JP2008224600A - Reaction quantity measurement method - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a reaction quantity measurement method for efficiently and sufficiently stirring a sample and a reagent when the reaction quantity of the sample is measured by using a solid phase carrier, and accurately measuring the reaction quantity of the sample. <P>SOLUTION: The reaction quantity measurement method of the invention introduces carrier magnetic particles, the sample, and the reaction reagent into a retention zone, stirs a reaction mixture by generating surface acoustic waves in the retention zone, continuously applies a magnetic field to the retention zone, and discharges the reaction mixture from the retention zone. The reaction quantity measurement method introduces a cleaning reagent into the retention zone, deactivates the magnetic field, stirs the cleaning reagent by generating the surface acoustic waves in the retention zone, continuously applies the magnetic field to the retention zone, and discharges the cleaning reagent from the retention zone. The reaction quantity measurement method introduces a measurement reagent into the retention zone, deactivates the magnetic field, stirs the measurement reagent by generating the surface acoustic waves in the retention zone, and measures the reaction quantity of the sample by considering the stirred measurement reagent and carrier magnetic particles as an object to be measured. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a reaction amount measuring method for measuring a reaction amount of a substance.

  Patent Document 1 is disclosed as a conventional technique for measuring a reaction amount of a substance. Patent Document 1 discloses an immunoassay device using an introduction part or a microchannel inflow part, a microchannel reaction tank part, and solid particles. Specifically, in Patent Document 1, a microchannel reaction tank part having a longitudinal cross-sectional area larger than the diameter of the solid fine particles, an introduction part or a microchannel inflow part for introducing the antigen and labeled antibody to the microchannel reaction tank part, A substrate made of glass, silicon, or the like provided with a labeled antibody / first antibody / washing liquid injection hole, a waste liquid, and a microchannel separation part having a vertical cross-sectional area smaller than the diameter of the solid fine particles (FIG. 1 of Patent Document 1) The solid particles as the reaction solid phase are introduced into the microchannel reaction vessel using the reference and the antigen and labeled antibody introduced from the introduction part or the microchannel inflow part, and if necessary, the antibody introduced from the microchannel inflow part. Reaction is performed on solid particles, unreacted substances are separated by a microchannel separator, and analyzed by photothermal conversion analysis. To.

  However, since Patent Document 1 does not disclose anything about the method of stirring the antigen, labeled antibody and solid fine particles introduced into the microchannel reaction vessel, the stirring of the antigen, labeled antibody and solid fine particles is insufficient. In Patent Document 1, the target chemical reaction and the solid fine particles cannot be sufficiently washed, and the measurement accuracy of the reaction amount may be reduced, for example, the accurate reaction amount cannot be measured. I can't.

  Therefore, Patent Document 2 is disclosed as a conventional technique related to liquid mixing and stirring. Patent Document 2 discloses a technique related to mixing / stirring of a small amount of liquid such as a droplet by surface acoustic wave (SAW).

JP 2001-4628 A JP-T-2004-534633

  However, Patent Document 2 discloses a technique for analyzing the surface adhesion force of an object such as a cell or bacteria on the surface using a mixing / stirring technique based on SAW, but it is not suitable for solid materials such as beads and chemical-permeable devices. Since no technology related to the analysis of biological samples using a phase carrier is disclosed, the above-mentioned fear in the case of using a solid phase carrier that the measurement accuracy of the reaction amount is lowered due to insufficient stirring. There was a problem that it still could not cope.

  The present invention has been made in view of the above problems, and can efficiently and sufficiently stir the sample and the reagent when measuring the reaction amount of the sample using the solid phase carrier. It is an object of the present invention to provide a reaction amount measurement method capable of measuring the reaction amount of a sample with high accuracy.

  In order to solve the above-described problems and achieve the object, a reaction amount measuring method according to claim 1 according to the present invention includes a holding section for holding a substance, a transfer means for transferring the substance, A surface acoustic wave stirring means for stirring the substance by generating a surface acoustic wave for the holding section; a magnetic field control means for generating a magnetic field for the holding section; and releasing the generated magnetic field; A reaction amount measuring method executed by a reaction amount measuring device equipped with a reaction amount measuring means for measuring a reaction amount of a substance, wherein the carrier magnetic particles, which are particles having magnetism and carrying an antibody or a nucleic acid probe, a sample And a reaction stage introduction step for introducing the reaction reagent into the holding section by the transfer means, and the carrier magnetic particles introduced in the reaction stage introduction step, the reaction mixture comprising the sample and the reaction reagent are retained. The surface acoustic wave is agitated by the reaction stage stirring step and the reaction stage stirring step of stirring the reaction mixture in the holding section by generating the surface acoustic wave with the surface acoustic wave stirring means for the holding section A reaction stage magnetic field application process in which the magnetic field control means continuously applies the magnetic field to the holding section holding the reaction mixture, and the magnetic field is applied in the reaction stage magnetic field application process. A reaction stage discharge process for discharging the reaction mixture from the holding section by the transfer means, and a cleaning stage introduction process for introducing a cleaning reagent by the transfer means to the holding section after the reaction mixture is discharged in the reaction stage discharge process. And the magnetic field continuously applied to the holding section holding the cleaning reagent and the carrier magnetic particles introduced in the cleaning stage introducing step. By generating the surface acoustic wave by the surface acoustic wave agitating means for the holding section in a state where the magnetic field is released in the cleaning stage magnetic field releasing step, the cleaning stage magnetic field releasing step that is released by the control means, A washing step stirring process for stirring the cleaning reagent in the holding section, and the magnetic field control means continuously applies the magnetic field to the holding section holding the cleaning reagent stirred in the washing step stirring process. A cleaning stage magnetic field applying process, a cleaning stage discharging process for discharging the cleaning reagent from the holding section in a state where the magnetic field is applied in the cleaning stage magnetic field applying process, and a cleaning stage discharging process. A measurement stage introduction step for introducing a measurement reagent by the transfer means into the holding section after discharging the cleaning reagent, the measurement reagent introduced in the measurement stage introduction step, and the A measurement stage magnetic field release step for releasing the magnetic field continuously applied to the holding section holding the carrier magnetic particles by the magnetic field control means, and the magnetic field is released in the measurement stage magnetic field release step. The surface acoustic wave stirring means generates the surface acoustic wave with respect to the holding section in a state where the measurement reagent is stirred in the measurement stage stirring process and the measurement stage stirring process in which the measurement reagent is stirred in the holding section. And a reaction amount measuring step of measuring the reaction amount of the sample by the reaction amount measuring means using the measurement reagent and the carrier magnetic particles as measurement targets.

  Further, the reaction amount measurement method according to claim 2 according to the present invention is the reaction amount measurement method according to claim 1, wherein at least the washing step introduction step, the washing step magnetic field release step, the washing step stirring step, The cleaning stage magnetic field application process and the cleaning stage discharge process are repeatedly performed a predetermined number of times, and the measurement stage introduction process is performed to the holding section after the cleaning reagent is discharged in the last cleaning stage discharge process repeatedly performed. The measuring reagent is introduced by a transfer means.

  The reaction amount measurement method according to claim 3 of the present invention is the reaction amount measurement method according to claim 1 or 2, wherein the measurement reagent and the carrier magnetic particles stirred in the measurement stage stirring step are retained. A measurement stage magnetic field application step for continuously applying the magnetic field to the holding section being applied by the magnetic field control means, and the transfer from the holding section in a state where the magnetic field is applied in the measurement stage magnetic field application step. A measurement stage discharge step of discharging the measurement reagent by means, wherein the reaction amount measurement step is left in the holding magnetic particles remaining in the holding section after discharging the measurement reagent in the measurement stage discharge step Is measured, and the reaction amount of the sample is measured by the reaction amount measuring means.

  According to a fourth aspect of the present invention, there is provided a reaction amount measuring method comprising: a holding section for holding a substance; and a member having a property of transmitting the substance and having a hole of a predetermined size. A permeable member disposed inside or near, a transfer means for transferring the substance, a surface acoustic wave stirring means for stirring the substance by generating a surface acoustic wave with respect to the holding section, and A reaction amount measuring method executed by a reaction amount measuring device comprising a reaction amount measuring means for measuring a reaction amount, wherein the size of the hole of the transparent member is a fluorescent dye or a semiconductor quantum dot A reaction step in which the carrier-encoded particles, the sample and the reaction reagent are introduced into the holding section by the transfer means, which is smaller than the size of the carrier-encoded particles, which are encoded particles carrying an antibody or nucleic acid probe The surface acoustic wave is applied to the holding section holding the reaction mixture composed of the carrier-encoded particles introduced in the reaction step introduction step and the sample and the reaction reagent by the surface acoustic wave stirring means. A reaction stage stirring step of stirring the reaction mixture in the holding section, and the transfer means from the holding section holding the reaction mixture stirred in the reaction stage stirring step. A reaction stage discharging process for discharging through the permeable member, a cleaning stage introducing process for introducing a cleaning reagent by the transfer means into the holding section after discharging the reaction mixture in the reaction stage discharging process, and the cleaning The surface acoustic wave is agitated by the surface acoustic wave agitation means for the holding section holding the cleaning reagent and the carrier-encoded particles introduced in the step introduction step. The cleaning reagent is agitated by the transfer means from the holding compartment holding the cleaning reagent stirred in the washing stage stirring step. A cleaning stage discharging process for discharging through the permeable member, a measuring stage introducing process for introducing the measuring reagent into the holding section after discharging the cleaning reagent in the cleaning stage discharging process, and the measurement By generating the surface acoustic wave with the surface acoustic wave stirring means for the holding section holding the measurement reagent introduced in the step introduction step and the carrier-encoded particles, the measurement reagent in the holding section And measuring the reaction amount of the sample with the measurement reagent and the carrier-encoded particles stirred in the measurement step stirring step. And a reaction amount measuring step of measuring by the reaction amount measuring means together with the position.

  The reaction amount measurement method according to claim 5 according to the present invention is the reaction amount measurement method according to claim 4, wherein the measurement reagent and the carrier-encoded particles stirred in the measurement stage stirring step are retained. A measuring stage discharging step of discharging the measuring reagent from the holding section by the transfer means through the permeable member, wherein the reaction amount measuring step discharges the measuring reagent in the measuring stage discharging step Using the carrier-encoded particles left in the later holding section as the measurement object, the reaction amount of the sample is measured by the reaction amount measuring unit together with the position of the sample.

  The reaction amount measuring method according to claim 6 of the present invention includes a holding section for holding a substance, and a member having a property of transmitting the substance and carrying an antibody or a nucleic acid probe. A permeable carrier member disposed in or near the inside, a transfer means for transferring the substance, a surface acoustic wave stirring means for stirring the substance by generating a surface acoustic wave for the holding section, A reaction amount measuring method that is executed by a reaction amount measuring device equipped with a reaction amount measuring device that measures a reaction amount, wherein a sample and a reaction reagent are introduced into the holding compartment by the transfer means; and By generating the surface acoustic wave with the surface acoustic wave stirring means for the holding section holding the reaction mixture composed of the sample and the reaction reagent introduced in the reaction stage introduction step, A reaction stage stirring step of stirring the reaction mixture in the holding section; and the permeable carrier member by the transfer means from the holding section holding the reaction mixture stirred in the reaction stage stirring step. A reaction stage discharge process for discharging through the reaction stage, a cleaning stage introduction process for introducing a cleaning reagent into the holding section after discharging the reaction mixture in the reaction stage discharge process, and a cleaning stage introduction process. A cleaning step stirring step of stirring the cleaning reagent in the holding section by generating the surface acoustic wave by the surface acoustic wave stirring means for the holding section holding the introduced cleaning reagent; A cleaning stage discharge for discharging the cleaning reagent through the permeable carrier member by the transfer means from the holding section holding the cleaning reagent stirred in the cleaning stage stirring step. Holding the measurement reagent introduced in the measurement stage introduction process, a measurement stage introduction process for introducing the measurement reagent into the holding section after the cleaning reagent is discharged in the washing stage discharge process, and the transfer means. Generating the surface acoustic wave with the surface acoustic wave agitating means for the holding section, and stirring the measurement reagent in the holding section, and stirring the measurement reagent in the measurement stage stirring process And a reaction amount measuring step of measuring the reaction amount of the sample together with the position of the sample by the reaction amount measuring means using the measurement reagent and the permeable carrier member as a measurement object.

  The reaction amount measurement method according to claim 7 of the present invention is the reaction amount measurement method according to claim 6, wherein the measurement reagent stirred in the measurement stage stirring step is held from the holding section. The method further includes a measurement step discharge step of discharging the measurement reagent through the permeable carrier member by the transfer means, and the reaction amount measurement step includes the permeability after the measurement reagent is discharged in the measurement step discharge step. Using the carrier member as the measurement object, the reaction amount of the sample is measured by the reaction amount measuring means together with the position of the sample.

  The reaction amount measurement method according to claim 8 of the present invention is the reaction amount measurement method according to any one of claims 4 to 7, wherein at least the washing step introduction step, the washing step stirring step, and The cleaning stage discharge step is repeatedly performed a predetermined number of times, and the measurement stage introduction step is configured to transfer the measurement reagent to the holding section after the cleaning reagent is discharged in the last repeatedly performed cleaning stage discharge step. It is characterized by introducing.

  The reaction amount measurement method according to claim 9 according to the present invention is the reaction amount measurement method according to any one of claims 1 to 8, wherein the holding section has hydrophilicity. To do.

  The reaction amount measurement method according to claim 10 of the present invention is the reaction amount measurement method according to any one of claims 1 to 9, wherein the reaction amount measurement device is discharged from the holding section. A storage compartment for storing the substance is provided in the vicinity of the holding compartment, and at least the reaction mixture is discharged to the storage compartment in the reaction stage discharge step, and the cleaning reagent is stored in the washing stage discharge step. It is characterized by discharging to the compartment.

  The reaction amount measurement method according to claim 11 according to the present invention is the reaction amount measurement method according to claim 10, wherein the reaction amount measurement device is configured such that the substance stored in the storage compartment holds the substance. A backflow prevention means for preventing backflow to the compartment is provided on a transport path when transporting the substance from the holding compartment to the storage compartment.

  The reaction amount measurement method according to claim 12 of the present invention is the reaction amount measurement method according to claim 10 or 11, wherein the reaction amount measurement device is configured such that the internal pressure of the storage compartment is higher than atmospheric pressure. A pressure adjusting means for adjusting the pressure so as not to increase is provided.

  The reaction amount measurement method according to claim 13 according to the present invention is the reaction amount measurement method according to any one of claims 10 to 12, wherein the storage compartment holds the substance therein. A porous holding member, which is a porous member having the property described above, is provided.

  The reaction amount measurement method according to claim 14 of the present invention is the reaction amount measurement method according to any one of claims 1 to 13, wherein the reaction amount measurement device is introduced into the holding section. A storage section for storing the substance is provided in the vicinity of the holding section. In the reaction stage introduction step, the reaction reagent is introduced from the storage section, and in the cleaning stage introduction process, the cleaning reagent is removed from the storage section. The measuring reagent is introduced from the storage section in the measuring step introducing step.

  The reaction amount measurement method according to claim 15 of the present invention is the reaction amount measurement method according to claim 14, wherein the reaction amount measurement device includes a slit having a predetermined volume and a hydrophilic inner wall surface. The reaction reagent is introduced between the storage compartment and the holding compartment, and the reaction reagent is introduced from the storage compartment through the slit in the reaction stage introduction process, and the cleaning reagent is introduced from the storage compartment in the cleaning stage introduction process. The measurement reagent is introduced through the slit, and the measurement reagent is introduced from the storage compartment through the slit in the measurement stage introduction step.

  The reaction amount measurement method according to claim 16 of the present invention is the reaction amount measurement method according to claim 15, wherein the reaction amount measurement device is connected to the storage section and stored in the storage section. A suction port for sucking the substance that is placed between the slit and the storage compartment, and the storage compartment is a separate cartridge from the holding compartment and has a penetrable partition wall The suction port passes through the partition wall and is connected to the holding section through the suction port. In the reaction stage introduction step, the reaction reagent is introduced from the storage section through the suction port and the slit. In the cleaning stage introduction step, the cleaning reagent is introduced from the storage compartment through the suction port and the slit, and in the measurement stage introduction step, the measurement reagent is provided in the preparation stage. And introducing through said suction port and said slit from the compartment.

  The reaction amount measurement method according to claim 17 according to the present invention is the reaction amount measurement method according to any one of claims 1 to 16, wherein the reaction amount measurement means calculates the reaction amount of the substance. It is characterized by optical measurement by chemiluminescence, fluorescence, turbidity or colorimetry.

  The reaction amount measurement method according to claim 18 of the present invention is the reaction amount measurement method according to any one of claims 1 to 17, wherein the reaction amount measurement device is a set of the reaction amount measurement device. Is provided with a plurality of sets.

  According to the present invention, carrier magnetic particles, which are magnetized particles carrying antibodies or nucleic acid probes, a sample and a reaction reagent are transported (specifically, surface acoustic waves, suction / discharge, pressurization, etc.) The surface acoustic wave is generated by the surface acoustic wave stirring means with respect to the holding compartment holding the introduced carrier magnetic particles and the reaction mixture composed of the sample and the reaction reagent. Thus, the reaction mixture is stirred in the holding section, the magnetic field is continuously applied to the holding section holding the stirred reaction mixture by the magnetic field control means, and the holding section in a state where the magnetic field is applied. The reaction mixture is discharged from the transfer means by the transfer means, the cleaning reagent is introduced into the holding section after the reaction mixture is discharged by the transfer means, and continuously with respect to the holding section holding the introduced cleaning reagent and carrier magnetic particles. The applied magnetic field is released by the magnetic field control means, and the surface acoustic wave is generated by the surface acoustic wave stirring means for the holding section in a state where the magnetic field is released, so that the cleaning reagent is stirred in the holding section. The magnetic field control means continuously applies a magnetic field to the holding section holding the stirred cleaning reagent, and the cleaning reagent is discharged from the holding section where the magnetic field is applied by the transfer means, and the cleaning reagent is discharged. Then, the measuring reagent is introduced into the holding section by the transfer means, the magnetic field continuously applied to the holding section holding the introduced measuring reagent and carrier magnetic particles is released by the magnetic field control means, and the magnetic field is A surface acoustic wave is generated by the surface acoustic wave agitating means for the holding compartment in the released state, and the measurement reagent is agitated in the holding compartment, and the agitated measurement reagent and carrier magnetic particles are used as measurement objects. Reaction amount Since it is measured by the reaction amount measurement means, it is possible to efficiently and sufficiently stir the sample and the reagent when measuring the reaction amount of the sample using the solid phase carrier, and as a result, measure the reaction amount of the sample with high accuracy. There is an effect that can be done.

  Further, according to the present invention, carrier-encoded particles, which are particles encoded with a fluorescent dye or a semiconductor quantum dot and carrying an antibody or a nucleic acid probe, a sample and a reaction reagent are transported (specifically, surface acoustic waves, Surface elasticity to the holding compartment that holds the reaction mixture consisting of the carrier-encoded particles and the sample and reaction reagent. The property that the reaction mixture is stirred in the holding section by generating surface acoustic waves by the wave stirring means, and the substance is permeated through the reaction mixture by the transfer means from the holding section holding the stirred reaction mixture. Is a member having a hole smaller than the size of the carrier-encoded particles, which is discharged through a permeable member disposed in or near the holding section, and the holding section after discharging the reaction mixture The cleaning reagent is introduced into the holding section by generating a surface acoustic wave with the surface acoustic wave agitating means for the holding section holding the introduced cleaning reagent and carrier-encoded particles. The reagent is agitated, the cleaning reagent is discharged from the holding section holding the stirred cleaning reagent by the transfer means through the permeable member, and the measuring reagent is introduced to the holding section after the cleaning reagent is discharged by the transfer means. Then, by generating a surface acoustic wave with the surface acoustic wave stirring means for the holding section holding the introduced measurement reagent and carrier-encoded particles, the measurement reagent is stirred in the holding section and stirred. Since the reaction amount of the sample is measured by the reaction amount measuring means together with the position of the sample with the reagent and carrier-encoded particles as measurement objects, the sample and the reagent are agitated when measuring the reaction amount of the sample using the solid phase carrier. You can make rates well enough, as a result, there is an effect that it is possible to measure the response of accurately sample. Further, in addition to the reaction amount of the sample, there is an effect that the two-dimensional position of the sample can be acquired.

  In addition, according to the present invention, the sample and the reaction reagent are introduced into the holding section by a transfer means (specifically, a means for transferring a substance by a transfer force such as surface acoustic wave, suction / discharge, pressurization, etc.) The surface acoustic wave is generated by the surface acoustic wave stirring means for the holding section holding the reaction mixture composed of the sample and the reaction reagent, and the reaction mixture is stirred in the holding section, and the stirred reaction mixture is The reaction mixture is discharged from the holding section held by the transfer means through a permeable carrier member that is a member that has a property of permeating the substance and supports an antibody or a nucleic acid probe and is arranged in or near the holding section. The cleaning reagent is introduced into the holding section after discharging the reaction mixture by the transfer means, and the surface acoustic wave is generated by the surface acoustic wave stirring means in the holding section holding the introduced cleaning reagent. The cleaning reagent is stirred in the holding section, the cleaning reagent is discharged from the holding section holding the stirred cleaning reagent through the permeable carrier member by the transfer means, and the cleaning reagent is discharged to the holding section The measuring reagent is introduced by the transfer means, and the surface acoustic wave is generated by the surface acoustic wave stirring means for the holding section holding the introduced measuring reagent, whereby the measuring reagent is stirred and stirred in the holding section. The measurement amount of the sample and the permeable carrier member are measured, and the reaction amount of the sample is measured by the reaction amount measuring means together with the position of the sample. Therefore, when measuring the reaction amount of the sample using the solid phase carrier, Stirring can be performed efficiently and sufficiently, and as a result, the reaction amount of the sample can be accurately measured. Further, in addition to the reaction amount of the sample, there is an effect that the two-dimensional position of the sample can be acquired.

  Embodiments of a reaction amount measuring method according to the present invention will be described below in detail with reference to the drawings. In addition, this invention is not limited by this Embodiment.

[Outline of the present invention]
First, the outline | summary of the reaction amount measuring method concerning this invention is demonstrated.
According to the reaction amount measurement method of the present invention, the following steps a1 to a13 are performed.
Step a1 (reaction stage introduction step): Carrier magnetic particles, which are particles having magnetism and carrying an antibody or a nucleic acid probe, a sample and a reaction reagent are transported (specifically, surface acoustic waves, suction / discharge, pressurization) The substance is introduced into the holding section by means of transferring the substance with a transfer force such as
Step a2 (reaction stage agitation step): The surface acoustic wave is generated by the surface acoustic wave agitation means for the retention compartment holding the introduced carrier magnetic particles and the reaction mixture composed of the sample and the reaction reagent. The reaction mixture is stirred at.
Step a3 (reaction stage magnetic field application step): A magnetic field is continuously applied to the holding section holding the stirred reaction mixture by the magnetic field control means.
Step a4 (reaction stage discharge step): The reaction mixture is discharged from the holding section in a state where a magnetic field is applied by the transfer means.
Step a5 (Washing stage introduction step): A washing reagent is introduced into the holding section after discharging the reaction mixture by a transfer means.
Step a6 (cleaning step magnetic field releasing step): The magnetic field continuously applied to the holding section holding the introduced cleaning reagent and carrier magnetic particles is released by the magnetic field control means.
Step a7 (Washing Step Stirring Step): A surface acoustic wave is generated by the surface acoustic wave stirring means for the holding section in a state where the magnetic field is released, thereby stirring the cleaning reagent in the holding section.
Step a8 (washing step magnetic field application step): A magnetic field is continuously applied to the holding section holding the stirred cleaning reagent by the magnetic field control means.
Step a9 (cleaning stage discharging step): The cleaning reagent is discharged by the transfer means from the holding section in a state where the magnetic field is applied.
Step a10 (measurement stage introduction step): The measurement reagent is introduced by the transfer means into the holding section after the cleaning reagent is discharged.
Step a11 (measurement stage magnetic field releasing step): The magnetic field continuously applied to the holding section holding the introduced measurement reagent and carrier magnetic particles is released by the magnetic field control means.
Step a12 (measuring step stirring step): A surface acoustic wave is generated by the surface acoustic wave stirring means with respect to the holding section in a state where the magnetic field is released, thereby stirring the measurement reagent in the holding section.
Step a13 (reaction amount measurement step): The reaction amount of the sample is measured by the reaction amount measurement means using the stirred measurement reagent and carrier magnetic particles as measurement targets.
As a result, the stirring and mixing of the sample and the reagent, and the removal of the reaction liquid or the cleaning liquid from the carrier magnetic particles pelletized by the application of magnetism are realized by the surface acoustic wave that conducts the bottom surface of the reaction chamber. The liquid can be efficiently and sufficiently removed, the analysis method is simple, and the analysis accuracy can be improved. Furthermore, the apparatus for the method can be simplified and further downsized.

  Moreover, according to the reaction amount measuring method of the present invention, at least the cleaning stage introduction process (process a5), the cleaning stage magnetic field release process (process a6), the cleaning stage stirring process (process a7), and the cleaning stage magnetic field application process (process) a8) and the cleaning stage discharging step (step a9) are repeatedly performed a predetermined number of times, and the measuring reagent is introduced into the holding section after the cleaning reagent is discharged in the last cleaning stage discharging step that has been repeatedly performed. Thereby, at least the carrier magnetic particles can be washed more sufficiently, and the measurement accuracy can be further improved.

  Further, according to the reaction amount measurement method of the present invention, the magnetic field is continuously applied to the holding section holding the stirred measurement reagent and the carrier magnetic particles by the magnetic field control means, and the magnetic field is applied. The measurement reagent is discharged from the holding section by the transfer means, and the reaction amount of the sample is measured by the reaction amount measurement means using the carrier magnetic particles remaining in the holding section after the measurement reagent is discharged as a measurement target. Thereby, the measurement sensitivity of the reaction amount can be increased. In addition, when measuring the reaction amount, the measurement reagent after the reaction is discharged and the carrier magnetic particles are held for measurement, so that the measurement can be performed with the position of the carrier magnetic particles fixed. Can be applied to measurements such as sensitization in which physical quantities such as chemiluminescence depending on the system are accumulated in the equipment, and the analysis accuracy can be further improved.

Moreover, according to the reaction amount measuring method according to the present invention, the following steps b1 to b9 are performed.
Step b1 (reaction step introduction step): carrier-encoded particles, which are particles encoded with a fluorescent dye or a semiconductor quantum dot and carrying an antibody or a nucleic acid probe, a sample, and a reaction reagent (for example, surface acoustic waves) The substance is introduced into the holding section by means of transferring the substance with a transfer force such as suction / discharge and pressurization.
Step b2 (reaction stage agitation step): The surface acoustic wave is generated by the surface acoustic wave agitation means for the holding compartment holding the introduced carrier-encoded particles and the reaction mixture composed of the sample and the reaction reagent, thereby holding the holding The reaction mixture is stirred in the compartment.
Step b3 (reaction stage discharge step): a member having a property that allows the substance to permeate the reaction mixture from the holding section holding the stirred reaction mixture, and has pores smaller than the size of the carrier-encoded particles. It discharges | emits through the permeable member arrange | positioned in the vicinity of a holding | maintenance division.
Step b4 (Washing stage introduction step): A washing reagent is introduced into the holding section after discharging the reaction mixture by a transfer means.
Step b5 (Washing Step Stirring Step): A surface acoustic wave is generated by the surface acoustic wave stirring means for the holding section holding the introduced cleaning reagent and carrier-encoded particles, so that the cleaning reagent is generated in the holding section. Stir.
Step b6 (washing stage discharging step): The cleaning reagent is discharged through the permeable member by the transfer means from the holding section holding the stirred cleaning reagent.
Step b7 (measurement stage introduction step): The measurement reagent is introduced by the transfer means into the holding section after the cleaning reagent is discharged.
Step b8 (measuring step stirring step): A surface acoustic wave is generated by the surface acoustic wave stirring means for the holding section holding the introduced measuring reagent and carrier-encoded particles, so that the measuring reagent in the holding section Stir.
Step b9 (reaction amount measurement step): Using the stirred measurement reagent and carrier-encoded particles as measurement targets, the reaction amount of the sample is measured together with the position of the sample by the reaction amount measuring means.
This makes it possible to separate unnecessary liquid from carrier-encoded particles using a carrier-encoded particle that can be identified by being encoded by a fluorescent dye or a semiconductor quantum dot. This can be done through the sex member. In addition, the carrier-encoded particles are not related to the magnetic material, and particles encoded by fluorescent dyes or semiconductor quantum dots for identifying the particles are used. Since the carrier-encoded particles are transported and removed by the elastic wave, and the carrier-encoded particles are captured by the permeable member and remain in the holding section, the sample and the reagent are not only sufficiently stirred and mixed by the surface elastic wave, but also the carrier-encoded particles. It is possible to sufficiently perform the cleaning, and the analysis accuracy can be improved. Furthermore, the apparatus for the method can be simplified and downsized.

  Further, according to the reaction amount measuring method of the present invention, the measuring reagent is discharged from the holding section holding the stirred measuring reagent and carrier-encoded particles through the permeable member by the transfer means, and the measuring reagent is removed. Using the carrier-encoded particles remaining in the holding section after discharge as a measurement target, the reaction amount of the sample is measured together with the position of the sample by the reaction amount measuring means. Thereby, the measurement sensitivity of the reaction amount can be increased. Also, when measuring the reaction amount, the measurement reagent after the reaction is discharged and the carrier-encoded particles are held on the permeable member, so that the position of the carrier-encoded particles is fixed. Measurement is possible, and it can be applied to measurement such as sensitization in which physical quantities such as chemiluminescence depending on the reaction amount are accumulated in the equipment, and the analysis accuracy can be further improved.

Moreover, according to the reaction amount measuring method concerning this invention, the following processes c1 to c9 are performed.
Step c1 (reaction stage introduction step): The sample and the reaction reagent are introduced into the holding section by a transfer means (specifically, a means for transferring a substance by a transfer force such as surface acoustic wave, suction / discharge, pressurization).
Step c2 (reaction stage stirring step): generating a surface acoustic wave by the surface acoustic wave stirring means for the holding section holding the reaction mixture composed of the introduced sample and the reaction reagent, thereby causing the reaction in the holding section Stir the mixture.
Step c3 (reaction stage discharge step): The reaction mixture is transferred from the holding section holding the stirred reaction mixture by a transfer means, and is a member that has the property of permeating the substance and supports the antibody or nucleic acid probe. Or it discharges | emits through the permeable support | carrier member arrange | positioned in the vicinity.
Step c4 (Washing stage introduction step): A washing reagent is introduced into the holding section after discharging the reaction mixture by a transfer means.
Step c5 (Washing Step Stirring Step): A surface acoustic wave is generated by the surface acoustic wave stirring means with respect to the holding section holding the introduced cleaning reagent, whereby the cleaning reagent is stirred in the holding section.
Step c6 (washing stage discharging step): The cleaning reagent is discharged from the holding section holding the stirred cleaning reagent through the permeable carrier member by the transfer means.
Step c7 (measurement stage introduction step): The measurement reagent is introduced by the transfer means into the holding section after the cleaning reagent is discharged.
Step c8 (measuring step stirring step): A surface acoustic wave is generated by the surface acoustic wave stirring means for the holding section holding the introduced measurement reagent, and the measurement reagent is stirred in the holding section.
Step c9 (reaction amount measurement step): The reaction amount of the sample is measured together with the position of the sample by the reaction amount measuring means using the agitated measurement reagent and the permeable carrier member as measurement targets.
This makes it possible to distinguish probes without using carrier-encoded particles by fixing the spatial position of the probes. In addition, unnecessary liquid such as cleaning liquid after cleaning is transferred and removed from the permeable carrier member through the permeable carrier member (permeable carrier substrate) by discharging force, so that the sample and reagent are stirred and mixed by surface acoustic waves. In addition, it is possible to sufficiently clean the permeable carrier member. In addition, since the probe is fixed to the permeable carrier member, the spot position information plays a role of encoding and many types of encoding can be used, and it is necessary to use particles dispersed in a liquid such as carrier encoded particles. The analysis accuracy can be improved. Also, the apparatus for such a method can be simplified and downsized.

  Further, according to the reaction amount measurement method of the present invention, after the measurement reagent is discharged from the holding section holding the stirred measurement reagent by the transfer means through the permeable carrier member, the measurement reagent is discharged. Using the permeable carrier member as a measurement object, the reaction amount of the sample is measured by the reaction amount measuring means together with the position of the sample. Thereby, the measurement sensitivity of the reaction amount can be increased. Further, when measuring the reaction amount, the measurement reagent after the reaction is discharged and the measurement is performed on the permeable carrier member, so that the measurement can be performed with the position of the permeable carrier member fixed. It can be applied to measurements such as sensitization in which physical quantities such as chemiluminescence depending on the quantity are accumulated in the equipment, and the analysis accuracy can be further improved.

  Further, according to the reaction amount measuring method of the present invention, at least the cleaning stage introduction process (process b4, process c4), the cleaning stage stirring process (process b5, process c5), and the cleaning stage discharge process (process b6, process c6). Is repeatedly executed a predetermined number of times, and the measurement reagent is introduced into the holding section after the cleaning reagent is discharged in the last cleaning stage discharging step repeatedly executed. Thereby, at least the carrier magnetic particles can be washed more sufficiently, and the measurement accuracy can be further improved.

  Moreover, according to the reaction amount measuring method according to the present invention, the holding section has hydrophilicity. As a result, the reaction solution can be brought into contact with only one surface of the holding section, and the reaction solution can be held in the form of droplets by its surface tension. It can be made minute. Further, since the liquid is in the droplet state, it is possible to efficiently perform the stirring and mixing by the surface acoustic wave as compared with the state in which the liquid is held in the container or the like. Further, for example, the liquid can be easily transferred by surface acoustic waves, and the apparatus for the method can be downsized.

  Moreover, according to the reaction amount measuring method of the present invention, at least in the reaction stage discharging step, the reaction mixture is transferred to a storage compartment (for storing substances discharged from the holding compartment) provided in the vicinity of the holding compartment. In the cleaning stage discharging process, the cleaning reagent is discharged to the storage compartment. Thereby, it becomes possible to hold the waste liquid from the holding section that becomes medical waste in the storage section, it is not necessary to discharge out of the processing system, and the possibility of leaking out of the processing system can be reduced. The ease and simplicity of the device used in such a method can be improved.

  In addition, according to the reaction amount measurement method of the present invention, the substance stored in the storage compartment is transferred from the holding compartment to the storage compartment via a backflow prevention means such as a valve for preventing the substance from flowing back to the holding compartment. Transport. Thereby, once the waste liquid that has flowed into the storage compartment is reliably held in the storage compartment and is prevented from flowing out again into the storage compartment, contamination of the sample is reduced, and as a result, the accuracy of inspection can be improved. it can.

  Moreover, according to the reaction amount measuring method according to the present invention, the pressure is adjusted by the pressure adjusting means so that the pressure inside the storage compartment does not become higher than the atmospheric pressure. As a result, the waste liquid that has flowed into the storage compartment does not increase the internal pressure of the storage compartment, and the waste liquid is reliably held in the storage compartment and is prevented from flowing out again into the holding compartment, thereby reducing sample contamination. As a result, the inspection accuracy can be improved.

  Further, according to the reaction amount measuring method of the present invention, the waste liquid is held by the porous holding member provided inside the storage compartment, which is a porous member having the property of holding the substance. Thereby, the waste liquid that has flowed into the storage compartment is reliably held in the storage compartment, and is prevented from flowing out again into the storage compartment, so that contamination of the sample is reduced, and as a result, the accuracy of the inspection can be improved.

  Further, according to the reaction amount measuring method of the present invention, in the reaction stage introduction step, the reaction reagent is introduced from a storage section (for storing a substance to be introduced into the holding section) provided in the vicinity of the holding section. In the cleaning stage introduction process, the cleaning reagent is introduced from the storage section, and in the measurement stage introduction process, the measurement reagent is introduced from the storage section. Thereby, it is possible to perform the analysis without dispensing and supplying the reagent from the outside of the holding section, and it is possible to simplify and easily use the apparatus used in such a method.

  Further, according to the reaction amount measuring method of the present invention, in the reaction stage introduction step, the reaction reagent is passed from the storage compartment to the slit (the inner wall surface is hydrophilic with a predetermined volume provided between the storage compartment and the holding compartment). In the cleaning stage introduction process, the cleaning reagent is introduced from the storage compartment through the slit, and in the measurement stage introduction process, the measurement reagent is introduced from the storage compartment through the slit. As a result, the reagent contained in the storage compartment and held can be easily measured by the amount specified by the volume by being sucked into the slit of a predetermined volume and transferred to the holding compartment. Thus, the accuracy of analysis can be improved. Furthermore, since the reagent can be measured with a slit having a fixed volume, when the reagent is contained in the storage compartment, it is only necessary to contain an amount larger than the amount of liquid to be used. It is possible to reduce the size of the apparatus.

  Further, according to the reaction amount measuring method of the present invention, the reaction reagent is stored in the storage compartment (separate from the holding compartment, in the form of a cartridge separate from the holding compartment, has a penetrating partition, and the suction port is By being penetrated through the partition wall, the suction port (which is connected to the holding section via the suction port) is provided between the slit and the storage section, and when connected to the storage section, it is stored in the storage section. In the cleaning stage introduction process, the cleaning reagent is introduced from the storage compartment through the suction port and the slit, and in the measurement stage introduction process, the measurement reagent is introduced from the storage compartment to the suction port and It introduces through a slit. In other words, the storage compartment is configured as a reagent cartridge joined via a separate or deformable member via a partition wall that can penetrate the holding compartment, and is sealed by containing at least one reagent. The reagent cartridge is connected to the holding compartment through the suction port, and this connection allows the suction port to penetrate the partition wall for sealing the reagent, and the inner wall surface is hydrophilic with a predetermined volume provided by connecting to the suction port. The reagent is sucked into the slit, and the sucked reagent is taken out from the slit by, for example, surface acoustic waves and transferred to the holding section. As a result, since it is contained in a reagent cartridge constituting a storage compartment and sealed and held by a partition wall, reliable sealing is possible, the storage stability of the reagent is improved, and the simplicity of the apparatus used in such a method is improved. To do. Furthermore, the reagent is easily sucked into a slit having a predetermined volume through a suction port penetrating the partition wall by the reagent cartridge, and an amount defined by this volume can be transferred to the holding section. , Analysis accuracy can be improved. Furthermore, because the reagent can be measured with a slit with a fixed volume, when the reagent is contained in the storage compartment of the reagent cartridge, it is only necessary to contain more than the amount of liquid to be used. The apparatus for such a method can be miniaturized.

  Further, according to the reaction amount measuring method of the present invention, the reaction amount of a substance is optically measured by chemiluminescence, fluorescence, turbidity, or colorimetry. In other words, the reaction amount is measured by an optical method such as chemiluminescence, fluorescence, turbidity, or colorimetry. Accordingly, the reaction amount can be measured in a non-contact manner, the influence of the measurement on the sample is slight, and the analysis accuracy can be improved.

  Moreover, according to the reaction amount measuring method according to the present invention, a plurality of sets of reaction amount measuring apparatuses used in the method are provided. In other words, a plurality of apparatus sets that can independently perform the method are provided. Thereby, a plurality of analyzes can be performed simultaneously, and the method can be further improved in simplicity and speed.

  Here, Patent Document 1 (Japanese Patent Laid-Open No. 2001-4628) presented in Background Art relates to a method of introducing (transferring) an antigen and a labeled antibody to a microchannel reaction tank through an introduction part or a microchannel inflow part. Is not disclosed at all. Further, in the method of damming the solid microparticles in the microchannel separation section in Patent Document 1 presented in the background art, there is a possibility that the solid microparticles may be clogged at the entrance of the microchannel separation section, and unreacted substances are removed from the microchannel reaction tank section There is a problem that it becomes difficult to reliably discharge to the waste liquid part via the microchannel separation part.

  As a method similar to the method disclosed in Patent Document 1 presented in the background art, a method of pumping a sample or a reagent from an injection hole to a fine channel is generally known. However, this method requires an electric motor type pump separately, and there is a problem that there is a limit to downsizing of the apparatus.

  Further, in JP-A No. 2002-323416, using a substrate further provided with a deformable reagent-containing compartment in addition to a fine channel and a reaction compartment, the reagent-containing compartment is deformed by an external stimulus, and a sample or reagent A technique for transferring the water to the reaction section through a fine channel is disclosed. However, this technique requires a mechanism for stimulating the reagent-containing compartment, and there is a problem that there is a limit to downsizing the apparatus.

  Also, Japanese Patent No. 3469585 discloses various techniques related to the transfer of samples and reagents. Specifically, this document discloses a technique for rotating a substrate provided with a fine flow path, a reaction compartment, and the like, and transferring a sample and a reagent mainly by the centrifugal force. However, this technique requires a rotation mechanism for rotating the substrate, and the shape of the flow path is restricted in order to use centrifugal force, so that there is a problem that there is a limit to downsizing of the apparatus. Furthermore, in this technique of transferring a sample or a reagent mainly by centrifugal force, there is a problem that it is difficult to sufficiently stir the sample and the reagent.

  Japanese Patent Laid-Open No. 2002-303627 discloses a technique for transferring a sample or a reagent through a fine channel by electroosmotic flow. However, this technique has a practical problem that the transfer speed is affected by the width of the flow path and the flow path must be filled with a liquid. Furthermore, this technique does not disclose anything about stirring of a sample and a reagent.

  Japanese Patent Application Publication No. 2002-536660 discloses a technique for applying magnetism in a reaction section using a magnetic substance as a carrier particle, although it is not a method using a fine channel. However, this technique requires a separate analysis mechanism such as a pump for transporting liquid and a waste liquid container, and there is a problem that there is a limit to downsizing of the apparatus.

  However, according to the reaction amount measuring method of the present invention, all the above problems can be solved, and the sample and the reagent can be efficiently stirred sufficiently when measuring the reaction amount of the sample using the solid phase carrier. As a result, the reaction amount of the sample can be accurately measured.

[First Embodiment]
Next, a reaction amount measurement method according to the first embodiment and a reaction amount measurement apparatus that executes the reaction amount measurement method will be described with reference to FIG. In addition, in 1st Embodiment, the thing similar to description in other embodiment may be abbreviate | omitted. FIG. 1 is a conceptual diagram relating to a reaction amount measuring method and a reaction amount measuring apparatus for executing the reaction amount measuring method according to the first embodiment.

  First, the structure of the reaction amount measurement apparatus 100 that executes the reaction amount measurement method according to the first embodiment will be described. The reaction amount measuring apparatus 100 is roughly composed of a substrate 102, a partition wall 104, and an optical measuring mechanism 106 (not shown).

  The substrate 102 is made of a member that can induce surface acoustic waves. A substrate portion where a stirring SAW electrode 102b described later is located and a substrate portion where a transfer SAW electrode 102d described later is located are made of a piezoelectric member such as a ferroelectric. The substrate 102 includes a reaction section 102a, a stirring SAW electrode 102b, an electromagnet 102c, a transfer SAW electrode 102d, and a waste liquid section 102e as illustrated.

  The reaction section 102a corresponds to the holding section in the present invention. The reaction compartment 102a holds, for example, a sample S, a reaction reagent R, a cleaning reagent W, a measurement reagent M, carrier magnetic particles P that are magnetic and have one or more types of antibodies or nucleic acid probes, This is a section for stirring the sample S and the reaction reagent R to cause them to react and for washing the carrier magnetic particles P with the washing reagent W. The reaction compartment 102 a is partially provided as a part of the substrate 102. The surface of the substrate portion corresponding to the reaction compartment 102a has stronger hydrophilicity or weaker hydrophobicity than other substrate portions in order to hold the liquid in the form of droplets.

  The stirring SAW electrode 102b corresponds to the surface acoustic wave stirring means in the present invention. The stirring SAW electrode 102b induces a surface acoustic wave for stirring the substance on the surface of the substrate portion corresponding to the reaction section 102a.

  The electromagnet 102c corresponds to the magnetic field control means in the present invention. As shown in the figure, the electromagnet 102c is provided immediately below the reaction section 102a. The electromagnet 102c collects and pellets the carrier magnetic particles P on the surface of the substrate portion corresponding to the reaction section 102a.

  The transfer SAW electrode 102d corresponds to the transfer means in the present invention. The transfer SAW electrode 102d induces a surface acoustic wave on the surface of the substrate 102 for transferring the substance (specifically, introducing the substance into the reaction section 102a or discharging the substance from the reaction section 102a). To do.

  The waste liquid compartment 102e corresponds to the storage compartment in the present invention. The waste liquid section 102e holds the substance discharged from the reaction section 102a as a waste liquid.

  The partition 104 is a plate-shaped member made of a predetermined member. As shown in the figure, the partition 104 is provided between the reaction section 102a and the waste liquid section 102e with a certain gap from the surface of the substrate 102. The wall surface of the partition wall 104 (at least the wall surface facing the substrate 102) has hydrophobicity. Thereby, an opening B is formed between the reaction section 102a and the waste liquid section 102e, and the formed opening B functions as a constricted flow path and a passive valve having a function of preventing backflow. Fulfill. That is, the opening B formed by combining the substrate 102 and the partition wall 104 as described above corresponds to the backflow prevention means in the present invention.

  The optical measuring mechanism 106 corresponds to the reaction amount measuring means in the present invention, and optically measures the reaction amount of the substance.

  An example of a reaction amount measurement method (reaction amount measurement method according to the first embodiment) executed by the reaction amount measurement apparatus 100 having the above configuration will be described with reference to FIG. 1 again.

(Step 101: Reaction stage introduction step) First, the sample S is dispensed into the reaction compartment 102a by the dispensing means. As a result, the sample S is held in the form of droplets in the reaction compartment 102a. Then, the reaction reagent R containing the carrier magnetic particles P previously held as droplets at a predetermined position on the substrate 102 is introduced into the reaction section 102a by the surface acoustic wave induced by the transfer SAW electrode 102d. Thereby, the sample S and the reaction reagent R containing the carrier magnetic particles P are integrated in the reaction section 102a.

(Step 102: Reaction Step Stirring Step) Next, the reaction mixture _MSR composed of the carrier magnetic particles P and the sample S and the reaction reagent R is stirred by the surface acoustic wave induced by the stirring SAW electrode 102b. And reagent R are reacted.

(Step 103: Reaction Step Magnetic Field Application Step) Next, the carrier magnetic particles P are collected on the bottom surface of the reaction section 102a and pelletized by a magnetic field induced by energizing the electromagnet 102c.

(Step 104: reaction step discharging process) Next, the surface acoustic wave induced by the transfer SAW electrode 102d, the reaction mixture _{M SR} from the reaction compartment 102a through the opening (valve) B is discharged to the waste liquid compartment 102e. As a result, the reaction mixture _MSR is separated from the carrier magnetic particles P as a reaction liquid supernatant by surface acoustic waves and transferred from the reaction compartment 102a to the valve B, and further passes through the valve B to the waste liquid compartment 102e. The waste liquid is retained in the waste liquid compartment 102e.

(Process 105: Cleaning Stage Introduction Process) Next, as in the process 101, the cleaning reagent W held in advance as a droplet at a predetermined position on the substrate 102 by the surface acoustic wave induced by the transfer SAW electrode 102d. Then, the pelletized carrier magnetic particles P are introduced into the reaction zone 102a.

(Step 106: Cleaning Stage Magnetic Field Release Step) Next, the electromagnet 102c is de-energized to eliminate the magnetic field.

(Step 107: Washing Step Stirring Step) Next, similarly to step 102, the washing reagent W is stirred by the surface acoustic wave induced by the stirring SAW electrode 102b, and the carrier magnetic particles P are suspended in the washing reagent W. .

(Step 108: washing step magnetic field application step) Next, similarly to step 103, the carrier magnetic particles P are collected on the bottom surface of the reaction zone 102a and pelletized by a magnetic field induced by energizing the electromagnet 102c. .

(Step 109: Cleaning Stage Ejecting Step) Next, as in step 104, the cleaning reagent W passes through the opening (valve) B from the reaction section 102a by the surface acoustic wave induced by the transfer SAW electrode 102d, and the waste liquid section. Discharge to 102e. As a result, the cleaning reagent W is separated from the carrier magnetic particles P as a cleaning liquid supernatant by surface acoustic waves and transferred from the reaction section 102a to the valve B, and further passes through the valve B to the waste liquid section 102e. Held in the waste liquid compartment 102e.

(Process 110: Measurement stage introduction process) Next, in the same manner as in the process 101 and the process 105, the surface acoustic wave induced by the transfer SAW electrode 102d is previously held as a droplet at a predetermined position on the substrate 102. The reagent M is introduced into the reaction zone 102a where the pelletized carrier magnetic particles P are present.

(Step 111: Measurement Step Magnetic Field Release Step) Next, as in step 106, the energization of the electromagnet 102c is released and the magnetic field disappears.

(Step 112: Measurement Step Stirring Step) Next, similarly to Step 102 and Step 107, the measurement reagent M is stirred by the surface acoustic wave induced by the stirring SAW electrode 102b, and the carrier magnetic particles P are changed to the measurement reagent M. Suspend.

(Step 113: Reaction amount measurement step) Next, the optical measurement mechanism 106 measures the reaction amount such as the degree of aggregation of the carrier magnetic particles P by an optical method such as a turbidimetric method.

As described above, according to the reaction amount measurement method according to the first embodiment, the reaction mixture _MSR and the cleaning reagent W from the carrier magnetic particles P pelletized by mixing and stirring the sample S and the reaction reagent R and applying magnetism. Is achieved by surface acoustic waves conducted on the bottom surface of the reaction compartment 102a. This makes it possible to efficiently and sufficiently perform mixing and stirring of liquids and removal of unnecessary liquids, and improve the analysis accuracy of the reaction amount. Furthermore, since the configuration of the reaction amount measurement apparatus 100 according to the first embodiment is simple, the entire apparatus can be reduced in size. A technique related to the transfer of a minute amount of liquid by surface acoustic waves is disclosed in Japanese Patent Publication No. 2003-535349, and a technique related to the mixing / stirring of a minute amount of liquid by surface acoustic waves is disclosed in Japanese Patent Publication No. 2004-534633 It is disclosed.

[Second Embodiment]
Next, a reaction amount measuring method according to the second embodiment and a reaction amount measuring apparatus for executing the reaction amount measuring method will be described with reference to FIG. Note that in the second embodiment, the same descriptions as in the other embodiments may be omitted. FIG. 2 is a conceptual diagram relating to a reaction amount measuring apparatus according to the second embodiment. 2A is a perspective view of the reaction amount measuring apparatus according to the second embodiment, and FIG. 2B is a cross-sectional view thereof.

  First, the structure of the reaction amount measuring apparatus 200 according to the second embodiment will be described. The reaction amount measuring apparatus 200 is roughly composed of an analysis chip 202, a SAW propagation mechanism 204, a chip mount 206, and a dispensing means 208.

  The analysis chip 202 is provided on the surface of the chip mount 206 described later via a SAW propagation mechanism 204 described later so as to be separable and / or movable. The analysis chip 202 includes a reaction section 202a, a slide lid 202b, a waste liquid section 202c, a pressure regulating valve 202d, a porous member 202e, and a bottom plate 202f as illustrated.

  The reaction section 202a corresponds to the holding section in the present invention. In the upper part of the reaction section 202a, a dispensing opening SL for supplying a chemical solution R made of a sample S or a reagent by a dispensing means 208 described later is provided.

  The slide lid 202b is a plate-like member for sealing the dispensing opening SL. The slide lid 202b is provided in the upper part of the reaction section 202a as shown in the figure.

  The waste liquid section 202c corresponds to the storage section in the present invention. The waste liquid section 202c holds the liquid discharged from the reaction section 102a as a waste liquid.

  The pressure regulating valve 202d corresponds to the pressure regulating means in the present invention. The pressure regulating valve 202d is provided adjacent to the waste liquid compartment 202c as shown in the figure. The pressure regulating valve 202d adjusts the pressure inside the waste liquid compartment 202c so as not to exceed at least atmospheric pressure.

  The porous member 202e corresponds to the porous holding member in the present invention. The porous member 202e is provided in the waste liquid compartment 202c as shown in the figure. The porous member 202e is made of a porous member for holding a liquid (waste liquid).

  The bottom plate 202f is a part of the analysis chip 202. The bottom plate 202f has an optically transmissive part for optically measuring the reaction amount. The bottom plate 202f has a characteristic of propagating surface acoustic waves.

  In the analysis chip 202, a valve B is provided between the reaction compartment 202a and the waste liquid compartment 202c to prevent the waste liquid inside the waste liquid compartment 202c from flowing back to the reaction compartment 202a. The valve B corresponds to the backflow preventing means in the present invention. The valve B is a passive valve composed of a constricted flow path having a hydrophobic inner wall surface.

  The SAW propagation mechanism 204 is an acoustic matching member for propagating the SAW.

  The chip mount 206 drives the analysis chip 202. The chip mount 206 is provided with a SAW transfer mechanism 206a, a SAW stirring mechanism 206b, an electromagnet 206c, and an optical measurement mechanism 206d.

  The SAW transfer mechanism 206a corresponds to the transfer means in the present invention. The SAW transfer mechanism 206 a induces a surface acoustic wave for transferring the liquid to the bottom surface 202 f via the SAW propagation mechanism 204.

  The SAW stirring mechanism 206b corresponds to the surface acoustic wave stirring means in the present invention. The SAW stirring mechanism 206b induces a surface acoustic wave for stirring the liquid to at least a portion corresponding to the reaction section 202a in the bottom surface 202f via the SAW propagation mechanism 204.

  The electromagnet 206c corresponds to the magnetic field control means in the present invention. The electromagnet 206c applies a magnetic field to the reaction section 202a.

  The optical measuring mechanism 206d corresponds to the reaction amount measuring means in the present invention, and optically measures the reaction amount of the substance.

  An example of a reaction amount measurement method (reaction amount measurement method according to the second embodiment) executed by the reaction amount measurement apparatus 200 having the above configuration will be described.

(Step 201: Reaction Stage Introduction Step) First, the sample S is dispensed into the reaction section 202a by the dispensing means 208. As a result, the sample S is held in the form of droplets in the reaction section 202a. Further, the dispensing reagent 208 dispenses the reaction reagent R containing the carrier magnetic particles P into the reaction section 202a. As a result, the sample S and the reaction reagent R including the carrier magnetic particles P are integrated in the reaction compartment 102a, and held as droplets as the reaction liquid _MSR .

(Step 202: Reaction Stage Stirring Step) Next, the reaction liquid _MSR is stirred by propagating the surface acoustic wave excited by the SAW stirring mechanism 206b to the reaction section 202a via the SAW propagation mechanism 204 and the bottom plate 202f. To do. Thereby, the sample S and the reaction reagent R containing the carrier magnetic particles P are sufficiently mixed and stirred, and the reaction between the analyte such as an antibody supported on the carrier magnetic particles P and the sample S is promoted.

(Step 203: Reaction Stage Magnetic Field Applying Step) Next, the carrier magnetic particles P are collected at the bottom of the reaction section 202a and pelletized by a magnetic field generated by energizing the electromagnet 206c.

(Step 204: Reaction Stage Discharge Step) Next, the reaction liquid _MSR excluding the carrier magnetic particles P is passed from the reaction section 202a through the valve B by the surface acoustic wave induced by the SAW transfer mechanism 206a, and the waste liquid section 202c. And discharged as waste liquid. Thus, reaction liquid _{M SR} is held is absorbed by the porous member 202e inside the waste liquid compartment 202c.

(Process 205: Cleaning Stage Introduction Process) Next, as in the process 201, the dispensing reagent 208 dispenses the cleaning reagent W to the reaction zone 202a where the pelletized carrier magnetic particles P are present. Thereby, the cleaning reagent W is held as a droplet on the pellet in the reaction section 202a.

(Step 206: Cleaning Stage Magnetic Field Canceling Step) Next, the electromagnet 206c is deenergized to disappear the magnetic field.

(Step 207: Washing Step Stirring Step) Next, as in step 202, the surface acoustic wave excited by the SAW stirring mechanism 206b is propagated to the reaction section 202a to stir the cleaning reagent W in the reaction section. . Thereby, the pelletized carrier magnetic particles P are suspended in the cleaning reagent W, mixed and stirred, and the cleaning of the particle surface of the carrier magnetic particles P is promoted.

(Step 208: washing step magnetic field application step) Next, in the same manner as in step 203, the carrier magnetic particles P are collected on the bottom surface of the reaction section 202a and pelletized by a magnetic field induced by energizing the electromagnet 206c. .

(Step 209: Washing Stage Discharge Step) Next, as in step 204, the cleaning reagent W, which is a supernatant, passes through the valve B from the reaction section 202a by the surface acoustic wave induced by the SAW transfer mechanism 206a. The waste liquid is discharged as waste liquid into the waste liquid section 202c. As a result, the cleaning reagent W is absorbed by the porous member 202e and held in the waste liquid compartment 202c.

(Process 210: Measurement Stage Introduction Process) Next, as in the process 201 and the process 205, the measuring reagent M is dispensed by the dispensing means 208 into the reaction zone 202a where the pelletized carrier magnetic particles P are present. As a result, the measurement reagent M is held as a droplet on the pellet in the reaction section 202a.

(Step 211: Measurement Step Magnetic Field Release Step) Next, as in step 206, the electromagnet 206c is de-energized and the magnetic field disappears.

(Step 212: Measurement Step Stirring Step) Next, similarly to step 202 and step 207, the surface acoustic wave excited by the SAW stirring mechanism 206b is propagated to the reaction section 202a via the SAW propagation mechanism 204 and the bottom plate 202f. Thus, the measuring reagent M is stirred. Thereby, the pelletized carrier magnetic particles P are suspended in the measurement reagent M, mixed and stirred, and the measurement reaction is promoted.

(Step 213: Reaction amount measurement step) Next, an optical measurement mechanism 206d is positioned below the optically transmissive portion provided on the bottom surface of the reaction section 202a, and the carrier measurement is performed by the optical measurement mechanism. The reaction amount such as the degree of aggregation of the particles P is measured and evaluated by an optical method such as a turbidimetric method.

  As described above, according to the reaction amount measurement method according to the second embodiment, the transfer SAW mechanism 206a, the stirring SAW mechanism 206b, and the electromagnet 206c for collecting magnets are provided on the chip mount 206 separately from the analysis chip 202. As a result, the structure of the analysis chip 202 is simplified, the analysis chip 202 can be further miniaturized, and the analysis chip 202 can be easily manufactured to realize an inexpensive analysis chip 202.

  Each configuration of the reaction amount measurement apparatus 200 according to the second embodiment can be variously modified and changed. For example, the porous member 202e provided in the waste liquid compartment 202c can be replaced with a moisture absorbing member such as silica gel. Further, the valve B is not limited to a tapered shape that narrows one of the openings particularly strongly, but can be a tube having a constant opening. Further, the valve B is not limited to a passive one, and an active valve such as an open / close mechanism using a valve structure can also be used. In FIG. 2, a chemical solution such as a reaction solution is held in a droplet shape in the reaction section 202 a, but a chemical solution such as a reaction solution is held in a non-droplet shape so as to be in contact with the bottom and side walls of the reaction section 202 a. May be.

[Third Embodiment]
Next, a reaction amount measurement method according to the third embodiment and a reaction amount measurement apparatus that executes the reaction amount measurement method will be described with reference to FIGS. 3 and 4. Note that in the third embodiment, the same descriptions as in the other embodiments may be omitted. FIG. 3 is a conceptual diagram related to the reaction amount measuring apparatus according to the third embodiment. FIG. 4 is another conceptual diagram regarding the reaction amount measuring apparatus according to the third embodiment. 3 and 4A are plan views showing the reaction amount measuring apparatus according to the third embodiment from above, and FIG. 3B and FIG. 4B are cross-sectional views thereof.

  First, the structure of the reaction amount measuring apparatus 300 according to the third embodiment will be described. The reaction amount measuring apparatus 300 is roughly composed of an analysis chip 302, a SAW propagation mechanism 304, a chip mount 306, a dispensing means 308, and an optical measurement mechanism 310.

  The analysis chip 302 is provided on a surface of a chip mount 306 described later via a SAW propagation mechanism 304 described later so as to be separable and / or movable from the chip mount. The analysis chip 302 includes a plurality of reaction compartments 302a, a plurality of slide lids 302b, a waste liquid compartment 302c, a pressure regulating valve 302d, a porous member 302e, and a bottom plate 302f as shown in the figure. That is, unlike the analysis chip 202 in the second embodiment described above, the analysis chip 302 has a common waste liquid compartment and is configured by arranging a plurality of reaction compartments as shown. Note that the outer peripheral wall of the analysis chip 302 that is in contact with the reaction section 302a is formed of an optically transmissive window that can be optically observed.

  The chip mount 306 drives the analysis chip 302. The chip mount 306 is provided with a plurality of SAW transfer mechanisms 306a, a plurality of SAW stirring mechanisms 306b corresponding to the respective reaction sections 302a, and a plurality of electromagnets 306c corresponding to the respective reaction sections 302a. A transfer SAW mechanism 306a is arranged in the reverse direction (opposite) on the chip mount 306 so as to transfer the chemical solution from the reaction compartment 302a facing each other to the waste liquid compartment 302c. In order to eliminate surface acoustic wave interference induced by each transfer SAW mechanism 306a, the arrangement of the transfer SAW mechanisms 306a may be discontinuous as shown in the figure, and a SAW absorption band is provided between the arrangements. May be.

  The optical measuring mechanism 310 corresponds to the reaction amount measuring means in the present invention, and optically measures the reaction amount of a substance. The optical measuring mechanism 310 is arranged as shown with respect to the corresponding window of each reaction section 302a.

  Although it is description about an example of the reaction amount measuring method (reaction amount measuring method concerning 3rd Embodiment) performed with the reaction amount measuring apparatus 300 of the above structures, it is the same as that of 2nd Embodiment mentioned above. Omitted.

  As described above, according to the reaction amount measurement method according to the third embodiment, a plurality of samples S can be obtained with a single analysis chip 302 by using a configuration in which a plurality of reaction compartments 302a are disposed so as to face each other with a common waste liquid compartment 302c. Alternatively, simultaneous analysis of a plurality of items with respect to the same sample S is possible, and the analysis is easy. In addition, since the transfer SAW mechanism 306a and the electromagnet 306c on the same side of the reaction section 302a can be integrated, the structure of the chip mount 306 is not complicated even if a plurality of reaction sections 302a are provided, and an apparatus mechanism for analysis is provided. It becomes simple and can be miniaturized. Further, by sharing the waste liquid section 302c in the analysis chip 302, the structure is not complicated, and the analysis chip is simplified and further miniaturization is further facilitated.

  In addition, various deformation | transformation and change are possible for each structure of the reaction amount measuring apparatus 300 concerning 3rd Embodiment. For example, the porous member 302e provided in the waste liquid compartment 302c can be replaced with a moisture absorbing member such as silica gel. Further, the valve B is not limited to a tapered shape that narrows one of the openings particularly strongly, but can be a tube having a constant opening. Further, the valve B is not limited to a passive one, and an active valve such as an open / close mechanism using a valve structure can also be used. 3 and 4, a chemical solution such as a reaction solution is held in a non-droplet form in the reaction section 302a so as to be in contact with the bottom and side walls of the reaction section. You may hold | maintain in the form of a droplet in the reaction zone 302a. Further, as shown in FIG. 4, the waste liquid compartment 302c may be provided independently without being shared.

[Fourth Embodiment]
Next, a reaction amount measurement method according to the fourth embodiment and a reaction amount measurement apparatus that executes the reaction amount measurement method will be described with reference to FIG. Note that in the fourth embodiment, the same descriptions as in the other embodiments may be omitted. FIG. 5 is a conceptual diagram related to the reaction amount measuring apparatus according to the fourth embodiment. 5A is a plan view showing the reaction amount measuring apparatus according to the fourth embodiment from above, and FIG. 5B is a cross-sectional view thereof.

  First, the configuration of the reaction amount measurement apparatus 400 according to the fourth embodiment will be described. The reaction amount measuring apparatus 400 is roughly composed of an analysis chip 402, a SAW propagation mechanism 404, a chip mount 406, and a dispensing means 408.

  The analysis chip 402 includes a reagent compartment 402g in addition to a reaction compartment 402a, a slide lid 402b, a waste liquid compartment 402c, a pressure regulating valve 402d, a porous member 402e, and a bottom plate 402f as shown in the figure. .

  The reagent section 402g corresponds to the storage section in the present invention. A plurality of reagent compartments 402g are provided on the side facing the waste liquid compartment 402c across the reaction compartment 402a. The reagent section 402g includes reagents necessary for analysis such as the reaction reagent R, the cleaning reagent W, and the measurement reagent M.

  The chip mount 406 drives the analysis chip 402. The chip mount 406 is provided with a SAW transfer mechanism 406a, a SAW stirring mechanism 406b, an electromagnet 406c, and an optical measurement mechanism 406d.

  The SAW transfer mechanism 406a is provided so as to straddle the region from the reagent section 402g of the analysis chip 402 through the reaction section 402a to the waste liquid section 402c.

  An example of a reaction amount measurement method (reaction amount measurement method according to the fourth embodiment) executed by the reaction amount measurement apparatus 400 having the above configuration will be described.

(Step 401: Reaction Stage Introduction Step) First, the sample S is dispensed by the dispensing means 408. As a result, the sample S is held in droplet form in the reaction section 402a. In addition, the surface acoustic wave excited by the transfer SAW mechanism 406a is propagated to the reagent section 402g through the SAW propagation mechanism 404 and the bottom plate 402f, so that the carrier magnetic particles held and held in one of the reagent sections 402g. The reaction reagent R containing P is transferred from the reagent section 402g to the reaction section 402a. As a result, the sample S and the reaction reagent R including the carrier magnetic particles P are integrated in the reaction section 402a, and held as droplets as the reaction liquid _MSR .

(Step 402: Reaction Step Stirring Step) Next, the surface acoustic wave excited by the SAW stirring mechanism 406b is propagated to the reaction section 402a via the SAW propagation mechanism 404 and the bottom plate 402f, thereby allowing the reaction liquid _MSR to flow. Stir. Thereby, the sample S and the reaction reagent R containing the carrier magnetic particles P are sufficiently mixed and stirred, and the reaction between the antibody carried on the carrier magnetic particles P and the sample S is promoted.

(Step 403: Reaction Step Magnetic Field Application Step) Next, the carrier magnetic particles P are collected at the bottom of the reaction section 402a by a magnetic field generated by energizing the electromagnet 406c and pelletized.

(Step 404: Reaction Stage Discharge Step) Next, the reaction liquid _MSR excluding the carrier magnetic particles P is passed from the reaction section 402a through the valve B by the surface acoustic wave induced by the SAW transfer mechanism 406a, and the waste liquid section 402c. Discharged as waste liquid. Thus, reaction liquid _{M SR} is held is absorbed by the porous member 402e inside the waste liquid compartment 402c.

(Step 405: Cleaning stage introduction step) Next, similarly to step 401, the surface acoustic wave excited by the transfer SAW mechanism 406a is propagated to the reagent section 402g via the SAW propagation mechanism 404 and the bottom plate 402f. The cleaning reagent W contained and held in one of the reagent compartments 402g is transferred from the reagent compartment 402g to the reaction compartment 402a having the pelletized carrier magnetic particles P. Thereby, the cleaning reagent W is held as a droplet on the pellet in the reaction section 402a.

(Step 406: Cleaning Stage Magnetic Field Release Step) Next, the electromagnet 406c is de-energized and the magnetic field disappears.

(Step 407: Washing Step Stirring Step) Next, as in step 402, the surface acoustic wave excited by the SAW stirring mechanism 406b is propagated to the reaction section 402a, thereby stirring the cleaning reagent W in the reaction section. . Thereby, the pelletized carrier magnetic particles P are suspended in the cleaning reagent W, mixed and stirred, and the cleaning of the particle surface of the carrier magnetic particles P is promoted.

(Step 408: washing step magnetic field application step) Next, in the same manner as in step 403, the carrier magnetic particles P are collected on the bottom surface of the reaction zone 402a and pelletized by a magnetic field induced by energizing the electromagnet 406c. .

(Step 409: Washing Step Discharge Step) Next, as in step 404, the cleaning reagent W, which is a supernatant, is passed from the reaction zone 402a through the valve B by the surface acoustic wave induced by the SAW transfer mechanism 406a. And discharged as waste liquid. As a result, the cleaning reagent W is absorbed by the porous member 402e and held in the waste liquid compartment 402c.

(Step 410: Measurement stage introduction step) Next, similarly to step 401 and step 405, the surface acoustic wave excited by the SAW transfer mechanism 406a is propagated to the reagent section 402g via the SAW propagation mechanism 404 and the bottom plate 402f. Thus, the measurement reagent M contained and held in one of the reagent compartments 402g is transferred from the reagent compartment 402g to the reaction compartment 402a where the pelletized carrier magnetic particles P are present. As a result, the measurement reagent M is held as a droplet on the pellet in the reaction section 402a.

(Step 411: Measurement Step Magnetic Field Release Step) Next, as in step 406, the energization of the electromagnet 406c is released and the magnetic field disappears.

(Step 412: Measurement Step Stirring Step) Next, similarly to Step 402 and Step 407, the surface acoustic wave excited by the SAW stirring mechanism 406b is propagated to the reaction section 402a through the SAW propagation mechanism 404 and the bottom plate 402f. Thus, the measuring reagent M is stirred. Thereby, the pelletized carrier magnetic particles P are suspended in the measurement reagent M, mixed and stirred, and the measurement reaction is promoted.

(Step 413: Reaction amount measurement step) Next, an optical measurement mechanism 406d is positioned below the optically transparent portion provided on the bottom surface of the reaction section 402a, and the magnetic properties of the carrier are measured by the optical measurement mechanism. The reaction amount such as the degree of aggregation of the particles P is measured and evaluated by an optical method such as a turbidimetric method.

  As described above, according to the reaction amount measurement method according to the fourth embodiment, the reagent necessary for the analysis is contained in the reagent section 402g and mounted on the analysis chip 402, whereby the dispensing means 408 for the sample S and A dispensing mechanism for the same type of reagent is not required, the apparatus mechanism for analysis is simplified, and the apparatus can be further miniaturized.

  Each configuration of the reaction amount measurement apparatus 400 according to the fourth embodiment can be variously modified and changed. For example, the porous member 402e provided in the waste liquid compartment 402c can be replaced with a moisture absorbing member such as silica gel. Further, the valve B is not limited to a tapered shape that narrows one of the openings particularly strongly, but can be a tube having a constant opening. Further, the valve B is not limited to a passive one, and an active valve such as an open / close mechanism using a valve structure can also be used.

[Fifth Embodiment]
Next, a reaction amount measurement method according to a fifth embodiment and a reaction amount measurement apparatus that executes the reaction amount measurement method will be described with reference to FIG. Note that in the fifth embodiment, the same descriptions as in the other embodiments may be omitted. FIG. 6 is a conceptual diagram related to the reaction amount measuring apparatus according to the fifth embodiment. 6A is a plan view showing the reaction amount measuring apparatus according to the fifth embodiment from above, and FIG. 6B is a cross-sectional view thereof.

  First, the structure of the reaction amount measuring apparatus 500 according to the fifth embodiment will be described. The reaction amount measuring apparatus 500 is roughly composed of an analysis chip 502, a SAW propagation mechanism 504, a chip mount 506, a dispensing means 508, and a reagent cartridge 510.

  The analysis chip 502 includes a reaction port 502a, a slide lid 502b, a waste liquid chamber 502c, a pressure regulating valve 502d, a porous member 502e, a bottom plate 502f, a suction port 502g, a dispensing slit 502h, and an atmospheric pressure. An adjustment port 502i is provided as shown.

  The suction port 502g corresponds to the suction port in the present invention. The suction port 502g has a hydrophilic inner wall surface. The suction port 502g is connected to the reaction section 502a through a dispensing slit 502h described later.

  The dispensing slit 502h corresponds to the slit in the present invention. The dispensing slit 502h has a volume corresponding to the dispensing amount of the reagent, and the inner wall surface is hydrophilic.

  The atmospheric pressure adjustment port 502i is for adjusting the atmospheric pressure inside the reagent compartment 510a described later.

  The reagent cartridge 510 is provided with a plurality of reagent compartments 510a and a plurality of mating partition walls 510b corresponding to the reagent compartments 510a, and each reagent compartment 510a contains at least a reagent amount to be used for analysis. The reagent cartridge 510 is separate from the analysis chip 502 and is movable. The analysis chip 502 and the reagent cartridge 510 are integrated with each other by fitting the reagent cartridge 510 with the suction port 502g and the atmospheric pressure adjustment port 502i via the fitting partition wall 510b corresponding to each reagent section 510a.

  An example of a reaction amount measurement method (reaction amount measurement method according to the fifth embodiment) executed by the reaction amount measurement apparatus 500 having the above configuration will be described.

  In the analysis, the analysis chip 502 and the sample cartridge 510 are connected in advance. Specifically, the reagent cartridge 510 provided as a separate body from the analysis chip 502 is pressed into a fitting site provided with the suction port 502g and the atmospheric pressure adjustment port 502i for fitting. Thereby, these two ports penetrate through the fitting partition wall 510b and are connected to the reagent section 510a. The reagent contained in the reagent section 510a is sucked into the dispensing slit 502h through the suction boat 502g. Note that the internal pressure of the reagent compartment 510a is maintained at atmospheric pressure by the atmospheric pressure adjustment port 502i fitted and connected to the reagent compartment 510a, so that the reagent can be smoothly sucked into the dispensing slit 502h.

(Step 501: Reaction stage introduction step) First, the sample S is dispensed by the dispensing means 508. As a result, the sample S is held in the form of droplets in the reaction compartment 502a. Further, the surface acoustic wave excited by the SAW transfer mechanism 506a is propagated to the analysis chip 502 through the SAW propagation mechanism 504 and the bottom plate 502f, so that it is sucked into the dispensing slit 502h and defined by the volume of the dispensing slit. A reaction reagent R containing a sufficient amount of carrier magnetic particles P is transferred from the dispensing slit 502h to the reaction section 502a. As a result, the sample S and the reaction reagent R including the carrier magnetic particles P are integrated in the reaction section 502a, and held as droplets as the reaction liquid _MSR .

(Step 502: reaction stage stirring step) Next, by propagating a surface acoustic wave excited by the SAW stirring mechanism 506b, to the reaction zone 502a via the SAW propagation mechanism 504 and the bottom plate 502f, the reaction solution _{M SR} Stir. Thereby, the sample S and the reaction reagent R containing the carrier magnetic particles P are sufficiently mixed and stirred, and the reaction between the antibody carried on the carrier magnetic particles P and the sample S is promoted.

(Step 503: Reaction Step Magnetic Field Application Step) Next, the carrier magnetic particles P are collected at the bottom of the reaction section 502a and pelletized with a magnetic field generated by energizing the electromagnet 506c.

(Step 504: reaction step discharging process) Next, the surface acoustic wave induced by the SAW transport mechanism 506a, the reaction liquid _{M SR} excluding carrier magnetic particles P, from the reaction compartment 502a through the valve B waste compartment 502c Discharged as waste liquid. Thus, reaction liquid _{M SR} is held is absorbed by the porous member 502e inside the waste liquid compartment 502c.

(Step 505: Cleaning Stage Introduction Step) Next, similarly to step 501, the surface acoustic wave excited by the SAW transfer mechanism 506a is propagated to the analysis chip 502 via the SAW propagation mechanism 504 and the bottom plate 502f. A quantity of the cleaning reagent W sucked into the dispensing slit 502h and defined by the volume of the dispensing slit is transferred from the dispensing slit 502h to the reaction compartment 502a where the pelletized carrier magnetic particles P are present. Thereby, the cleaning reagent W is held as droplets on the pellet in the reaction section 502a.

(Step 506: Cleaning Stage Magnetic Field Release Step) Next, the electromagnet 506c is de-energized and the magnetic field disappears.

(Step 507: Washing Step Stirring Step) Next, as in step 502, the surface acoustic wave excited by the SAW stirring mechanism 506b is propagated to the reaction section 502a to stir the cleaning reagent W in the reaction section. . Thereby, the pelletized carrier magnetic particles P are suspended in the cleaning reagent W, mixed and stirred, and cleaning of the carrier magnetic particles P on the particle surface is promoted.

(Step 508: washing step magnetic field application step) Next, similarly to step 503, the carrier magnetic particles P are collected and pelletized on the bottom surface of the reaction section 502a by a magnetic field induced by energizing the electromagnet 506c. .

(Step 509: Washing Step Discharge Step) Next, as in step 504, the cleaning reagent W, which is a supernatant, is passed from the reaction compartment 502a through the valve B to the waste liquid compartment 502c by the surface acoustic wave induced by the SAW transfer mechanism 506a. And discharged as waste liquid. As a result, the cleaning reagent W is absorbed by the porous member 502e and held in the waste liquid compartment 502c.

(Step 510: Measurement Stage Introduction Step) Next, similarly to step 501 and step 505, the surface acoustic wave excited by the SAW transfer mechanism 506a is propagated to the analysis chip 502 via the SAW propagation mechanism 504 and the bottom plate 502f. Thus, the measuring reagent M, which is sucked into the dispensing slit 502h and defined by the volume of the dispensing slit, is transferred from the dispensing slit 502h to the reaction zone 502a where the pelletized carrier magnetic particles P are present. As a result, the measurement reagent M is held as a droplet on the pellet in the reaction section 502a.

(Step 511: Measurement Step Magnetic Field Release Step) Next, as in step 506, the electromagnet 506c is de-energized and the magnetic field disappears.

(Step 512: Measurement Step Stirring Step) Next, similarly to step 502 and step 507, the surface acoustic wave excited by the SAW stirring mechanism 506b is propagated to the reaction section 502a via the SAW propagation mechanism 504 and the bottom plate 502f. Thus, the measuring reagent M is stirred. Thereby, the pelletized carrier magnetic particles P are suspended in the measurement reagent M, mixed and stirred, and the measurement reaction is promoted.

(Step 513: Reaction amount measurement step) Next, an optical measurement mechanism 506d is positioned below the optically transmissive portion provided on the bottom surface of the reaction section 502a, and the carrier measurement is performed by the optical measurement mechanism. The reaction amount such as the degree of aggregation of the particles P is measured and evaluated by an optical method such as a turbidimetric method.

  As described above, according to the reaction amount measurement method according to the fifth embodiment, the reagents necessary for the analysis are contained in the reagent cartridge 510 that is separate from the analysis chip 502 and combined with the analysis chip 502 at the time of analysis. Thus, since the reagent is introduced into the analysis chip 502, the analysis chip 502 can be configured as a similar structure without depending on the contents to be analyzed, and the analysis chip 502 can be simplified. Further, by measuring the reagent using the dispensing slit 502h, a dispensing mechanism for the reagent becomes unnecessary, the apparatus mechanism relating to the analysis is simplified, and the apparatus can be further downsized. In addition, since the reagent contained in the reagent cartridge 510 may be an amount that is equal to or larger than the amount used for analysis, the structure of the reagent cartridge 510 can be simplified.

  Each configuration of the reaction amount measurement apparatus 500 according to the fifth embodiment can be variously modified and changed. For example, the porous member 502e provided in the waste liquid compartment 502c can be replaced with a moisture absorbing member such as silica gel. Further, the valve B is not limited to a tapered shape that narrows one of the openings particularly strongly, but can be a tube having a constant opening. Further, the valve B is not limited to a passive one, and an active valve such as an open / close mechanism using a valve structure can also be used.

[Sixth Embodiment]
Next, a reaction amount measurement method according to the sixth embodiment and a reaction amount measurement apparatus that executes the reaction amount measurement method will be described with reference to FIG. Note that in the sixth embodiment, the same descriptions as in the other embodiments may be omitted. FIG. 7 is a conceptual diagram related to the reaction amount measuring apparatus according to the sixth embodiment. FIG. 7A is a plan view showing the reaction amount measuring apparatus according to the sixth embodiment from above, and FIG. 7B is a cross-sectional view thereof.

  First, the configuration of the reaction amount measurement apparatus 600 according to the sixth embodiment will be described. The reaction amount measuring apparatus 600 is roughly composed of an analysis chip 602, a SAW propagation mechanism 604, a chip mount 606, a dispensing means 608, and an optical measurement mechanism 610.

  In addition to the reaction compartment 602a, the slide lid 602b, the waste fluid compartment 602c, the pressure regulating valve 602d, the porous member 602e, the bottom plate 602f, and the reagent compartment 602g, the analysis chip 602 further includes a liquid permeable device 602h. As shown in the figure.

  The liquid permeable device 602h corresponds to the permeable member in the present invention. As shown in the drawing, the liquid permeable device 602h is provided so as to separate the reaction section 602a vertically. Thereby, the valve B for discharging the liquid to the waste liquid compartment 602c is connected to the lower side of the reaction compartment 602a partitioned by the liquid permeable device 602h. The pores of the liquid permeable device 602h are smaller than the diameter of the carrier-encoded particles P that are particles that are encoded with a fluorescent dye or a semiconductor quantum dot and carry an antibody or a nucleic acid probe. As a result, the carrier-encoded particles P cannot reach the lower side of the partitioned reaction section 602a beyond the liquid-permeable device 602h.

  The optical measuring mechanism 610 distributes the liquid permeable device 602h that forms the upper bottom of the reaction compartment 602a and the carrier-encoded particles P held on the upper surface of the liquid permeable device 602h from above the reaction compartment 602a. It is provided so as to be movable so that it can be observed optically.

  An example of a reaction amount measurement method (reaction amount measurement method according to the sixth embodiment) executed by the reaction amount measurement apparatus 600 having the above configuration will be described.

(Step 601: Reaction Stage Introduction Step) First, the sample S is dispensed by the dispensing means 608. Thereby, the dispensed sample S is accommodated and held in the reaction section 602a. Further, the surface acoustic wave excited by the SAW transfer mechanism 606a is propagated to the reagent section 602g via the SAW propagation mechanism 604 and the bottom plate 602f, whereby the carrier coding included and held in one of the reagent sections 602g is encoded. The reaction reagent R containing the particles P is transferred from the reagent compartment 602g to the reaction compartment 602a. As a result, the sample S and the reaction reagent R including the carrier-encoded particles P are integrated in the reaction section 602a and held as the reaction liquid _MSR .

(Step 602: reaction stage stirring step) Next, by propagating a surface acoustic wave excited by the SAW stirring mechanism 606b, to the reaction zone 602a via the SAW propagation mechanism 604 and the bottom plate 602f, the reaction solution _{M SR} Stir. Thereby, the sample S and the reaction reagent R containing the carrier-encoded particles P are sufficiently mixed and stirred, and the reaction between the analyte such as an antibody supported on the carrier-encoded particles P and the sample S is promoted. At that time, the carrier-encoded particles P are held in the reaction compartment 602a on the upper side of the liquid-permeable device 602h.

(Step 603: reaction step discharging process) Next, the surface acoustic wave induced by the SAW transport mechanism 606a, the reaction liquid _{M SR} excluding carrier coded particles P, a liquid pervious equipment 602h through the valve B Discharge as waste liquid to the waste liquid compartment 602c. Thus, reaction liquid _{M SR} is held is absorbed by the porous member 602e inside the waste liquid compartment 602c.

(Step 604: Cleaning Stage Introduction Step) Next, similarly to step 601, the surface acoustic wave excited by the SAW transfer mechanism 606a is propagated to the reagent section 602g via the SAW propagation mechanism 604 and the bottom plate 602f. The cleaning reagent W contained and held in one of the reagent compartments 602g is transferred from the reagent compartment 602g to the reaction compartment 602a with the carrier-encoded particles P.

(Step 605: Washing Step Stirring Step) Next, as in step 602, the surface acoustic wave excited by the SAW stirring mechanism 606b is propagated to the reaction section 602a, thereby stirring the cleaning reagent W in the reaction section. . As a result, the carrier-encoded particles P pelletized on the liquid permeable device 602h are suspended in the cleaning reagent W, mixed and stirred, and the cleaning of the particle surface of the carrier-encoded particles P is promoted.

(Step 606: Cleaning Stage Ejecting Step) Next, in the same manner as in step 603, the cleaning reagent W excluding the carrier-encoded particles P after cleaning is removed from the liquid permeable equipment by the surface acoustic wave induced by the SAW transfer mechanism 606a. From 602h, it passes through the valve B and is discharged as waste liquid to the waste liquid section 602c. As a result, the cleaning reagent W, which is a supernatant, is absorbed and held by the porous member 602e.

(Step 607: Measurement Stage Introduction Step) Next, similarly to the steps 601 and 604, the surface acoustic wave excited by the SAW transfer mechanism 606a is propagated to the reagent section 602g via the SAW propagation mechanism 604 and the bottom plate 602f. Thus, the measurement reagent M contained and held in one of the reagent compartments 602g is transferred from the reagent compartment 602g to the reaction compartment 602a with the carrier-encoded particles P.

(Step 608: Measurement Step Stirring Step) Next, as in step 602 and step 605, the surface acoustic wave excited by the SAW stirring mechanism 606b is propagated to the reaction section 602a, thereby measuring reagent M in the reaction section. Stir. Thereby, the carrier-encoded particles P pelletized on the liquid permeable device 602h are suspended in the cleaning reagent W, mixed and stirred, and the measurement reaction is promoted.

(Step 609: Reaction amount measurement step) Next, the optical measuring mechanism 610 is moved to be positioned above the dispensing opening SL and the slide lid 602b is opened (however, the slide lid 602b is an optically transparent member). If the optical measurement can be performed through the slide lid, the slide lid may be closed.), This corresponds to the reaction amount such as fluorescence of the carrier-encoded particles P held on the upper surface of the liquid permeable device 602h. The positional information of the carrier-encoded particle P is measured and evaluated by an optical method.

  As described above, according to the reaction amount measurement method according to the sixth embodiment, the reagent necessary for analysis is enclosed in the reagent section 602g and mounted on the analysis chip 602, so that the same kind as the dispensing means 608 for the sample S is provided. The reagent dispensing mechanism is not required, the apparatus mechanism for analysis is simplified, and the apparatus can be further miniaturized. In addition, it is possible to optically measure the amount of reaction related to the analyte held by the carrier-encoded particle P while the carrier-encoded particle P is held on the upper surface of the liquid permeable device 602h and the position of each particle can be specified. As a result, a plurality of types of analytes can be analyzed.

  Each configuration of the reaction amount measurement apparatus 600 according to the sixth embodiment can be variously modified and changed. For example, the porous member 602e provided in the waste liquid compartment 602c can be replaced with a moisture absorbing member such as silica gel. Further, the valve B is not limited to a tapered shape that narrows one of the openings particularly strongly, but can be a tube having a constant opening. Further, the valve B is not limited to a passive one, and an active valve such as an open / close mechanism using a valve structure can also be used.

[Seventh Embodiment]
Next, a reaction amount measurement method according to the seventh embodiment and a reaction amount measurement apparatus that executes the reaction amount measurement method will be described with reference to FIG. Note that in the seventh embodiment, the same descriptions as in the other embodiments may be omitted. FIG. 8 is a conceptual diagram related to the reaction amount measuring apparatus according to the seventh embodiment. FIG. 8A is a plan view showing the reaction amount measuring apparatus according to the seventh embodiment from above, and FIG. 8B is a cross-sectional view thereof.

  First, the structure of the reaction amount measuring apparatus 700 according to the seventh embodiment will be described. The reaction amount measuring apparatus 700 is roughly divided into an analysis chip 702, a SAW propagation mechanism 704, a chip mount 706, a dispensing means 708, an optical measurement mechanism 710, and a liquid permeable carrier device 712. Yes.

  The reaction section 702a has a characteristic of propagating surface acoustic waves, and includes a side wall having an optically transmissive portion capable of optically measuring a reaction amount.

  The liquid permeable carrier device 712 corresponds to the permeable carrier member in the present invention. The liquid permeable carrier device 712 is made of a porous ceramic or the like. The liquid permeable carrier device 712 carries a plurality of types of nucleic acid probes in spots divided for each type. The liquid permeable carrier device 712 is provided inside the reaction compartment 702a.

  An example of a reaction amount measurement method (reaction amount measurement method according to the seventh embodiment) executed by the reaction amount measurement apparatus 700 having the above configuration will be described.

(Step 701: Reaction Stage Introduction Step) First, the sample S is dispensed into the reaction section 702a by the dispensing means 708. Thereby, the sample S is accommodated and held in the reaction section 702a. Further, the dispensing reagent 708 dispenses the reaction reagent R into the reaction section 702a. Thus, the sample S and the reagent R is accommodated in the reaction zone 702a as reaction _{M SR} together in the reaction zone 702a. Then, the reaction liquid _{M SR,} the spot portion of the liquid pervious equipment 712 with at least immersed with, is maintained in the reaction zone 702a.

(Step 702: reaction stage stirring step) Next, by propagating a surface acoustic wave excited by the SAW stirring mechanism 706b to the reaction zone 702a via the SAW propagation mechanism 704 and the bottom plate 702f, the reaction was stirred _{M SR} To do. Thereby, the sample S and the reaction reagent R are sufficiently mixed and stirred, and the reaction between the nucleic acid probe carried on the liquid permeable device 712 and the sample S is promoted.

(Step 703: reaction step discharging process) Next, the surface acoustic wave induced by the SAW transport mechanism 706a, the reaction solution _{M SR,} to the waste compartment 702c from the reaction compartment 702a through the valve B, and discharged as waste . Thus, reaction liquid _{M SR} is held is absorbed by the porous member 702e inside the waste liquid compartment 702c.

(Step 704: Washing Stage Introduction Step) Next, as in the step 701, the washing reagent W is dispensed into the reaction section 702a by the dispensing means 708. Accordingly, the cleaning reagent W is held in the reaction section 702a in a state where the spot portion of the liquid permeable device 712 is at least immersed.

(Step 705: Washing Step Stirring Step) Next, as in step 702, the surface acoustic wave excited by the SAW stirring mechanism 706b is propagated to the reaction section 702a, thereby stirring the cleaning reagent W in the reaction section. . Accordingly, the cleaning reagent W is sufficiently permeated into the liquid permeable device 712 and stirred, and the cleaning of the liquid permeable device 712 is promoted.

(Step 706: Washing Stage Discharge Step) Next, as in step 703, the cleaning reagent W, which is the supernatant, is passed from the reaction section 702a through the valve B by the surface acoustic wave induced by the SAW transfer mechanism 706a. The waste liquid is discharged as waste liquid to the waste liquid section 702c. As a result, the cleaning reagent W is absorbed by the porous member 702e and held in the waste liquid compartment 702c.

(Step 707: Measurement Stage Introduction Step) Next, similarly to the steps 701 and 704, the measuring reagent M is dispensed into the reaction section 702a by the dispensing means 708. Thereby, the measurement reagent M is held in the reaction section 702a in a state where the spot portion of the liquid permeable device 712 is at least immersed.

(Step 708: Measurement Step Stirring Step) Next, similarly to Step 702 and Step 705, the surface acoustic wave excited by the SAW stirring mechanism 706b is propagated to the reaction section 702a via the SAW propagation mechanism 704 and the bottom plate 702f. Thus, the measuring reagent M is stirred. As a result, the measurement reagent M is sufficiently permeated into the liquid permeable device 712 and stirred, and the measurement reaction related to the nucleic acid probe carried on the spot portion of the liquid permeable device 712 and the measurement reagent M is promoted.

(Step 709: Reaction amount measurement step) Next, an optical measurement mechanism 710 is positioned in the vicinity of the optically transparent portion provided on the side wall of the reaction section 702a, and the optical measurement mechanism is used to The amount of reaction such as fluorescence is measured and evaluated by an optical method such as fluorescence photometry.

  As described above, according to the reaction amount measurement method according to the seventh embodiment, the analyte type is a spot by supporting the analyte such as a plurality of types of nucleic acid probes on the liquid permeable device 712 as a spot having a different position for each type. It is possible to identify the position information as follows, and it is possible to identify without using codes such as carrier-encoded particles. In addition, since the reaction between the chemical solution and the analyte supported on the liquid permeable device 712 is sufficiently promoted by using the liquid permeable device 712 and the agitation technique using the surface acoustic wave, the dispersibility of the carrier particles and the like can be improved. Equipment may not be used, and as a result, handling of the chemical solution can be simplified.

  Each configuration of the reaction amount measuring apparatus 700 according to the seventh embodiment can be variously modified and changed. For example, the porous member 702e provided in the waste liquid compartment 702c can be replaced with a moisture absorbing member such as silica gel. Further, the valve B is not limited to a tapered shape that narrows one of the openings particularly strongly, but can be a tube having a constant opening. Further, the valve B is not limited to a passive one, and an active valve such as an open / close mechanism using a valve structure can also be used.

  As described above, the reaction amount measurement method according to the present invention can be suitably used in various fields such as biotechnology, pharmaceuticals, and medicine, and is particularly suitable for measuring the reaction amount of a sample using a solid phase carrier. Can be used.

BRIEF DESCRIPTION OF THE DRAWINGS It is a conceptual diagram regarding the reaction amount measuring method concerning 1st Embodiment, and the reaction amount measuring apparatus which performs the said reaction amount measuring method. It is a conceptual diagram regarding the reaction amount measuring apparatus concerning 2nd Embodiment. It is a conceptual diagram regarding the reaction amount measuring apparatus concerning 3rd Embodiment. It is another conceptual diagram regarding the reaction amount measuring apparatus concerning 3rd Embodiment. It is a conceptual diagram regarding the reaction amount measuring apparatus concerning 4th Embodiment. It is a conceptual diagram regarding the reaction amount measuring apparatus concerning 5th Embodiment. It is a conceptual diagram regarding the reaction amount measuring apparatus concerning 6th Embodiment. It is a conceptual diagram regarding the reaction amount measuring apparatus concerning 7th Embodiment.

Explanation of symbols

100, 200, 300, 400, 500, 600, 700 Reaction amount measuring apparatus 102a, 202a, 302a, 402a, 502a, 602a, 702a Reaction section 102b Stirring SAW electrode 102d Transfer SAW electrode 206a, 306a, 406a, 506a, 606a, 706a SAW transfer mechanism 206b, 306b, 406b, 506b, 606b, 706b SAW stirring mechanism 102c, 206c, 306c, 406c, 506c Electromagnet 102e, 202c, 302c, 402c, 502c, 602c, 702c Waste liquid compartment 402g, 510a, 602g Reagent compartment 106, 206d, 310, 406d, 506d, 610, 710 Optical measuring mechanism 602h Liquid-permeable device 712 Liquid-permeable carrier device

Claims (18)

A holding section for holding the substance, a transfer means for transferring the substance, a surface acoustic wave stirring means for stirring the substance by generating a surface acoustic wave for the holding section, and a magnetic field for the holding section A reaction amount measuring method executed by a reaction amount measuring device comprising: a magnetic field control means for generating or releasing the generated magnetic field; and a reaction amount measuring means for measuring a reaction amount of the substance. ,
A reaction stage introducing step of introducing carrier magnetic particles, which are particles having magnetism and carrying an antibody or a nucleic acid probe, a sample, and a reaction reagent into the holding section by the transfer means;
By generating the surface acoustic wave with the surface acoustic wave stirring means for the holding section holding the reaction mixture composed of the carrier magnetic particles and the sample and the reaction reagent introduced in the reaction stage introduction step, A reaction stage stirring step of stirring the reaction mixture in the holding compartment;
A reaction stage magnetic field application step of continuously applying the magnetic field by the magnetic field control means to the holding section holding the reaction mixture stirred in the reaction stage stirring step;
A reaction stage discharging step of discharging the reaction mixture by the transfer means from the holding section in a state where the magnetic field is applied in the reaction stage magnetic field applying step;
A cleaning stage introducing step of introducing a cleaning reagent by the transfer means into the holding section after discharging the reaction mixture in the reaction stage discharging step;
A cleaning stage magnetic field release step for releasing the magnetic field continuously applied to the holding section holding the cleaning reagent and the carrier magnetic particles introduced in the cleaning stage introduction step by the magnetic field control means;
Cleaning that stirs the cleaning reagent in the holding section by generating the surface acoustic wave with the surface acoustic wave stirring means for the holding section in a state where the magnetic field is released in the cleaning stage magnetic field releasing step. A step stirring step;
A cleaning step magnetic field applying step of continuously applying the magnetic field by the magnetic field control means to the holding section holding the cleaning reagent stirred in the cleaning step stirring step;
A cleaning step discharging step of discharging the cleaning reagent by the transfer means from the holding section in a state where the magnetic field is applied in the cleaning step magnetic field applying step;
A measurement stage introduction process for introducing a measurement reagent by the transfer means into the holding section after the cleaning reagent is discharged in the washing stage discharge process;
A measurement stage magnetic field release step of releasing the magnetic field continuously applied to the holding section holding the measurement reagent introduced in the measurement stage introduction step and the carrier magnetic particles by the magnetic field control means;
Measurement in which the measurement reagent is stirred in the holding section by generating the surface acoustic wave with the surface acoustic wave stirring means for the holding section in a state where the magnetic field is released in the measurement stage magnetic field releasing step. A step stirring step;
A reaction amount measurement step of measuring the reaction amount of the sample with the reaction amount measuring means, with the measurement reagent and the carrier magnetic particles stirred in the measurement step stirring step as measurement targets;
A reaction amount measurement method comprising: At least the cleaning stage introduction process, the cleaning stage magnetic field release process, the cleaning stage agitation process, the cleaning stage magnetic field application process, and the cleaning stage discharge process are repeatedly performed a predetermined number of times,
The said measurement stage introduction process introduce | transduces the said measurement reagent to the said holding | maintenance section after discharging | emitting the said washing | cleaning reagent in the last said washing | cleaning stage discharge | emission process performed repeatedly. Reaction amount measurement method. A measurement step magnetic field application step of continuously applying the magnetic field by the magnetic field control means to the holding section holding the measurement reagent and the carrier magnetic particles stirred in the measurement step stirring step;
A measurement stage discharge step of discharging the measurement reagent by the transfer means from the holding section in a state where the magnetic field is applied in the measurement stage magnetic field application step,
The reaction amount measurement step uses the carrier magnetic particles remaining in the holding section after the measurement reagent is discharged in the measurement stage discharge step as the measurement target, and measures the reaction amount of the sample as the reaction amount. The reaction amount measuring method according to claim 1, wherein the reaction amount is measured by means. A holding section for holding a substance, a permeable member having a property of transmitting the substance and having a hole of a predetermined size and disposed in or near the holding section, and a transfer for transferring the substance Reaction amount measuring apparatus comprising: means; surface acoustic wave stirring means for stirring the substance by generating surface acoustic waves with respect to the holding section; and reaction amount measuring means for measuring the reaction amount of the substance The reaction amount measurement method executed in
The size of the hole of the transmissive member is smaller than the size of the carrier-encoded particle, which is a particle encoded with a fluorescent dye or a semiconductor quantum dot and carrying an antibody or a nucleic acid probe,
A reaction stage introduction step of introducing the carrier-encoded particles, the sample and the reaction reagent into the holding section by the transfer means;
By generating the surface acoustic wave by the surface acoustic wave stirring means for the holding section holding the reaction mixture composed of the carrier-encoded particles introduced in the reaction stage introduction step and the sample and the reaction reagent. A reaction stage stirring step of stirring the reaction mixture in the holding section;
A reaction stage discharging step of discharging the reaction mixture through the permeable member by the transfer means from the holding section holding the reaction mixture stirred in the reaction stage stirring step;
A cleaning stage introducing step of introducing a cleaning reagent by the transfer means into the holding section after discharging the reaction mixture in the reaction stage discharging step;
By generating the surface acoustic wave by the surface acoustic wave stirring means for the holding section holding the cleaning reagent and the carrier-encoded particles introduced in the cleaning stage introduction step, the surface acoustic wave is generated in the holding section. A cleaning step stirring step of stirring the cleaning reagent;
A cleaning step discharging step of discharging the cleaning reagent through the permeable member by the transfer means from the holding section holding the cleaning reagent stirred in the cleaning step stirring step;
A measurement stage introduction process for introducing a measurement reagent by the transfer means into the holding section after the cleaning reagent is discharged in the washing stage discharge process;
The surface acoustic wave is generated by the surface acoustic wave stirring means with respect to the holding section holding the measurement reagent and the carrier-encoded particles introduced in the measurement stage introduction step, so that the surface acoustic wave is generated in the holding section. A measurement step of stirring the measurement reagent; and
A reaction amount measuring step of measuring the reaction amount of the sample together with the position of the sample by the reaction amount measuring means, with the measurement reagent and the carrier-encoded particles stirred in the measurement step stirring step as measurement targets;
A reaction amount measurement method comprising: A measurement step discharging step of discharging the measurement reagent from the holding section holding the measurement reagent stirred in the measurement step stirring step and the carrier-encoded particles through the permeable member by the transfer means. ,
In the reaction amount measurement step, the reaction amount of the sample is set as the measurement target using the carrier-encoded particles remaining in the holding section after the measurement reagent is discharged in the measurement stage discharge step. The reaction amount measuring method according to claim 4, wherein the reaction amount is measured together with the position by the reaction amount measuring means. A holding section for holding a substance, a permeable carrier member having a property of transmitting the substance and supporting an antibody or a nucleic acid probe and disposed in or near the holding section, and a transfer for transferring the substance Reaction amount measuring apparatus comprising: means; surface acoustic wave stirring means for stirring the substance by generating surface acoustic waves with respect to the holding section; and reaction amount measuring means for measuring the reaction amount of the substance The reaction amount measurement method executed in
A reaction stage introduction step of introducing a sample and a reaction reagent into the holding section by the transfer means;
By generating the surface acoustic wave by the surface acoustic wave stirring means for the holding section holding the reaction mixture composed of the sample and the reaction reagent introduced in the reaction stage introduction step, in the holding section A reaction stage stirring step of stirring the reaction mixture;
A reaction stage discharging step of discharging the reaction mixture through the permeable carrier member by the transfer means from the holding section holding the reaction mixture stirred in the reaction stage stirring step;
A cleaning stage introducing step of introducing a cleaning reagent by the transfer means into the holding section after discharging the reaction mixture in the reaction stage discharging step;
Cleaning that stirs the cleaning reagent in the holding section by generating the surface acoustic wave with the surface acoustic wave stirring means for the holding section holding the cleaning reagent introduced in the cleaning stage introduction step A step stirring step;
A cleaning stage discharging step of discharging the cleaning reagent through the permeable carrier member by the transfer means from the holding section holding the cleaning reagent stirred in the cleaning stage stirring step;
A measurement stage introduction process for introducing a measurement reagent by the transfer means into the holding section after the cleaning reagent is discharged in the washing stage discharge process;
Measurement of stirring the measurement reagent in the holding section by generating the surface acoustic wave with the surface acoustic wave stirring means for the holding section holding the measurement reagent introduced in the measurement stage introduction step A step stirring step;
A reaction amount measurement step of measuring the reaction amount of the sample together with the position of the sample by the reaction amount measuring means, with the measurement reagent and the permeable carrier member stirred in the measurement step stirring step as measurement targets;
A reaction amount measurement method comprising: A measurement stage discharging step of discharging the measurement reagent from the holding section holding the measurement reagent stirred in the measurement stage stirring step via the permeable carrier member by the transfer means,
In the reaction amount measuring step, the reaction amount measuring means together with the position of the sample and the reaction amount of the sample are measured with the permeable carrier member after the measurement reagent is discharged in the measurement stage discharging step as the measurement object. The reaction amount measurement method according to claim 6, wherein At least the cleaning stage introduction process, the cleaning stage stirring process and the cleaning stage discharge process are repeatedly performed a predetermined number of times,
8. The measurement step introduction step introduces the measurement reagent to the holding section after the cleaning reagent is discharged in the last cleaning step discharge step that has been repeatedly executed by the transfer means. The reaction amount measuring method according to any one of the above. The reaction amount measurement method according to claim 1, wherein the holding section has hydrophilicity. The reaction amount measuring device includes a storage compartment for storing the substance discharged from the holding compartment in the vicinity of the holding compartment,
At least in the reaction stage discharging step, the reaction mixture is discharged to the storage compartment, and in the cleaning stage discharging step, the cleaning reagent is discharged to the storage compartment. The reaction amount measuring method described in 1. The reaction amount measuring device includes a backflow prevention means for preventing the substance stored in the storage compartment from flowing back to the holding compartment, and transferring the substance from the holding compartment to the storage compartment. The reaction amount measurement method according to claim 10, wherein the reaction amount measurement method is provided on a route. The reaction amount measuring method according to claim 10 or 11, wherein the reaction amount measuring device includes pressure adjusting means for adjusting the pressure so that the pressure inside the storage compartment does not become higher than atmospheric pressure. . 13. The storage section according to claim 10, wherein a porous holding member, which is a porous member having a property of holding the substance, is provided in the storage compartment. Reaction amount measurement method. The reaction amount measuring device includes a storage section for storing the substance to be introduced into the holding section in the vicinity of the holding section,
In the reaction stage introduction process, the reaction reagent is introduced from the storage section, in the cleaning stage introduction process, the cleaning reagent is introduced from the storage section, and in the measurement stage introduction process, the measurement reagent is introduced from the storage section. The method for measuring a reaction amount according to any one of claims 1 to 13, wherein: The reaction amount measuring device is provided with a slit having a predetermined volume and a hydrophilic inner wall between the storage compartment and the holding compartment,
In the reaction stage introduction process, the reaction reagent is introduced from the storage section through the slit, in the cleaning stage introduction process, the cleaning reagent is introduced from the storage section through the slit, and in the measurement stage introduction process, The reaction amount measurement method according to claim 14, wherein the measurement reagent is introduced from the storage section through the slit. The reaction amount measuring device includes a suction port for sucking the substance stored in the storage section when connected to the storage section, between the slit and the storage section.
The storage compartment is a separate cartridge from the holding compartment, has a penetrating partition, and is connected to the holding compartment through the suction port by passing the suction port through the partition. ,
In the reaction stage introduction process, the reaction reagent is introduced from the storage compartment through the suction port and the slit, and in the cleaning stage introduction process, the cleaning reagent is introduced from the storage compartment through the suction port and the slit. The reaction amount measurement method according to claim 15, wherein in the measurement stage introduction step, the measurement reagent is introduced from the storage compartment through the suction port and the slit. The reaction amount according to any one of claims 1 to 16, wherein the reaction amount measuring means optically measures the reaction amount of the substance by chemiluminescence, fluorescence, turbidity, or colorimetry. Measuring method. The reaction amount measurement method according to any one of claims 1 to 17, wherein the reaction amount measurement device includes a plurality of sets of the set provided therein.

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