contact with the ninth opening 117 c of the seventh channel 117.
- the gravity direction is an angle within the angle range indicated by ⁇ 6 of the sample analysis substrate 162.
- the substrate solution in the fourth chamber 107 comes into contact with the first portion 117a of the seventh channel 117 through the ninth opening 117c, the substrate solution is sucked into the entire first portion 117a by the capillary force, and the seventh channel 117 The first portion 117a and the second portion 117b are filled with the substrate solution. Thereby, the substrate solution is weighed.
- the seventh flow path 117 In order to ensure that the seventh flow path 117 is filled with the substrate solution, it may be rotated about the sixth angle alternately about several degrees clockwise or counterclockwise, that is, it may be swung. Since capillary force acts on the seventh flow path 117, the cleaning liquid does not move from the second portion 117 b of the seventh flow path 117 to the second chamber 102 at this time.
- Step S31 (Process (j))
- the sample analysis substrate 162 is rotated. Centrifugal force due to rotation acts on the substrate solution in the seventh flow path 117 and the fourth chamber 107.
- the substrate solution in the seventh flow path 117 moves to the second chamber 102 by centrifugal force.
- the substrate solution positioned on the fourth chamber 107 side with respect to the ninth opening 117c is pressed against the side surface farthest from the rotation axis 110 of the fourth chamber 107 by the centrifugal force, and remains in the fourth chamber 107. .
- the substrate solution moved to the second chamber 102 contains a substrate.
- This substrate reacts with the labeling substance 307 contained in the labeling antibody 308 in the magnetic particles 311 held in the second chamber 102, or changes in light emission, fluorescence or absorption wavelength by the catalytic reaction of the labeling substance 307. Arise.
- the seventh angle is such that the light receiving element of the optical measurement unit 207 can detect a change in light emission, fluorescence, or absorption wavelength of the substrate in the second chamber 102 such that the light receiving element is close to the second chamber 102. Is an angle at which the optical measurement unit 207 is arranged in a predetermined positional relationship.
- the optical measurement unit 207 performs optical measurement of the liquid held in the second chamber 102. Specifically, the optical measurement unit 207 detects a signal such as a dye, luminescence, or fluorescence of a substrate corresponding to the labeling substance 307 of the labeled antibody 308 bound to the complex 310 included in the magnetic particle 311. Thereby, detection of the antigen 306, quantification of the concentration of the antigen 306, and the like can be performed.
- a signal such as a dye, luminescence, or fluorescence of a substrate corresponding to the labeling substance 307 of the labeled antibody 308 bound to the complex 310 included in the magnetic particle 311.
- Optical measurement by the optical measurement unit 207 may be performed with the sample analysis substrate 162 rotated.
- the substrate analysis substrate 162 may be rotated and signals such as the substrate dye, luminescence, and fluorescence may be detected.
- the centrifugal force stronger than the capillary force acts on the liquid in the second flow path 112 due to the rotation of the sample analysis substrate 162
- the substrate solution in the second chamber 102 passes through the second flow path 112 to the third chamber 103. This is because the measurement is not possible.
- 34 and 35 show another configuration example of the first chamber 101, the second chamber 102, the fourth chamber 107, the first flow path 111, and the seventh flow path 117 of the sample analysis substrate 162.
- the first chamber 101 and the fourth chamber 107 are located on the opposite sides of the second chamber 102. Specifically, the first chamber 101 and the fourth chamber 107 are respectively disposed in two regions separated by a straight line (indicated by a broken line) connecting the vicinity of the center of the second chamber 102 and the rotation shaft 110.
- the cleaning liquid held in the first chamber 101 is introduced into the first flow path 111 in a plurality of times, It can be weighed and moved to the second chamber 102.
- the substrate solution can be held in the fourth chamber 107 by appropriately selecting an angle at which the sample analysis substrate is stopped for introducing the cleaning liquid into the first flow path 111.
- the substrate solution held in the fourth chamber 107 can be introduced into the seventh channel 117, weighed, and moved to the second chamber 102.
- the cleaning liquid can be maintained in the first chamber 101 by appropriately selecting an angle at which the sample analysis substrate is stopped.
- the sample analysis substrate is rotated counterclockwise in order to move the cleaning liquid.
- the sample analysis substrate The direction of rotation may be reversed.
- the sample analysis substrate is rotated in the same direction (clockwise in the example of FIG. 34), so that the substrate solution is held in the fourth chamber 107 and the first chamber 101 is washed. Can be transferred to the second chamber 102 in a plurality of times. Further, by rotating the sample analysis substrate in the reverse direction, the substrate solution can be transferred to the second chamber 102 while the cleaning liquid is held in the first chamber 101.
- the first chamber 101 and the fourth chamber 107 are located on the same side with respect to the second chamber 102.
- both the first chamber 101 and the fourth chamber 107 are disposed only in one of two regions separated by a straight line (shown by a broken line) connecting the vicinity of the center of the second chamber 102 and the rotation shaft 110. ing.
- the cleaning liquid held in the first chamber 101 is First, when the sample analysis substrate is brought into contact with the first flow path 111 and the sample analysis substrate is further rotated, the substrate solution in the fourth chamber 107 comes into contact with the seventh flow path 117.
- the sample analysis substrate is rotated clockwise, the cleaning liquid comes into contact with the first flow path 111, and the substrate solution is By stopping at an angle that does not come into contact with the seventh flow path 117, the cleaning solution in the first chamber 101 is divided into a plurality of times while the substrate solution is held in the fourth chamber 107, and weighed to the second chamber 102. Can be transported.
- the sample analysis substrate is rotated clockwise from the state where the first chamber 101 and the fourth chamber 107 are positioned below the gravitational direction, and the substrate solution is By stopping at an angle in contact with the seventh channel 117, the substrate solution is moved from the fourth chamber 107 to the seventh channel 117, weighed by the seventh channel 117, and moved to the second chamber 102. Can do.
- the sample analysis substrate is rotated in the same direction (clockwise in the example of FIG. 35), so that the substrate solution is held in the fourth chamber 107 and the first chamber 101 is washed. Can be transferred to the second chamber 102 in a plurality of times, and after all the cleaning liquid in the first chamber 101 has been transferred to the second chamber 102, the substrate for sample analysis is rotated in the same direction, whereby the substrate The solution can be transferred to the second chamber 102.
- the measurement system using magnetic particles has been described.
- the sample analysis substrate, the sample analysis apparatus, the sample analysis system, and the sample analysis system program according to one embodiment of the present application are magnetic. It is not limited to a measurement system using particles.
- the target to which the primary antibody is immobilized may be a wall surface in the chamber instead of the magnetic particles. That is, when the chamber is made of a material such as polystyrene or polycarbonate, the primary antibody can be immobilized on the wall surface in the chamber by physical adsorption, and sandwiched with antigen or labeled antibody in the chamber. The reaction can be triggered.
- a primary antibody has a functional group (for example, amino group or carboxyl group) that can bind to the primary antibody on the wall surface in the chamber, and the primary antibody can be immobilized by chemical bonding. And a sandwich-type binding reaction.
- a primary antibody can be couple
- the primary antibody When the primary antibody is immobilized on the wall surface of the chamber by physical adsorption or chemical bonding, it is mainly used in a system for detecting a dye, chemiluminescent or fluorescent signal. On the other hand, when the primary antibody is immobilized on a metal substrate, it is mainly used as a signal in a system for detecting an electrochemical signal (for example, current) or an electrochemiluminescence signal. In this case, the magnet 126 shown in FIG. 3B is not necessary. Further, the reaction field for forming the complex 310 is not the reaction chamber 105 but the second chamber 102. Therefore, the primary antibody needs to be immobilized on the wall surface of the second chamber 102.
- sample analysis substrate, sample analysis apparatus, sample analysis system, and sample analysis system program of the present disclosure can be applied not only to non-competitive methods (sandwich immunoassay methods) but also to competitive methods and gene detection methods by hybridization. It is.
- the sample analysis substrate, the sample analysis apparatus, and the sample analysis system of this embodiment divide a solution other than the cleaning liquid into a plurality of times as described above. It is applicable to various sample analysis methods introduced into the same chamber.
- the liquid is continuously introduced into the chamber.
- the rotation and stop of the sample analysis substrate and the angle at the time of stop the other can be performed in between. It is also possible to include a process.
- the cleaning is performed twice, but may be performed three or more times as necessary.
- sample analysis substrate, sample analysis apparatus, sample analysis system, and sample analysis system program disclosed in the present application can be applied to analysis of specific components in a sample using various reactions.
- Sample analysis substrate 100 ′ Substrate 100a Base substrate 100b Cover substrate 101 First chamber 101a First region 101a ′ First region 101b Second region 101c Connection portion 101d Opening 102 Second chamber 102a First region 102b Second region 102s Side surface 103 3rd chamber 103A 1st subchamber 103B 2nd subchamber 104 Storage chamber 105 Reaction chamber 108 Air hole 109 Opening 110 Rotating shaft 111 1st flow path 111a 1st part 111b 2nd part 111c 1st opening 111d 2nd opening 112 Second channel 112a First bent portion 112b Second bent portion 113 Third channel 114 Fourth channel 114a First bent portion 114b Second bent portion 115 Fifth channel 116 Magnet 1 50 Sample analysis substrate 200 Sample analysis apparatus 201 Motor 201a Turntable 203 Origin detector 204 Rotation angle detection circuit 205 Control circuit 206 Drive circuit 207 Optical measurement unit 302 Magnetic particle 304 Primary antibody 305 Magnetic particle immobilized antibody 306 Antigen 307 Labeling substance 308 Labeled antibody
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Abstract
Description
[項目1]
回転運動によって、液体の移送を行う試料分析用基板であって、
回転軸を有する基板と、
前記基板内に位置し、液体を保持するための第1空間を有する第1チャンバーと、
前記基板内に位置し、前記第1チャンバーから排出される前記液体を保持するための第2空間を有する第2チャンバーと、
前記基板内に位置しており、前記第1チャンバーおよび前記第2チャンバーを接続する経路を有し、毛細管現象により前記第1空間内に保持された液体で満たすことが可能な第1流路と、
を備え、
前記第1流路は第1開口および第2開口を有し、前記第1開口および前記第2開口がそれぞれ前記第1チャンバーおよび前記第2チャンバーに接続され、前記第1開口は、前記第2開口よりも回転軸に近い側に位置し、
前記第1空間は前記第1開口と接続し、前記第1開口から前記回転軸より遠い側に向けて延伸する部分を含む第1領域を有し、
前記第1チャンバーの前記第1空間は、前記第1流路の容積よりも大きい、試料分析用基板。
[項目2]
前記第1空間は、前記第1開口よりも前記回転軸から遠い位置において前記第1領域の前記延伸する部分と接続した第2領域をさらに有する、項目1に記載の試料分析用基板。
[項目3]
前記第1チャンバーの一部と前記第1流路の一部とは、前記第1開口を挟んで前記回転軸を中心とする半径方向に位置している項目1に記載の試料分析用基板。
[項目4]
前記第1流路は、前記第1開口を有する第1部分および前記第2開口を有する第2部分を含み、
前記第2部分の毛細管力は、前記第1部分の毛細管力よりも大きい、項目1または2に記載の試料分析用基板。
[項目5]
前記基板は所定の厚さを有する基板形状を備え、前記所定の厚さの方向において、前記第2部分の厚さは、前記第1部分の厚さより小さい、項目4に記載の試料分析用基板。
[項目6]
前記第1流路は、前記第1部分に隣接し、前記第1部分よりも前記回転軸側に位置する空間と、前記空間に連通する開口をさらに備え、
前記空間は毛管路ではない、項目4または5に記載の試料分析用基板。
[項目7]
前記第1空間の前記第1領域は、前記第1開口と接続する接続部を含み、前記接続部は、毛細管現象により前記第1空間内に保持された液体を吸引することが可能であり、
前記接続部は、前記第1領域内において、前記第1開口よりも大きな開口を有する項目1から6のいずれかに記載の試料分析用基板。
[項目8]
前記所定の厚さの方向において、接続部の厚さは、前記第1領域の厚さより小さい、項目7に記載の試料分析用基板。
[項目9]
前記第1領域の前記延伸する部分は、毛細管現象により前記第2領域内に保持された液体を吸引することが可能である、項目2に記載の試料分析用基板。
[項目10]
前記第1チャンバーの第1空間は、前記第1流路の容積の2倍以上である、項目1から9のいずれかに記載の試料分析用基板。
[項目11]
前記基板内において、前記第2チャンバーよりも前記回転軸から遠くに位置し、前記第2チャンバーから排出される前記液体を保持するための第3空間を有する第3チャンバーと、
前記基板内に位置しており、前記第2チャンバーおよび前記第3チャンバーを接続する経路を有し、毛細管現象により前記第2空間内に保持された液体で満たすことが可能な第2流路と、
をさらに備える項目1から10のいずれかに記載の試料分析用基板。
[項目12]
前記基板内に位置し、液体を保持するための第4空間を有する第4チャンバーと、
前記基板内に位置しており、前記第4チャンバーおよび前記第2チャンバーを接続する経路を有し、毛細管現象により前記第4空間内に保持された液体で満たすことが可能な他の流路と、
をさらに備える項目11に記載の試料分析用基板。
[項目13]
前記第1チャンバーおよび前記第4チャンバーは、前記基板内において前記第2チャンバーの中心近傍と前記回転軸とを結ぶ直線で分けられる2つの領域にそれぞれ配置されている、項目12に記載の試料分析用基板。
[項目14]
前記第1チャンバーおよび前記第4チャンバーの両方は、前記基板内において前記第2チャンバーの中心近傍と前記回転軸とを結ぶ直線で分けられる2つの領域の一方に配置されている、項目12に記載の試料分析用基板。
[項目15]
前記第2チャンバーに近接して位置する磁石をさらに備える項目1から14のいずれかに記載の試料分析用基板。
[項目16]
項目1から15のいずれかに記載の試料分析用基板と、
前記回転軸を重力方向に対して0°より大きく90°以下の角度にした状態で、前記試料分析用基板を前記回転軸周りに回転させるモータ、
前記モータの回転軸の回転角度を検出する回転角度検出回路 、
前記回転角度検出回路の検出結果に基づき、前記モータの回転および停止時の回転角度を制御する駆動回路、および
演算器、メモリおよびメモリに記憶され、前記演算器に実行可能なように構成されたプログラムを含み、前記プログラムに基づき、前記モータ、前記回転角度検出回路、および前記駆動回路の動作を制御する制御回路
を有する試料分析装置と、
を備えた試料分析システムであって、
前記プログラムは、
前記第1チャンバーに液体が充填された試料分析用基板が前記試料分析装置に装填された場合において、
(a)前記試料分析用基板を、所定の第1の角度で停止させることによって 、前記第1流路を、毛細管現象によって、前記第1チャンバーの液体の一部により満たし、
(b)前記試料分析用基板を回転させることで、前記第1流路中の前記一部の液体を前記第2チャンバーへ移送させる、
試料分析システム。
[項目17]
前記試料分析用基板は項目11に記載の試料分析用基板であり、
前記プログラムは、前記工程(b)の後、
(c)前記試料分析用基板を所定の第2の角度で停止させることによって 、前記第2流路を、毛細管現象によって、前記第2チャンバーに移送された前記液体の一部により満たし、
(d)前記試料分析用基板を回転させることにより、前記第2チャンバーに移送された前記液体を、遠心力によって、前記第2流路を通って前記第3チャンバーへ移動させる、
項目16に記載の試料分析システム。
[項目18]
前記プログラムは、前記工程(d)の後、
(e)前記試料分析用基板を、所定の第3の角度で停止させることによって 、前記第1流路を、毛細管現象によって、前記第1チャンバーの液体の他の一部により満たし、
(f)前記試料分析用基板を回転させることで、第1流路中の前記他の一部の液体を前記第2チャンバーへ移送させる、
項目17に記載の試料分析システム。
[項目19]
前記プログラムは、前記工程(f)の後、
(g)前記試料分析用基板を所定の第4の角度で停止させることによって 、前記第2流路を、毛細管現象によって、前記第2チャンバーに移送された前記他の一部の液体により満たし、
(h)前記試料分析用基板を回転させることにより、前記第2チャンバーに移送された前記他の一部の液体を、遠心力によって、前記第2流路を通って前記第3チャンバーへ移動させる、
項目18に記載の試料分析システム。
[項目20]
前記プログラムは、前記工程(h)の後、
(i)前記試料分析用基板を、所定の第5の角度で停止させることによって 、前記他の流路を、毛細管現象によって、前記第4チャンバーの液体の一部により満たし、
(j)前記試料分析用基板を回転させることで、前記一部の液体を前記第2チャンバーへ移送させる、
項目19に記載の試料分析システム。
[項目21]
前記試料分析装置は、光学測定ユニットをさらに備え、
前記プログラムは、前記工程(j)の後、
(k)前記光学測定ユニットに、前記第2チャンバーへ移送された前記一部の液体の光学的測定を行わせる、
項目20に記載の試料分析システム。
[項目22]
前記プログラムは、前記工程(a)および(b)を2回以上繰り返して行う、項目16に記載の試料分析システム。
[項目23]
項目1から15のいずれかに記載の試料分析用基板を、前記回転軸を重力方向に対して0°より大きく90°以下の角度にした状態で、前記回転軸周りに回転させるモータ、
前記モータの回転軸の回転角度を検出する回転角度検出回路 、
前記回転角度検出回路の検出結果に基づき、前記モータの回転および停止時の回転角度を制御する駆動回路、および
演算器、メモリおよびメモリに記憶され、前記演算器に実行可能なように構成されたプログラムを含み、前記プログラムに基づき、前記モータ、前記回転角度検出回路および前記駆動回路の動作を制御する制御回路
を有する試料分析装置と、
を備え、
前記プログラムは、
前記第1チャンバーに液体が充填された試料分析用基板が前記試料分析装置に装填された場合において、
(a)前記試料分析用基板を、所定の第1の角度で停止させることによって 、前記第1流路を、毛細管現象によって、前記第1チャンバーの液体の一部により満たし、
(b)前記試料分析用基板を回転させることで、前記第1流路中の前記一部の液体を前記第2チャンバーへ移送させる、
試料分析装置。
[項目24]
項目1から15のいずれかに記載の試料分析用基板と、
前記回転軸を重力方向に対して0°より大きく90°以下の角度にした状態で、前記試料分析用基板を前記回転軸周りに回転させるモータ、
前記モータの回転軸の回転角度を検出する回転角度検出回路 、
前記回転角度検出回路の検出結果に基づき、前記モータの回転および停止時の回転角度を制御する駆動回路、および
演算器、メモリおよびメモリに記憶され、前記演算器に実行可能なように構成されたプログラムを含み、前記プログラムに基づき、前記モータ、前記回転角度検出回路および前記駆動回路の動作を制御する制御回路
を有する試料分析装置と、
を備えた試料分析システム用プログラムであって、
前記プログラムは、
前記第1チャンバーに液体が充填された試料分析用基板が前記試料分析装置に装填された場合において、
(a)前記試料分析用基板を、所定の第1の角度で停止させることによって 、前記第1流路を、毛細管現象によって、前記第1チャンバーの液体の一部により満たし、
(b)前記試料分析用基板を回転させることで、前記第1流路中の前記一部の液体を前記第2チャンバーへ移送させる、
試料分析システム用プログラム。
図2Aは、試料分析システム501の全体の構成を示す模式図である。試料分析システム501は、試料分析用基板100と試料分析装置200とを含む。
試料分析装置200は、モータ201と、原点検出器203と、回転角度検出回路204と、制御回路205と、駆動回路206と、光学測定ユニット207とを備える。
図3Aは、試料分析用基板100の分解斜視図である。試料分析用基板100は、回転軸110および回転軸110に平行な方向に所定の厚さを有する板形状の基板100’を備える。試料分析用基板100の基板100’は、ベース基板100aとカバー基板100bによって構成されている。本実施形態では、試料分析用基板100の基板100’は円形形状を有しているが、例えば、多角形形状、楕円形状、扇形形状等を有していてもよい。基板100’は、2つの主面100c、100dを有している。本実施形態では、主面100cおよび主面100dは互いに平行であり、主面100cおよび主面100dの間隔で規定される基板100’の厚さ(2つの主面の間の距離)は、基板100’のどの位置でも同じである。しかし、主面100c、100dは、平行でなくてもよい。例えば、2つの主面の一部分が非平行または平行であってもよいし、全体的に非平行であってもよい。また、基板100’の主面100cおよび100dの少なくも一方に凹部ないし凸部を有する構成を備えていてもよい。
第2流路112
条件1:2R1>2R2
条件2:2R4>2R3
第4流路114
条件1:4R1>4R2
条件2:4R4>4R3
試料分析システム501の動作を説明する。図4は、試料分析システム501の動作を示すフローチャートである。試料分析システム501を動作させるための、試料分析システム501の各部を制御する手順を規定したプログラムが、例えば制御回路205のメモリに記憶されており、演算器によるプログラムの実行により、以下の動作が実現する。以下の工程に先立ち、試料分析用基板100を試料分析装置200に装填し、試料分析用基板100の原点を検出する。
まず、図5に示すように、洗浄液を試料分析用基板100の貯蔵チャンバー104に導入する。また、反応チャンバー105に、磁性粒子固定化抗体305と、抗原306を含む検体と、標識抗体308を導入する。例えば、反応チャンバー105に磁性粒子固定化抗体305を含む液体が保持されており、試料分析用基板100に設けられた図示しないチャンバーが抗原306および標識抗体308を含む液体をそれぞれ別々に保持しており、試料分析用基板100の回転による遠心力でこれらが反応チャンバー105へ移送されてもよい。反応チャンバー105において、磁性粒子固定化抗体305と、抗原306を含む検体と、標識抗体308とを抗原抗体反応により、同時に反応させて複合体310を形成させる。この時点で第3流路113および第4流路114は、毛細管現象によって、それぞれ、洗浄液および複合体310を含む反応液で満たされている。
複合体310が生成した後、試料分析用基板100を回転させ、複合体310を含む反応液を第2チャンバー102へ移動させる。この際、第4流路114は、毛細管現象によって、反応液で満たされている。このため、反応チャンバー105の複合体310を含む反応液に、試料分析用基板100の回転により第4流路114内の反応液にかかる毛細管力よりも強い遠心力が働くと、反応液は第2チャンバー102へ移送される。第2チャンバー102へ移送された反応液は、試料分析用基板100が回転している状態では、続いて第3チャンバー103へ移送されることはない。上述したように第2流路112がサイフォンを構成しているため、遠心力に逆らって、液体が第2流路112を回転軸110に向かう方向へ移動しないからである。第2チャンバー102へ移送された複合体310を含む反応液のうち、磁性粒子311の多くは、磁石126の吸引力により側面102sに捕捉される。
試料分析用基板100を回転させる。回転にともない遠心力が発生し、第2チャンバー102内の反応液および磁性粒子311(複合体310および未反応の磁性粒子固定化抗体305)に働く。この遠心力は、液体および複合体が第2チャンバー102の側面102s側へ移動するように働く。このため、図7に示すように、磁性粒子311は、側面102sに押し付けられる。
図8に示すように、試料分析用基板100を少し回転させ、所定の第2の角度で停止させる。第2の角度は第1チャンバー101へ移送された洗浄液が、第1チャンバー101の接続部101cと接触する角度である。例えば図8に示す例では、試料分析用基板100のδ2で示す角度範囲内に重力方向が位置する角度である。
続いて、試料分析用基板100を回転させる。回転による遠心力が第1流路111および第1チャンバー101内の洗浄液に働く。図9に示すように、第1流路111内の洗浄液は、遠心力によって第2チャンバー102へ移送される。一方、第1チャンバー101内の第1領域101aに位置していた余分な洗浄液は、遠心力によって第1チャンバー101内の第2領域101bへ移動する。よって、第1流路111によって秤量された洗浄液だけが第2チャンバー102へ移送される。第2チャンバー102へ移送された洗浄液にも遠心力が働くため、洗浄液は第2流路112において回転軸110方向に移動せず、洗浄液は実質的に第2チャンバー102内にとどまる。これにより、第2チャンバー102内の磁性粒子311が洗浄液と接触し、1回目の洗浄が行われる。
試料分析用基板100を回転させる。回転にともない遠心力が発生し、第2チャンバー102内の洗浄液および磁性粒子311に働く。この遠心力は、洗浄液および磁性粒子311が第2チャンバー102の側面102s側へ移動するように働き、磁性粒子311は遠心力および磁石126による吸引力によって側面102sにおいて捕捉される。
図12に示すように、試料分析用基板100を少し回転させ、所定の第4の角度で停止させる。第4の角度は第1チャンバー101へ移送された洗浄液が、第1チャンバー101の接続部101cと接触する角度である。例えば図12に示す例では、試料分析用基板100のδ4で示す角度範囲内に重力方向が位置する角度である。第1チャンバー101内に残っている洗浄液の量がステップS4とは異なるため、角度範囲δ4は角度範囲δ2と異なり得る。
続いて、試料分析用基板100を回転させる。回転による遠心力が第1流路111および第1チャンバー101内の洗浄液に働く。図13に示すように、第1流路111内の洗浄液は、遠心力によって第2チャンバー102へ移送される。一方、第1チャンバー101内の第1領域101aに位置していた余分な洗浄液は、遠心力によって第1チャンバー101内の第2領域101bへ移動する。よって、第1流路111によって秤量された洗浄液だけが第2チャンバー102へ移送される。第2チャンバー102へ移送された洗浄液にも遠心力が働くため、洗浄液は第2流路112において回転軸110方向に移動せず、洗浄液は実質的に第2チャンバー102内にとどまる。これにより、第2チャンバー102内の磁性粒子311が洗浄液と接触し、2回目の洗浄が行われる。
試料分析用基板100を回転させる。回転にともない遠心力が発生し、第2チャンバー102内の洗浄液および磁性粒子311に働く。この遠心力は、洗浄液および磁性粒子311が第2チャンバー102の側面102s側へ移動するように働き、磁性粒子311は遠心力および磁石126による吸引力によって側面102sにおいて捕捉される。
以下、本開示の第2の実施形態による試料分析システムを説明する。第2の実施形態の試料分析システムは、試料分析用基板162と試料分析装置200とを含む。試料分析装置200の構成は第1の実施形態の試料分析システム501における試料分析装置200と同じである。
まず、図20に示すように、洗浄液を試料分析用基板162の貯蔵チャンバー104に導入し、基質溶液を貯蔵チャンバー106に導入する。基質溶液は、標識物質307との反応または標識物質307による触媒作用によって、発光、蛍光、あるいは、吸収波長の変化を生じる基質を含む。また、反応チャンバー105に、磁性粒子固定化抗体305と、抗原306と、標識抗体308を含む検体を導入する。例えば、反応チャンバー105に磁性粒子固定化抗体305を含む液体が保持されており、試料分析用基板162に設けられた図示しないチャンバーが抗原306および標識抗体308を含む液体を保持しており、試料分析用基板162の回転による遠心力でこれらが反応チャンバー105へ移送されてもよい。反応チャンバー105において、磁性粒子固定化抗体305と、検体中の抗原306と、標識抗体308とを抗原抗体反応により結合させ、複合体310を形成させる。この時点で第3流路113、第4流路114は、毛細管現象によって、それぞれ、洗浄液および複合体310を含む反応液で満たされている。図20に示す例では、第6流路116は、基質溶液で満たされていない。しかし、第6流路116が基質溶液で満たされていてもよい。
複合体310が生成した後、試料分析用基板162を回転させ、複合体310を含む反応液を第2チャンバー102へ移動させる。この際、第4流路114は、毛細管現象によって、反応液で満たされている。このため、反応チャンバー105の複合体310を含む反応液に、試料分析用基板162の回転により第4流路114内の反応液にかかる毛細管力よりも強い遠心力が働くと、反応液は第2チャンバー102へ移送される。第2チャンバー102へ移送された反応液は、試料分析用基板162が回転している状態では、続いて第3チャンバー103へ移送されることはない。上述したように第2流路112がサイフォンを構成しているため、遠心力に逆らって、液体が第2流路112を回転軸110に向かう方向へ移動しないからである。第2チャンバー102へ移送された複合体310を含む反応液のうち、磁性粒子311の多くは、磁石126の吸引力により側面102sに捕捉される。
試料分析用基板162を回転させる。回転にともない遠心力が発生し、第2チャンバー102内の反応液、磁性粒子311(複合体310および未反応の磁性粒子)に働く。この遠心力は、液体および複合体310が第2チャンバー102の側面102s側へ移動するように働く。このため、磁性粒子311は、側面102sに押し付けられる。
図23に示すように、前のステップで第2の角度で停止させない場合には、反時計回りに試料分析用基板162を少し回転させ、所定の第2の角度で停止させる。第2の角度は第1チャンバー101へ移送された洗浄液が、第1流路111の第1開口111cと接触する角度である。例えば図23に示す例では、試料分析用基板162のδ2で示す角度範囲内に重力方向が位置する角度である。
続いて、試料分析用基板162を回転させる。回転による遠心力が第1流路111および第1チャンバー101内の洗浄液に働く。図17Aを参照して説明したように、図23に示す直線dbを基準として第1流路111側に位置する洗浄液は第1流路111を介して第2チャンバー102へ移動する。また、直線dbを基準として第1チャンバー101側に位置する洗浄液は、遠心力によって、第1チャンバー101へ戻される。よって、図24に示すように、第1流路111によって秤量された洗浄液だけが第2チャンバー102へ移送される。第2チャンバー102へ移送された洗浄液にも遠心力が働くため、洗浄液は第2流路112において回転軸110方向に移動せず、洗浄液は実質的に第2チャンバー102内にとどまる。これにより、第2チャンバー102内の磁性粒子311が洗浄液と接触し、1回目の洗浄が行われる。
試料分析用基板162を回転させる。回転にともない遠心力が発生し、第2チャンバー102内の洗浄液および磁性粒子311に働く。この遠心力は、洗浄液および磁性粒子311が第2チャンバー102の側面102s側へ移動するように働き、磁性粒子311は遠心力および磁石126による吸引力によって側面102sにおいて捕捉される。
図27に示すように、前のステップで第4の角度で停止させない場合には、反時計回りに試料分析用基板162を少し回転させ、所定の第4の角度で停止させる。第4の角度は第1チャンバー101へ移送された洗浄液が、第1流路111の第1開口111cと接触する角度である。例えば図27に示す例では、試料分析用基板162のδ4で示す角度範囲内に重力方向が位置する角度である。第1チャンバー101内に残っている洗浄液の量がステップS4とは異なるため、角度範囲δ4は角度範囲δ2と異なり得る。
続いて、試料分析用基板162を回転させる。回転による遠心力が第1流路111および第1チャンバー101内の洗浄液に働く。1回目の洗浄と同様、図27に示す直線dbを基準として第1流路111側に位置する洗浄液は第1流路111を介して第2チャンバー102へ移動する。また、直線dbを基準として第1チャンバー101側に位置する洗浄液は、遠心力によって、第1チャンバー101へ戻される。よって、図28に示すように、第1流路111によって秤量された洗浄液だけが第2チャンバー102へ移送される。第2チャンバー102へ移送された洗浄液にも遠心力が働くため、洗浄液は第2流路112において回転軸110方向に移動せず、洗浄液は実質的に第2チャンバー102内にとどまる。これにより、第2チャンバー102内の磁性粒子311が洗浄液と接触し、2回目の洗浄が行われる。
試料分析用基板162を回転させる。回転にともない遠心力が発生し、第2チャンバー102内の洗浄液および磁性粒子311に働く。この遠心力は、洗浄液および磁性粒子311が第2チャンバー102の側面102s側へ移動するように働き、磁性粒子311は遠心力および磁石126による吸引力によって側面102sにおいて捕捉される。
図32に示すように、前のステップで第6の角度で停止させない場合には、試料分析用基板162を少し回転させ、所定の第6の角度で停止させる。これまでの手順とは異なり、この時、試料分析用基板162は、時計回りに回転させる。第6の角度は第4チャンバー107に移送された基質溶液が第7流路117の第9開口117cと接触する角度である。例えば図32に示す例では、試料分析用基板162のδ6で示す角度範囲内に重力方向が位置する角度である。
続いて、試料分析用基板162を回転させる。回転による遠心力が第7流路117および第4チャンバー107内の基質溶液に働く。第7流路117内の基質溶液は、遠心力によって、第2チャンバー102へ移動する。第9開口117cよりも第4チャンバー107側に位置している基質溶液は、遠心力によって、第4チャンバー107の回転軸110から最も遠くに位置する側面へ押し付けられ、第4チャンバー107内に留まる。
光学測定ユニット207は、第2チャンバー102に保持された液体の光学的測定を行う。具体的には、光学測定ユニット207は、磁性粒子311に含まれる複合体310に結合した標識抗体308の標識物質307に応じた基質の色素、発光、蛍光等のシグナルを検出する。これにより、抗原306の検出、抗原306の濃度の定量等を行うことができる。
以下、試料分析用基板162の他の形態の例を説明する。図34および図35は、試料分析用基板162の第1チャンバー101、第2チャンバー102、第4チャンバー107、第1流路111および第7流路117の他の構成例を示している。これらの図は、分かりやすさのため、試料分析用基板162における、回転軸110、第1チャンバー101、第2チャンバー102、第4チャンバー107、第1流路111および第7流路117のみを示している。
100’ 基板
100a ベース基板
100b カバー基板
101 第1チャンバー
101a 第1領域
101a’ 第1領域
101b 第2領域
101c 接続部
101d 開口
102 第2チャンバー
102a 第1領域
102b 第2領域
102s 側面
103 第3チャンバー
103A 第1副チャンバー
103B 第2副チャンバー
104 貯蔵チャンバー
105 反応チャンバー
108 空気孔
109 開口
110 回転軸
111 第1流路
111a 第1部分
111b 第2部分
111c 第1開口
111d 第2開口
112 第2流路
112a 第1屈曲部
112b 第2屈曲部
113 第3流路
114 第4流路
114a 第1屈曲部
114b 第2屈曲部
115 第5流路
116 磁石
150 試料分析用基板
200 試料分析装置
201 モータ
201a ターンテーブル
203 原点検出器
204 回転角度検出回路
205 制御回路
206 駆動回路
207 光学測定ユニット
302 磁性粒子
304 一次抗体
305 磁性粒子固定化抗体
306 抗原
307 標識物質
308 標識抗体
310 複合体
311 磁性粒子
501 試料分析システム
Claims (24)
- 回転運動によって、液体の移送を行う試料分析用基板であって、
回転軸を有する基板と、
前記基板内に位置し、液体を保持するための第1空間を有する第1チャンバーと、
前記基板内に位置し、前記第1チャンバーから排出される前記液体を保持するための第2空間を有する第2チャンバーと、
前記基板内に位置しており、前記第1チャンバーおよび前記第2チャンバーを接続する経路を有し、毛細管現象により前記第1空間内に保持された液体で満たすことが可能な第1流路と、
を備え、
前記第1流路は第1開口および第2開口を有し、前記第1開口および前記第2開口がそれぞれ前記第1チャンバーおよび前記第2チャンバーに接続され、前記第1開口は、前記第2開口よりも回転軸に近い側に位置し、
前記第1空間は前記第1開口と接続し、前記第1開口から前記回転軸より遠い側に向けて延伸する部分を含む第1領域を有し、
前記第1チャンバーの前記第1空間は、前記第1流路の容積よりも大きい、試料分析用基板。 - 前記第1空間は、前記第1開口よりも前記回転軸から遠い位置において前記第1領域の前記延伸する部分と接続した第2領域をさらに有する、請求項1に記載の試料分析用基板。
- 前記第1チャンバーの一部と前記第1流路の一部とは、前記第1開口を挟んで前記回転軸を中心とする半径方向に位置している請求項1に記載の試料分析用基板。
- 前記第1流路は、前記第1開口を有する第1部分および前記第2開口を有する第2部分を含み、
前記第2部分の毛細管力は、前記第1部分の毛細管力よりも大きい、請求項1または2に記載の試料分析用基板。 - 前記基板は所定の厚さを有する基板形状を備え、前記所定の厚さの方向において、前記第2部分の厚さは、前記第1部分の厚さより小さい、請求項4に記載の試料分析用基板。
- 前記第1流路は、前記第1部分に隣接し、前記第1部分よりも前記回転軸側に位置する空間と、前記空間に連通する開口をさらに備え、
前記空間は毛管路ではない、請求項4または5に記載の試料分析用基板。 - 前記第1空間の前記第1領域は、前記第1開口と接続する接続部を含み、前記接続部は、毛細管現象により前記第1空間内に保持された液体を吸引することが可能であり、
前記接続部は、前記第1領域内において、前記第1開口よりも大きな開口を有する請求項1から6のいずれかに記載の試料分析用基板。 - 前記所定の厚さの方向において、前記接続部の厚さは、前記第1領域の厚さより小さい、請求項7に記載の試料分析用基板。
- 前記第1領域の前記延伸する部分は、毛細管現象により前記第2領域内に保持された液体を吸引することが可能である、請求項2に記載の試料分析用基板。
- 前記第1チャンバーの前記第1空間は、前記第1流路の容積の2倍以上である、請求項1から9のいずれかに記載の試料分析用基板。
- 前記基板内において、前記第2チャンバーよりも前記回転軸から遠くに位置し、前記第2チャンバーから排出される前記液体を保持するための第3空間を有する第3チャンバーと、
前記基板内に位置しており、前記第2チャンバーおよび前記第3チャンバーを接続する経路を有し、毛細管現象により前記第2空間内に保持された液体で満たすことが可能な第2流路と、
をさらに備える請求項1から10のいずれかに記載の試料分析用基板。 - 前記基板内に位置し、液体を保持するための第4空間を有する第4チャンバーと、
前記基板内に位置しており、前記第4チャンバーおよび前記第2チャンバーを接続する経路を有し、毛細管現象により前記第4空間内に保持された液体で満たすことが可能な他の流路と、
をさらに備える請求項11に記載の試料分析用基板。 - 前記第1チャンバーおよび前記第4チャンバーは、前記基板内において前記第2チャンバーの中心近傍と前記回転軸とを結ぶ直線で分けられる2つの領域にそれぞれ配置されている、請求項12に記載の試料分析用基板。
- 前記第1チャンバーおよび前記第4チャンバーの両方は、前記基板内において前記第2チャンバーの中心近傍と前記回転軸とを結ぶ直線で分けられる2つの領域の一方に配置されている、請求項12に記載の試料分析用基板。
- 前記第2チャンバーに近接して位置する磁石をさらに備える請求項1から14のいずれかに記載の試料分析用基板。
- 請求項1から15のいずれかに記載の試料分析用基板と、
前記回転軸を重力方向に対して0°より大きく90°以下の角度にした状態で、前記試料分析用基板を前記回転軸周りに回転させるモータ、
前記モータの回転軸の回転角度を検出する回転角度検出回路 、
前記回転角度検出回路の検出結果に基づき、前記モータの回転および停止時の回転角度を制御する駆動回路、および
演算器、メモリおよびメモリに記憶され、前記演算器に実行可能なように構成されたプログラムを含み、前記プログラムに基づき、前記モータ、前記回転角度検出回路および前記駆動回路の動作を制御する制御回路
を有する試料分析装置と、
を備えた試料分析システムであって、
前記プログラムは、
前記第1チャンバーに液体が充填された試料分析用基板が前記試料分析装置に装填された場合において、
(a)前記試料分析用基板を、所定の第1の角度で停止させることによって 、前記第1流路を、毛細管現象によって、前記第1チャンバーの液体の一部により満たし、
(b)前記試料分析用基板を回転させることで、前記第1流路中の前記一部の液体を前記第2チャンバーへ移送させる、
試料分析システム。 - 前記試料分析用基板は請求項11に記載の試料分析用基板であり、
前記プログラムは、前記工程(b)の後、
(c)前記試料分析用基板を所定の第2の角度で停止させることによって 、前記第2流路を、毛細管現象によって、前記第2チャンバーに移送された前記液体の一部により満たし、
(d)前記試料分析用基板を回転させることにより、前記第2チャンバーに移送された前記液体を、遠心力によって、前記第2流路を通って前記第3チャンバーへ移動させる、
請求項16に記載の試料分析システム。 - 前記プログラムは、前記工程(d)の後、
(e)前記試料分析用基板を、所定の第3の角度で停止させることによって 、前記第1流路を、毛細管現象によって、前記第1チャンバーの液体の他の一部により満たし、
(f)前記試料分析用基板を回転させることで、第1流路中の前記他の一部の液体を前記第2チャンバーへ移送させる、
請求項17に記載の試料分析システム。 - 前記プログラムは、前記工程(f)の後、
(g)前記試料分析用基板を所定の第4の角度で停止させることによって 、前記第2流路を、毛細管現象によって、前記第2チャンバーに移送された前記他の一部の液体により満たし、
(h)前記試料分析用基板を回転させることにより、前記第2チャンバーに移送された前記他の一部の液体を、遠心力によって、前記第2流路を通って前記第3チャンバーへ移動させる、
請求項18に記載の試料分析システム。 - 前記プログラムは、前記工程(h)の後、
(i)前記試料分析用基板を、所定の第5の角度で停止させることによって 、前記他の流路を、毛細管現象によって、前記第4チャンバーの液体の一部により満たし、
(j)前記試料分析用基板を回転させることで、前記一部の液体を前記第2チャンバーへ移送させる、
請求項19に記載の試料分析システム。 - 前記試料分析装置は、光学測定ユニットをさらに備え、
前記プログラムは、前記工程(j)の後、
(k)前記光学測定ユニットに、前記第2チャンバーへ移送された前記一部の液体の光学的測定を行わせる、
請求項20に記載の試料分析システム。 - 前記プログラムは、前記工程(a)および(b)を2回以上繰り返して行う、請求項16に記載の試料分析システム。
- 請求項1から15のいずれかに記載の試料分析用基板を、前記回転軸を重力方向に対して0°より大きく90°以下の角度にした状態で、前記回転軸周りに回転させるモータ、
前記モータの回転軸の回転角度を検出する回転角度検出回路 、
前記回転角度検出回路の検出結果に基づき、前記モータの回転および停止時の回転角度を制御する駆動回路、および
演算器、メモリおよびメモリに記憶され、前記演算器に実行可能なように構成されたプログラムを含み、前記プログラムに基づき、前記モータ、前記回転角度検出回路および前記駆動回路の動作を制御する制御回路
を有する試料分析装置と、
を備え、
前記プログラムは、
前記第1チャンバーに液体が充填された試料分析用基板が前記試料分析装置に装填された場合において、
(a)前記試料分析用基板を、所定の第1の角度で停止させることによって 、前記第1流路を、毛細管現象によって、前記第1チャンバーの液体の一部により満たし、
(b)前記試料分析用基板を回転させることで、前記第1流路中の前記一部の液体を前記第2チャンバーへ移送させる、
試料分析装置。 - 請求項1から15のいずれかに記載の試料分析用基板と、
前記回転軸を重力方向に対して0°より大きく90°以下の角度にした状態で、前記試料分析用基板を前記回転軸周りに回転させるモータ、
前記モータの回転軸の回転角度を検出する回転角度検出回路 、
前記回転角度検出回路の検出結果に基づき、前記モータの回転および停止時の回転角度を制御する駆動回路、および
演算器、メモリおよびメモリに記憶され、前記演算器に実行可能なように構成されたプログラムを含み、前記プログラムに基づき、前記モータ、前記回転角度検出回路および前記駆動回路の動作を制御する制御回路
を有する試料分析装置と、
を備えた試料分析システム用プログラムであって、
前記プログラムは、
前記第1チャンバーに液体が充填された試料分析用基板が前記試料分析装置に装填された場合において、
(a)前記試料分析用基板を、所定の第1の角度で停止させることによって 、前記第1流路を、毛細管現象によって、前記第1チャンバーの液体の一部により満たし、
(b)前記試料分析用基板を回転させることで、前記第1流路中の前記一部の液体を前記第2チャンバーへ移送させる、
試料分析システム用プログラム。
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2018163102A (ja) * | 2017-03-27 | 2018-10-18 | Phcホールディングス株式会社 | 試料分析装置、試料分析システムおよび試料の発光を測定する方法 |
US20210270861A1 (en) * | 2018-06-20 | 2021-09-02 | Phc Holdings Corporation | Substrate for sample analysis |
JP2022503948A (ja) * | 2018-10-11 | 2022-01-12 | エルジー・ケム・リミテッド | 一体型カートリッジ |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10520521B2 (en) * | 2014-06-30 | 2019-12-31 | Phc Holdings Corporation | Substrate for sample analysis, sample analysis device, sample analysis system, and program for sample analysis system |
WO2016002728A1 (ja) | 2014-06-30 | 2016-01-07 | パナソニックヘルスケアホールディングス株式会社 | 試料分析用基板、試料分析装置、試料分析システムおよび磁性粒子を含む液体から液体を取り除く方法 |
EP3163306A4 (en) | 2014-06-30 | 2018-01-24 | Panasonic Healthcare Holdings Co., Ltd. | Substrate for sample analysis, and sample analysis apparatus |
US10539583B2 (en) | 2014-12-12 | 2020-01-21 | Phc Holdings Corporation | Substrate for sample analysis, sample analysis device, sample analysis system, and program for sample analysis system |
WO2017122314A1 (ja) * | 2016-01-14 | 2017-07-20 | 株式会社島津製作所 | 試料採取装置、その試料採取装置用ホルダ及びその試料採取装置を用いた試料前処理方法 |
KR101965963B1 (ko) * | 2017-08-24 | 2019-08-13 | 경희대학교 산학협력단 | 시료 분석용 칩, 이를 포함하는 시료 분석용 디바이스, 그리고 시료 분석용 칩에 장착되는 카트리지 |
US11946943B2 (en) * | 2018-02-09 | 2024-04-02 | Phc Holdings Corporation | Substrate for sample analysis, sample analysis device, sample analysis system, and method for controlling sample analysis device |
GB201806931D0 (en) * | 2018-04-27 | 2018-06-13 | Radisens Diagnostics Ltd | An improved point-of-care diagnostic assay cartridge |
WO2020100987A1 (ja) * | 2018-11-16 | 2020-05-22 | Phcホールディングス株式会社 | 試料分析用基板 |
CN117085754B (zh) * | 2023-10-20 | 2024-07-23 | 天津微纳芯科技股份有限公司 | 微流控基板和微流控芯片 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2006177850A (ja) * | 2004-12-24 | 2006-07-06 | Matsushita Electric Ind Co Ltd | 流路と、この流路を用いた液体計量装置と、この液体計量装置を用いた液体分析装置と、その液体計量方法 |
JP2007530938A (ja) * | 2004-03-24 | 2007-11-01 | オーミック・アクチボラゲット | アッセイ装置及び方法 |
JP2007315879A (ja) * | 2006-05-25 | 2007-12-06 | Matsushita Electric Ind Co Ltd | 光学分析用デバイス及び光学分析装置 |
JP2010122022A (ja) * | 2008-11-19 | 2010-06-03 | Panasonic Corp | 分析用デバイスとこの分析用デバイスを使用した分析方法 |
Family Cites Families (195)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4495295A (en) | 1979-05-21 | 1985-01-22 | New York Blood Center, Inc. | Immunoassays using support-containing separate antigens and antibodies derived from an immune complex |
GB8401368D0 (en) | 1984-01-19 | 1984-02-22 | Amersham Int Plc | Assay method |
FR2579756B1 (fr) | 1985-03-26 | 1987-05-07 | Guigan Jean | Procede pour realiser des analyses biologiques utilisant des reactions immunologiques et dispositif de mise en oeuvre |
JPH0737989B2 (ja) | 1986-07-04 | 1995-04-26 | 東ソー株式会社 | 免疫反応の測定方法および装置 |
US4918025A (en) | 1987-03-03 | 1990-04-17 | Pb Diagnostic Systems, Inc. | Self contained immunoassay element |
US5173262A (en) | 1987-07-17 | 1992-12-22 | Martin Marietta Energy Systems, Inc. | Rotor assembly and method for automatically processing liquids |
AU609241B2 (en) | 1988-01-29 | 1991-04-26 | Abbott Laboratories | Ion-capture assays and devices |
US4990075A (en) | 1988-04-11 | 1991-02-05 | Miles Inc. | Reaction vessel for performing sequential analytical assays |
US5160702A (en) * | 1989-01-17 | 1992-11-03 | Molecular Devices Corporation | Analyzer with improved rotor structure |
SE465742B (sv) | 1989-04-26 | 1991-10-21 | Migrata Uk Ltd | Kyvett foer upptagning foer minst ett fluidum |
US5242606A (en) | 1990-06-04 | 1993-09-07 | Abaxis, Incorporated | Sample metering port for analytical rotor having overflow chamber |
US5466574A (en) | 1991-03-25 | 1995-11-14 | Immunivest Corporation | Apparatus and methods for magnetic separation featuring external magnetic means |
US5186827A (en) | 1991-03-25 | 1993-02-16 | Immunicon Corporation | Apparatus for magnetic separation featuring external magnetic means |
JPH05297001A (ja) | 1992-04-15 | 1993-11-12 | Fujirebio Inc | 磁性粒子を用いた自動免疫測定方法及び装置 |
US5637469A (en) | 1992-05-01 | 1997-06-10 | Trustees Of The University Of Pennsylvania | Methods and apparatus for the detection of an analyte utilizing mesoscale flow systems |
JPH05322894A (ja) | 1992-05-18 | 1993-12-07 | Tdk Corp | 生体物質量の測定方法及びそのための装置 |
US5627041A (en) | 1994-09-02 | 1997-05-06 | Biometric Imaging, Inc. | Disposable cartridge for an assay of a biological sample |
JPH08262024A (ja) | 1995-01-26 | 1996-10-11 | Nippon Paint Co Ltd | 生体内物質の免疫測定用キットおよび免疫測定方法 |
AU4213396A (en) | 1995-01-26 | 1996-08-01 | Nippon Paint Co., Ltd. | Kit for immunologically assaying biological substance and assay process |
ATE172890T1 (de) | 1995-02-21 | 1998-11-15 | Iqbal W Dr Siddiqi | Apparat und verfahren zum mischen und trennen durch verwendung von magnetischen teilchen |
DE69619400T2 (de) | 1995-06-16 | 2002-09-26 | Univ Washington Seattle | Flacher mikrogefertigter querstromfilter für flüssigkeiten |
US5741714A (en) | 1995-07-18 | 1998-04-21 | Immunivest Corporation | Detection of bound analyte by magnetic partitioning and masking |
JPH09218201A (ja) | 1995-12-07 | 1997-08-19 | Seiko Instr Inc | 磁性粒子の分離方法 |
US6709869B2 (en) * | 1995-12-18 | 2004-03-23 | Tecan Trading Ag | Devices and methods for using centripetal acceleration to drive fluid movement in a microfluidics system |
JP3670383B2 (ja) | 1996-03-19 | 2005-07-13 | オリンパス株式会社 | 分析装置および分析方法 |
US5885470A (en) | 1997-04-14 | 1999-03-23 | Caliper Technologies Corporation | Controlled fluid transport in microfabricated polymeric substrates |
JP3213798B2 (ja) | 1996-06-04 | 2001-10-02 | 株式会社日立製作所 | 化学分析装置 |
US6074827A (en) | 1996-07-30 | 2000-06-13 | Aclara Biosciences, Inc. | Microfluidic method for nucleic acid purification and processing |
GB9620278D0 (en) | 1996-09-28 | 1996-11-13 | Central Research Lab Ltd | Apparatus for chemical analysis |
US5958704A (en) | 1997-03-12 | 1999-09-28 | Ddx, Inc. | Sensing system for specific substance and molecule detection |
JP4035199B2 (ja) | 1997-04-22 | 2008-01-16 | ロッシュ ディアグノスティクス ゲゼルシャフト ミット ベシュレンクテル ハフツング | 試料分析装置 |
JP3469585B2 (ja) | 1997-05-23 | 2003-11-25 | ガメラ バイオサイエンス コーポレイション | ミクロ流体工学システムでの流動運動を駆動するために向心的加速を使用するための装置および方法 |
US6632399B1 (en) | 1998-05-22 | 2003-10-14 | Tecan Trading Ag | Devices and methods for using centripetal acceleration to drive fluid movement in a microfluidics system for performing biological fluid assays |
US6103537A (en) | 1997-10-02 | 2000-08-15 | Aclara Biosciences, Inc. | Capillary assays involving separation of free and bound species |
EP1084391A4 (en) | 1998-06-08 | 2006-06-14 | Caliper Life Sciences Inc | MICROFLUIDIC DEVICES, SYSTEMS AND METHODS FOR REALIZING INTEGRATED REACTIONS AND SEPARATIONS |
FR2782729B1 (fr) | 1998-09-01 | 2002-10-25 | Bio Merieux | Carte de denombrement et de caracterisation de micro-organismes |
US20020019059A1 (en) | 1999-01-28 | 2002-02-14 | Calvin Y.H. Chow | Devices, systems and methods for time domain multiplexing of reagents |
CA2401782A1 (en) | 2000-01-31 | 2001-08-02 | John T. Mcdevitt | Portable sensor array system |
EP1284819A2 (en) | 2000-05-15 | 2003-02-26 | Tecan Trading AG | Microfluidics devices and methods for high throughput screening |
US20020151078A1 (en) | 2000-05-15 | 2002-10-17 | Kellogg Gregory J. | Microfluidics devices and methods for high throughput screening |
AU2001290879A1 (en) | 2000-09-15 | 2002-03-26 | California Institute Of Technology | Microfabricated crossflow devices and methods |
US8900811B2 (en) | 2000-11-16 | 2014-12-02 | Caliper Life Sciences, Inc. | Method and apparatus for generating thermal melting curves in a microfluidic device |
JP2002236131A (ja) | 2000-12-08 | 2002-08-23 | Minolta Co Ltd | マイクロチップ |
JP2002365211A (ja) | 2001-04-02 | 2002-12-18 | Fuji Photo Film Co Ltd | 測定装置 |
JP2003043052A (ja) | 2001-08-02 | 2003-02-13 | Mitsubishi Chemicals Corp | マイクロチャネルチップ,マイクロチャネルシステム及びマイクロチャネルチップにおける流通制御方法 |
US7060227B2 (en) | 2001-08-06 | 2006-06-13 | Sau Lan Tang Staats | Microfluidic devices with raised walls |
ATE271919T1 (de) | 2001-10-18 | 2004-08-15 | Aida Eng Ltd | Mikrodosier- und probennahmevorrichtung sowie mikrochip mit dieser vorrichtung |
JP3749991B2 (ja) | 2001-10-18 | 2006-03-01 | アイダエンジニアリング株式会社 | 微量液体秤取構造及び該構造を有するマイクロチップ |
US20030138819A1 (en) | 2001-10-26 | 2003-07-24 | Haiqing Gong | Method for detecting disease |
US7749442B2 (en) | 2001-12-14 | 2010-07-06 | Arkray, Inc. | Sample measuring device |
DE10218988C1 (de) | 2002-04-24 | 2003-11-20 | Horst Dieter Becker | Vorrichtung und Verfahren zum Benetzen von Objekten |
US7384602B2 (en) | 2002-05-08 | 2008-06-10 | Hitachi High-Technologies Corporation | Chemical analysis apparatus and genetic diagnostic apparatus |
AU2003283663A1 (en) | 2002-11-01 | 2004-05-25 | Cellectricon Ab | Computer programs,workstations, systems and methods for microfluidic substrates in cell |
US20050221281A1 (en) | 2003-01-08 | 2005-10-06 | Ho Winston Z | Self-contained microfluidic biochip and apparatus |
US20040137607A1 (en) | 2003-01-09 | 2004-07-15 | Yokogawa Electric Corporation | Biochip cartridge |
JP2005010031A (ja) | 2003-06-19 | 2005-01-13 | Asahi Kasei Corp | 混合機構 |
US20070166721A1 (en) | 2003-06-27 | 2007-07-19 | Phan Brigitte C | Fluidic circuits, methods and apparatus for use of whole blood samples in colorimetric assays |
DE10354351B3 (de) | 2003-11-20 | 2005-06-16 | november Aktiengesellschaft Gesellschaft für Molekulare Medizin | Verfahren und Vorrichtung zur verbesserten Reinigung einer an paramagnetische Mikropartikel gebundenen Substanz |
WO2005069015A1 (ja) | 2004-01-15 | 2005-07-28 | Japan Science And Technology Agency | 化学分析装置及び化学分析方法 |
US20050178218A1 (en) | 2004-01-28 | 2005-08-18 | Jean Montagu | Micro-volume blood sampling device |
WO2005075997A1 (ja) | 2004-02-03 | 2005-08-18 | Asahi Kasei Kabushiki Kaisha | 磁気ビーズを用いた被検物質の検出方法 |
SE0400403D0 (sv) | 2004-02-20 | 2004-02-20 | Karl Andersson | Method and device for the characterization of interactions between different species |
JP2005345160A (ja) | 2004-05-31 | 2005-12-15 | Advance Co Ltd | 生体情報分析ユニット |
JP2006010535A (ja) | 2004-06-25 | 2006-01-12 | Canon Inc | 標的物質捕捉方法および装置 |
JP2006068384A (ja) | 2004-09-03 | 2006-03-16 | Advance Co Ltd | 体液移送具及び体液移送具を用いた体液検査システム |
JP4375183B2 (ja) | 2004-09-22 | 2009-12-02 | ウシオ電機株式会社 | マイクロチップ |
JP2006112824A (ja) | 2004-10-12 | 2006-04-27 | Terametsukusu Kk | 自動免疫分析装置におけるb/f分離方法 |
US20070141576A1 (en) | 2004-12-13 | 2007-06-21 | Bbk Bio Corporpation | Biological chip and use thereof |
JP4645211B2 (ja) * | 2005-02-07 | 2011-03-09 | パナソニック株式会社 | Hdl−コレステロール分析用ディスク、及びhdl−コレステロール分析用装置 |
JP2006258696A (ja) | 2005-03-18 | 2006-09-28 | Matsushita Electric Ind Co Ltd | 分析用ディスク、及びそれを使用する分析装置 |
WO2006108559A2 (de) | 2005-04-09 | 2006-10-19 | Boehringer Ingelheim Microparts Gmbh | Vorrichtung und verfahren zur untersuchung einer probenflüssigkeit |
JP4524262B2 (ja) | 2005-04-11 | 2010-08-11 | 東洋機械金属株式会社 | 縦型射出成形機 |
WO2006110098A1 (en) | 2005-04-14 | 2006-10-19 | Gyros Patent Ab | Meander |
CN101203596A (zh) | 2005-04-21 | 2008-06-18 | 塞莱勒斯诊断公司 | 用于自动快速免疫组织化学的并行处理流体方法和设备 |
JP4630785B2 (ja) | 2005-09-30 | 2011-02-09 | 富士フイルム株式会社 | 秤量チップ及びそれを用いた検査方法 |
US7846716B2 (en) | 2005-04-28 | 2010-12-07 | Fujifilm Corporation | Microchip and analysis method using the same |
JP4501793B2 (ja) | 2005-06-24 | 2010-07-14 | パナソニック株式会社 | バイオセンサ |
EP1898222A1 (en) | 2005-06-24 | 2008-03-12 | Arkray, Inc. | Cartridge |
JP2007003414A (ja) | 2005-06-24 | 2007-01-11 | Arkray Inc | 分析装置用カートリッジ |
JP4660662B2 (ja) | 2005-09-06 | 2011-03-30 | アークレイ株式会社 | カートリッジ |
JP2007010341A (ja) | 2005-06-28 | 2007-01-18 | Sumitomo Bakelite Co Ltd | 免疫分析方法 |
US20070009382A1 (en) | 2005-07-05 | 2007-01-11 | William Bedingham | Heating element for a rotating multiplex fluorescence detection device |
JP2007024851A (ja) | 2005-07-16 | 2007-02-01 | Adobic:Kk | 検体分析チップおよび検体分析チップの使用方法 |
JP2007047031A (ja) | 2005-08-10 | 2007-02-22 | Arkray Inc | 分析方法および分析用具 |
JP4802925B2 (ja) | 2005-08-19 | 2011-10-26 | パナソニック株式会社 | 分析用デバイス、およびこれを使用する分析装置 |
JP2007064742A (ja) | 2005-08-30 | 2007-03-15 | Nec Corp | 化学チップおよび接続装置 |
JP2007071557A (ja) | 2005-09-05 | 2007-03-22 | Rohm Co Ltd | チップ |
EP1971861A4 (en) | 2005-12-21 | 2014-10-22 | Samsung Electronics Co Ltd | BIOLOGICAL MEMORY DISK AND BIOLOGICAL MEMORY DISK READ APPARATUS, AND ASSAY METHOD USING SUCH APPARATUS |
KR101159880B1 (ko) | 2006-03-09 | 2012-06-26 | 세키스이가가쿠 고교가부시키가이샤 | 마이크로 유체 디바이스 및 미량 액체 희석 방법 |
JP2007279069A (ja) | 2006-03-09 | 2007-10-25 | Sekisui Chem Co Ltd | マイクロ流体デバイスおよび微量液体希釈方法 |
EP2004541A1 (en) | 2006-03-13 | 2008-12-24 | Gyros Patent Ab | Enhanced magnetic particle steering |
WO2007116909A1 (ja) | 2006-04-04 | 2007-10-18 | Panasonic Corporation | 試料液分析用パネル |
JP4754394B2 (ja) | 2006-04-14 | 2011-08-24 | ローム株式会社 | マイクロチップ |
EP2023139B1 (en) | 2006-04-25 | 2011-01-19 | Panasonic Corporation | Immunoassay method and chip |
JP2008015708A (ja) | 2006-07-04 | 2008-01-24 | Fuji Electric Holdings Co Ltd | 広告システム、そのWebサーバ、ICカード・リーダ/ライタ装置、携帯端末 |
KR101335920B1 (ko) | 2006-08-02 | 2013-12-03 | 삼성전자주식회사 | 박막화학분석장치 및 이를 이용한 분석방법 |
JP5065803B2 (ja) | 2006-08-08 | 2012-11-07 | 積水化学工業株式会社 | 微量液体秤取装置、それを有するマイクロチップ及び微量な液体の秤取方法 |
EP1939629A3 (en) | 2006-08-11 | 2011-03-09 | Samsung Electronics Co., Ltd. | Centrifugal Force Based Magnet Position Control Device and Disk-Shaped Micro Fluidic System |
KR100754409B1 (ko) | 2006-08-30 | 2007-08-31 | 삼성전자주식회사 | 원심력을 이용한 자성비드 팩킹 유닛, 이를 구비한미세유동 장치 및 상기 미세유동 장치를 이용한 면역학적검정 방법 |
JP2008064701A (ja) | 2006-09-11 | 2008-03-21 | Matsushita Electric Ind Co Ltd | 回転分析デバイス及び計量方法及び検査方法 |
EP2096444B1 (en) | 2006-10-31 | 2016-12-07 | Panasonic Healthcare Holdings Co., Ltd. | Microchip and analyzer using the same |
US7384798B2 (en) * | 2006-10-31 | 2008-06-10 | Hewlett-Packard Development Company, L.P. | Method of detecting analytes in a microfluidic sample and a system for performing the same |
JP2008128906A (ja) | 2006-11-22 | 2008-06-05 | Fujifilm Corp | マイクロ流体チップの駆動制御方法 |
JP4811247B2 (ja) | 2006-11-28 | 2011-11-09 | パナソニック株式会社 | マイクロチップ及びそれを用いた分析デバイス |
JP5004577B2 (ja) | 2006-12-27 | 2012-08-22 | ローム株式会社 | 液体試薬内蔵型マイクロチップにおける液体試薬の液量および/または品質が正常であるかを判定する方法、および液体試薬内蔵型マイクロチップ |
JP2008164434A (ja) | 2006-12-28 | 2008-07-17 | Matsushita Electric Ind Co Ltd | 生体サンプル判別装置 |
US8409877B2 (en) | 2006-12-29 | 2013-04-02 | Intel Corporation | Enzymatic signal generation and detection of binding complexes in stationary fluidic chip |
JP5005511B2 (ja) | 2007-02-09 | 2012-08-22 | アボットジャパン株式会社 | 非特異反応を減少させた免疫診断薬 |
CA2682275C (en) | 2007-03-28 | 2017-05-09 | Bionanomatrix, Inc. | Methods of macromolecular analysis using nanochannel arrays |
ES2687620T3 (es) | 2007-05-04 | 2018-10-26 | Opko Diagnostics, Llc | Dispositivo y método para análisis en sistemas microfluídicos |
WO2008139697A1 (ja) | 2007-05-10 | 2008-11-20 | Panasonic Corporation | チャンバを有する流路部位を含む基板、およびそれを含む多段送液装置 |
JP2009014529A (ja) | 2007-07-05 | 2009-01-22 | Panasonic Corp | 分析用デバイス、分析用デバイスを用いる分析装置、および液体試料成分測定方法 |
JP4614992B2 (ja) | 2007-07-27 | 2011-01-19 | パナソニック株式会社 | 分析用デバイスとこれを使用する分析装置および分析方法 |
JP2009042104A (ja) | 2007-08-09 | 2009-02-26 | Canon Inc | 物質固定装置、物質検出装置および物質固定方法 |
KR101335727B1 (ko) | 2007-08-22 | 2013-12-04 | 삼성전자주식회사 | 원심력 기반의 혈액 검사용 디스크형 미세유동장치 |
JP5348901B2 (ja) | 2008-02-01 | 2013-11-20 | パナソニック株式会社 | 分析用デバイスを用いた分析方法 |
CN101796420B (zh) | 2007-10-04 | 2013-09-11 | 松下电器产业株式会社 | 分析用仪器和使用该分析用仪器的分析装置及分析方法 |
CN102721822B (zh) | 2007-10-29 | 2013-11-06 | 松下电器产业株式会社 | 分析用仪器驱动装置 |
JP5137528B2 (ja) | 2007-10-29 | 2013-02-06 | パナソニック株式会社 | 分析用デバイスとこれを使用する分析装置および分析方法 |
US9134286B2 (en) | 2007-10-30 | 2015-09-15 | Panasonic Healthcare Co., Ltd. | Analyzing device, analyzing apparatus using the device, and analyzing method |
JP5376429B2 (ja) | 2007-10-30 | 2013-12-25 | パナソニック株式会社 | 分析用デバイスとこれを使用する分析装置および分析方法 |
JP5376428B2 (ja) | 2008-09-16 | 2013-12-25 | パナソニック株式会社 | 分析用デバイス |
JP5178224B2 (ja) | 2008-02-06 | 2013-04-10 | パナソニック株式会社 | 分析用デバイスおよびこれを使用する分析装置 |
JP2009121860A (ja) | 2007-11-13 | 2009-06-04 | Panasonic Corp | 生体試料判別用プレート及びそれを用いた生体試料移送方法 |
US20090155125A1 (en) | 2007-11-14 | 2009-06-18 | Rohm Co., Ltd. | Microchip |
JP2009287971A (ja) | 2008-05-27 | 2009-12-10 | Rohm Co Ltd | マイクロチップ |
EP2214822A1 (en) | 2007-11-26 | 2010-08-11 | Atonomics A/S | Integrated separation and detection cartridge using magnetic particles with bimodal size distribution |
JP5137010B2 (ja) | 2007-11-28 | 2013-02-06 | ローム株式会社 | マイクロチップの製造方法 |
KR20090057691A (ko) | 2007-12-03 | 2009-06-08 | 삼성전자주식회사 | 원심력 기반의 플랫폼, 이를 구비한 미세유동 시스템, 및상기 플랫폼의 홈 위치 결정 방법 |
JP4808699B2 (ja) | 2007-12-10 | 2011-11-02 | パナソニック株式会社 | 分析装置 |
WO2009075076A1 (ja) | 2007-12-10 | 2009-06-18 | Panasonic Corporation | 分析装置 |
JP4808701B2 (ja) | 2007-12-27 | 2011-11-02 | パナソニック株式会社 | 分析装置 |
JP2009156778A (ja) | 2007-12-27 | 2009-07-16 | Rohm Co Ltd | マイクロチップとその製造方法 |
JP2009162701A (ja) | 2008-01-10 | 2009-07-23 | Panasonic Corp | 生体サンプル分析用プレート |
JP2009180697A (ja) | 2008-02-01 | 2009-08-13 | Panasonic Corp | 分析プレート |
CN103175782B (zh) * | 2008-02-05 | 2015-05-13 | 松下健康医疗器械株式会社 | 分析用仪器和使用该分析用仪器的分析方法 |
JP5376436B2 (ja) | 2008-02-05 | 2013-12-25 | パナソニック株式会社 | 分析用デバイスを使用する分析装置および分析方法 |
US7854893B2 (en) | 2008-03-28 | 2010-12-21 | Panasonic Corporation | Analysis device and an analysis apparatus using the analysis device |
EP2133149A1 (en) | 2008-06-13 | 2009-12-16 | F.Hoffmann-La Roche Ag | Lab-on-disc device |
JP5408992B2 (ja) | 2008-12-24 | 2014-02-05 | パナソニック株式会社 | 分析用デバイスとこの分析用デバイスを使用した分析方法 |
CN102981004B (zh) * | 2008-07-17 | 2014-01-01 | 松下电器产业株式会社 | 分析用器件及使用该分析用器件的分析方法 |
KR100997144B1 (ko) | 2008-09-23 | 2010-11-30 | 삼성전자주식회사 | 미세유동장치 |
KR101099495B1 (ko) | 2008-10-14 | 2011-12-28 | 삼성전자주식회사 | 원심력 기반의 미세유동장치, 이의 제조 방법 및 이를 이용한 시료분석방법 |
CN105403695B (zh) | 2008-11-19 | 2018-08-10 | 皇家飞利浦电子股份有限公司 | 用于致动磁性粒子的生物传感器*** |
TWI369494B (en) | 2008-12-12 | 2012-08-01 | Univ Nat Taiwan | Compact disk based platform for separating and detecting immunomagnetic bead labeled cells |
KR101189129B1 (ko) | 2008-12-23 | 2012-10-10 | 한국전자통신연구원 | 미세유체 소자의 유체 흐름 조절 방법 및 미세유체분석장치 |
GB2466644B (en) | 2008-12-30 | 2011-05-11 | Biosurfit Sa | Liquid handling |
JP5174723B2 (ja) | 2009-03-12 | 2013-04-03 | パナソニック株式会社 | 分析用デバイス |
JP2010243373A (ja) | 2009-04-08 | 2010-10-28 | Panasonic Corp | 分析用デバイスにおける分析方法と分析装置 |
EP2253958B1 (en) | 2009-05-18 | 2013-04-17 | F. Hoffmann-La Roche AG | Centrifugal force based microfluidic system and method for the automated analysis of samples |
JP2010286297A (ja) | 2009-06-10 | 2010-12-24 | Beckman Coulter Inc | 免疫測定方法及び免疫測定装置 |
JP5361633B2 (ja) | 2009-09-24 | 2013-12-04 | パナソニック株式会社 | 分析用デバイス |
EP2311565A1 (en) | 2009-10-14 | 2011-04-20 | F. Hoffmann-La Roche AG | Method, structure, device, kit and system for the automated analysis of liquid samples |
US9700889B2 (en) | 2009-11-23 | 2017-07-11 | Cyvek, Inc. | Methods and systems for manufacture of microarray assay systems, conducting microfluidic assays, and monitoring and scanning to obtain microfluidic assay results |
JP2011183589A (ja) | 2010-03-05 | 2011-09-22 | Toppan Printing Co Ltd | シール装置 |
JP2011196849A (ja) | 2010-03-19 | 2011-10-06 | Rohm Co Ltd | 回転式分析チップおよびそれを用いた測定システム |
GB2479139A (en) | 2010-03-29 | 2011-10-05 | Biosurfit Sa | A liquid distribution and metering device |
TW201207392A (en) | 2010-08-02 | 2012-02-16 | Univ Nat Taiwan | Disk-based fluid sample separation device |
DE102010041621B4 (de) | 2010-09-29 | 2016-11-03 | Hahn-Schickard-Gesellschaft für angewandte Forschung e.V. | Verfahren zum Transport magnetischer Partikel |
JP2012127696A (ja) | 2010-12-13 | 2012-07-05 | Sharp Corp | 分析装置および分析方法 |
JP5716406B2 (ja) | 2011-01-13 | 2015-05-13 | ソニー株式会社 | 細胞核観察基板及び細胞核観察装置 |
JP2012159325A (ja) | 2011-01-31 | 2012-08-23 | Fujifilm Corp | 検出方法、および該検出方法に用いられる磁性体含有誘電体粒子 |
US20140004505A1 (en) | 2011-03-10 | 2014-01-02 | Biodetection Instruments, Llc | Cartridge based system and method for detecting an analyte in a sample |
CN102688787B (zh) | 2011-03-23 | 2016-01-27 | 罗姆股份有限公司 | 圆盘式分析芯片 |
JP5728273B2 (ja) | 2011-04-01 | 2015-06-03 | ローム株式会社 | 円盤型分析チップ |
US20120261256A1 (en) | 2011-04-13 | 2012-10-18 | Chang Chia-Pin | Sample holders and analytical instrument for point-of-care qualification of clinical samples |
JP5736230B2 (ja) | 2011-04-26 | 2015-06-17 | ローム株式会社 | マイクロチップ |
US9897596B2 (en) | 2011-06-03 | 2018-02-20 | Radisens Diagnostics Limited | Microfluidic disc for use in with bead-based immunoassays |
JP5889639B2 (ja) | 2011-07-29 | 2016-03-22 | ローム株式会社 | 円盤型分析チップ |
JP5565398B2 (ja) | 2011-09-30 | 2014-08-06 | ブラザー工業株式会社 | 検査対象受体 |
WO2013089887A2 (en) | 2011-09-30 | 2013-06-20 | The Regents Of The University Of California | Microfluidic devices and methods for assaying a fluid sample using the same |
KR101257700B1 (ko) | 2011-12-05 | 2013-04-24 | 삼성전자주식회사 | 미세유동장치 및 이를 포함하는 미세유동시스템 |
EP2825885B1 (en) | 2012-03-12 | 2021-05-12 | The Board of Trustees of the University of Illinois | Optical analyte detection systems with magnetic enhancement |
JP2013205305A (ja) | 2012-03-29 | 2013-10-07 | Enplas Corp | 流体取扱装置、流体取扱方法および流体取扱システム |
US9810658B2 (en) | 2012-04-18 | 2017-11-07 | Board Of Regents, The University Of Texas System | Method for the detection and quantification of analytes using three-dimensional paper-based devices |
CN102671726B (zh) | 2012-04-23 | 2014-04-02 | 北京博晖创新光电技术股份有限公司 | 一种有导流体的微流体芯片及其应用 |
TWI456196B (zh) | 2012-04-24 | 2014-10-11 | Ind Tech Res Inst | 檢體免疫分析檢測裝置 |
JP5705329B2 (ja) | 2012-07-24 | 2015-04-22 | パナソニックヘルスケアホールディングス株式会社 | 分析用デバイス |
JP2014032018A (ja) | 2012-08-01 | 2014-02-20 | Panasonic Corp | 生体化学分析システム、及び、それを用いる温度調整方法 |
JP6011156B2 (ja) | 2012-08-24 | 2016-10-19 | ブラザー工業株式会社 | 検査チップ |
JP5998760B2 (ja) | 2012-08-31 | 2016-09-28 | ブラザー工業株式会社 | 試薬容器および検査チップ |
US20140270459A1 (en) | 2012-10-29 | 2014-09-18 | Mbio Diagnostics, Inc. | Particle Identification System, Cartridge And Associated Methods |
JP2014106207A (ja) | 2012-11-29 | 2014-06-09 | Brother Ind Ltd | 検査チップ |
US9757726B2 (en) | 2013-03-14 | 2017-09-12 | Inguran, Llc | System for high throughput sperm sorting |
JP6221296B2 (ja) | 2013-03-28 | 2017-11-01 | ブラザー工業株式会社 | 検査チップ、および検査システム |
JP2014232023A (ja) | 2013-05-28 | 2014-12-11 | シャープ株式会社 | 分析チップ |
US20150111778A1 (en) | 2013-10-21 | 2015-04-23 | William Marsh Rice University | Bio-nano-chip for anticonvulsant drug salivary assay |
JP6349721B2 (ja) | 2013-12-24 | 2018-07-04 | 凸版印刷株式会社 | 試料分析チップ |
JP5910658B2 (ja) | 2014-03-31 | 2016-04-27 | ブラザー工業株式会社 | 検査チップ |
JP2015223562A (ja) | 2014-05-28 | 2015-12-14 | 国立大学法人お茶の水女子大学 | 微量液体移送デバイス |
US10520521B2 (en) | 2014-06-30 | 2019-12-31 | Phc Holdings Corporation | Substrate for sample analysis, sample analysis device, sample analysis system, and program for sample analysis system |
EP3163306A4 (en) | 2014-06-30 | 2018-01-24 | Panasonic Healthcare Holdings Co., Ltd. | Substrate for sample analysis, and sample analysis apparatus |
WO2016002728A1 (ja) * | 2014-06-30 | 2016-01-07 | パナソニックヘルスケアホールディングス株式会社 | 試料分析用基板、試料分析装置、試料分析システムおよび磁性粒子を含む液体から液体を取り除く方法 |
WO2016002727A1 (ja) * | 2014-06-30 | 2016-01-07 | パナソニックヘルスケアホールディングス株式会社 | 試料分析用基板、試料分析装置、試料分析システムおよび試料分析システム用プログラム |
US10539583B2 (en) | 2014-12-12 | 2020-01-21 | Phc Holdings Corporation | Substrate for sample analysis, sample analysis device, sample analysis system, and program for sample analysis system |
-
2015
- 2015-12-11 US US15/535,345 patent/US10539583B2/en active Active
- 2015-12-11 CN CN201580067495.2A patent/CN107209193B/zh active Active
- 2015-12-11 EP EP15866519.0A patent/EP3232203B1/en active Active
- 2015-12-11 WO PCT/JP2015/084738 patent/WO2016093332A1/ja active Application Filing
- 2015-12-11 JP JP2016563741A patent/JP6660305B2/ja active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007530938A (ja) * | 2004-03-24 | 2007-11-01 | オーミック・アクチボラゲット | アッセイ装置及び方法 |
JP2006177850A (ja) * | 2004-12-24 | 2006-07-06 | Matsushita Electric Ind Co Ltd | 流路と、この流路を用いた液体計量装置と、この液体計量装置を用いた液体分析装置と、その液体計量方法 |
JP2007315879A (ja) * | 2006-05-25 | 2007-12-06 | Matsushita Electric Ind Co Ltd | 光学分析用デバイス及び光学分析装置 |
JP2010122022A (ja) * | 2008-11-19 | 2010-06-03 | Panasonic Corp | 分析用デバイスとこの分析用デバイスを使用した分析方法 |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2018163102A (ja) * | 2017-03-27 | 2018-10-18 | Phcホールディングス株式会社 | 試料分析装置、試料分析システムおよび試料の発光を測定する方法 |
JP7013137B2 (ja) | 2017-03-27 | 2022-01-31 | Phcホールディングス株式会社 | 試料分析装置、試料分析システムおよび試料の発光を測定する方法 |
US20210270861A1 (en) * | 2018-06-20 | 2021-09-02 | Phc Holdings Corporation | Substrate for sample analysis |
JP2022503948A (ja) * | 2018-10-11 | 2022-01-12 | エルジー・ケム・リミテッド | 一体型カートリッジ |
JP7191440B2 (ja) | 2018-10-11 | 2022-12-19 | エルジー・ケム・リミテッド | 一体型カートリッジ |
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CN107209193A (zh) | 2017-09-26 |
EP3232203B1 (en) | 2022-02-02 |
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