Classifications

• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
  • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
  • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
  • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
  • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
  • G01N33/54313—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
  • G01N33/54326—Magnetic particles
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
  • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
  • B03C1/00—Magnetic separation
  • B03C1/005—Pretreatment specially adapted for magnetic separation
  • B03C1/01—Pretreatment specially adapted for magnetic separation by addition of magnetic adjuvants
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
  • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
  • B03C1/00—Magnetic separation
  • B03C1/02—Magnetic separation acting directly on the substance being separated
  • B03C1/025—High gradient magnetic separators
  • B03C1/031—Component parts; Auxiliary operations
  • B03C1/033—Component parts; Auxiliary operations characterised by the magnetic circuit
  • B03C1/0332—Component parts; Auxiliary operations characterised by the magnetic circuit using permanent magnets
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
  • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
  • B03C1/00—Magnetic separation
  • B03C1/02—Magnetic separation acting directly on the substance being separated
  • B03C1/025—High gradient magnetic separators
  • B03C1/031—Component parts; Auxiliary operations
  • B03C1/033—Component parts; Auxiliary operations characterised by the magnetic circuit
  • B03C1/0335—Component parts; Auxiliary operations characterised by the magnetic circuit using coils
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
  • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
  • B03C1/00—Magnetic separation
  • B03C1/02—Magnetic separation acting directly on the substance being separated
  • B03C1/28—Magnetic plugs and dipsticks
  • B03C1/288—Magnetic plugs and dipsticks disposed at the outer circumference of a recipient
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
  • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
  • B03C1/00—Magnetic separation
  • B03C1/02—Magnetic separation acting directly on the substance being separated
  • B03C1/30—Combinations with other devices, not otherwise provided for
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
  • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
  • G01N21/76—Chemiluminescence; Bioluminescence
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
  • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
  • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
  • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
  • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
  • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
  • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
  • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
  • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
  • G01N33/551—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being inorganic
  • G01N33/553—Metal or metal coated
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
  • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
  • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
  • G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
  • G01N33/581—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with enzyme label (including co-enzymes, co-factors, enzyme inhibitors or substrates)
• • 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
  • G01N35/02—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 plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
  • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
  • B03C2201/00—Details of magnetic or electrostatic separation
  • B03C2201/18—Magnetic separation whereby the particles are suspended in a liquid
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
  • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
  • B03C2201/00—Details of magnetic or electrostatic separation
  • B03C2201/26—Details of magnetic or electrostatic separation for use in medical or biological applications

Definitions

• This disclosure relates to a magnetic collection unit and an inspection device.
• Testing devices that quantitatively or qualitatively detect test substances in samples are known. Many of these testing devices use the principle of immunoassay, such as chemiluminescent enzyme immunoassay devices or fluorescent immunoassay devices (for example, JP 2016-085093 A).
• a detection process is carried out to detect the test substance in the sample by using an immune reaction to detect luminescence or fluorescence based on a labeling substance, such as an enzyme label or fluorescent label, that is attached to the test substance in the sample.
• a labeling substance such as an enzyme label or fluorescent label
• the sample is subjected to a pretreatment process, such as attaching a labeling substance to the test substance in the sample.
• a process using magnetic particles as a solid phase is performed as follows. First, in a reaction cell, magnetic particles modified with a first binding substance (e.g., a primary antibody) that specifically binds to the target substance (e.g., an antigen) are mixed with the specimen, and the target substance and the first binding substance are bound to each other to generate an immune complex. As a result, the target substance is captured by the magnetic particles via the first binding substance. Then, the immune complex is separated from the sample-derived components that have not formed an immune complex (unreacted substances), that is, so-called B/F (Bound/Free) separation is performed.
• a first binding substance e.g., a primary antibody
• the target substance e.g., an antigen
• the liquid is sucked in while the magnetic particles are temporarily adsorbed to the inner wall surface of the reaction cell by a magnet placed outside the reaction cell. Then, a washing solution is discharged into the reaction cell, and the mixed solution is sucked in and discharged in a state where the washing solution and the magnetic particles are mixed, thereby washing the magnetic particles.
• a labeling reagent that is a second binding substance (e.g., a secondary antibody) that specifically binds to the target substance and contains the second binding substance bound to the labeling substance is mixed with the magnetic particles.
• the target substance captured by the magnetic particles via the first binding substance binds to the second binding substance, generating a sandwich-type immune complex in which the target substance is sandwiched between the first binding substance and the second binding substance.
• the washing solution and the magnetic particles are mixed again for B/F separation, and the magnetic particles are washed.
• the label is an enzyme label
• the magnetic particles are further mixed with a reagent containing a luminescent substrate and subjected to a detection process.
• JP 2006-218442 A proposes a magnet device (magnetic collection unit) that can generate a high gradient magnetic field to shorten the time required to attract magnetic particles to the inner wall surface during B/F separation.
• the magnet device in JP 2006-218442 A is a pair of magnets with the same poles that repel each other arranged facing each other, and the separation container (reaction cell) is placed close to the gap between the poles, increasing the magnetic field strength generated in the reaction cell.
• JP 2006-218442 A By providing the magnet pair described in JP 2006-218442 A, it becomes possible to collect magnetic particles in a short time on the inner surface of the side wall of the reaction cell that faces the gap between the magnetic pole pairs.
• the inventors have found that if magnetic particles are collected on the inner surface of the side wall of a reaction cell, as in JP 2006-218442 A, and then a cleaning solution or reagent is dispensed while the magnetic field is released, and the magnetic particles are redispersed, the dispersibility of the magnetic particles may decrease.
• the present disclosure has been made in consideration of the above circumstances, and aims to provide a magnetic collection unit that can improve the dispersibility of collected magnetic particles, and an inspection device that can improve the dispersibility of magnetic particles and suppress the occurrence of measurement errors.
• the magnetic collection unit of the present disclosure is a magnetic collection unit that generates a magnetic field inside a reaction cell that contains a suspension containing magnetic particles during a washing process for separating a labeled substance that is bound to a test target substance from a labeled substance that is not bound to the test target substance in a testing device that uses magnetic particles as a solid phase in an antigen-antibody reaction, and magnetically collects the magnetic particles in the suspension onto an inner wall surface of the reaction cell
• the reaction cell is provided with a magnetic field generating unit including a magnet having a length equal to or greater than the distance from the liquid surface of the suspension in the reaction cell to the bottom surface of the reaction cell, and which simultaneously generates a magnetic field in the range from the liquid surface to the bottom surface, and a moving mechanism which moves the magnetic field generating unit in the depth direction from the liquid surface toward the bottom surface while the upper end of the magnet is positioned at or above the liquid surface.
• the magnetic field generating unit is preferably arranged with the magnetic poles of the magnet abutting against the side of the reaction cell, and the moving mechanism is preferably moved in the depth direction with the magnetic poles of the magnet abutting against the side of the reaction cell.
• the magnet is preferably a neodymium magnet.
• the magnet may be an electromagnet.
• the magnetic field generating unit includes two magnets having a length and a non-magnetic body, and it is preferable that the two magnets are arranged with the faces without magnetic poles facing each other across the non-magnetic body, and it is preferable that the two magnets are arranged with their different magnetic poles facing the reaction cell.
• the magnetic field generating unit may be provided with a shield plate at the end of the arrangement direction of the two magnets to block magnetic force.
• Multiple magnetic field generating units may be arranged in parallel, in which case it is preferable that the movement mechanism moves the multiple magnetic field generating units as a unit.
• a shield plate that blocks magnetic force may be provided at the end of the arrangement direction of multiple magnetic field generating units arranged in parallel.
• the inspection device of the present disclosure is a cleaning processing unit including a magnetic flux collecting unit according to the present disclosure and performing a cleaning process; A detection unit that detects light caused by a labeling substance; a transport mechanism for transporting the reaction cell; The cleaning process section and the detection section are arranged along the transport direction of the reaction cell.
• the magnetic collection unit of the disclosed technology can improve the dispersibility of the collected magnetic particles.
• the inspection device of the disclosed technology can improve the dispersibility of the magnetic particles and suppress the occurrence of measurement errors.
• FIG. 1 is a schematic diagram showing an overall configuration of an inspection device; 2 is a diagram showing processing steps in each section within a processing section of an inspection device.
• FIG. 2 is a diagram showing processing steps in each section within a processing section of an inspection device.
• FIG. FIG. 2 is a diagram showing a main part of a cleaning processing section.
• 4 is a diagram showing the relationship between a magnetic field generating section of a magnetic flux collecting unit and a reaction cell.
• FIG. 6A is a view seen from an arrow VIA in FIG. 5
• 1A to 1C are diagrams showing cleaning processing steps (steps ST16 to ST21).
• FIG. 13 is a perspective view showing a modified example of the magnetic field generating unit.
• 10A is a view taken along the arrow XA in FIG. 9, and FIG. 10B is a view taken along the arrow XB in FIG.
• FIG. 11A is a top view of a reaction cell when linear magnetic flux is collected by a magnetic field generating unit
• FIG. 11B is a top view of a reaction cell when linear magnetic flux is collected by a magnetic field generating unit of a modified example.
• FIG. 12A is a diagram showing a case where point magnetic flux is concentrated by a magnetic field generating unit
• FIG. 12B is a diagram showing a case where point magnetic flux is concentrated by a magnetic field generating unit of a modified example.
• FIG. 13 is a diagram showing a cleaning processing section provided with a magnetic flux collecting unit in which a plurality of magnetic field generating sections are arranged in parallel. 13 is a diagram showing a configuration in which a shield plate is provided in a magnetic flux collecting unit in which a plurality of magnetic field generating units are arranged.
• FIG. 1 is a schematic diagram showing the overall configuration of a testing device 10 according to an embodiment of the present disclosure.
• the testing device 10 is an immunoanalysis device that uses an antigen-antibody reaction to attach a labeling substance to a test substance in a specimen, and detects the test substance by detecting light resulting from the labeling substance.
• the testing device 10 performs testing based on a chemiluminescent enzyme immunoassay method.
• the testing device 10 uses magnetic particles MB (see FIG. 2) as a solid phase for the antigen-antibody reaction.
• the testing device 10 uses a reaction cell R0 equipped with magnetic particles MB as a solid phase, and within the reaction cell R0, a process is performed in which a labeling substance is attached to the test substance in the specimen by an antigen-antibody reaction.
• the specimen is a bodily fluid such as blood collected from a living organism. If the specimen is blood, it may be any of whole blood, plasma, and serum. Furthermore, test subjects that may be contained in the specimen include antigens, antibodies, proteins, and low molecular weight compounds. Note that the specimen is not limited to blood, and may be any substance collected from a living organism, such as urine and bodily fluids.
• the magnetic particles MB used as the solid phase for example when spherical, have a diameter of about 0.1 to 10 ⁇ m, preferably 0.1 to 5 ⁇ m, and more preferably 1 to 3 ⁇ m.
• a first binding substance that specifically binds to the test target substance is attached to the magnetic particles MB.
• the inspection device 10 includes, for example, a processing unit 12, a detection unit 13, and a transport mechanism 14.
• the transport mechanism 14 transports the reaction cell R0 within the inspection device 10.
• the processing section 12 and the detection section 13 are arranged along the transport direction of the reaction cell R0 by the transport mechanism 14. Therefore, the reaction cell R0 transported by the transport mechanism 14 is transported sequentially to the processing section 12 and the detection section 13.
• the detection unit 13 executes a detection process to detect the test substance in the specimen.
• the detection unit 13 includes a photodetector 16 such as a photomultiplier tube or a photodiode.
• the photodetector 16 is disposed opposite the reaction cell R0 and detects light L caused by a labeling substance bound to the test substance.
• an enzyme is used as the labeling substance, and chemiluminescence (hereinafter referred to as chemiluminescence L) generated by the reaction of the enzyme with a luminescent substrate is detected as the light L caused by the labeling substance.
• the photodetector 16 optically detects the test substance to which the labeling substance has been added by receiving the chemiluminescence L.
• the inspection device 10 includes a processor (not shown), and the photodetector 16 outputs a light receiving signal according to the amount of light received to the processor.
• the processor detects whether or not the test substance is contained in the specimen and its concentration based on the light receiving signal output by the photodetector 16.
• a process is carried out in which a labeling substance is attached to the test substance by the antigen-antibody reaction described above.
• a first reaction processing section 21, a first cleaning processing section 22A, a second reaction processing section 23, a second cleaning processing section 22B, and a luminescent reagent dispensing section 24 are arranged in this order from the upstream side along the transport direction of the reaction cell R0.
• Figures 2 and 3 are schematic diagrams showing the processes carried out in each section of the processing section 12.
• a specimen 31 is dispensed into a reaction cell R0, and the specimen 31 is mixed with a reagent 36 containing magnetic particles MB to which a first binding substance B1 is fixed in the reaction cell R0.
• the first binding substance B1 is a substance that specifically binds to a test target substance A, and when the test target substance A is present in the specimen 31, a first reaction occurs in which the test target substance A binds to the first binding substance B1.
• This first reaction forms an immune complex between the test target substance A and the first binding substance B1, and the test target substance A is captured by the magnetic particles MB via the first binding substance B1.
• the first reaction is promoted by sufficiently dispersing the magnetic particles MB in the reagent 36 and specimen 31.
• the first cleaning processing unit 22A performs a cleaning process to perform B/F separation, which separates reacted and unreacted substances in a mixture of a reagent 36 containing magnetic particles MB and a sample 31.
• the first cleaning processing unit 22A is equipped with a magnetic collection unit 40, which will be described later, and is used during B/F separation.
• the double-headed arrows in the figure show a schematic diagram of liquid being introduced into and removed from the reaction cell R0. The cleaning process will be described in detail later.
• the labeled reagent 37 is dispensed into the reaction cell R0, and the labeled reagent 37 containing the second binding substance B2 attached to the labeled substance S is mixed with the magnetic particles MB in the reaction cell R0.
• the second binding substance B2 is a substance that specifically binds to the test target substance A, and when the test target substance A is captured by the magnetic particles MB, a second reaction occurs in which the second binding substance B2 binds to the test target substance A.
• This second reaction forms a sandwich-type immune complex in which the test target substance A is sandwiched between the first binding substance B1 and the second binding substance B2, and the second binding substance B2 is captured by the magnetic particles MB via the test target substance A and the first binding substance B1.
• the second reaction is promoted by sufficiently dispersing the magnetic particles MB in the labeled reagent 37.
• a cleaning process is carried out to perform B/F separation, which separates reacted and unreacted substances in a mixture of magnetic particles MB and labeled reagent 37.
• the second cleaning processing section 22B is equipped with a magnetic collection unit 40, which is used during B/F separation.
• the cleaning method is the same as the process carried out in the first cleaning processing section 22A, and will be described in detail later.
• the double arrows indicate the flow of liquid into and out of the reaction cell R0.
• the luminescent reagent 38 is dispensed into the reaction cell R0, and the magnetic particles MB and the luminescent reagent 38 are mixed.
• the luminescent reagent 38 is a reagent that reacts with the labeling substance S to generate chemiluminescence L (see Figure 1). The generation of chemiluminescence L is promoted by sufficiently dispersing the magnetic particles MB in the luminescent reagent 38.
• the first cleaning processing unit 22A and the second cleaning processing unit 22B have substantially the same configuration, and therefore, unless there is a need to distinguish between them, the configuration and function will be described as the cleaning processing unit 22.
• the mixture of the specimen 31 and the reagent 36 containing the magnetic particles MB, the mixture of the magnetic particles MB and the labeled reagent 37, and the mixture of the magnetic particles MB and the luminescent reagent 38 are all suspensions 30 (see FIG. 7) in which the magnetic particles MB are dispersed in the liquid 32, and in the following description of the cleaning process, the above-mentioned mixtures will be collectively referred to as the suspension 30.
• the liquid 32 is a general term for the reagent in which the magnetic particles MB are dispersed.
• the cleaning processing unit 22 includes a magnetic collection unit 40 that collects magnetic particles MB in the reaction cell R0, an aspirating and discharging mechanism 54 equipped with a nozzle 52 that aspirates and discharges cleaning solution 50 into the reaction cell R0, and a moving mechanism for the nozzle 52 (not shown).
• the magnetic flux collecting unit 40 generates a magnetic field inside the reaction cell R0, and collects the magnetic particles MB in the suspension 30 on the inner wall surface of the reaction cell R0.
• the magnetic flux collecting unit 40 includes a magnetic field generating section 42 and a moving mechanism 44.
• the magnetic field generating unit 42 includes a magnet 45.
• the magnet 45 has a length C that is at least equal to or greater than the distance D from the liquid level Z1 of the suspension 30 in the reaction cell R0 to the bottom surface Z2 of the reaction cell R0.
• the amount of liquid 32 dispensed into the reaction cell R0 is predetermined, and the position of the liquid level Z1 is known. Therefore, the distance D is known.
• the length C of the magnet 45 can be set appropriately according to the distance D.
• the length C of the magnet 45 may be equal to or greater than the above-mentioned distance D, but is preferably longer than the distance D, as shown as an example in FIG. 4.
• the length C of the magnet 45 is preferably equal to or less than 130% of the distance D.
• magnet 45 When collecting magnetic particles MB in suspension 30, magnet 45 is positioned so that its length is aligned with the depth direction in reaction cell R0 and magnet 45 is positioned in the range from liquid surface Z1 to bottom surface Z2 of suspension 30. That is, when collecting magnetic particles, magnet 45 is positioned so that upper end 45a of magnet 45 is positioned at liquid surface Z1 or above liquid surface Z1 and lower end 45b of magnet 45 is positioned at bottom surface Z2 or below bottom surface Z2. When positioned in this way, magnet 45 can simultaneously generate a magnetic field in the range from liquid surface Z1 to bottom surface Z2 in reaction cell R0.
• the upper end 45a of the magnet 45 is positioned, for example, about 1 mm above the liquid surface Z1.
• the magnet 45 is a permanent magnet or an electromagnet.
• the magnet 45 is a permanent magnet.
• a permanent magnet a neodymium magnet, which has a particularly strong magnetic force, is preferable.
• the moving mechanism 44 moves the magnetic field generating unit 42 in the depth direction (up and down in the figure) from the liquid surface Z1 toward the bottom surface Z2, from a state in which the upper end 45a of the magnet 45 is positioned at or above the liquid surface Z1.
• the moving mechanism 44 can move the magnet 45 between a first position where the upper end 45a of the magnet 45 is at position P1 above the liquid surface Z1, and a second position where the upper end 45a of the magnet 45 is at position P2 below the bottom surface Z2 of the reaction cell R0.
• the second position is a retracted position where the magnetic field from the magnet 45 has almost no effect on the inside of the reaction cell R0.
• the magnet 45 is supported by a support 46, and the movement mechanism 44 moves the magnet 45 together with the support 46.
• the movement mechanism 44 is composed of, for example, a linear actuator.
• Figure 5 is a perspective view showing the positional relationship between the magnet 45 of the magnetic field generating unit 42 and the reaction cell R0.
• the magnet 45 is positioned so that the magnetic pole (here, the south pole) 45s abuts against the side of the reaction cell R0.
• the moving mechanism 44 is configured to be able to move in the vertical direction, that is, in the depth direction from the liquid surface Z1 toward the bottom surface Z2, with the magnetic pole 45s abutting against the side of the reaction cell R0.
• FIG. 6A is a VIA arrow view of the reaction cell R0 and magnet 45 in FIG. 5 as viewed from the VIA direction
• FIG. 6B is a VIB arrow view as viewed from the VIB direction.
• magnet 45 generates a magnetic field, shown diagrammatically by magnetic field lines 47, inside reaction cell R0.
• Magnetic particles MB in suspension 30 in reaction cell R0 are attracted to magnet 45, move in the direction of the arrow, and are collected on the inner wall surface of reaction cell R0.
• magnet 45 is disposed from liquid surface Z1 to bottom surface Z2 of reaction cell R0, so that magnetic particles MB are collected in a linear region indicated by the dashed line in the figure along the length of magnet 45.
• the reaction cell R0 immediately before the start of the cleaning process contains a suspension 30 in which magnetic particles MB are dispersed in a liquid 32.
• the magnet 45 is in a position where it does not exert a magnetic field on the reaction cell R0. From this state, the magnet 45 is moved upward and positioned on the side of the reaction cell R0 as shown in step ST12. As a result, the magnetic particles MB in the reaction cell R0 are attracted to the magnet 45 and move in the direction of the arrow.
• the magnet 45 Since the magnet 45 is positioned along the side wall surface of the reaction cell R0 from the liquid surface Z1 to the bottom surface Z2 of the suspension 30, the magnetic particles MB dispersed in the liquid 32 move approximately horizontally in the liquid 32 toward the magnet 45, which is the shortest distance they can travel.
• step ST13 the magnetic particles MB are magnetically attracted in a straight line along the length of the magnet 45 on the inner wall surface of the reaction cell R0.
• step ST14 With the magnetic particles MB collected in a straight line on the inner wall surface of the reaction cell R0, a cleaning nozzle 52 is inserted into the reaction cell R0, and the liquid 32 in the reaction cell R0 is aspirated.
• the cleaning nozzle 52 is gradually lowered to the bottom side of the reaction cell R0 while aspirating the liquid 32.
• step ST15 the cleaning nozzle 52 is pulled up and the cleaning liquid 50 is ejected from the cleaning nozzle 52. Note that steps ST14 to ST15, which involve aspirating and ejecting the magnetic particles MB while they are collected, may be repeated multiple times.
• the magnet 45 is gradually moved downward along the wall surface of the reaction cell R0 from the state in which the magnetic particles MB are magnetically collected in a straight line on the inner wall surface of the reaction cell R0.
• the magnetic particles MB move downward, and change from the state in which they were magnetically collected in a straight line (see step ST16) to a state in which they are magnetically collected in a dot pattern on the inner wall surface near the bottom of the reaction cell R0 (see step ST18).
• step ST18 the movement of the magnet 45 is stopped with the magnetic particles MB collected in a dot shape, and then, as shown in step ST19, the cleaning nozzle 52 aspirates the cleaning solution 50 in the reaction cell R0. At this time, the magnetic particles MB are collected in a dot shape at a position offset from the tip of the nozzle 52 so that the nozzle 52 does not aspirate the magnetic particles MB.
• the magnet 45 is moved to a retracted position as shown in step ST20. This ensures that the magnetic field from the magnet 45 does not affect the reaction cell R0.
• the cleaning solution 50 is then ejected from the nozzle 52 into the reaction cell R0. This causes the magnetic particles MB to be dispersed in the cleaning solution 50 as shown in step ST21.
• the reference numerals 50 and 32 are written together in step ST21 of FIG. 8, indicating that in this step, the cleaning solution 50 is the liquid 32 in which the magnetic particles MB are dispersed.
• the liquid 32 is a general term for the reagent or the like in which the magnetic particles MB are dispersed, and in step 21 of FIG. 8, the cleaning solution 50 corresponds to the liquid 32.
• the above steps ST11 to ST21 are repeated multiple times, for example, about three times. B/F separation is performed by this cleaning processing step.
• the magnetic collection unit 40 has a length C equal to or greater than the distance D from the liquid surface Z1 of the suspension 30 in the reaction cell R0 to the bottom surface Z2 of the reaction cell R0, and includes a magnetic field generating section 42 including a magnet 45 that simultaneously generates a magnetic field in the range from the liquid surface Z1 to the bottom surface Z2. Therefore, when the magnet 45 is arranged so that the length of the magnet 45 is aligned with the depth direction in the reaction cell R0 and the magnet 45 is positioned in the range from the liquid surface Z1 to the bottom surface Z2 of the suspension 30, the magnet 45 can simultaneously generate a magnetic field in the range from the liquid surface Z1 to the bottom surface Z2 in the reaction cell R0.
• the magnetic particles MB in the suspension 30 When a magnet with a length shorter than the distance D between the liquid surface Z1 and the bottom surface Z2 is used, at least a part of the magnetic particles MB in the suspension 30 will move in an oblique direction intersecting with the horizontal direction to reach the inner wall surface. In contrast, in this embodiment, the magnetic particles MB in the suspension 30 are collected by moving in a substantially horizontal direction in the reaction cell R0, so that the magnetic particles MB reach the inner wall surface in the shortest distance. Therefore, magnetic particles MB can be collected very quickly.
• the magnetic collection unit 40 also includes a moving mechanism 44, which moves the magnetic field generating unit 42 (here, the magnet 45) in the depth direction from the liquid surface Z1 toward the bottom surface Z2, from a state in which the upper end 45a of the magnet 45 is positioned at or above the liquid surface Z1. This allows the magnetic particles MB that are magnetically collected linearly in the length direction of the magnet 45 to be magnetically collected in a dot shape near the bottom surface of the reaction cell R0.
• a moving mechanism 44 which moves the magnetic field generating unit 42 (here, the magnet 45) in the depth direction from the liquid surface Z1 toward the bottom surface Z2, from a state in which the upper end 45a of the magnet 45 is positioned at or above the liquid surface Z1. This allows the magnetic particles MB that are magnetically collected linearly in the length direction of the magnet 45 to be magnetically collected in a dot shape near the bottom surface of the reaction cell R0.
• the dispersibility of the magnetic particles MB can be improved when the magnetic particles MB are redispersed in the liquid. If the dispersibility of the magnetic particles MB is improved, the cleaning ability of the magnetic particles MB is improved, and B/F separation can be performed more accurately.
• the inspection device 10 by using such a magnetic flux collection unit 40, it is possible to reduce noise by improving the accuracy of B/F separation, which in turn makes it possible to suppress the occurrence of measurement errors and obtain highly accurate measurement results.
• the moving mechanism 44 is configured to magnetically collect the magnetic particles MB in a line, change the magnetic collection form to a dot, and furthermore, to be capable of moving only in one axial direction (up and down) to the retracted position.
• the form of the moving mechanism 44 is not limited to this, and it may be configured to be capable of moving in the up and down direction within a range in which the magnetic collection form of the magnetic particles MB can be changed from a line to a dot, and furthermore, to be capable of moving in a direction moving horizontally away from the reaction cell R0.
• the retracted position may be a position horizontally away from the reaction cell R0 where the magnetic field from the magnetic field generating unit 42 does not affect the reaction cell R0.
• the magnetic field generating unit 42 is arranged with the magnetic pole 45s of the magnet 45 in contact with the side surface of the reaction cell R0, and the moving mechanism 44 moves the magnetic field generating unit 42 in the depth direction with the magnetic pole 45s of the magnet 45 in contact with the side surface of the reaction cell R0.
• the magnetic field generating unit 42 may be arranged close to the side surface of the reaction cell R0 without the magnetic pole 45s of the magnet 45 in contact with the side surface of the reaction cell R0.
• the strength of the magnetic field generated in the reaction cell R0 can be increased, the magnetic flux collecting effect can be improved, and more rapid magnetic flux collecting can be achieved.
• the magnetic particles MB can smoothly follow the magnet 45 when changing the magnetic flux collecting form from linear to dot-like.
• the magnet provided in the magnetic field generating unit 42 is not limited to a permanent magnet, and may be an electromagnet. If an electromagnet is used, the magnetic field generated in the reaction cell R0 can be turned on and off by turning the current on and off, so that the magnet can be moved to change the magnetic collection form from a line to a point, and after the liquid has been sucked in, the current can be turned off, eliminating the need to move the magnet to a retracted position. On the other hand, if a permanent magnet is used, no power is required to generate a magnetic field, and wiring, etc. can be simplified.
• the magnetic field generating unit 42 includes only one magnet 45, and one of the magnetic poles 45s is positioned to face the side of the reaction cell R0 to collect magnetic flux.
• the magnetic flux collecting unit of the present disclosure is not limited to a configuration including only one magnet 45.
• FIG. 9 shows a modified magnetic field generating unit 42A.
• FIG. 10A is a view of the reaction cell R0 and magnetic field generating unit 42A in FIG. 9 as seen from the direction XA
• FIG. 10B is a view of the reaction cell R0 and magnetic field generating unit 42A as seen from the direction XB.
• the magnetic field generating unit 42A of the modified example includes two magnets 45A, 45B and a non-magnetic body 48 sandwiched between the two magnets 45A, 45B.
• the two magnets 45A, 45B are arranged with the faces without magnetic poles facing each other across the non-magnetic body 48.
• the two magnets 45A, 45B are arranged with their different magnetic poles facing the reaction cell R0.
• the magnet 45A is arranged with the magnetic pole 45As, which is the S pole, facing the side surface of the reaction cell R0
• the magnet 45B is arranged with the magnetic pole 45Bn, which is the N pole, facing the side surface of the reaction cell R0.
• the magnets 45A and 45B in this example like the magnet 45, have a length C that is at least equal to the distance D from the liquid level Z1 of the suspension 30 in the reaction cell R0 to the bottom surface Z2 of the reaction cell R0.
• the magnets 45A and 45B are positioned so that their lengthwise direction is aligned with the depth direction in the reaction cell R0, and the magnets 45A and 45B are positioned in the range from the liquid level Z1 to the bottom surface Z2 of the suspension 30.
• the upper end 45Aa of the magnet 45A and the upper end 45Ba of the magnet 45B are each located above the liquid level Z1.
• the lower end 45Ab of the magnet 45A and the lower end 45Bb of the magnet 45B are each located below the bottom surface Z2.
• the non-magnetic material 48 has a flat plate shape, and an aluminum plate made of aluminum is suitable.
• a magnetic field shown diagrammatically by magnetic field lines 49, is generated in reaction cell R0 by magnetic field generator 42A.
• Magnetic particles MB in suspension 30 in reaction cell R0 are attracted to magnets 45A and 45B, move horizontally in the direction of the arrow, and are collected on the inner wall surface of reaction cell R0.
• magnetic particles MB are collected linearly along magnets 45A and 45B. In other words, magnetic particles MB are collected in two straight lines on the inner wall surface of reaction cell R0.
• the magnetic field strength can be improved, and the magnetic collecting force can be improved.
• magnetic field lines 49 in FIG. 10A by having different magnetic poles 45As and 45Bn adjacent to each other with the non-magnetic body 48 in between, it is possible to form two straight lines with high magnetic field strength, and therefore magnetic particles can be collected in two straight lines.
• the magnetic particles MB can be collected more quickly than when only one magnet 45 is provided.
• the thickness t2 of the collection of collected magnetic particles MB can be made thinner than when the magnetic particles MB are collected in a single straight line (see FIG. 11A), and loss of magnetic particles MB when the nozzle 52 sucks the liquid 32 can be suppressed.
• FIG. 11A is a top view showing the state in which the nozzle 52 is inserted into the reaction cell R0 in which the magnetic particles MB are collected in a single straight line as shown in FIG. 6A.
• FIG. 11B is a top view showing the state in which the nozzle 52 is inserted into the reaction cell R0 in which the magnetic particles MB are collected in two straight lines as shown in FIG. 10A.
• the nozzle 52 is shown in cross section.
• the thickness t2 of the assembly of magnetic particles MB magnetized in two straight lines in the reaction cell R0 shown in FIG. 11B is thinner than the thickness t1 of the assembly of magnetic particles MB magnetized in one straight line in the reaction cell R0 shown in FIG. 11A.
• the thicknesses t1 and t2 of the assembly of magnetic particles MB are the distances between the inner wall surface corresponding to the side of the reaction cell R0 to which the magnet 45 or magnets 45A and 45B are abutted, and the position of the assembly of magnetic particles MB closest to the center of the reaction cell R0.
• the magnetic particles MB When the magnetic particles MB come into contact with the nozzle tip and adhere to the tip of the nozzle 52 when the nozzle 52 is inserted, and/or when the distance from the tip of the nozzle 52 to the aggregate of magnetic particles MB is close during suction, the magnetic particles MB are more easily sucked in when the nozzle 52 sucks the liquid 32.
• the thickness of the aggregate of magnetic particles MB becomes thinner (t1>t2).
• FIG. 12A is a diagram showing the case where the magnetic collection form is changed from linear to dotted by a magnetic field generating unit 42 having only one magnet 45
• FIG. 12B is a diagram showing the case where the magnetic collection form is changed from linear to dotted by a magnetic field generating unit 42A having two magnets 45A, 45B.
• the thickness t22 of the aggregate of magnetic particles MB from the inner wall surface of the reaction cell R0 in FIG. 12B is thinner than the thickness t12 of the aggregate of magnetic particles MB from the inner wall surface of the reaction cell R0 in FIG. 12A.
• the magnetic particles are collected in two straight lines by two magnets 45A, 45B, so when the magnetic collection form is changed from linear to dotted, the magnetic particles are collected in two dotted shapes. Therefore, the thickness t22 of the aggregate collected in one dotted shape can be thinner than when one magnet 45 is used.
• the thinner the thickness t22 of the collection of magnetic particles MB the more the tip of the nozzle 52 can be separated from the magnetic particles MB. Therefore, when magnetic particles MB are collected by the magnetic field generating unit 42A, the effect of suppressing particle loss caused by the magnetic particles MB being sucked by the nozzle 52 during suction is higher than when magnetic particles MB are collected by the magnetic field generating unit 42.
• the magnetic field generating unit 42A of the modified example is supported by a support portion 46A (see FIG. 13), and is moved vertically together with the support portion 46A by the moving mechanism 44, similar to the magnetic field generating unit 42 shown in FIG. 4.
• the magnetic field generating unit 42A is provided with a shield plate 60 that blocks magnetic force at the end in the arrangement direction of the two magnets 45A, 45B.
• the shield plate 60 is provided on the outside of the support unit 46A.
• the reaction cell R0 is transported by the transport mechanism 14 in the transport direction indicated by the arrow in FIG. 13.
• the transport mechanism 14 can transport multiple reaction cells R0 simultaneously, and as shown in FIG. 13, multiple reaction cells R0 are transported adjacent to each other.
• each processing unit is arranged in order along the transport direction, so when the magnetic field generating unit 42A generates a magnetic field for B/F separation for the reaction cell R0 indicated by the solid line in FIG. 13, the reaction cell R0 indicated by the dashed line arranged adjacently may be undergoing a process that requires the magnetic particles MB to be dispersed in the liquid.
• Examples of processes that require the magnetic particles MB to be dispersed in the liquid include the first reaction process, the second reaction process, and the luminescent reagent dispensing process.
• the magnetic field generated by the magnetic field generating unit 42A reaches the reaction cell R0 in which such a process that requires the magnetic particles MB to be dispersed in the liquid is being performed, the magnetic particles MB may become biased in the reaction cell R0, and the dispersibility may decrease.
• a shield plate 60 it is possible to suppress the generation of a magnetic field in the reaction cell R0 adjacent to the reaction cell R0 in which the magnetic field is to be generated.
• a shield plate 60 it is possible to reduce adverse effects such as impairing the dispersibility of magnetic particles MB in the reaction cell R0 adjacent to the reaction cell R0 in which the magnetic field is to be generated.
• the magnetic flux collecting unit of the present disclosure may have multiple magnetic field generating units 42 (or 42A) arranged in parallel so that magnetic fields can be generated simultaneously for multiple reaction cells R0.
• Figure 14 shows a magnetic flux collecting unit 140 equipped with multiple magnetic field generating units 42A.
• the magnetic flux collecting unit 140 shown in FIG. 14 has three magnetic field generating units 42A arranged in parallel.
• the magnetic field generating units 42A1, 42A2, 42A3 and the magnetic field generating unit 42A are denoted by sub-reference numbers 1 to 3. When there is no need to distinguish between them, they are simply referred to as magnetic field generating unit 42A.
• the three magnetic field generating units 42A are arranged so that adjacent magnets between adjacent magnetic field generating units 42A have different magnetic poles adjacent to each other.
• magnet 45B arranged on the magnetic field generating unit 42A2 side of magnetic field generating unit 42A1 and magnet 45A arranged on the magnetic field generating unit 42A1 side of magnetic field generating unit 42A2 are arranged so that their south poles and north poles are adjacent to each other.
• Each of the magnetic field generating units 42A is supported by a support portion 46A, and the moving mechanism 44A is configured to be able to move each of the three magnetic field generating units 42A together with its corresponding support portion 46A.
• the moving mechanism 44A moves the three magnetic field generating units 42A as a unit.
• the moving mechanism 44A is configured, for example, by a linear actuator, similar to the moving mechanism 44 described above.
• the transport mechanism 14 transports multiple reaction cells R0 simultaneously, and the multiple reaction cells R0 are processed in parallel in each processing unit.
• the cleaning process (steps ST11 to ST21) described using FIG. 7 and FIG. 8 is repeated, for example, three times.
• the cleaning processing unit 22 is provided from position PS1 to position PS3, and a cleaning process is possible at each of positions PS1, PS2, and PS3, cleaning processes can be performed simultaneously on three reaction cells R0.
• one reaction cell R0 at position PS1 is given a sub-reference number 1 and is shown as reaction cell R01.
• the reaction cell R01 is moved to position PS2, a second cleaning process is performed, and the reaction cell R01 is further moved to position PS3, and a third cleaning process is performed.
• the system is configured to transport the substrate sequentially from position PS1 to position PS3 and perform cleaning processing at each position, processing can be performed efficiently.
• the three magnetic field generating units 42A can be driven as a unit by a single moving mechanism 44A to collect magnetic flux.
• the three magnetic field generating units 42A are driven as a unit by a single moving mechanism 44A, so costs can be reduced compared to when a moving mechanism is provided individually for each of positions PS1 to PS3.
• the magnetic collection unit 140 also includes a shield plate 60 for blocking magnetic force at the end of the arrangement direction of the multiple magnetic field generating units 42A arranged in parallel. If the shield plate 60 is not provided as in FIG. 14, the magnetic field generated by the magnetic field generating unit 42A may affect the reaction cell R0 located outside the cleaning processing unit 22 and located next to the reaction cell R0 to be collected. In that case, as shown in FIG. 14, the magnetic particles MB will be biased in the reaction cell R0 located next to the reaction cell R0 to be collected.
• by providing the shield plate 60 it is possible to suppress the influence of the magnetic field generated by the magnetic field generating unit 42A on the reaction cell R0 that is not the target of magnetic collection. In other words, by providing the shield plate 60, it is possible to suppress the decrease in the dispersibility of the magnetic particles MB in the liquid in the reaction cell R0 that is not the target of magnetic collection, that is, the reaction cell R0 located outside the cleaning processing unit 22.
• a magnetic collection unit In a testing device using magnetic particles as a solid phase in an antigen-antibody reaction, a magnetic collection unit generates a magnetic field inside a reaction cell containing a suspension containing magnetic particles during a washing process for separating a labeled substance bound to a test target substance from a labeled substance not bound to the test target substance, and magnetically collects the magnetic particles in the suspension on an inner wall surface of the reaction cell,
• a magnetic field generating unit including a magnet having a length equal to or greater than the distance from the liquid surface of the suspension in a reaction cell to the bottom surface of the reaction cell, and generating a magnetic field simultaneously in the range from the liquid surface to the bottom surface, and a moving mechanism for moving the magnetic field generating unit in a depth direction from the liquid surface toward the bottom surface while the upper end of the magnet is positioned at or above the liquid surface.
• the magnetic field generating unit is disposed with the magnetic poles of the magnet in contact with the side surface of the reaction cell, 2.
• (Appendix 3) 3.
• (Appendix 4) 3.
• the magnetic field generating unit includes two magnets having a length and a non-magnetic body, the two magnets are arranged with their faces that do not have a magnetic pole facing each other across the non-magnetic body, and the two magnets are arranged with their different magnetic poles facing the reaction cell.
• Appendix 6 6.
• a plurality of magnetic field generating units are arranged in parallel, 7.
• the magnetic flux collecting unit according to claim 7, further comprising a shield plate for blocking magnetic force at an end in an arrangement direction of the plurality of magnetic field generating units arranged in parallel.
• a cleaning processing unit including the magnetic flux collecting unit according to any one of Supplementary Note 1 to Supplementary Note 8 and performing a cleaning processing;
• a detection unit that detects light caused by a labeling substance;
• the cleaning processing section and the detection section are arranged along a transport direction of the reaction cell.

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