EP2480323B1 - Procédé et dispositif de mélange d'une solution hétérogène en solution homogène - Google Patents

Procédé et dispositif de mélange d'une solution hétérogène en solution homogène Download PDF

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Publication number
EP2480323B1
EP2480323B1 EP20100769027 EP10769027A EP2480323B1 EP 2480323 B1 EP2480323 B1 EP 2480323B1 EP 20100769027 EP20100769027 EP 20100769027 EP 10769027 A EP10769027 A EP 10769027A EP 2480323 B1 EP2480323 B1 EP 2480323B1
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EP
European Patent Office
Prior art keywords
vessel
rotation
axis
container
support
Prior art date
Legal status (The legal status 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 status listed.)
Active
Application number
EP20100769027
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German (de)
English (en)
French (fr)
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EP2480323A1 (fr
Inventor
Tom Beumer
Wilco Brusselaars
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Biomerieux SA
Original Assignee
Biomerieux SA
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Filing date
Publication date
Application filed by Biomerieux SA filed Critical Biomerieux SA
Publication of EP2480323A1 publication Critical patent/EP2480323A1/fr
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Publication of EP2480323B1 publication Critical patent/EP2480323B1/fr
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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F31/00—Mixers with shaking, oscillating, or vibrating mechanisms
    • B01F31/10—Mixers with shaking, oscillating, or vibrating mechanisms with a mixing receptacle rotating alternately in opposite directions
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F31/00—Mixers with shaking, oscillating, or vibrating mechanisms
    • B01F31/20—Mixing the contents of independent containers, e.g. test tubes
    • B01F31/22—Mixing the contents of independent containers, e.g. test tubes with supporting means moving in a horizontal plane, e.g. describing an orbital path for moving the containers about an axis which intersects the receptacle axis at an angle
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F2101/00—Mixing characterised by the nature of the mixed materials or by the application field
    • B01F2101/23—Mixing of laboratory samples e.g. in preparation of analysing or testing properties of materials
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F2215/00—Auxiliary or complementary information in relation with mixing
    • B01F2215/04—Technical information in relation with mixing
    • B01F2215/0413—Numerical information
    • B01F2215/0418—Geometrical information
    • B01F2215/0422—Numerical values of angles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F23/00—Mixing according to the phases to be mixed, e.g. dispersing or emulsifying
    • B01F23/40—Mixing liquids with liquids; Emulsifying
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F23/00—Mixing according to the phases to be mixed, e.g. dispersing or emulsifying
    • B01F23/50—Mixing liquids with solids

Definitions

  • the present invention relates to a method for mixing a heterogeneous solution containing a liquid and a solid entity or at least two different liquids and, optionally, a solid entity in order to obtain a homogeneous solution, in which method the heterogeneous solution is available in a container.
  • the method is particularly interesting because it proposes the combination of a circular or orbital non-circular movement of the container which has an axis of symmetry which is itself inclined with respect to gravity.
  • the invention also proposes a device allowing the implementation of such a method.
  • a mixture should not be performed with too much force that could create a suspension desired solutions to be mixed either by centrifugation, with phase separation, or in the form of aerosols or emulsion, which can generate, for example if one treats nucleic acids, cross-contamination detrimental to a reliable subsequent diagnosis .
  • a mixture must, in certain cases, be carried out within a defined period of time in order to prevent the solutions to be mixed from being subjected to temperature variations or else a secondary reaction to take place.
  • the mixing techniques used in the laboratory are more or less complex to implement.
  • One of the mixing techniques consists, when adding a second solution to a first solution present in a container, to alternately perform suction several times followed by a discharge in the container using a cone by the action of the piston of a pipette.
  • the disadvantage of this method is that it requires during its implementation a certain dexterity and delicacy on the part of the user. The repetitiveness of such an operation is also doubtful depending on this user and its state of fatigue, nervousness, etc. Indeed, too high frequency of suction / discharge related to a bad position of the cone in the container may cause the appearance of air bubbles within the mixture.
  • the enzymes, buffers and other reagents useful for the amplification reaction are added to the biological sample and a small volume of oil.
  • This volume of oil covers the amplification mixture and prevents the evaporation of the amplification reagents during the different heating cycles during the amplification.
  • the oily phase mixes with the aqueous phase creating an emulsion which will prevent the action of the enzyme.
  • the patent application US-2006/0177936 offers a universal tube holder that is configured to perform sample preparation.
  • An apparatus for centrifugally vortexing includes a motor with a rotating system on which the portable universal tube holder is mounted for rotation and oscillation thereof. This technique results in the ability to more effectively mix at least two liquids or at least one liquid and at least one solid entity, for example, consisting of magnetic particles. More effectively, it should be understood that this patent application advocates back-and-forth movements, called oscillations.
  • the prior art US Patent 5,921,676 also discloses a mixing technique using a mixing device whose platform is driven by an orbital movement horizontal and / or vertical.
  • This device makes it possible to mix volumes of large or medium quantity, that is to say of the order of milliliter.
  • it does not make it possible to effectively mix volumes smaller than one milliliter. Indeed, as the diameter of the container containing the solutions to be mixed is greater than the diameter of the orbital movement, the mixture of solutions will be effective.
  • the center of the container performs an orbital distance equivalent to the orbital distance of the platform, thereby generating centrifugal forces in the liquid that change diametrically direction at each half rotation and allow mixing of the solutions.
  • the document FR-A-2436624 apparatus for mixing a fluid material in a container comprising: a first container support means for rotating about a first axis; second means for supporting the container, allowing its rotation about a second axis which is not perpendicular to the first; first drive means connected to said second support means for rotating the container about said second axis; and a second driving means which is connected to said first support means for rotating the container about said first axis while the container is rotating about said second axis.
  • the problem with this type of device is that both axes of rotation are always intersected. There is therefore an area in the vicinity of this intersection that has almost no movement, so there will be a mixture that will be differential between the closest and the farthest points of this intersection point and therefore a non-homogeneous mixture at the intersection. within the liquid or liquids.
  • the devices of the prior art fail to mix small volumes of heterogeneous solutions into a homogeneous solution while preventing the formation of emulsions and / or aerosols (risk of contamination in the medical field for example) and wetting all the walls of the container. There is therefore still a need for a new mixing device counteracting the disadvantages of those of the prior art.
  • the Applicant proposes a new device for mixing heterogeneous solutions to obtain a homogeneous solution. Thanks to the device according to the invention, the solutions contained in the container undergo successive accelerations and decelerations whose sinusoidal intensity allows their gentle agitation while avoiding wetting of the entire walls of the container and / or a dispersion of the phases of the different solutions. This device also makes it possible to dispense with a centrifugation step after mixing.
  • heterogeneous solution means at least two liquids or fluids which are miscible in the aqueous phase and have different properties and viscosities. These fluids may contain solid entities or suspended particles. These liquids and possibly the solid entities that are contained in these liquids are unevenly and irregularly distributed in the container containing them.
  • homogeneous solution means a solution whose constituent elements are uniformly and regularly distributed in the container which contains them.
  • mixing in the sense of the present invention, means joining in a container at least two liquids having different properties so that they form a single liquid whose constituent elements are distributed uniformly and homogeneous. It can also be at least one liquid associated with at least one type of solid entities or particles in suspension.
  • solid entity is intended to mean particles which may be made of latex, glass (GPC), silica, polystyrene, agarose, sepharose, nylon, etc. These materials may possibly allow the confinement of magnetic material. It can also be a filter, a film, a membrane or a strip. These materials are well known to those skilled in the art.
  • rotation in the sense of the present invention defines a plane motion of a body where all the points of the body describe trajectories of the same geometrical shape but which have different centers, the centers being parallel to each other during the movement.
  • the trajectory can be in the form of a circle; the body rotates.
  • the trajectory can be elliptical; the body undergoes a elliptical translation.
  • the end of the cap is located at a distance L1 from the axis of the rotational movement (the position said to be closest to the axis) and the end of the bottom of the tube is at a distance L2 from the axis of the rotational movement (so-called position furthest from the axis).
  • L1 the position said to be closest to the axis
  • L2 the axis of the rotational movement
  • the end of the cap and the end of the bottom form a segment which moves in a parallel manner about this axis; the segment describing for example a trajectory in the form of a circle.
  • the end of the cap and the end of the circle are at the same distance L3 from the axis of the movement.
  • sufficient air volume denotes a portion of a space of the air-filled vessel allowing during the rotational movement the free movement of liquids within the container.
  • substantially vertical position is meant in the present invention, any position varying from an angle between 0 ° and ⁇ 2 ° with respect to an axis of gravity.
  • This method can also be applied to mixing a heterogeneous solution containing at least one liquid and at least one solid entity.
  • the longitudinal axis of the container crosses twice the axis of rotation of said support per revolution.
  • the container contains in addition to the heterogeneous solution a volume of air sufficient to allow agitation without all or part of said heterogeneous solution can not leave said container during mixing.
  • the container contains in addition to the heterogeneous solution a volume of air sufficient to allow agitation and is closed by a plug, so that all or part of said heterogeneous solution can not leave said container when mixing.
  • the inclination of the longitudinal axis of the container varies according to the speed of rotation and / or according to its position during rotation.
  • the movement of the support is circular.
  • the movement of the support is ellipsoidal.
  • the axis of rotation of the support is in a substantially vertical position and that the longitudinal axis of the container is not in a substantially vertical position.
  • an angle of inclination of the longitudinal axis of the container relative to the axis of rotation of the support exists, and when the two axes are intersected, the angle is between 1 and 60 °, preferably between 20 and 50 ° and even more preferably between 25 and 45 °.
  • the container is closed.
  • the mixer according to the invention essentially uses a known "orbital" mixing device, but instead of placing the tube with its axis of symmetry parallel to the axis of rotation, we place the axis of symmetry of the tube at a non-symmetrical angle. parallel with the axis of rotation of the device and with gravity.
  • the method can be used with reaction vessels of virtually any shape, and has the most benefit in cases where conventional orbital or vortex oscillation methods are not suitable.
  • the normal mechanical arrangement for orbital motion as a mixing medium for liquids is shown on the figure 1 .
  • a solid support for example a horizontal table 1, movements confined in small circles or rotation 2 having a radius 5 and an axis of symmetry / rotation 3 of the table 1, preferably parallel to the gravity.
  • Each container 7, the contents of which must be mixed, is placed vertically on said table 1 with its axis of symmetry 4 parallel to the axis of rotation 3.
  • axis of symmetry 4 parallel to the axis of rotation 3.
  • an orbital mixer 9 in which the container 7 containing the liquid 8 to be mixed is placed at an angle 6 with respect to the axis of rotation 3, itself parallel to gravity. More and this is represented on the figure 3 , the inclination of the container 7 is always the same relative to the horizontal or the vertical for an outside observer in lateral position. In other words, an observer in this position will have the feeling that the container 7 will move alternately left and right and vice versa, said container 7 which remains a stable inclination.
  • the quality of the blend was judged visually, using high-speed video images, recorded at 200 frames per second, providing a time resolution of approximately 5 milliseconds (ms).
  • a cylindrical tube 11 of constant radius is used; in this case, a low viscosity of relatively small amounts of liquid mixes well even at near-zero angles. But if the viscosity and / or volume increases or when the oil is added, the zero degree mixture becomes much more difficult.
  • the improvement of the mixture is detectable even at small angles ( figure 8 ). Even small changes help to reduce mixing time, but we see that the best performance is achieved for angles greater than 20 degrees and even with larger angles, mixing time is decreased to levels close to mixing times the fastest for small volumes.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Mixers With Rotating Receptacles And Mixers With Vibration Mechanisms (AREA)
  • Mixers Of The Rotary Stirring Type (AREA)
EP20100769027 2009-09-25 2010-09-24 Procédé et dispositif de mélange d'une solution hétérogène en solution homogène Active EP2480323B1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR0904580A FR2950541B1 (fr) 2009-09-25 2009-09-25 Procede et dispositif de melange d'une solution heterogene en solution homogene
PCT/FR2010/052008 WO2011039453A1 (fr) 2009-09-25 2010-09-24 Procédé et dispositif de mélange d'une solution hétérogène en solution homogène

Publications (2)

Publication Number Publication Date
EP2480323A1 EP2480323A1 (fr) 2012-08-01
EP2480323B1 true EP2480323B1 (fr) 2014-11-12

Family

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Application Number Title Priority Date Filing Date
EP20100769027 Active EP2480323B1 (fr) 2009-09-25 2010-09-24 Procédé et dispositif de mélange d'une solution hétérogène en solution homogène

Country Status (5)

Country Link
US (1) US9084974B2 (ja)
EP (1) EP2480323B1 (ja)
JP (1) JP5683595B2 (ja)
FR (1) FR2950541B1 (ja)
WO (1) WO2011039453A1 (ja)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
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FR2950541B1 (fr) * 2009-09-25 2011-10-21 Biomerieux Sa Procede et dispositif de melange d'une solution heterogene en solution homogene
CN109991049B (zh) * 2017-12-29 2024-03-01 同方威视技术股份有限公司 用于食品安全检测的前处理装置以及前处理方法

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Also Published As

Publication number Publication date
FR2950541A1 (fr) 2011-04-01
FR2950541B1 (fr) 2011-10-21
US20120182829A1 (en) 2012-07-19
JP2013505821A (ja) 2013-02-21
WO2011039453A1 (fr) 2011-04-07
EP2480323A1 (fr) 2012-08-01
US9084974B2 (en) 2015-07-21
JP5683595B2 (ja) 2015-03-11

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