EP2203246B1 - Dispositif et procédé assurant une distribution uniforme de microparticules dans un liquide - Google Patents

Dispositif et procédé assurant une distribution uniforme de microparticules dans un liquide Download PDF

Info

Publication number
EP2203246B1
EP2203246B1 EP08804783A EP08804783A EP2203246B1 EP 2203246 B1 EP2203246 B1 EP 2203246B1 EP 08804783 A EP08804783 A EP 08804783A EP 08804783 A EP08804783 A EP 08804783A EP 2203246 B1 EP2203246 B1 EP 2203246B1
Authority
EP
European Patent Office
Prior art keywords
suspension
storage chamber
microparticles
liquid
mixing head
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.)
Not-in-force
Application number
EP08804783A
Other languages
German (de)
English (en)
Other versions
EP2203246A1 (fr
Inventor
Jörg FELDHUSEN
Hartmut SCHLÜTER
Joachim Thiemann
Johannes Lemburg
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.)
Charite Universitaetsmedizin Berlin
Rheinisch Westlische Technische Hochschuke RWTH
Original Assignee
Charite Universitaetsmedizin Berlin
Rheinisch Westlische Technische Hochschuke RWTH
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 Charite Universitaetsmedizin Berlin, Rheinisch Westlische Technische Hochschuke RWTH filed Critical Charite Universitaetsmedizin Berlin
Publication of EP2203246A1 publication Critical patent/EP2203246A1/fr
Application granted granted Critical
Publication of EP2203246B1 publication Critical patent/EP2203246B1/fr
Not-in-force legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F25/00—Flow mixers; Mixers for falling materials, e.g. solid particles
    • B01F25/50—Circulation mixers, e.g. wherein at least part of the mixture is discharged from and reintroduced into a receptacle
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F35/00—Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
    • B01F35/55—Baffles; Flow breakers
    • 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

Definitions

  • the invention relates to a device for producing a suspension with uniformly distributed microparticles in a carrier liquid or for maintaining a uniform distribution of microparticles in the carrier liquid.
  • the device comprises a storage chamber 1 with the suspension, a mixing head 2 and a pump 3, which is connected to the storage chamber 1 and the mixing head 2, wherein the mixing head 2 at least one cavity 4 with a Strömungsverwirbler 5 and an overflow 6, by a Opening 7 is connected to the storage chamber 1, characterized in that the storage chamber 1, a pin 14 and / or a rotary inlet 15 and a rotary return 16, which are connected to the pump 3 comprises.
  • the device can be used to identify, characterize and purify proteins.
  • the invention also provides a process for the uniform distribution of microparticles in a liquid in which a turbulent, quasistatic state is generated.
  • microparticles so-called beads, which are a few micrometers to about 0.1 mm large plastic spheres and whose surfaces have certain reactive properties. These microparticles are stored after their preparation in a protective carrier liquid, with which they form a suspension.
  • a fundamental problem of the handling of microparticles is the equal quantitative dosage of these particles on a large number of sample carriers. A direct weighing or counting of the microparticles precipitates because they can not be removed from the carrier liquid and allowed.
  • the patent US 5,705,610 teaches a device comprising mixing and reaction vessels, between which can be transported reagents or suspensions, which are mixed by the introduction of gas.
  • the gas input associated with the formation of bubbles is critical both from the point of view of process technology (increase in volume, unequal volumes of liquid during sampling, etc.) and in terms of the sensitivity of biological structures.
  • WO 2007/064635 A1 a device which operates without air passage, by moving a suspension through an opening between two pump mixing chambers and the mixed suspension is removed through a valve port.
  • the device requires a complex Interaction of the two pumps and prevents sampling in the turbulence range.
  • a device for the uniform distribution of microparticles in a liquid which comprises a storage chamber 1 with a suspension of microparticles and liquid, a mixing head 2 for receiving the suspension and a pump 3 connected to the storage chamber 1 and the mixing head 2 for sucking the Suspension of the storage chamber 1 is connected to the mixing head 2, wherein the mixing head 2, at least one cavity 4 with a Strömungsverwirbler 5 and an overflow 6, which is connected through an opening 7 to the storage chamber 1, characterized in that the storage chamber 1 a pin 14 and / or a rotary inlet 15 and a rotary return 16, which are connected to the pump 3 comprises.
  • the point of interest is an interface 8 to the adjacent laboratory system 10, through which the microparticles or structures associated therewith can be removed and / or analyzed.
  • the structures preferably include biomolecules, such as. For example, proteins, nucleic acids, peptides, carbohydrates, polymers or molecules having a molecular weight between 50 and 1000 Da, or microorganisms or eukaryotic cells.
  • the storage chamber 1 has a pin 14 and / or a rotary inlet 15 and a rotary return 16, which are connected to the pump 3 on.
  • These components are particularly advantageous for generating a second suspension cycle which prevents sedimentation of the microparticles in the storage chamber 1.
  • the microparticles transported in the first cycle between the storage chamber 1 and the mixing head 2 are distributed uniformly in the carrier liquid in the cavity 4, their concentration could decrease there over time. This would be the case if, for example, sedimented microparticles are sucked in at the beginning in the storage chamber and, subsequently, a suspension thinned out at particles.
  • the pin 14 and / or rotational inlet 15 and outlet 16 so not only the uniform distribution in a cycle of the first cycle is achieved, but the maintenance of a constantly distributed suspension over the entire time course of operation of the device.
  • the time course is determined by the filling volume of the storage chamber 1 with suspension and their successive removal from the cavity 4.
  • the pump 3 promotes the suspension in two parallel circuits in this embodiment.
  • the added second cycle ensures the rotation of the suspension stored in the storage chamber 1 by the suspension sucked by the rotation return 16, transported in a rotary loop and then transferred to the rotary feed 15 back into the storage chamber. It is preferable to arrange the rotary feed 15 and the rotary return 16 at different heights of the storage chamber 1.
  • the rotating flow can be swirled by means of a flow swirler 5, as represented by the pin 14.
  • a suction 17 is arranged, via which the mixing head 2 suspension is supplied.
  • the device according to the invention also consists of two units, a pump unit 3 and a unit with storage chamber 1 and mixing head 2, which are connected by lines for transporting the suspension between them are. It is understood that each pump 3 has a motor and is driven by an external power source 9.
  • Pantry 1 and mixing head 2 may form an integral component or otherwise secured together.
  • the storage chamber 1 represents a cavity of any geometric shape, for example, has a non-rotationally symmetrical cross section, in particular an elliptical cross section, polygonal cross section or rectangular cross section with a semicircular surface or two semi-circular surfaces on opposite rectangular surfaces.
  • a rotationally symmetrical, cylindrical design is preferred.
  • the cavity should be of a size suitable for storing a certain amount of microparticles for a particular application.
  • the storage chamber 1 is therefore interchangeable by the user.
  • the pantry is filled either by hand or by machine, the latter having the advantage of a possible automation.
  • the pump 3 promotes the suspension in the circulation by first sucking the suspension out of the storage chamber 1.
  • pumps of any type can be used as long as a minimum velocity of the flow and thus a particle transport are effected.
  • the minimum speed depends i.a. on the nature of the line connections and the properties of the suspension, including in particular the amount and mass of the particles and the viscosity of the carrier liquid count.
  • the parameters can be experimentally determined experimentally in routine experiments.
  • a peristaltic pump is used in the device according to the invention.
  • the aspirated suspension is transported by means of transport lines, preferably by means of hoses 11, into the mixing head 2.
  • the mixing head comprises at least one cavity, the so-called cavity 4.
  • the mixing head 2 eight cavities 4, whereby the simultaneous processing of several samples is given.
  • such a mixing head 2 is compatible with the 96-well format, as z. B. represent microtiter plates. Pre-switching the device to high-throughput robots thus enables automation of basic research, pharmaceutical, chemical, diagnostic and biotechnology industries.
  • the cavity 4 comprises an inflow region 12, a region with flow swirler 5 and a turbulence region.
  • the inflow area 12 is at the bottom of the cavity 4, followed by the area with flow swirler 5 and the turbulence area above it.
  • the change from the area with flow swirler 5 to the turbulence area can be fluid.
  • the aforementioned regions have the same geometric shape of the cross section.
  • the geometric shape is not limited, as long as the installation of Strömungsverwirblungs instituten remains possible. With regard to possible shapes, reference is made to the comments on the storage chamber 1.
  • the cavity 4 has a rotationally symmetrical cross section.
  • the cavity 4 is designed such that a turbulent flow can be generated in it, for which purpose a Strömungsverwirbler 5 is installed.
  • a "flow swirler 5" is any constructional measure and / or in the cavity 4, which is both an external component connected to the cavity or not, and the shape of the cavity 4 itself may include.
  • Nonlimiting examples of flow swirlers 5 are stirrers or shakers (as external, non-connected elements), pin or grid (as external, connected elements), discontinuous extensions or tapers of the cross section, and bulges of the sidewalls (as internal elements).
  • the Strömungsverwirbler 5 comprises at least one discontinuous enlargement of the cross section in an extension region 13 above the Zustrom Anlagens 12.
  • discontinuous magnification refers in the context of the invention to a sudden expansion of the diameter or cross section, wherein the Extension on edges and thus in the form of a stage completes.
  • the suspension flows through the inflow region 12, which is followed by the extension region 13. That is, in this embodiment, the area with flow swirler 5 is represented by the extension area 13.
  • the extension region 13 is preferably arranged in the lower half of the cavity 4, more preferably in the lower third thereof, most preferably in the lower fourth.
  • a ground-level arrangement ensures a large range of turbulence.
  • the turbulence needed to obtain a uniformly distributed suspension can be advantageously adjusted by the configuration of discontinuous magnification.
  • the degree of turbulence is determined by the interaction of various parameters, including the relative height of the extension region 13 with respect to the total height of the cavity 4, the extent of the discontinuous magnification and the nature of the step.
  • the relative height of the extension region 13 should be as small as possible in order to ensure a large range of turbulence.
  • the height of the extension region 13 is less than 25% of the height of the cavity 4, more preferably less than 15%. This is determined inter alia by the inclination of the inner walls in the extension region 13.
  • the cross section in the extension region 13 increases linearly, preferably with an increase tan ⁇ of less than 70 °, more preferably less than 50 °, most preferably less than 30 °.
  • the cavity 4 is formed as a cylinder, so that it diverges conically in the extension region 13 with the aforementioned increase.
  • the extent of the discontinuous enlargement should be dimensioned so that there is sufficient space for the demolition of the flow on the inner wall and turbulence and this Room can also be filled with turbulence.
  • the discontinuous enlargement is designed so that the cross-section in the extension region 13 at least doubles, preferably at least fivefold, particularly preferably at least tenfold.
  • the cavity 4 contains an overflow 6, which is located in the upper part of the turbulence zone. This ensures that the pumped inflow does not lead to an overflow of the cavity 4, provided that no withdrawal or only a withdrawal of suspension takes place, the withdrawn volume is less than the inflowing volume.
  • the overflow 6 represents a sheathed cavity in the cavity 4, the length of which corresponds at least to the wall thickness of the cavity 4.
  • the overflow 6 has a length which exceeds the wall thickness of the cavity 4.
  • the overflow 6 is inclined so that the suspension can drain.
  • the mixing head 2 is preferably arranged above the storage chamber 1 in order to allow the suspension, which is at or above the level of the overflow 6, to flow out by gravity into the lower storage chamber 1.
  • the overflow 6 is arranged above the preferred extension area 13 according to the invention.
  • the mixing head 2 it is also conceivable to position the mixing head 2 at the same or even lower height than the storage chamber 1 and to initially collect the overflowing suspension in a basin before it is returned to the storage chamber 1 by means of a pump or by utilizing capillary forces.
  • an opening 7, which represents the upper open surface of the storage chamber 1, or serve another opening, the latter may also be below the liquid level in the storage chamber 1 upon application of an external pressure on the line leading to the opening.
  • the prerequisite for suspension removal is that the cavity 4 has an interface 8 to an adjacent laboratory system 10.
  • This laboratory system 10 may be, for example, a liquid handling robot (liquid removal robot), which by means of removal needles Suspension sucks.
  • the interface 8 can be understood, for example, as the suspension surface.
  • the removal needles dip at the interface 8 in the suspension.
  • an interface 8 at a constant height is desired, as provided by the invention. Due to the inventive arrangement and design of the pump 3, pantry 1 and cavity 4 (each with at least two openings), which allow driving the suspension in the circulation, a quasi-static state with respect to the turbulence and the position of the interface 8 in the cavity 4 is formed ,
  • the invention also relates to the use of the device according to the invention for the uniform distribution of microparticles in a liquid.
  • the invention also relates to the use of the device according to the invention for obtaining a suspension of uniformly distributed microparticles in a carrier liquid and / or for maintaining a uniform distribution of microparticles in a carrier liquid.
  • the invention further relates to the use of the device according to the invention for taking a suspension of uniformly distributed microparticles in a liquid, preferably with a liquid extraction robot.
  • the device is used for the identification, characterization and / or purification of proteins.
  • Proteins are often involved in the development of serious diseases such. As cancer or Alzheimer's involved.
  • microparticles with a diameter of a few micrometers to 0.1 mm are becoming increasingly important. Their surface has several reactive properties that allow the identification and characterization of proteins.
  • the laboratory automation in the field of Characterization and identification of proteins is a growing market, so that high-throughput robots are indispensable for the effective design of microparticle-based proteomics research.
  • the device according to the invention is constructed in such a way that a liquid handling robot can remove the constantly distributed suspension from the wells (cavities 4) of a mixing head 2, preferably from a mixing head with eight wells, by means of removal needles. This makes it possible to connect the device to high-throughput robots.
  • the use of the device according to the invention is preferably suitable for providing constantly distributed quantities of microparticles for carrying out automated protein purification processes by means of chromatography in the 96-well batch format.
  • the device of the present invention is used in the activity determination of enzymes by mass spectrometry. It has been repeatedly demonstrated that mass spectrometry is a fast, sensitive and reliable tool for the determination of enzymatic activities ( Hsieh et al. 1995, Anal. Biochem. 229, 20 ; Bothner et al. 2000, J. Biol. Chem. 275, 13455 ; Wu et al. 1997, Chem. Biol. 4, 653 ).
  • MALDI-MS is characterized by its resistance to buffer solutions and its ability to analyze complex mixtures, making it predestined for direct screening of enzyme activities that require minimal sample preparation.
  • Enzymatic activities in complex protein fractions can be determined with a mass spectrometer using mass spectrometry-assisted enzyme screening (MES).
  • MES mass spectrometry-assisted enzyme screening
  • the enzyme activity is determined by incubating the immobilized proteins with a reaction-specific probe, followed by analysis of the reaction mixture by MALDI-MS after defined incubation times. Only the use of the device according to the invention ensures a constantly distributed suspension of microparticles, as a result, a uniform surface loading and constant protein concentration and the removal of an identical amount of microparticles for incubation with the probe is made possible and reproducible data is generated.
  • Another object of the invention is a method for uniform distribution of microparticles in a liquid in which the device according to the invention is used.
  • the sequence of steps illustrates that the process is circulated, for which in each case two openings of the storage chamber 1 or the mixing head 2 are essential, which are each different from each other. That is, in the storage chamber 1, the suction 17 for sucking the suspension in the direction of mixing head 2 and the opening 7 for receiving from the mixing head 2 overflowed suspension and in the cavity 4 in the mixing head 2, the inflow 13 of the suspension from the storage chamber 1 and the overflow 6 to return the suspension in the storage chamber 1 are located. Step (g) is carried out until the storage chamber 1 is empty or no mixing of the particles is desired, because the removal and / or analysis of the particle suspension is completed.
  • the turbulent flow in step (e) can be effected by any measure that results in a Reynolds number above the critical value of 2300. Suitable measures are in particular the increase of the flow rate of the suspension, the surface roughness of the cavity 4 and / or the density of the suspension and / or the reduction of the dynamic viscosity.
  • the turbulent flow is generated by the installation of a Strömungsverwirblers 5, more preferably by the incorporation of at least one discontinuous increase in the cross-section in an extension region 13 above a Zustrom Anlagens 12th
  • the method can also be carried out in such a way that, after step (e), (f) or (g), a further step (h) is followed, in which the suspension is removed from a fluid extraction robot.
  • an apparatus and a method for the uniform distribution of microparticles in a liquid are provided for the first time.
  • the invention uses the design of a flow-through sampling cavity 4 in order to generate turbulence in a simple and reliable way, which in turn entails a constant mixing of microparticles in a suspension.
  • the separation of storage chamber 1 and mixing head 2 advantageously allows a uniform distribution of the microparticles at the location of particle removal or analysis (cavity 4).
  • this system is coupled to a second circuit which ensures that the distribution of the microparticles remains homogeneous over a relatively long period of time or both at the beginning and at a time when the device has already been in operation for some time.
  • the mixing head 2 has a plurality of cavities 4, which together drive an identical mixing of the microparticles show and thus an automated microparticle quantity measurement are accessible. While only a gas flow is described in the prior art, the flow of the suspension itself is exploited here. Due to the surprising combination of this turbulence with an overflow 6, a liquid circuit is formed, which leads to a quasi-static state in the cavities 4. Apparatus and method of the invention are characterized by a simple and inexpensive handling and open up a variety of application perspectives, of which biochemistry in particular may be mentioned.
  • the prototype of the overall system, as in Fig. 5 is shown, as a power source 9, a 12 V DC power supply, which is the overall system supplied with electrical energy.
  • the power source powers pump 3, which is a Watson Marlow 102R peristaltic pump powered by a Faulhaber 3540K024C motor. Pump 3 and motor are put into operation via a switch.
  • Fig. 1 pump 3 and motor are covered to protect against external influences with a cover 18 which is fastened with screws DIN 912 (M4x10) to a flange plate 19.
  • the screw type is also used for all other fasteners.
  • Both the pump 3 and the suspension mixer cylinder chamber are mounted on a base plate 20.
  • the suspension mixer cylinder chamber comprises the pantry base 21, mixing head 2, cylinder pin 14 type DIN 7 (3x15) and four connectors type connector M6 250-6.
  • the suspension mixer cylinder chamber is screwed to the storage chamber base 21 with the base plate 20.
  • the base 21 has a cylindrical storage chamber 1 in the center and above it, an 8-well mixing head 2 is screwed.
  • Fig. 2 It can be seen that the wells or withdrawal cavities 4 are shaped in such a way that the conveyed inflow becomes turbulent due to a discontinuous tube expansion in the entry area (extension area 13). In this way, the suspension in the cavity 4 is vortexed and mixed. The removal of the suspension by the liquid handling robot reduces the total volume in the system. In order to achieve a constant high liquid level for the removal of suspension, the cavities 4 have an overflow 6.
  • the pump delivers the suspension in two parallel circuits ( Fig. 3 ).
  • the first circuit supplies the withdrawal cavities 4 ( Fig. 2a . 3 ).
  • the suspension is sucked on a cylindrical suction 17 and passed through hoses 11.
  • the suspension enters the mixing head 2 and is transported by means of a conduit system in the inflow region 12 of the individual cavities 4.
  • the overflowing liquid flows through the opening 7 directly into the storage chamber 1. So it is a liquid circulation, in which the cavity 4 a quasi-static state is generated, is removed from the constantly distributed suspension.
  • the second circuit ensures rotation of the stored suspension in the storage chamber 1 (FIG. Fig. 3, 4 ).
  • suspension is sucked through a rotary return 16, transported by a rotation loop in hoses 11 and returned to the storage chamber 1 via a rotary feed 15.
  • the storage chamber 1 has a cylindrical pin 14 which swirls the rotating flow in such a way that no beads can deposit in the center of the chamber (similar to a teacup with tea crumbs).
  • the suction 17 In the dead water of the pen is the suction 17, which feeds the removal cavities 4 through the riser 22.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Feeding, Discharge, Calcimining, Fusing, And Gas-Generation Devices (AREA)
  • Peptides Or Proteins (AREA)

Claims (14)

  1. Dispositif assurant une distribution régulière de microparticules dans un liquide, comprenant un compartiment réservoir (1) contenant une suspension de microparticules et de liquide, une tête mélangeuse (2) recevant la suspension et une pompe (3) qui est reliée au compartiment réservoir (1) et à la tête mélangeuse (2) pour aspirer la suspension du compartiment réservoir (1) dans la tête mélangeuse (2), moyennant quoi la tête mélangeuse (2) comprend au moins une cavité (4) dotée d'un dispositif producteur de turbulences 5 et un trop-plein (6), qui est relié par une ouverture (7) au compartiment réservoir (1),
    caractérisé en ce que
    le compartiment réservoir (1) comporte une entrée à écoulement rotatif (15) et un retour à écoulement rotatif (16) reliés à la pompe (3) et destinés à générer une seconde circulation de suspension parallèle.
  2. Dispositif selon la revendication 1, caractérisé en ce que le compartiment réservoir comprend en plus une tige (14).
  3. Dispositif selon la revendication 1 ou 2, caractérisé en ce que le dispositif producteur de turbulences 5 est au moins un agrandissement discret de la section transversale dans une zone d'élargissement (13) au-dessus d'un domaine d'afflux (12).
  4. Dispositif selon la revendication 3, caractérisé en ce que la section transversale dans la zone d'élargissement (13) est au moins doublée, de préférence au moins quintuplée et de manière encore plus préférée au moins décuplée.
  5. Dispositif selon la revendication 3 ou 4, caractérisé en ce que la section transversale dans la zone d'élargissement (13) s'agrandit de façon linéaire, de préférence avec une augmentation tanϕ inférieure à 70°, de préférence inférieure à 50° et de manière encore plus préférée inférieure à 30°.
  6. Dispositif selon l'une quelconque des revendications précédentes, caractérisé en ce que la cavité (4) a une section transversale symétrique en rotation et diverge de manière conique dans la zone d'élargissement (13).
  7. Dispositif selon l'une quelconque des revendications précédentes, caractérisé en ce que la suspension aspirée dans la cavité (4) forme une interface (8) de hauteur constante pour un robot de prélèvement de liquide.
  8. Dispositif selon l'une quelconque des revendications précédentes, caractérisé en ce que la tête mélangeuse (2) comprend huit cavités 4.
  9. Utilisation d'un dispositif selon l'une quelconque des revendications 1 à 8 pour assurer une distribution régulière des microparticules dans un liquide.
  10. Utilisation d'un dispositif selon l'une quelconque des revendications 1 à 8 pour prélever une suspension contenant des microparticules distribuées régulièrement dans un liquide.
  11. Utilisation selon la revendication 10 pour identifier, caractériser et/ou purifier des protéines, de préférence pour déterminer l'activité enzymatique par spectrométrie de masse.
  12. Procédé assurant une distribution régulière de microparticules dans un liquide, comprenant les étapes suivantes :
    (a) remplissage d'un compartiment réservoir (1) avec une suspension de microparticules et de liquide,
    (b) aspiration de la suspension avec une pompe (3) via une aspiration (17) à partir du compartiment réservoir (1),
    (c) transport de la suspension aspirée dans une tête mélangeuse (2), qui comprend au moins une cavité (4),
    (d) transfert de la suspension dans la cavité (4),
    (e) production d'un courant turbulent dans la cavité (4),
    (f) transport de la suspension au-dessus d'un trop-plein (6) par une ouverture (7) dans le compartiment réservoir (1), et facultativement
    (g) répétition des étapes (b) à (f),
    caractérisé en ce que, parallèlement aux étapes (b) à (g), une circulation qui comprend les étapes suivantes est opérée :
    (b') aspiration de la suspension avec la pompe (3) via un retour à écoulement rotatif (16) à partir du compartiment réservoir (1),
    (c') transport de la suspension aspirée dans une ligne en boucle rotative,
    (d') transfert de la suspension via une entrée à écoulement rotatif (15) dans le compartiment réservoir (1),
    (e') production d'un courant turbulent dans le compartiment réservoir (1), et facultativement
    répétition des étapes (b') à (e').
  13. Procédé selon la revendication 12, caractérisé en ce que, dans l'étape (e), le courant turbulent est produit par le montage d'un dispositif producteur de turbulences 5, de préférence par le montage d'au moins un agrandissement discret de la section transversale dans une zone d'élargissement (13) au-dessus d'un domaine d'afflux (12).
  14. Procédé selon la revendication 12 ou 13, caractérisé en ce qu'une étape complémentaire mentionnée ci-après est mise en oeuvre après l'étape (e), (f) ou (g) :
    (h) prélèvement de la suspension par un robot de prélèvement de liquide.
EP08804783A 2007-09-27 2008-09-26 Dispositif et procédé assurant une distribution uniforme de microparticules dans un liquide Not-in-force EP2203246B1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102007047478A DE102007047478A1 (de) 2007-09-27 2007-09-27 Vorrichtung und Verfahren zur gleichmäßigen Verteilung von Mikropartikeln in einer Flüssigkeit
PCT/EP2008/062905 WO2009043813A1 (fr) 2007-09-27 2008-09-26 Dispositif et procédé assurant une distribution uniforme de microparticules dans un liquide

Publications (2)

Publication Number Publication Date
EP2203246A1 EP2203246A1 (fr) 2010-07-07
EP2203246B1 true EP2203246B1 (fr) 2011-05-25

Family

ID=40085628

Family Applications (1)

Application Number Title Priority Date Filing Date
EP08804783A Not-in-force EP2203246B1 (fr) 2007-09-27 2008-09-26 Dispositif et procédé assurant une distribution uniforme de microparticules dans un liquide

Country Status (5)

Country Link
US (1) US20110026356A1 (fr)
EP (1) EP2203246B1 (fr)
AT (1) ATE510612T1 (fr)
DE (1) DE102007047478A1 (fr)
WO (1) WO2009043813A1 (fr)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012127257A1 (fr) 2011-03-19 2012-09-27 Dental Care Innovation Gmbh Système pour dissolution d'une pastille ou d'un granulé dans un courant d'eau
USD825741S1 (en) 2016-12-15 2018-08-14 Water Pik, Inc. Oral irrigator handle
KR102625450B1 (ko) 2017-03-16 2024-01-16 워어터 피이크, 인코포레이티드 구강 작용제와 함께 사용하기 위한 구강 세척기 핸들

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3105778A (en) * 1959-06-12 1963-10-01 Kaiser Aluminium Chem Corp Heating and mixing methods
DE1275512B (de) * 1962-01-08 1968-08-22 Willi Walbersdorf Sondermaschb Mischvorrichtung
GB1189162A (en) * 1966-05-03 1970-04-22 Inst Wlokien Sztucznych I Synt A Process and Apparatus for Dissolving a Solid in a Liquid Solvent therefor
GB1183887A (en) * 1968-08-13 1970-03-11 British Motor Corp Ltd Slurry Treatment Plant
US4211733A (en) * 1978-12-26 1980-07-08 Chang Shih Chih Gas-liquid mixing process and apparatus
DE3844174A1 (de) * 1988-12-29 1990-07-05 Fresenius Ag Anlage zur herstellung von konzentraten durch mischung von fluessigkeit mit loeslichem feststoff
HUT61909A (en) * 1989-04-21 1993-03-29 Techno Bio Kk Method and mixer for mixing more materials and mixture produced by the same
US5252296A (en) 1990-05-15 1993-10-12 Chiron Corporation Method and apparatus for biopolymer synthesis
GB2285588B (en) * 1994-01-17 1997-04-30 Ea Tech Ltd Method and apparatus for mixing a metal matrix composite
US6255166B1 (en) 1999-08-05 2001-07-03 Aalo Lsi Design & Device Technology, Inc. Nonvolatile memory cell, method of programming the same and nonvolatile memory array
US7100851B2 (en) * 2001-04-27 2006-09-05 Kansai Paint Co., Ltd. Method and apparatus for dispersing pigment in liquid medium
US6881363B2 (en) * 2001-12-07 2005-04-19 Symyx Technologies, Inc. High throughput preparation and analysis of materials
WO2005090998A1 (fr) * 2004-03-23 2005-09-29 Matsushita Electric Industrial Co., Ltd. Procede d'agitation, cellule, equipement de mesure utilisant la cellule, et procede de mesure
US7763453B2 (en) 2005-11-30 2010-07-27 Micronics, Inc. Microfluidic mixing and analytic apparatus

Also Published As

Publication number Publication date
US20110026356A1 (en) 2011-02-03
EP2203246A1 (fr) 2010-07-07
WO2009043813A1 (fr) 2009-04-09
DE102007047478A1 (de) 2009-04-16
ATE510612T1 (de) 2011-06-15

Similar Documents

Publication Publication Date Title
DE69126690T2 (de) Automatisiertes labor für molekularbiologie
US8858066B2 (en) Liquid dispensing for high-throughput experimentation
EP1160573A2 (fr) Plaque de microtitrage et dispositif de pipetage multivoies couplé à celui
DE102006002258B4 (de) Modul zur Aufbereitung einer biologischen Probe, Biochip-Satz und Verwendung des Moduls
DE102016222072A1 (de) Vorrichtung und Verfahren zur geneigten Prozessierung von mikrofluidischen Kartuschen
DE10246211A1 (de) Labor-Arbeitsstation zum Bereitstellen von Proben
EP1260265A1 (fr) Appareil pour la préparation d'une chambre d'hybridation, set de traitament et système pour l'hybridation d'échantillons d'acide nucléique, protéines et tissus
DE69824315T2 (de) Verfahren zur charakterisierung komplexer flüssigkeiten und vorrichtungen zur durchführung des verfahrens
DE112016000200T5 (de) Mikrofluidik-Sondenkopf zum Bereitstellen einer Sequenz getrennter Flüssigkeitsvolumina, getrennt durch Abstandhalter
DE2009993A1 (de) Vorrichtung zur photometrischen Analyse
WO2002058850A1 (fr) Dispositif de retenue
EP2203246B1 (fr) Dispositif et procédé assurant une distribution uniforme de microparticules dans un liquide
DE60027009T2 (de) Schwach bindende vorrichtung zur rückhaltung von flüssigkeiten und zur filterung
DE112016000223T5 (de) Mikrofluidik-Sondenkopf zum Verarbeiten einer Sequenz von Flüssigkeitsvolumina, getrennt durch Abstandhalter
US20220241773A1 (en) Assay plate with nano-vessels and sample recovery assembly
LU102325B1 (de) Probenbehältnis für eine Dispensiervorrichtung
DE60012952T2 (de) Mischkammer
CH697426B1 (de) Dosiervorrichtung und Verfahren zum Betrieb derselben.
WO2021032464A1 (fr) Dispositif de préparation et procédé de préparation d'une suspension cellulaire pour un procédé d'analyse
EP4065265A1 (fr) Catalyseur et procédé pour produire une formulation
DE10260691A1 (de) Vorrichtung und Verfahren zur parallelen, automatisierten Kultivierung von Zellen unter technischen Bedingungen
EP1287328B1 (fr) Dispositif et procede de traitement de prelevements lies a un substrat
EP4122604A2 (fr) Dispositif et procédé de génération des séquences de fluide dans un canal de transport de fluides multiples et de conditionnement et de détection des séquences de fluide générées dans le canal de transport de fluides multiples
DE10236122A1 (de) Vorrichtung und Verfahren zur Bestimmung der Viskositäten und Flüssigkeiten mittels der Kapillarkraft
DE4142967A1 (de) Bioreaktor

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20100324

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MT NL NO PL PT RO SE SI SK TR

AX Request for extension of the european patent

Extension state: AL BA MK RS

RIN1 Information on inventor provided before grant (corrected)

Inventor name: FELDHUSEN, JOERG

Inventor name: THIEMANN, JOACHIM

Inventor name: LEMBURG, JOHANNES

Inventor name: SCHLUETER, HARTMUT

GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

DAX Request for extension of the european patent (deleted)
GRAS Grant fee paid

Free format text: ORIGINAL CODE: EPIDOSNIGR3

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MT NL NO PL PT RO SE SI SK TR

REG Reference to a national code

Ref country code: GB

Ref legal event code: FG4D

Free format text: NOT ENGLISH

REG Reference to a national code

Ref country code: CH

Ref legal event code: EP

REG Reference to a national code

Ref country code: IE

Ref legal event code: FG4D

Free format text: LANGUAGE OF EP DOCUMENT: GERMAN

REG Reference to a national code

Ref country code: DE

Ref legal event code: R096

Ref document number: 502008003714

Country of ref document: DE

Effective date: 20110707

RIN2 Information on inventor provided after grant (corrected)

Inventor name: SCHLUETER, HARTMUT

Inventor name: THIEMANN, JOACHIM

Inventor name: FELDHUSEN, JOERG

Inventor name: LEMBURG, JOHANNES

REG Reference to a national code

Ref country code: NL

Ref legal event code: VDEP

Effective date: 20110525

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110525

Ref country code: NO

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110825

Ref country code: PT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110926

Ref country code: SE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110525

Ref country code: HR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110525

REG Reference to a national code

Ref country code: DE

Ref legal event code: R083

Ref document number: 502008003714

Country of ref document: DE

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: GR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110826

Ref country code: FI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110525

Ref country code: SI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110525

Ref country code: ES

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110905

Ref country code: LV

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110525

Ref country code: IS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110925

Ref country code: CY

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110525

REG Reference to a national code

Ref country code: IE

Ref legal event code: FD4D

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: NL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110525

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: IE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110525

Ref country code: CZ

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110525

Ref country code: EE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110525

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: DK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110525

Ref country code: SK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110525

Ref country code: RO

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110525

Ref country code: PL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110525

PLBE No opposition filed within time limit

Free format text: ORIGINAL CODE: 0009261

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT

BERE Be: lapsed

Owner name: CHARITE - UNIVERSITATSMEDIZIN BERLIN

Effective date: 20110930

Owner name: RHEINISCH-WESTFALISCHE TECHNISCHE HOCHSCHULE AACH

Effective date: 20110930

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MC

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20110930

26N No opposition filed

Effective date: 20120228

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: IT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110525

REG Reference to a national code

Ref country code: DE

Ref legal event code: R097

Ref document number: 502008003714

Country of ref document: DE

Effective date: 20120228

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: BE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20110930

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: GB

Payment date: 20120920

Year of fee payment: 5

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: DE

Payment date: 20121130

Year of fee payment: 5

Ref country code: FR

Payment date: 20121008

Year of fee payment: 5

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110525

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LU

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20110926

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: BG

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110825

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: TR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110525

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: HU

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20110525

REG Reference to a national code

Ref country code: CH

Ref legal event code: PL

GBPC Gb: european patent ceased through non-payment of renewal fee

Effective date: 20130926

REG Reference to a national code

Ref country code: DE

Ref legal event code: R119

Ref document number: 502008003714

Country of ref document: DE

Effective date: 20140401

REG Reference to a national code

Ref country code: FR

Ref legal event code: ST

Effective date: 20140530

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: GB

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20130926

Ref country code: LI

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20130930

Ref country code: CH

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20130930

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: DE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20140401

Ref country code: FR

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20130930

REG Reference to a national code

Ref country code: AT

Ref legal event code: MM01

Ref document number: 510612

Country of ref document: AT

Kind code of ref document: T

Effective date: 20130926

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: AT

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20130926