EP0969917B1 - Verfahren und vorrichtung zum produzieren von suspensionen aus partikeln und flüssigkeit - Google Patents

Verfahren und vorrichtung zum produzieren von suspensionen aus partikeln und flüssigkeit Download PDF

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Publication number
EP0969917B1
EP0969917B1 EP98917266A EP98917266A EP0969917B1 EP 0969917 B1 EP0969917 B1 EP 0969917B1 EP 98917266 A EP98917266 A EP 98917266A EP 98917266 A EP98917266 A EP 98917266A EP 0969917 B1 EP0969917 B1 EP 0969917B1
Authority
EP
European Patent Office
Prior art keywords
particles
liquid
container
process according
volume
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.)
Expired - Lifetime
Application number
EP98917266A
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English (en)
French (fr)
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EP0969917A1 (de
Inventor
Bruno Colin
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
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Biomerieux SA
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Publication date
Application filed by Biomerieux SA filed Critical Biomerieux SA
Publication of EP0969917A1 publication Critical patent/EP0969917A1/de
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00—Other mixers; Mixing plants; Combinations of mixers
    • B01F33/45—Magnetic mixers; Mixers with magnetically driven stirrers
    • B01F33/451—Magnetic mixers; Mixers with magnetically driven stirrers wherein the mixture is directly exposed to an electromagnetic field without use of a stirrer, e.g. for material comprising ferromagnetic particles or for molten metal

Definitions

  • the present invention relates to the suspension of particles of a solid, in a predetermined volume of liquid, the particles and the volume of liquid being contained together inside of a container itself delimited by a wall.
  • the invention is concerned with the implementation suspension, or resuspension of particles, forming a deposit adhering to the inner face of the container wall, in the form of a film continuous or aggregates, and bringing together at least some of these particles in the agglomerated state, and this in a predetermined volume of the liquid, contained inside said container.
  • particles / liquid defined above is encountered in particular during certain biological analyzes, using particles, of size at most equal to 10 ⁇ m, and preferably between 0.01 ⁇ m and 10 ⁇ m, and for example between 1 and 5 ⁇ m, these particles comprising a magnetic substrate on which is attached at least one analyte, or at least one reagent, and being dispersed in a continuous liquid phase, for example an aqueous phase.
  • these particles under the effect of a magnetic field, from the liquid phase, partly leads to their accumulation and agglomeration in the form of a deposit, continuous or discontinuous, adhering to the face inner wall of the container.
  • the breakdown of the particle deposit agglomerated on the wall of the container is obtained by bringing a flow additional liquid, for example under pressure, within the containing, and more specifically liquid volume, so as to entrain and suspend the previously agglomerated particles, by hydrodynamic action.
  • This solution has the major drawback add a certain amount of liquid phase to the container, which even controlled or predetermined results in a dilution of particles, this which reduces the sensitivity of the analysis process used.
  • the previously described process is specific to particles magnetic, and can only be used with such particles, because it is the conjunction of the rotational movement of said particles, generated by the rotating magnetic field, and the translational movement relative, alternative, between said field and the container, which detaches and disperses any deposit of magnetic particles likely to agglomerate on the inner side of the container.
  • the present invention therefore relates to a method of setting suspension of particles, from the physical state described or defined previously, independent of the nature of the particles, and purely mechanical or hydrodynamic, without introducing into the container a additional amount of liquid.
  • the solution according to the invention also provides another advantage.
  • the maximum height of the reflux flow obtained according to this invention mechanically allows to lick and loosen particles agglomerated on the inside of the container, above normal level (at rest) of the liquid contained in said container, including with a small amount of liquid.
  • a container 12 is considered determined by a wall 3, with an internal face 3a.
  • This container contains on the one hand a predetermined volume 2 of liquid, for example of a reagent in liquid form, and on the other hand particles 1 of a solid, by example of particles as shown schematically in the FIG. 3, that is to say each constituted by a magnetic substrate 7, for example on which is fixed a ligand 8, linked to an analyte.
  • a predetermined volume 2 of liquid for example of a reagent in liquid form
  • particles 1 of a solid by example of particles as shown schematically in the FIG. 3, that is to say each constituted by a magnetic substrate 7, for example on which is fixed a ligand 8, linked to an analyte.
  • the implementation of the present invention is independent of the magnetic nature or not of the particles.
  • the particles are either totally gathered and agglomerated in the form of a deposit 4 adherent on the internal face 3a of the wall 3, or partly dispersed within the volume liquid and partly collected and agglomerated in the form of a deposit 4 as described above.
  • the particles 1 are found, in part dispersed within the volume of liquid, and remain partly collected and agglomerated in the form of a deposit 4 (continuous film or aggregates) adhering to the internal face 3a of the wall 3.
  • a means 9 for securing the container there is a means 9 for securing the container, and a means 10 for alternative displacement of the securing means 9, according to a reference direction 6, for example vertical.
  • This means of alternative displacement can consist of a simple cooperating eccentric with the means 9 for securing the container.
  • the container 12 is subjected to a movement alternative 5 along the reference direction 6, with a frequency relatively large, at least equal to 10 Hz, and we obtain or observes, within the predetermined volume of liquid, a flow / reflux 7 against the wall 3 of the container, on either side of the direction of reference 6, breaking the deposit 4, and dispersing the particles 1 towards the center of liquid volume.
  • the predetermined volume 2 of liquid contains, homogeneously and completely dispersed, the particles 1, so that the analysis process can be continued.
  • the present invention has been implemented in the context of a quantitative analysis of a pathogenic microorganism, namely Toxoplasma M (analyte), with magnetic particles coated with a ligand (antibody) specific for said microorganism.
  • the particles are incubated in an analysis cuvette (container), with a sample or inoculum containing said microorganism. Then the particles which reacted with said microorganism are separated by a magnetic field, bringing them together and fixing them against the wall of the bowl. The bowl is then emptied, then washed. A predetermined volume of a reagent (antibody labeled, for example by a enzyme such as alkaline phosphatase, directed against the analyte is then introduced and incubated in the cuvette, after removing the field magnetic. After incubation and separation of the elements not having reacted, a luminescent detection reagent is introduced into the cuvette. The light signal corresponding to the reagent that reacted with the particles is measured.
  • a reagent antibody labeled, for example by a enzyme such as alkaline phosphatase
  • the resuspension of the particles according to the method and the device of the invention facilitates the contact of the particles with the reactive entities (analyte and / or detection reagent), which results in an increase in the measured signal, for example the signal luminous.
  • the implementation of the resuspension or resuspension according to the invention makes it possible to increase the measurement light signal by at least 60%, or even in certain cases of the order of 100%, according to the magnetic particles used, for example under the commercial references Estapor NH 2 -gluta, Dynal M280, and Seradyn.
  • the agitation significantly increases the light signal obtained, thereby improving the performance of the biological assay.

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  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Processes Of Treating Macromolecular Substances (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Manufacturing Of Micro-Capsules (AREA)
  • Devices And Processes Conducted In The Presence Of Fluids And Solid Particles (AREA)

Claims (8)

  1. Verfahren zum Suspendieren von Feststoffteilchen (1) in einem bestimmten Flüssigkeitsvolumen (2), das im Innern eines Behältnisses (12) enthalten ist, welches durch eine Wand (3) begrenzt ist, wobei letztere teilweise gegenüber einem Kern der Flüssigkeit durch eine Ablagerung (4) getrennt ist, die an deren Innenseite (3a) haftet und die zumindest einen Teil der Teilchen in agglomeriertem Zustand gesammelt hält, wobei der Inhalt in zumindest einer Bezugsrichtung (6) einer Hin- und Herbewegung (5) unterworfen wird, dadurch gekennzeichnet, daß die Feststoffteilchen (1) eine Größe von höchstens gleich 10 µm aufweisen, daß die Hin- und Herbewegung (5) eine Frequenz von zumindest gleich 10 Hz mit einer Amplitude von 1 mm bis 15 mm aufweist, und zwar derart, daß man im Innern des bestimmten Flüssigkeitsvolumens, ohne weitere äußere Einwirkung, entgegengerichtet in der Bezugsrichtung einen Fluß/Rückfluß (7) erhält, wodurch die Ablagerung abgelöst wird und die Teilchen in Richtung zur Mitte des Flüssigkeitsvolumens dispergiert werden.
  2. Verfahren nach Anspruch 1, dadurch gekennzeichnet, daß die Feststoffteilchen (1) eine Größe von 0,01 µm bis 10 µm und beispielsweise von 1 µm bis 5 µm aufweisen.
  3. Verfahren nach Anspruch 1, dadurch gekennzeichnet, daß die Teilchen (1) ein magnetisches Substrat (7) aufweisen, auf dem zumindest ein Ligand (8) fixiert ist.
  4. Verfahren nach Anspruch 1, dadurch gekennzeichnet, daß die Hin- und Herbewegung (5) eine Amplitude von 1 mm bis 8 mm und beispielsweise von 3 mm bis 6 mm aufweist.
  5. Verfahren nach Anspruch 1, dadurch gekennzeichnet, daß die Hin- und Herbewegung (5) eine Frequenz von 15 Hz bis 60 Hz, insbesondere von 15 Hz bis 30 Hz, und beispielsweise gleich 16 Hz aufweist.
  6. Verfahren nach Anspruch 1, dadurch gekennzeichnet, daß das Flüssigkeitsvolumen (2) eine horizontale Grenzfläche (2a) definiert, wobei die Richtung der Hin- und Herbewegung (5) vertikal ist.
  7. Verfahren nach Anspruch 1, dadurch gekennzeichnet, daß das Flüssigkeitsvolumen (2) eine horizontale Grenzfläche (2a) definiert, wobei die Richtung der Hin- und Herbewegung (5) eine vertikale Hauptkomponente und eine horizontale Sekundärkomponente aufweist.
  8. Vorrichtung zum Durchführen des Verfahrens nach einem der Ansprüche 1 bis 7, enthaltend ein Behältnis, das durch eine Wand begrenzt ist, Mittel (9) zum Festlegen des Behältnisses und Mittel (10) zum Hin- und Herbewegen der Festlegemittel, um eine Hin- und Herbewegung auszuüben, und zwar mit einer Amplitude von 1 bis 15 mm und einer Frequenz von zumindest gleich 10 Hz in Richtung der Bezugsrichtung (6).
EP98917266A 1997-03-27 1998-03-27 Verfahren und vorrichtung zum produzieren von suspensionen aus partikeln und flüssigkeit Expired - Lifetime EP0969917B1 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
FR9704017 1997-03-27
FR9704017A FR2761277B1 (fr) 1997-03-27 1997-03-27 Procede et dispositif de mise en suspension de particules d'un solide dans un liquide
PCT/FR1998/000639 WO1998043730A1 (fr) 1997-03-27 1998-03-27 Procede et dispositif de mise en suspension de particules d'un solide dans un liquide

Publications (2)

Publication Number Publication Date
EP0969917A1 EP0969917A1 (de) 2000-01-12
EP0969917B1 true EP0969917B1 (de) 2002-01-16

Family

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EP98917266A Expired - Lifetime EP0969917B1 (de) 1997-03-27 1998-03-27 Verfahren und vorrichtung zum produzieren von suspensionen aus partikeln und flüssigkeit

Country Status (10)

Country Link
US (1) US6390660B1 (de)
EP (1) EP0969917B1 (de)
JP (1) JP2001517149A (de)
AT (1) ATE211946T1 (de)
AU (1) AU7053198A (de)
CA (1) CA2283687A1 (de)
DE (1) DE69803166T2 (de)
ES (1) ES2171017T3 (de)
FR (1) FR2761277B1 (de)
WO (1) WO1998043730A1 (de)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6808304B2 (en) * 2002-08-27 2004-10-26 Dade Behring Inc. Method for mixing liquid samples using a linear oscillation stroke
US7258480B2 (en) * 2005-01-10 2007-08-21 Dade Behring Inc. Apparatus for mixing liquid samples using a two dimensional stirring pattern
EP2033715B1 (de) * 2007-08-14 2010-06-23 Qiagen GmbH Verfahren zum Suspendieren oder Resuspendieren von Partikeln in einer Lösung sowie daran angepasste Vorrichtung
US11318429B2 (en) * 2017-03-06 2022-05-03 Northeastern University Enclosed mixture stirrer using intermittent resonance and method

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Also Published As

Publication number Publication date
EP0969917A1 (de) 2000-01-12
ES2171017T3 (es) 2002-08-16
FR2761277B1 (fr) 2000-01-28
JP2001517149A (ja) 2001-10-02
ATE211946T1 (de) 2002-02-15
DE69803166T2 (de) 2002-08-29
WO1998043730A1 (fr) 1998-10-08
US6390660B1 (en) 2002-05-21
AU7053198A (en) 1998-10-22
CA2283687A1 (fr) 1998-10-08
FR2761277A1 (fr) 1998-10-02
DE69803166D1 (de) 2002-02-21

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