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 enabling 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, moreover, doubtful depending on this user and his 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 action of the enzyme.
• 36.624 relates to an 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 second drive means connected to said first support means for rotating the container about said first axis as the container rotates about said second axis.
• the problem with this type of device is that the two 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 nearest and farthest points of this intersection point and therefore a nonhomogeneous 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 distributed non-uniformly and irregularly in the container that contains 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 eventually 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 an elliptical translation.
• the end of the cap is at a distance L1 from the axis of the rotational movement (the position 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).
• the rotational movement starts about its axis, 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.
• the end of the cap When the segment has traveled a half-circle distance from the initial position, because of this parallel displacement of the segment, the end of the cap is at a distance L2 from the axis of the movement and the end of the bottom
• the tube is located at the distance L1 from the axis of the movement.
• the term "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.
• the present invention relates to a method of mixing a heterogeneous solution containing at least two different liquids and, optionally, at least one solid entity to obtain a homogeneous solution, the process comprising the following steps:
• This method can also be applied to mixing a heterogeneous solution containing at least one liquid and at least one solid entity.
• step (c) the setting in motion of the support carrying said container allows the part of the container closest to said axis of rotation to be in the furthest position from this axis after a half-rotation, and to the part the container farthest from the axis of rotation to be in the closest position thereof after half a rotation.
• 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 stirring without all or part of said heterogeneous solution born out of 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 present invention also relates to a device for mixing a heterogeneous solution containing at least two different liquids and, optionally, at least one solid entity, or containing at least one liquid and at least one solid entity, in order to obtain a homogeneous solution, which consists of: i. a static chassis which may possibly be placed on a table or other surface, ii. a mobile support that can accommodate at least one container having a longitudinal axis,
• the action of the transmission means positions the container so that the part of the container closest to the axis of rotation is found in the position farthest from this axis after a half rotation, and that the part of the container farthest from the axis of rotation is found in the closest position thereof after half a rotation.
• 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 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.
• FIG. 1 shows an orbital mixer according to the state of the art.
• Figure 2 shows a mixer according to the present invention.
• FIG. 3 highlights the container in two different positions of its movement when actuated by the orbital mixer according to the invention and the intensity of the forces that are applied to the liquid.
• Figure 4 provides a representation of the most important movement undergone by the liquid during the deceleration shown in Figure 3.
• FIG. 5 shows the main liquid flows that improve the mixture during a rotation of the mixer.
• Figure 6 shows two different types of containers used by the inventors.
• FIG. 7 is a graph with the abscissa of the engine speeds, which correspond to the frequencies in revolutions per minute, and the ordinate the orbital rotation amplitude, expressed in millimeters (mm).
• FIG. 8 is a graph with the abscissa of the angle of inclination of the container, measured in degrees relative to the vertical, and the ordinate the mixing time (MT expressed in seconds) to achieve homogeneity with a cylindrical container. according to Figure 6b.
• FIG. 9 is a graph with the abscissa angle of the inclination of the container, measured in degrees (Ang. (Deg)) relative to the vertical, and the ordinate the mixing time in seconds (MT (s)) for achieve homogeneity with an Eppendorf® container according to Figure 6a.
• FIG. 10 shows a graph 'with the abscissa the frequency of the rotational movement of the cylindrical container having a fixed angle of inclination of 45 ° relative to the vertical, and the ordinate in the second mixing time to achieve the homogeneity with a cylindrical container according to Figure 6b according to different concentrations of a viscous product and in the presence or absence of an oil layer.
• Fig. 1 The normal mechanical arrangement for orbital motion as a mixing means for liquids is shown in Fig. 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.
• this same geometry is used. In this geometry the mechanism works to generate a vortex.
• the liquid in fact the two liquids that we wish to mix, but for practical reasons we will use the singular later
• the liquid is accelerated and, in an oscillation-like movement, begins to move synchronously along the vertical wall of the container with the center of gravity of the liquid outside the orbit.
• 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.
• the inclination of the container 7 is always the same with respect 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).
• FIG. 8 thus shows the reduction in the time required to mix the liquid by changing the angle of the cylindrical tube between 0 degrees (depending on the use with a conventional orbital mixture) up to the values of 50 degrees.
• 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 the volume increases or when the oil is added, the mixture at zero degrees becomes much more difficult.
• the improvement of the mixture is detectable even at small angles (FIG. 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.
• liquids that can not be mixed at 0 degrees can be perfectly mixed at angles exceeding 0 degrees, with optimized mixing times approaching those of water-like liquids. 0 degree.
• the angle for the best mixing performance depends on the volume of the container and typically increases with the viscosity of the liquid (fluid) and the presence of oil on the aqueous liquid. At angles exceeding substantially 30 degrees most of the examined configurations permitted mixing in seconds, usually 5 seconds. It should be noted that this is proven for a liquid containing:

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)

Applications Claiming Priority (2)

Publications (2)

Family

ID=42133613

Family Applications (1)

Country Status (5)

Families Citing this family (3)

Family Cites Families (54)

• 2009
  • 2009-09-25 FR FR0904580A patent/FR2950541B1/fr not_active Expired - Fee Related
• 2010
  • 2010-09-24 EP EP20100769027 patent/EP2480323B1/de active Active
  • 2010-09-24 WO PCT/FR2010/052008 patent/WO2011039453A1/fr not_active Ceased
  • 2010-09-24 US US13/497,993 patent/US9084974B2/en active Active
  • 2010-09-24 JP JP2012530320A patent/JP5683595B2/ja active Active

Non-Patent Citations (1)

Also Published As

Similar Documents

Legal Events