WO2010029785A1 - Récipient de réaction, microplaque et analyseur - Google Patents

Récipient de réaction, microplaque et analyseur Download PDF

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Publication number
WO2010029785A1
WO2010029785A1 PCT/JP2009/055459 JP2009055459W WO2010029785A1 WO 2010029785 A1 WO2010029785 A1 WO 2010029785A1 JP 2009055459 W JP2009055459 W JP 2009055459W WO 2010029785 A1 WO2010029785 A1 WO 2010029785A1
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WO
WIPO (PCT)
Prior art keywords
reaction
liquid
amount
reaction vessel
microplate
Prior art date
Application number
PCT/JP2009/055459
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English (en)
Japanese (ja)
Inventor
真也 松山
Original Assignee
オリンパス株式会社
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by オリンパス株式会社 filed Critical オリンパス株式会社
Publication of WO2010029785A1 publication Critical patent/WO2010029785A1/fr

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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/028Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations having reaction cells in the form of microtitration plates
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1009Characterised by arrangements for controlling the aspiration or dispense of liquids
    • G01N2035/1025Fluid level sensing

Definitions

  • the present invention relates to a reaction vessel, a microplate, and an analyzer for performing an immunological agglutination reaction.
  • a microplate in which a plurality of reaction containers called wells are arranged in a matrix is used (see Patent Document 3).
  • a specimen containing a substance to be analyzed and a reaction reagent containing a substance that causes an antigen-antibody reaction with the substance to be analyzed are dispensed.
  • an imaging means such as a CCD camera, and the components of the specimen are analyzed using the image data obtained by this imaging .
  • JP 2001-174469 A JP-A-5-52853 JP-A-57-66361
  • the confirmation method shown in Patent Document 1 is a method of imaging one reaction container, when imaging a microplate having a plurality of reaction containers (wells) from the side, the reaction containers overlap, There is a problem that only the dispensing amount of the reaction container located on the outermost side can be confirmed.
  • the confirmation method shown in Patent Document 2 directly adds a solution whose color tone changes depending on the hydrogen ion concentration to the reaction solution in which the specimen and the reagent are mixed, the reactivity may be lowered.
  • the microplate to visually confirm the dispensing amount. In this case, in the microplate as shown in Patent Document 3, it takes time and effort to determine the liquid amount even if the reaction container is observed from above. There was a problem that it was necessary.
  • the present invention has been made in view of the above, and provides a reaction container, a microplate, and an analyzer that can easily and easily confirm the amount of solution contained in each of a plurality of reaction containers. With the goal.
  • a reaction container is a reaction container that contains and reacts a reagent and a specimen, and the amount of reaction liquid in the reaction container is placed on the reaction container side wall. When the amount exceeds a predetermined amount, a liquid intrusion part is provided on the liquid intrusion part for allowing the reaction liquid to enter.
  • the reaction vessel according to the present invention is characterized in that, in the above invention, the liquid intrusion portion is a step portion in a radial direction inclined with respect to a horizontal plane.
  • the reaction container according to the present invention is characterized in that, in the above invention, the step portion is inclined so as to indicate the amount of the reaction solution depending on the position of the reaction liquid that has entered the step portion. .
  • the reaction vessel according to the present invention is characterized in that, in the above invention, the liquid intrusion portion is a groove portion formed in a side wall of the reaction vessel.
  • the reaction vessel according to the present invention is characterized in that, in the above invention, the groove is a recess formed in a side wall of the reaction vessel.
  • the reaction vessel according to the present invention is characterized in that, in the above invention, a plurality of the recesses are provided, and each recess has a different intrusion position of the reaction solution.
  • micropileate according to the present invention is characterized in that, in the above-mentioned invention, a plurality of the reaction containers according to any one of claims 1 to 6 are provided.
  • micropileate according to the present invention is characterized in that, in the above invention, the reaction vessels are arranged in alignment.
  • micropileate according to the present invention is characterized in that, in the above-mentioned invention, a scale indicating an appropriate border position is provided between the reaction vessels.
  • the analysis apparatus includes an image acquisition unit that acquires an image of the upper surface of the microplate, and an image acquired by the image acquisition unit.
  • a determination means for determining a border position of the reaction liquid that has entered the liquid intrusion portion or whether or not the reaction liquid has entered, and a determination means for determining whether or not the amount of the reaction liquid is appropriate based on the determination result by the determination means And.
  • the liquid intrusion part into which the reaction liquid infiltrates is provided on the reaction container side wall of each reaction container. From the top of the plate, the amount of the solution stored in each of the plurality of reaction containers can be easily and easily confirmed.
  • FIG. 1 is a plan view schematically showing a microplate according to a first embodiment of the present invention.
  • FIG. 2 is a schematic diagram illustrating a plane and a side surface of the reaction container of the microplate according to the first embodiment of the present invention.
  • FIG. 3 is a schematic diagram showing a plane and side surfaces of a reaction vessel of a microplate according to a modification of the first embodiment of the present invention.
  • FIG. 4 is a schematic diagram illustrating an analyzer that performs analysis using the microplate according to the first embodiment of the present invention.
  • FIG. 5 is a partial plan schematic view in which an appropriate amount confirmation line is provided on the microplate according to the first embodiment of the present invention.
  • FIG. 6 is a schematic diagram illustrating a plane and a side surface of a reaction vessel of a microplate according to a second embodiment of the present invention.
  • FIG. 7 is a schematic diagram showing a plane and side surfaces of a reaction vessel of a microplate according to a modification of the second embodiment of the present invention.
  • FIG. 8 is a schematic diagram illustrating a plane and a side surface of the reaction vessel having the configuration according to the first embodiment of the present invention.
  • FIG. 1 is a schematic diagram illustrating a schematic configuration of a microplate according to a first embodiment of the present invention.
  • the microplate 1 has a circular opening on a plate-like plane, and a plurality of reaction vessels 2, which are reaction vessels formed with recesses for dispensing a sample or a reagent to cause a reaction, are arranged in a matrix.
  • the microplate 1 is formed by injection molding a synthetic resin such as acrylic.
  • the microplate 1 displays a reaction vessel identification information display for displaying reaction vessel identification information for identifying each reaction vessel 2 on the front surface or back surface outside the region passing through the opening surfaces of the plurality of reaction vessels 2. You may each provide in the reaction container 2 vicinity.
  • FIG. 2 is a plan view and a side view schematically showing the reaction vessel 2 of the microplate 1 shown in FIG.
  • the reaction vessel 2 has an arbitrary cross section (cross section) in a direction parallel to the opening surface, and the diameter of the circle formed by each cross section decreases from the opening surface to the bottom.
  • the bottom of the reaction liquid storage unit 20 serves as a liquid storage tank during dispensing, the bottom of the reaction liquid storage unit 20 has a substantially conical shape with a convex bottom, and this inclined part expands the surface area and causes an antigen-antibody reaction.
  • it may have a stepped shape (not shown) whose diameter slightly changes stepwise.
  • the reaction vessel 2 is formed with a step portion 21 as a liquid intrusion portion on the upper side wall of the reaction solution storage portion 20 where the amount of the reaction solution can be confirmed.
  • the step portion 21 forms a cylindrical region that is coaxial with the reaction solution storage unit 20 and has a diameter larger than the diameter of the reaction solution storage unit 20, and a region obtained by subtracting the region of the reaction solution storage unit 20 from this region. It is a cylindrical region to be formed, and the lower section (bottom) is inclined with respect to the liquid surface (opening surface).
  • the step portion 21 is formed so that the border position S of the reaction liquid that has entered the step portion 21 enters the slope of the step portion 21 when a predetermined amount of the reaction solution is stored in the reaction solution storage portion 20. Is done.
  • the diameter of the step portion 21 is the same as the opening surface of the reaction vessel 2.
  • the reaction solution when the amount of the reaction solution is less than the appropriate amount, the reaction solution does not enter the stepped portion 21 and only the reaction solution storage unit 20 is filled with the reaction solution. When the amount exceeds the appropriate amount, the reaction solution enters the entire surface on the step portion 21. Note that the inclination of the stepped portion 21 may be adjusted according to the appropriate amount position of the reaction liquid. Further, the waterfront position S is easily discriminated because the refractive index or transmittance of light in the vicinity of the waterfront position S changes depending on the surface tension of the reaction liquid with respect to the stepped portion 21.
  • the analysis device 3 using the imaging device 31 confirms the analysis result and confirms the amount of the reaction solution.
  • the analysis device 3 includes an imaging device 31 and a light source 32, and the imaging device 31 captures an image on the upper surface of the microplate 1 and outputs the captured image to the image processing unit 33.
  • the shore position determination unit 34 determines the position of the shore position S based on the input image, and the liquid amount determination unit 35 uses the determination result of the shore position determination unit 34.
  • the analysis unit 36 analyzes the aggregation reaction result of each reaction vessel based on the input image and outputs the analysis result to the output unit 37.
  • the output unit 37 outputs the determination result input from the liquid amount determination unit 35 and the analysis result input from the analysis unit 36.
  • liquid level confirmation line L corresponding to the border position S where the liquid volume of the reaction liquid is appropriate on the surface excluding the opening surface of the microplate 1. Based on the positional relationship between the liquid amount confirmation line L and the border position S, it can be easily confirmed whether or not the amount of the reaction liquid is an appropriate amount. In particular, it is suitable for visual confirmation.
  • the stepped portion 21 may be formed in a spiral shape that gradually increases in the circumferential direction.
  • the border position S is positioned so as to go around the reaction solution storage unit 20 as the amount of the reaction solution increases or decreases.
  • the circumferential height of the spiral shape may be changed stepwise. By providing this stepwise difference in height, the border position S can be confirmed discretely, and visual confirmation becomes easy. Further, in this case, it is possible to easily confirm whether or not each dispensed amount is an appropriate amount in an analysis in which several steps are dispensed.
  • the amount of the reaction solution is changed by using the change in the refractive index or transmittance of the light at the border position S of the reaction solution. It can be easily confirmed from the side. In addition, the amount of the reaction solution can be simultaneously confirmed with a simple configuration using the imaging result of the imaging device used for analysis.
  • FIG. 6 is a schematic diagram illustrating a plane and a side surface of the reaction container 2 of the microplate according to the second embodiment.
  • the reaction vessel 2 is provided with a recess 23 in the vicinity of the side wall of the reaction solution storage unit 20 via a barrier 24 instead of the stepped portions 21 and 22.
  • the reaction liquid exceeding the barrier 24 is stored.
  • the height of the barrier 24 is set to be the same as the appropriate liquid level of the reaction solution.
  • FIG. 6 shows a state where the amount of the reaction solution slightly exceeds an appropriate amount.
  • the amount of the reaction solution When determining whether or not the amount of the reaction solution is an appropriate amount, it can be set by varying the capacity of the recess 23 to store the reaction solution. Increasing the capacity of the recess 23 increases the application range.
  • the appropriate amount range can be a state in which the reaction solution is filled in the opening surface of the recess 23 and the reaction solution is not filled in the barrier 24. When the barrier 24 is filled with the reaction solution, it can be determined that the appropriate amount has been exceeded. Whether or not the barrier 24 is filled with the reaction liquid can be confirmed by whether or not the reaction liquid on the opening surface of the recess 23 is hemispherical, that is, circular due to surface tension.
  • FIG. 6 only one recess 23 is provided in FIG. 6, but the present invention is not limited to this, and a plurality of recesses 23 and 25 may be provided as shown in FIG. In this case, it is preferable to make the heights of the barriers 24 and 26 of the recesses 23 and 25 different. By providing the plurality of recesses 23 and 25 and the barriers 24 and 26, the amount of the reaction solution can be confirmed stepwise.
  • the amount of the reaction solution can be automatically determined by the imaging process by the analyzer 3.
  • each reaction vessel 2 of the first and second embodiments can be used as a single reaction vessel.
  • FIG. 8 is a schematic diagram illustrating a plane and a side surface of the reaction container having the configuration according to the first embodiment.
  • the reaction vessel 4 shown in FIG. 8 has a step portion 41 as a liquid intrusion portion formed on the upper portion of the reaction solution storage portion 40 in the same manner as the reaction vessel 2 shown in FIG. 2, and the amount of liquid can be easily confirmed visually. it can.
  • the configuration according to the second embodiment can be similarly applied.
  • the reaction vessel 4 can also check the liquid volume using the analyzer 3 described above.
  • the step portions 21 and 22 and the recesses 23 and 25 are preferably formed with hydrophobicity.
  • the stepped portions 21 and 22 of the first embodiment are formed by forming the stepped portions 21 and 22 with hydrophobicity in order to confirm the border position S using a change in refractive index or transmittance due to surface tension.
  • 22 is preferably increased in surface tension of the reaction solution.
  • the barriers 24 and 26 are made hydrophobic so that the reaction solution does not remain on the barriers 24 and 26 until the recesses 23 and 25 are filled with the reaction solution. The amount can be confirmed easily and accurately.
  • the shape of the bottom of the reaction vessel may be a cone or a prism, and can be used in a shape suitable for the application.
  • reaction container, microplate and analyzer are useful for confirming the amount of dispensed liquid, and are particularly used for immunological analysis including blood and body fluid. Suitable for automatic analyzers.

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  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)

Abstract

La présente invention concerne une microplaque et un analyseur comportant une pluralité de récipients de réaction (2), dans lesquels un réactif et un échantillon sont amenés à réagir, dans un plan en forme de plaque. Chaque récipient de réaction (2) comporte une partie irrégulière (21), dans laquelle le mélange réactionnel liquide pénètre lorsque la quantité de mélange réactionnel liquide présente dans le récipient de réaction (2) dépasse un niveau prédéterminé, sur la paroi latérale. Dans la partie irrégulière (21), un gradin, incliné en direction du plan horizontal, est présent dans le sens radial pour indiquer la quantité de mélange réactionnel liquide sur la base de la position du front d'eau (S) du mélange réactionnel liquide pénétrant dans la partie irrégulière (21). La quantité à l’emplacement du mélange réactionnel liquide peut être confirmée à partir de ladite position du front d'eau (S).
PCT/JP2009/055459 2008-09-11 2009-03-19 Récipient de réaction, microplaque et analyseur WO2010029785A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2008-233584 2008-09-11
JP2008233584 2008-09-11

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WO2010029785A1 true WO2010029785A1 (fr) 2010-03-18

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2971145A4 (fr) * 2013-03-15 2016-12-07 Qiagen Gaithersburg Inc Appareil d'aspiration guidé par la vue et procédés associés

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5766361A (en) * 1980-10-09 1982-04-22 Olympus Optical Co Ltd Plate-shaped apparatus for judging cohesion of particle
JPS6320039A (ja) * 1986-07-10 1988-01-27 テクニコン、インストルメンツ、コ−ポレ−シヨン 試料液体カツプ
JPS6363769U (fr) * 1986-10-16 1988-04-27
JPH10221243A (ja) * 1996-11-25 1998-08-21 Porvair Plc マイクロプレート及びマイクロプレート製造方法
WO2002025289A1 (fr) * 2000-09-18 2002-03-28 I-Card Corporation Ensemble de micro-coupelles et procede permettant d'enfermer hermetiquement des liquides au moyen de cet ensemble
JP2007298445A (ja) * 2006-05-01 2007-11-15 Olympus Corp 液面検知装置

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5766361A (en) * 1980-10-09 1982-04-22 Olympus Optical Co Ltd Plate-shaped apparatus for judging cohesion of particle
JPS6320039A (ja) * 1986-07-10 1988-01-27 テクニコン、インストルメンツ、コ−ポレ−シヨン 試料液体カツプ
JPS6363769U (fr) * 1986-10-16 1988-04-27
JPH10221243A (ja) * 1996-11-25 1998-08-21 Porvair Plc マイクロプレート及びマイクロプレート製造方法
WO2002025289A1 (fr) * 2000-09-18 2002-03-28 I-Card Corporation Ensemble de micro-coupelles et procede permettant d'enfermer hermetiquement des liquides au moyen de cet ensemble
JP2007298445A (ja) * 2006-05-01 2007-11-15 Olympus Corp 液面検知装置

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2971145A4 (fr) * 2013-03-15 2016-12-07 Qiagen Gaithersburg Inc Appareil d'aspiration guidé par la vue et procédés associés

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