WO1999001209A1 - Micromelangeur dynamique commutable avec des volumes morts minimums - Google Patents

Micromelangeur dynamique commutable avec des volumes morts minimums Download PDF

Info

Publication number
WO1999001209A1
WO1999001209A1 PCT/EP1998/003942 EP9803942W WO9901209A1 WO 1999001209 A1 WO1999001209 A1 WO 1999001209A1 EP 9803942 W EP9803942 W EP 9803942W WO 9901209 A1 WO9901209 A1 WO 9901209A1
Authority
WO
WIPO (PCT)
Prior art keywords
mixing chamber
switchable
micromixer according
discharge
channels
Prior art date
Application number
PCT/EP1998/003942
Other languages
German (de)
English (en)
Inventor
John S. Mccaskill
Kristina Schmidt
Original Assignee
Institut für Molekulare Biotechnologie E.V.
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 Institut für Molekulare Biotechnologie E.V. filed Critical Institut für Molekulare Biotechnologie E.V.
Publication of WO1999001209A1 publication Critical patent/WO1999001209A1/fr

Links

Classifications

    • 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
    • B01F33/30—Micromixers
    • 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
    • B01F33/452—Magnetic mixers; Mixers with magnetically driven stirrers using independent floating stirring elements

Definitions

  • the invention relates to a switchable dynamic micromixer with a minimal dead volume, which is used for the cyclical or continuous mixing of the smallest amounts of liquid in the order of 1 nl to 10 ⁇ l.
  • the micromixer is used with particular preference, in particular in connection with several micromixers with one another, in biotechnology, medical diagnostics, for pharmaceutical screening or DNA computing.
  • Static micromixers as described for example in MST-news 19/97 p. 30 - 31 (ISSN 09483128), use diffusion to homogenize solutions when using long contact paths and small channel diameters.
  • the disadvantages of this mixing variant consist, due to the necessarily long flow channels, in the resulting pressure losses in the flow system, the low efficiency of the mixing process, the relatively large dead volume and the relatively long mixing times.
  • DE 195 11 603 AI an arrangement for static mixing is described, which achieves a shortening of the diffusion paths by dividing two or more liquids several times and moving them layer by layer. This also enables mixing of insoluble fluids.
  • the dead volume of the mixing device is very large, due to repeated rerouting and layering of the liquids, and the mixing times are also very long.
  • Another static micro-mixer is described in DE 44 16 343 C2. According to this proposal, the mixing of several solutions also takes place difiusively, the fluids to be mixed in front of the mixing chamber being composed of plate-like, layered elements which are crossed by channels which run obliquely to the longitudinal axis of the micro-mixer, and the channels of adjacent elements cross without contact and in the Mix chamber open. Since the mixing effect is brought about by diffusion, a disadvantage of this arrangement is the long mixing time for complete homogenization.
  • Dynamic mixers use rotating mixing tools that bring the mixing energy into the mix to homogenize the components to be mixed. Because of the design-related, relatively large-volume design of these mixers, they are not suitable for mixing the smallest amounts of liquid which, on the one hand, are not required for the intended use of the present invention or, e.g. cannot be provided due to cost reasons.
  • a microflow processor closest to the invention is described in EP 0495 255 AI. The aim of this microflow processor is to mix small amounts of samples with the smallest possible dead volume, whereby it can be operated with flow rates in the range from ml / min to ⁇ l / min.
  • a component of this microflow processor is a micromixer which, due to its miniaturization, which cannot be further increased, can have a volume of 0.1 ⁇ l.
  • the invention has for its object to provide a micromixer that mixes two or more liquids that are present in very small volumes, preferably in a range below 100 nl, in a very short time, with low dead volume and high efficiency, if necessary the mixing can be designed to be interruptible and which allows the integration of several micromixers within a basic body.
  • FIG. 1 a shows a first possible embodiment of a micromixer in the assembled state without infestation of the media to be mixed
  • FIG. 1b shows a micromixer according to FIG. 1 with filling of the media to be mixed
  • FIG. 2a shows a second embodiment of a micromixer in the assembled state without filling the media to be mixed
  • FIG. 2b shows a micromixer according to FIG. 2 with filling the media to be mixed
  • 3 a shows a third possible embodiment of a micromixer in the assembled state with filling of the mixture to be mixed
  • FIG. 4 an interconnection of three micromixers according to FIG. 1 and FIG. 5, a preferred embodiment of one per se a Misclü ⁇ ammer subsequent discharge channel.
  • Figure 1 shows a first embodiment of a micromixer 1 according to the present invention.
  • the micromixer 1 is formed from a first base plate 20, into which a mixing chamber 23 and two feed channels 21 and 22 adjoining the mixing chamber 23 are introduced.
  • the misclic chamber 23 is followed by comb-shaped capillary paths 24 which open into a trench 25 to which a discharge duct 26 is connected.
  • a plurality of magnetizable beads 4, in particular made of a ferromagnetic material, are also introduced into the mixing chamber 23. The diameter of these beads 4 is such that it lies somewhat below the clear chamber height, which is limited by a cover plate 30 at the top.
  • a magnet 5 which can be set in rotation (cf. FIG.
  • this magnet 5 effects a linear and adjacent one Alignment of the beads 4, which undergo a rotation within the mixing chamber 23 following the magnetic rotation.
  • the diameter of the pearls can be between 1 ⁇ m and 100 ⁇ m. Their total number is then further determined so that the length of the linearly oriented pearl structure is below the smallest lateral extent of the mixing chamber 23.
  • the mixing chamber 23, the feed channels 21, 22, the discharge channel 26, the comb-like capillary paths 24 and the trench 25 are introduced into the base body 20 with the aid of microstriction technologies. Both wet chemical or physical etching techniques for the structuring of silicon or photostructurable glass, laser cutting processes or molding techniques for polymers can be used to produce the structures.
  • the basic body 20, which carries the structures made in this way, is sealed with a cover plate 30, consisting of a glass or a transparent polymer. This means that the mixing result in the mixing chamber or in the subsequent channels can be detected at any time.
  • the beads 4 can be introduced before the base body 20 is sealed to the cover plate 30 or at a later point in time when the beads 4 are pumped into the mixing chamber 23 together with a liquid, with the feed channels 21, 22 appropriately designed .
  • a return transport of the beads 4 from the mixing chamber 23 is prevented by a flow flow maintained in the micromixer. If the beads 4 are finally brought into the mixing chamber 23, they are demagnetized before being transported into the mixing chamber 23 in order to avoid clogging due to a plurality of beads 4 being connected. When an external magnetic field is switched on for the first time, the beads 4 are magnetized and only then exhibit a ferromagnetic behavior.
  • the design of the capillary paths 24, which adjoin the mixing chamber 23, each with an opening cross-section that is smaller than the diameter of the beads 4 used, represents an effective retention means for the beads 4. It is within the scope of the invention, to provide further discharge channels 26 on the trench 25 in order to derive the identical mixing result C.
  • the fluids A, B to be mixed are permanently mixed with one another.
  • the discharge channel can additionally be used as a detection channel, for which purpose a particularly preferred embodiment is described in FIG. 5.
  • the mixing chamber 23 is given a volume of 1 nl to 10 ⁇ l.
  • Figures 2a and 2b basically describe a design identical to Figures la and lb; Identical functional elements are provided with the same reference symbols. The only difference is that here the retaining means for the beads 4 is formed by an overflow channel 24 '. In its width dimension b, this overflow channel 24 'extends essentially over the width of the mixing chamber 23 to which it is attached. The gap-shaped vertical extension of the overflow channel 24 ', which is bounded at the top by the cover plate 30 which is then attached, is dimensioned in comparison with the bead diameters used so that the beads 4 cannot get into the overflow channel 24'.
  • the micromixers 1 designed according to FIGS. 1 a, 1 b, 2 a, 2 b are designed for purely dynamic operation, that is to say for the constant mixing of fluids.
  • These designs of the micromixers 1 have a plurality, at least two, of the inputs 21 and 22, which in this operating mode are not necessarily in one plane with the others Components such as 23 and the following need to be maintained, via which the solutions A and B can be fed to the mixing chamber 23, are mixed there by means of the beads 4 in the manner described, so that a mixture C can be removed from the discharge channel 26.
  • the micromixer 1 undergoes a certain modification for further uses, as is indicated in FIGS. 3a and 3b. These designs represent a switchable micromixer. If the micromixer 1 according to FIGS. 1 a, 1 b, 2 a, 2 b each contains only one discharge channel 26, three discharge channels 26, 27, 28 are provided in an embodiment according to FIG 2a are designed analogously to the height dimensioning of the overflow channel 24 ', as a result of which the channel edge designs 261, 271, 281 simultaneously assume the function of the overflow channel 24'.
  • FIG. 3 a shows the FaU that the micromixer works in dynamic operation, analogously to the previous figures, and thus the Hquid media A and B supplied via the feed channels 21, 22 are mixed.
  • an identical mixed solution C can be taken from all discharge channels 26, 27, 28.
  • the discharge channels 26, 27, 28 are assigned with the proviso that the two discharge channels 21, 22 provided in the example are the three discharge channels 26, 27, 28 are assigned at the other end of the mixing chamber in such a way that the first feed channel 21, and thus the first medium A that can be fed through it, a first discharge channel 27, the second feed channel 22, and thus the second medium B that can be fed through this a second discharge channel 28 and a third discharge channel 26, the contents of which are discarded, are assigned to a common flow zone formed by media A and B. If the micromixer in the example according to FIG.
  • 3 a and 3 b can be expanded within the scope of the invention to a plurality of feed and discharge channels, the above requirements in each case being observed and a further channel for a partially mixed component W of the respective border zone area being to be provided between two channels that discharge pure components . It is possible to switch alternately between the operating states according to FIGS. 3a and 3b, which is advantageous, for example, for combinatorial processing of a large number of components and, for example, requires synthesis in the flow.
  • micromixers described in FIGS. 1 a to 3 b can be connected in series in any number, as a result of which entire networks of mixing agents are possible.
  • Such a design is shown in FIG. 4 using three micromixers 1a, 1b, 1c designed according to FIG.
  • Each of these micromixers contains a mixing chamber 23a, 23b, 23c.
  • several micromixers can be accommodated in one piece in a base body 20 and covered by a common cover plate 30.
  • FIG. 5 shows a special design of a discharge channel 26, in particular for the last-mentioned, but not limited to, the integrated embodiment variant.
  • This discharge channel like the one shown in FIGS. 1 a to 3 b, presses against the mixing chamber or subordinate assemblies on the one hand and is meandered several times over a length adapted to the mixing chamber volume.
  • the volume of the channel 26 should in this case be dimensioned such that it takes up at least three times the volume of the mixing chamber volume.
  • This meandering design of the discharge channel favors the use of commercially available detection units, for example optical spectroscopes, with the aid of which a relatively large sample volume and thus increased signals are available when imaged by a transparent cover plate 30, since several meandering channel sections can be detected at the same time.
  • the embodiments described have an extremely low dead volume, since practically the entire mixing chamber volume can be used for further uses.
  • the structures introduced into the base body 20 are also mirror-image inserted identically into the cover plate 30.
  • Such training opens e.g. based on the figures la and lb with appropriate material selection for the base body and the cover plate, for example pyrex glass, a circular cross-sectional design of the capiaries 24, which then symmetrical to the mixing chamber 23, with the provision of further, not shown magnet systems, the positioning of individual beads 4 in individual or Allow a switchable closure of the discharge path on the capillary mouth areas.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)

Abstract

L'invention concerne un micromélangeur dynamique commutable avec des volumes morts minimums, destiné au mélange cyclique ou continu de petites quantités de fluides de l'ordre de 1 nl à 10 νl. L'invention a pour objet de créer un micromélangeur qui, d'un côté, est en liaison avec au moins deux canaux d'alimentation (21, 22) et, de l'autre, présente au moins un canal d'évacuation (26) opposé des canaux d'alimentation (21, 22). Ce micromélangeur présente dans la chambre de mélange (23) plusieurs perles magnétisables (4) qui, d'un côté, sont recouvertes d'un couvercle (30), qui peuvent se déplacer librement et dont la longueur totale disposées en une rangée linéaire est légèrement inférieure à la plus petite dimension latérale de la chambre de mélange. Une système magnétique (5) peut être mis en rotation et en circuit, de telle façon qu'il permette un alignement des perles magnétisables (4) juxtaposées et une rotation commune de cette rangée linéaire de perles.
PCT/EP1998/003942 1997-07-04 1998-06-27 Micromelangeur dynamique commutable avec des volumes morts minimums WO1999001209A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19728520.1 1997-07-04
DE19728520A DE19728520A1 (de) 1997-07-04 1997-07-04 Schaltbarer dynamischer Mikromischer mit minimalem Totvolumen

Publications (1)

Publication Number Publication Date
WO1999001209A1 true WO1999001209A1 (fr) 1999-01-14

Family

ID=7834593

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1998/003942 WO1999001209A1 (fr) 1997-07-04 1998-06-27 Micromelangeur dynamique commutable avec des volumes morts minimums

Country Status (2)

Country Link
DE (1) DE19728520A1 (fr)
WO (1) WO1999001209A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10218280C1 (de) * 2002-04-19 2003-11-20 Fraunhofer Ges Forschung Integriertes Misch- und Schaltsystem für die Mikroreaktionstechnik

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6186659B1 (en) 1998-08-21 2001-02-13 Agilent Technologies Inc. Apparatus and method for mixing a film of fluid
DE19917148C2 (de) * 1999-04-16 2002-01-10 Inst Mikrotechnik Mainz Gmbh Verfahren und Mikrovermischer zur Herstellung einer Dispersion
US6258593B1 (en) 1999-06-30 2001-07-10 Agilent Technologies Inc. Apparatus for conducting chemical or biochemical reactions on a solid surface within an enclosed chamber
US6420114B1 (en) 1999-12-06 2002-07-16 Incyte Genomics, Inc. Microarray hybridization chamber
DE10213003B4 (de) * 2002-03-22 2006-08-03 Forschungszentrum Karlsruhe Gmbh Mikromischer und Verfahren zum Mischen von mindestens zwei Flüssigkeiten und Verwendung von Mikromischern
DE102004013551A1 (de) * 2004-03-19 2005-10-06 Goldschmidt Gmbh Alkoxylierungen in mikrostrukturierten Kapillarreaktoren
US20050277187A1 (en) * 2004-06-07 2005-12-15 Bioprocessors Corp. Creation of shear in a reactor
EP2105202A1 (fr) * 2008-03-28 2009-09-30 Stichting Dutch Polymer Institute Appareil et procédé pour mélangeur et pompe microfluide
DE102008021483A1 (de) * 2008-04-29 2009-12-03 Forschungszentrum Jülich GmbH Zuleitungssystem
DE202015104827U1 (de) 2015-09-11 2015-10-22 Leibniz-Institut Für Photonische Technologien E.V. Flusssteuerbaustein

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0090192A1 (fr) * 1982-03-26 1983-10-05 Holger Behnk Appareil pour l'étude et la mesure du temps de coagulation du sang par impulsion en changeant la position d'une bille d'acier dans un tube d'essai contenant le réactif
US4475821A (en) * 1980-10-07 1984-10-09 Bruker-Analytische Messtechnik Gmbh Mixing chamber
US4730789A (en) * 1982-12-10 1988-03-15 Gebruder Buhler Ag Agitator mill
SU1655550A1 (ru) * 1985-10-08 1991-06-15 Предприятие П/Я Г-4805 Устройство дл перемешивани
EP0495255A1 (fr) * 1991-01-17 1992-07-22 Lc Packings Nederland B.V. Processeur de microdébit
DE4311666A1 (de) * 1993-04-08 1994-10-13 Hans Otto Arnold Verfahren zum malfertigen Aufbereiten von Schmelzfarben am Arbeitsplatz eines Glas- oder Porzellanmalers

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1251277B (fr) *
JPS55147143A (en) * 1979-03-29 1980-11-15 Toyo Eng Corp Agitation method

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4475821A (en) * 1980-10-07 1984-10-09 Bruker-Analytische Messtechnik Gmbh Mixing chamber
EP0090192A1 (fr) * 1982-03-26 1983-10-05 Holger Behnk Appareil pour l'étude et la mesure du temps de coagulation du sang par impulsion en changeant la position d'une bille d'acier dans un tube d'essai contenant le réactif
US4730789A (en) * 1982-12-10 1988-03-15 Gebruder Buhler Ag Agitator mill
SU1655550A1 (ru) * 1985-10-08 1991-06-15 Предприятие П/Я Г-4805 Устройство дл перемешивани
EP0495255A1 (fr) * 1991-01-17 1992-07-22 Lc Packings Nederland B.V. Processeur de microdébit
DE4311666A1 (de) * 1993-04-08 1994-10-13 Hans Otto Arnold Verfahren zum malfertigen Aufbereiten von Schmelzfarben am Arbeitsplatz eines Glas- oder Porzellanmalers

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10218280C1 (de) * 2002-04-19 2003-11-20 Fraunhofer Ges Forschung Integriertes Misch- und Schaltsystem für die Mikroreaktionstechnik

Also Published As

Publication number Publication date
DE19728520A1 (de) 1999-01-07

Similar Documents

Publication Publication Date Title
DE60300980T2 (de) Lochmikromischer
EP0879083B1 (fr) Dispositif de melange de petites quantites de liquides
EP1242171B1 (fr) Micromelangeur
DE60208235T2 (de) Mikrofluidische vorrichtungen mit verteilungseinlässen
DE69630036T2 (de) Durchflusszelle für proben und deren verwendung
DE60122854T2 (de) Lineare Küvettenmatrix, damit gebaute zweidimensionale Küvettenmatrix und solche zweidimensionale Küvettenmatrizen umfassendes System
DE10228767A1 (de) Mikrovorrichtung und Verfahren für eine Komponententrennung in einem Fluid
DE112018001955B4 (de) Anwendungsspezifisch ausgestaltbare Mikrofluidik-Einheit mit programmierbaren Mikrofluidik-Knoten
DE10334341A1 (de) Kaskadierte hydrodynamische Fokussierung in Mikrofluidikkanälen
EP0484278A1 (fr) Appareil de préparation d'échantillons liquides pour l'analyse chimique
DE19935433A1 (de) Mikrofluidischer Reaktionsträger
WO1999001209A1 (fr) Micromelangeur dynamique commutable avec des volumes morts minimums
EP2329877A1 (fr) Elément micro-fluidique destiné à l'analyse d'un échantillon de liquide
DE60201017T2 (de) Mikrokanalvorrichtung und verfahren
DE10123092A1 (de) Verfahren und statischer Mischer zum Mischen mindestens zweier Fluide
WO2005018772A1 (fr) Procede d'extraction faisant intervenir un micro-melangeur statique
EP1165227B1 (fr) Reacteur a microcolonnes
EP1075326B1 (fr) Dispositif pour transporter des liquides le long de voies de guidage predeterminees
DE102008009199A1 (de) Reaktionsmischersystem zur Vermischung und chemischer Reaktion von mindestens zwei Fluiden
DE102009005925A1 (de) Vorrichtung und Verfahren zur Handhabung von Biomolekülen
DE10250406B4 (de) Reaktionsvorrichtung und Mischsystem
DE4308697A1 (de) Verfahren zur Anreicherung eines ersten gasförmigen oder flüssigen Mediums mit einem zweiten Gas oder einer zweiten Flüssigkeit sowie ein Reaktor zur Durchführung des Verfahrens
DE10154601B4 (de) Ein Mikrobauelement mit einem integrierten hervorstehenden Elektrospray-Emitter und ein Verfahren zum Herstellen des Mikrobauelements
EP1776183A1 (fr) Dispositif et procede pour mettre en oeuvre en continu des processus chimiques
EP1343587A2 (fr) Dispositif d'extraction et d'emission de substances liquides

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): JP US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase