[go: up one dir, main page]

WO1999001221A1 - Cuve de microreaction, systeme de cuves de microreaction et procede pour delivrer un liquide contenu dans des cuves de microreaction - Google Patents

Cuve de microreaction, systeme de cuves de microreaction et procede pour delivrer un liquide contenu dans des cuves de microreaction Download PDF

Info

Publication number
WO1999001221A1
WO1999001221A1 PCT/EP1998/003953 EP9803953W WO9901221A1 WO 1999001221 A1 WO1999001221 A1 WO 1999001221A1 EP 9803953 W EP9803953 W EP 9803953W WO 9901221 A1 WO9901221 A1 WO 9901221A1
Authority
WO
WIPO (PCT)
Prior art keywords
microreaction
microreaction vessel
arrangement
vessel
vessels
Prior art date
Application number
PCT/EP1998/003953
Other languages
German (de)
English (en)
Inventor
Wolfgang Ehrfeld
Lutz Weber
Rainer Pommersheim
Renate Konrad
Monika Niggemann
Original Assignee
INSTITUT FüR MIKROTECHNIK MAINZ GMBH
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 MIKROTECHNIK MAINZ GMBH filed Critical INSTITUT FüR MIKROTECHNIK MAINZ GMBH
Publication of WO1999001221A1 publication Critical patent/WO1999001221A1/fr

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5025—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures for parallel transport of multiple samples
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0046—Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0093—Microreactors, e.g. miniaturised or microfabricated reactors
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5025—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures for parallel transport of multiple samples
    • B01L3/50255—Multi-well filtration
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00653—Making arrays on substantially continuous surfaces the compounds being bound to electrodes embedded in or on the solid supports
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00781—Aspects relating to microreactors
    • B01J2219/00783—Laminate assemblies, i.e. the reactor comprising a stack of plates
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00781—Aspects relating to microreactors
    • B01J2219/00819—Materials of construction
    • B01J2219/00833—Plastic
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00781—Aspects relating to microreactors
    • B01J2219/00851—Additional features
    • B01J2219/00853—Employing electrode arrangements
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00781—Aspects relating to microreactors
    • B01J2219/00873—Heat exchange
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00781—Aspects relating to microreactors
    • B01J2219/00891—Feeding or evacuation

Definitions

  • the invention relates to microreaction vessels, their arrangements and a method for dispensing a liquid from a microreaction vessel or an arrangement of microreaction vessels.
  • biochemistry and pharmaceutical active ingredient research especially using the concepts of combinatorial chemistry, the smallest amounts of biochemically active substances are converted or tested for their effectiveness.
  • the aim is to implement a large number of samples in the shortest possible time, which is associated with a minimal number of work steps with simultaneous automation.
  • titer plates are currently used which have depressions into which substances are pipetted and react with one another.
  • To transfer the reaction products into other titer plates for example, it is necessary to take up the contents of the wells in pipettes. It is also known to move thin rods into the wells of the titer plate in order to transfer the adhering substances to other vessels.
  • additional devices such as pipettes or rods, for transferring the reaction products from one titer plate to another has disadvantages. Additional devices mean additional work steps, a risk of sample contamination and a loss of sample quantity.
  • a Tiier plate is described in WO 97/15394, the recesses of which have a comparatively large filling opening and a small outlet opening.
  • the surface tension prevents the liquid from flowing out.
  • the liquid can be discharged through the outlet opening by means of a gas pressure surge.
  • WO 92/02303 describes a titer plate, the recesses of which are closed off by a porous membrane which retains the liquid. The liquid is only dispensed when a gas pressure surge is applied.
  • a disadvantage of such titer plates is that the dissolved components crystallize out to close the outlet openings or the membrane pores can lead.
  • Another disadvantage is that the dimensioning of the outlet openings or the membrane pores depends on the surface tension of the respective liquid.
  • the object of the invention is to provide microreaction vessels and arrangements of such microreaction vessels which allow a liquid to be dispensed in a simple manner without having to use devices for this purpose which come into contact with the contents of the microreaction vessel and which do not have the aforementioned disadvantages of known titer plates exhibit. Furthermore, it is an object of the invention to provide a corresponding method for dispensing a liquid from a microreaction vessel or an arrangement of microreaction vessels.
  • the bottom of the microreaction vessel comprising at least one filling opening and a reaction chamber is designed such that at least one outlet opening can be produced by the action of an external force and / or local heat supply.
  • microreaction vessel initially has no outlet openings, and that at least one outlet opening is only formed by the action of an external force and / or local heat supply.
  • microreaction vessel With the microreaction vessel according to the invention it is therefore possible to add various substances, preferably liquids, metered through the filling opening, to react with one another in the reaction chamber and to dispense a depression, for example, into a titer plate located under the microreaction vessel through the outlet opening to be produced.
  • This partial or complete transfer of the contents of the microreaction vessel does not require a device that comes into contact with the contents of the microreaction vessel. A risk of contamination and the loss of the contents of the microreaction vessel is minimized. Since the outlet opening is only being created, there is also no problem of closure by crystallization.
  • the outlet opening can be generated as an external force by a gas pressure surge introduced via the filling opening.
  • a gas pressure surge introduced via the filling opening.
  • the liquid in the chamber is also partially or completely released.
  • a type of stamp can also be provided as the external force, which preferably engages on the underside of the bottom of the microreaction vessel.
  • At least one outlet channel located in the bottom of the microreaction vessel is closed by a material serving as a plug, which can be removed by the action of a force such as a blast of compressed air.
  • a material serving as a plug which can be removed by the action of a force such as a blast of compressed air.
  • Plastic, elastic or highly viscous materials are preferably provided for this purpose.
  • the microreaction vessel has at least one outlet channel which is covered with a thin layer on the underside of the bottom of the microreaction vessel.
  • the entire underside of the microreaction vessel can also be covered with this layer.
  • This layer can be held on the underside of the bottom of the microreaction vessel by adhesive bonding, fusing or by adhesive forces.
  • the thin layer can advantageously be an integral part of at least the bottom of the microreaction vessel.
  • the action of a force for example a blast of compressed air, destroys the thin layer in the manner of a rupture disk or detaches it from the underside of the bottom of the microreaction vessel, so as to produce the outlet opening.
  • the base it is also conceivable for the base to be deflected to such an extent by a stamp engaging on the underside of the base that the thin layer tears.
  • the stamp is advantageously designed in this case, for example as a hollow cylinder, and the point of application selected so that the stamp does not come into contact with the contents of the reaction chamber.
  • the underside and / or the top of the bottom of the microreaction vessel have one or more predetermined breaking points, for example notches. At these points, one or more outlet openings open under the action of a force, for example by means of a plunger engaging from below.
  • a fourth embodiment provides that the bottom of the microreaction vessel has one or more incisions at the location of the outlet opening to be created, which cut through the bottom from the bottom to the top partially or completely. Under the action of force from the inside of the microreaction vessel on the top of the bottom, the bottom bulges, as a result of which the outlet opening is opened in the form of a gap in the region of the incision. It is also conceivable to apply force to the underside of the bottom of the microreaction vessel, for example by means of a hollow cylinder as a stamp, to arch the bottom in the direction of the chamber of the microreaction vessel and thus to produce the outlet opening. If the material of the floor has elastic properties, the outlet opening can be opened and closed reversibly.
  • the outlet opening can be generated by local heat supply by means of electrical energy. This can be supported by an external force, for example a gas pressure surge introduced via the filling opening.
  • a first embodiment variant provides that the microreaction vessel in the region of the opening to be produced has two electrodes, which are arranged on the underside of the base or in the base and are spaced apart from one another and form an electrical spark gap. By applying a sufficiently high voltage, a spark is formed between the two electrodes and thus a rapid, strong temperature increase in this area.
  • At least one heating resistor is arranged on the underside of the floor or in the floor itself in the region of the opening to be produced.
  • the electrical heating resistor is connected to electrical leads. When an electrical current flows through the Heating resistance there is a local temperature increase in the bottom of the microreaction vessel.
  • the electrodes, heating resistors or electrical leads can advantageously be applied by means of thin-film techniques, for example printed on the bottom of the microreaction vessel or the arrangement of microreaction vessels.
  • An outlet opening can be produced in a simple manner by local heat supply, preferably according to one of the two design variants described above, in connection with one of the four design variants listed above for designing the bottom of the microreaction vessel.
  • the outlet channel can be closed by a material serving as a plug, which can be softened when heated and, if necessary supported by a gas pressure surge, can be removed from the outlet channel.
  • this layer is preferably designed in such a way that it cracks, melts or decomposes at this point when heat is applied.
  • This can be a thin plastic layer, for example. In connection with the third embodiment variant, this can be supported by predetermined breaking points.
  • the fourth embodiment variant with incisions in the bottom of the microreaction vessel can also be combined with the embodiment that provides for local heating.
  • the floor in the area of the incisions can be designed such that an outlet opening in the form of a gap is opened when heated by thermal expansion.
  • the reaction chamber of the microreaction vessel can be designed in such a way that it has approximately the same diameter as the filling opening.
  • a cylindrical shape of the chamber can be provided, which tapers conically at the end opposite the filling opening to the diameter of the outlet channel.
  • the reaction chamber can also have a larger diameter than the filling opening. So has a spherical shape Chamber the advantage of less evaporation and a reduced risk of splashing when adding liquids.
  • microreaction vessels can have, for example, a chamber volume of 1 ⁇ l to 500 ⁇ l. Depending on the application, other dimensions for the diameter and chamber volume can also be used.
  • the outlet opening to be created is formed into a tip. It can also be advantageous if the outlet opening widens outwards in a conical manner.
  • a sieve or a filter can be fitted in the chamber or between the chamber and the outlet channel, so that when the chamber is acted upon by a blast of compressed air with the discharge of the liquid through the outlet opening, solid components are simultaneously separated.
  • the microreaction vessel preferably consists of a material which is chemically inert to the liquids used and which is biocompatible with the biochemical substances used.
  • plastics which include, for example, polycarbonate, polyethylene ether ketone, cyclic olefin copolymers, polymethyl methacrylate or mixtures thereof are suitable.
  • the microreaction vessel is preferably a one-piece molded body made of plastic.
  • the use of microtechnologically manufactured mold inserts during manufacture, for example in the injection molding process, enables the high precision required.
  • these advantageously have connecting elements, such as plug-in and / or locking elements.
  • the independent claim 17 relates to an arrangement of several microreaction vessels according to the invention side by side in a row or in rows and columns in the form of a matrix. With such arrangements, a large number of samples can be handled simultaneously.
  • the matrix-like arrangement advantageously has the same number of chambers, for example 96, 384 or 864, and the same external dimensions as standard titer plates. This enables automated handling using commercially available devices.
  • the arrangement can consist of individual microreaction vessels or arrangements, such as rows, of microreaction vessels which are connected to one another in a detachable or non-detachable manner.
  • a detachable connection is made possible, for example, via latching and / or plug-in elements.
  • An inseparable connection is achieved by gluing or welding.
  • the microreaction vessels are an integral part of the arrangement.
  • the arrangement can consist of a single molded body produced by injection molding.
  • This arrangement can also include microreaction vessels which have electrical heating resistors arranged in the region of the outlet openings to be produced on the underside of the base or in the base itself or electrodes spaced apart from one another, each forming an electrical spark gap.
  • the arrangement has electrical contacts which are connected to the heating resistors or electrodes via electrical leads. If the arrangement is a titer plate, these electrical contacts can be arranged, for example, on the side, on the top or on the bottom. Individual outlet openings can thus be produced in a targeted manner via an electrical control unit.
  • the further arrangement according to the invention according to claim 22 has at least one microreaction vessel according to the invention and at least one further microreaction vessel which comprises a filling opening and a reaction chamber, the microreaction vessel according to the invention and the further microreaction vessel each having at least one lateral connection channel via which the at least two microreaction vessels are fluidly connected to one another are connected. Due to the fluidic connection of at least two microreaction vessels, reactions can also be carried out in several steps with several reaction partners in a single arrangement of microreaction vessels. In this way, intermediates for inclusion in subsequent reactions can be transferred from one microreaction vessel to another via the side connection and reacted there with another starting material.
  • the contents of the reaction chamber can then be dispensed from the microreaction vessel according to the invention in accordance with one of the methods described above, for example by means of a gas pressure surge.
  • the transfer of the contents of one reaction chamber into another via lateral connecting channels can also be carried out via a gas pressure surge.
  • the method for dispensing a liquid from a microreaction vessel or an arrangement of microreaction vessels provides, according to claim 23, that at least one outlet opening is created by the action of an external force and / or by local heat supply.
  • the microreaction vessels and their arrangements according to claims 1 to 22 are particularly suitable for this.
  • a gas pressure surge is preferably provided as the external force, which creates the outlet opening and at least partially releases the liquid.
  • the generation of an outlet opening by local heating is preferably achieved by softening, melting or destroying a thin plastic layer.
  • the heat is advantageously supplied locally by an electrical resistance heater or an electrical discharge.
  • FIG. 1 shows a microreaction vessel with a plug in the outlet channel in cross section from the side
  • Figure 2 shows a microreaction vessel with a thin layer on the underside of the
  • FIG. 3 shows a microreaction vessel in which the thin layer is an integral part of the bottom, in cross section from the side,
  • Figure 4 shows a microreaction vessel with predetermined breaking points in the bottom in cross section of the
  • Figure 5a shows a microreaction vessel with an incision in the bottom in cross section of the
  • FIG. 5b shows the microreaction vessel according to FIG. 5a in cross section from above.
  • FIG. 6 shows a matrix-like arrangement of microreaction vessels in perspective
  • FIG. 8 shows a microreaction vessel with an electrical heating resistor in cross section from the side, 9a and 9b a microreaction vessel with an electrical heating resistor in a top view from below,
  • FIG. 9c shows a microreaction vessel with spaced electrodes in a top view from below
  • Figure 10 shows a microreaction vessel with spaced electrodes in cross section from the
  • 11a shows an arrangement of 3x3 microreaction vessels with electrical contacts in a perspective view
  • Figure 11 b shows the arrangement of Figure 11a in plan view from below.
  • FIG. 1 shows a microreaction vessel 1 in which the bottom has an outlet channel 4 connecting the upper side 20 to the lower side 21, a plug 22 being located in the outlet channel 4.
  • the plug 22 can be pushed out to the underside 21 of the base by a gas pressure surge introduced via the filling opening 2, whereby an outlet opening 5 is created and a liquid in the chamber 3 is dispensed.
  • the outlet channel 4 is closed by a thin layer 23 located on the underside 21 of the bottom of the microreaction vessel 1, which can be, for example, a laminated thin plastic film.
  • This layer 23 can also be an integral part of the floor, as shown in FIG. 3.
  • the layer 23 is preferably so thin that it is destroyed in the manner of a rupture disk under the action of, for example, a gas pressure surge, and an outlet opening is thus formed.
  • FIG. 4 shows a microreaction vessel 1 with notches 24 in the top 20 and the bottom 21 of the bottom. These indentations 24 surrounding a central region 26 represent predetermined breaking points. Under the action The central region 26 can be separated from the rest of the floor by an external force, as a result of which an outlet channel 4 with an outlet opening 5 is formed.
  • FIGS. 5a and 5b A microreaction vessel with two incisions 25 penetrating the bottom from the top 20 to the bottom 21 is shown in FIGS. 5a and 5b.
  • FIG. 5a shows the microreaction vessel in cross section from the side, a section 25 being visible.
  • Figure 5b shows the top 20 of the bottom of the microreaction vessel with two intersecting incisions 25 and the wall 6 of the microreaction vessel 1 in section from above.
  • FIG. 6 A one-piece matrix-like arrangement 30 of microreaction vessels is shown in FIG. 6, a row of microreaction vessels 1 being shown in cross section from the side.
  • microreaction vessels arranged in the manner of known titer plates allow simple handling of a large number of substances under the same conditions.
  • the microreaction vessels shown here correspond to the microreaction vessel according to FIG. 2 with a thin layer 23 located on the underside 21 of the bottom.
  • other microreaction vessels according to the invention can also be used for such an arrangement.
  • the contents of individual microreaction vessels can be released, for example, by targeted pressurization of individual filling openings 2 with compressed air blasts.
  • the thin layer in the area of the respective outlet channel 4 is destroyed in the manner of a rupture disk by the compressed air blast.
  • the middle microreaction vessel 1 represents a microreaction vessel according to the invention in the manner of a microreaction vessel according to FIG. 2 with a thin layer 23 on the underside 21 of the bottom. This is via additional connecting channels 7 and 9 with the two connecting channels 14 and 13 of the laterally arranged microreaction vessels 10a , 10b connected. Furthermore, the middle microreaction vessel 1 has an outlet channel 4 at the bottom of the reaction chamber 3, which leads to the thin layer 23 located on the underside of the middle microreaction vessel 1. Substances or liquids which react with one another in the chamber 12a can be added via the filling opening 11a of the microreaction vessel 10a arranged on the left in FIG.
  • the left microreaction vessel 10a is simultaneously pressurized via the filling opening 11a and the middle microreaction vessel 1 via the filling opening 2, the contents of the left microreaction vessel 1 can be conveyed into the middle microreaction vessel 1 and from there into the right microreaction vessel 10b (FIG 7b). If all three microreaction vessels 1, 10a, 10b are acted upon by a blast of compressed air through the filling openings 2, 11a, 11b, the contents of the central microreaction vessel 1 can be dispensed via the outlet channel 4 to form an outlet opening 5 in the thin layer 23 (FIG. 7c).
  • microreaction vessels 1, 10a, 10b can be detachably connected to one another, for example with the aid of plug-in elements in the manner of tongue and groove.
  • the microreaction vessels 1, 10a, 10b can also be permanently connected to one another or can be produced as a one-piece molded body, preferably made of a plastic.
  • FIGS. 8 to 11 b show microreaction vessels and their arrangements in which an outlet opening can be generated by local heat supply, here in the form of electrical energy.
  • FIG. 8 shows a microreaction vessel 1 in cross section from the side, the underside 21 of the bottom of which has a heating resistor 40 connected to electrical leads 41a, 41b.
  • the heating resistor 40 is located in the region of the outlet channel 4, which opens out on a thin layer 23. When current flows through the heating resistor heats up this thin layer, depending on the material used at this point tears open, melts or decomposes. This can be supported by a gas pressure surge, which at the same time pushes out at least part of the liquid in the reaction chamber 3 through the outlet channel 4 and the outlet opening, not shown here.
  • the underside of this microreaction vessel is shown in Figure 9a.
  • the heating resistor 40 can be made of the same material as the feeds 41 a, 41 b, for example by means of thin film technology. By reducing the cross section compared to the feeds 41 a, 41 b, a higher resistance is achieved.
  • FIG. 9b Another embodiment of the electrical heating resistor 40, in the form of two semicircles surrounding a central region, is shown in FIG. 9b.
  • the outlet opening to be produced lies in this middle region, in which the highest temperatures are reached when heated.
  • the electrical feeds are designed as two electrodes 43a, 43b, which form an electrical spark gap 42 due to their spacing. If the voltage is sufficiently high, an electrical discharge takes place between the opposing electrodes 43a and 43b, as a result of which the floor is locally heated in the region of the gap 42.
  • FIG. 9c A further variant of two spaced electrodes 43a, 43b forming a spark gap 42 is shown in FIG.
  • the electrodes are arranged in the bottom of the microreaction vessel. This enables a targeted heating of the material in the region of the outlet opening to be produced.
  • FIGS. 11 a and 11 b An arrangement of 3 ⁇ 3 microreaction vessels is shown in FIGS. 11 a and 11 b, the outlet openings of which can be generated by means of local heat supply by electrical energy.
  • FIG. 11b in which the position of the reaction chambers 3 is indicated by broken circles, shows the arrangement with a view of the underside 21.
  • the electrical leads 44a, 44b,.. connect the laterally arranged electrical contacts 45.
  • Microreaction vessel filling opening reaction chamber outlet channel outlet opening wall side connecting channel side connecting channel a, 10b microreaction vessel a, 11b filling opening a, 12b reaction chamber side connecting channel side connecting channel top of the bottom underside of the bottom grafting thin layer notch incision middle area arrangement of microreaction vessels arrangement of fluidly connected microreaction vessels Arrangement of microreaction vessels with electrical heating elements electrical heating resistor a, 41 b electrical supply gap a, 43b electrode a, 44b electrical supply electrical connection contacts

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)

Abstract

L'invention concerne une cuve de microréaction, des systèmes de cuves de microréaction, ainsi qu'un procédé pour délivrer un liquide contenu dans une cuve de microréaction ou dans un système de cuves de microréaction. La base inférieure de la cuve de microréaction se présente de manière à créer un orifice de décharge, uniquement sous l'effet d'une force extérieure, par exemple un à-coup d'air comprimé, et/ou sous l'effet d'apport local de chaleur, par exemple à l'aide d'un chauffage ohmique électrique, et à permettre ainsi la décharge d'un liquide se trouvant dans la chambre de réaction (3). A cet effet, le canal de sortie (4) est fermé par un bouchon ou par une couche (23) située sur la face inférieure (21) de la base inférieure et servant de plaque de rupture. Il est également possible de prévoir des encoches sous forme de points destinés à la rupture ou d'entailles dans la zone du canal de sortie. Ce procédé présente l'avantage de ne pas nécessiter l'utilisation de dispositifs et de pipettes pour transférer le contenu de la cuve de microréaction. L'invention concerne en outre des systèmes (30) de cuves de microréaction disposés par rangées ou en lignes et en colonnes, sous forme de matrice, à la manière de plaques de titrage. Ce système peut également comprendre des cuves de microréaction en liaison fluidique mutuelle par l'intermédiaire de canaux de jonction latéraux.
PCT/EP1998/003953 1997-06-30 1998-06-29 Cuve de microreaction, systeme de cuves de microreaction et procede pour delivrer un liquide contenu dans des cuves de microreaction WO1999001221A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19727509 1997-06-30
DE19727509.5 1997-06-30

Publications (1)

Publication Number Publication Date
WO1999001221A1 true WO1999001221A1 (fr) 1999-01-14

Family

ID=7833920

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1998/003953 WO1999001221A1 (fr) 1997-06-30 1998-06-29 Cuve de microreaction, systeme de cuves de microreaction et procede pour delivrer un liquide contenu dans des cuves de microreaction

Country Status (2)

Country Link
DE (1) DE19828995B4 (fr)
WO (1) WO1999001221A1 (fr)

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000035583A1 (fr) * 1998-12-17 2000-06-22 INSTITUT FüR MIKROTECHNIK MAINZ GMBH Procede de liberation d'un fluide, element pour fluide ainsi que dispositif permettant la manipulation desdits elements
WO2000051720A3 (fr) * 1999-03-03 2001-04-05 Symyx Technologies Inc Microsystemes de traitement chimique, microreacteurs a diffusion mixte et procedes de preparation et d'utilisation associes
WO2001089694A1 (fr) * 2000-05-22 2001-11-29 Biorobotics Limited Dispositif pour transfert de liquides
WO2001066242A3 (fr) * 2000-03-07 2002-05-02 Meinhard Knoll Dispositif et procede pour realiser des syntheses, des analyses ou des processus de transport
WO2001070402A3 (fr) * 2000-03-22 2002-05-16 Dewalch Technologies Inc Procede et appareil destines a traiter des substances dans un conteneur unique
DE10336850A1 (de) * 2003-08-11 2005-03-10 Thinxxs Gmbh Mikrospeicher
DE10344229A1 (de) * 2003-09-24 2005-05-19 Steag Microparts Gmbh Mikrostruktuierte Vorrichtung zum entnehmbaren Speichern von kleinen Flüssigkeitsmengen und Verfahren zum Entnehmen der in dieser Vorrichtung gespeicherten Flüssigkeit
WO2008006746A3 (fr) * 2006-07-11 2008-03-27 Tecan Trading Ag Récipient pour amener et transférer des liquides
JP2011221030A (ja) * 2003-06-19 2011-11-04 Abbott Laboratories 分析用の流体を取り扱う装置および方法
EP2480896A2 (fr) 2009-09-21 2012-08-01 Akonni Biosystems Cartouche intégrée

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19917330B4 (de) * 1999-04-16 2004-08-26 INSTITUT FüR MIKROTECHNIK MAINZ GMBH Mikroreaktormodul
DE10004135B4 (de) * 2000-01-31 2005-04-28 Ibidi Gmbh Kammer für Zellkulturen
EP1681570B1 (fr) 2003-06-19 2008-11-05 Abbott Laboratories Appareil et procédé de manipulation de fluides pour analyse
DE102008031666B4 (de) * 2008-07-04 2010-05-12 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Kryobehälter
DE102008047902A1 (de) 2008-09-19 2010-03-25 Albert-Ludwigs-Universität Freiburg Bausatz für Reaktoren und Reaktor

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4198135A (en) * 1979-04-04 1980-04-15 Polaroid Corporation Method and apparatus for releasing processing fluid from a fluid applicator by application of thermal energy
US4642220A (en) * 1981-04-10 1987-02-10 Pharmacia Ab Apparatus for carrying out analysis
EP0329120A2 (fr) * 1988-02-16 1989-08-23 Rms Laboratories, Inc. Appareil pour le test et l'exposition à la luminescence
WO1992002303A1 (fr) * 1990-08-07 1992-02-20 Pharmacia Lkb Biotechnology Ab Appareil servant a effectuer des reactions biochimiques
WO1997015394A1 (fr) * 1995-10-24 1997-05-01 Smithkline Beecham Corporation Plaques a micropuits

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5472672A (en) * 1993-10-22 1995-12-05 The Board Of Trustees Of The Leland Stanford Junior University Apparatus and method for polymer synthesis using arrays
US5604130A (en) * 1995-05-31 1997-02-18 Chiron Corporation Releasable multiwell plate cover

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4198135A (en) * 1979-04-04 1980-04-15 Polaroid Corporation Method and apparatus for releasing processing fluid from a fluid applicator by application of thermal energy
US4642220A (en) * 1981-04-10 1987-02-10 Pharmacia Ab Apparatus for carrying out analysis
EP0329120A2 (fr) * 1988-02-16 1989-08-23 Rms Laboratories, Inc. Appareil pour le test et l'exposition à la luminescence
WO1992002303A1 (fr) * 1990-08-07 1992-02-20 Pharmacia Lkb Biotechnology Ab Appareil servant a effectuer des reactions biochimiques
WO1997015394A1 (fr) * 1995-10-24 1997-05-01 Smithkline Beecham Corporation Plaques a micropuits

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000035583A1 (fr) * 1998-12-17 2000-06-22 INSTITUT FüR MIKROTECHNIK MAINZ GMBH Procede de liberation d'un fluide, element pour fluide ainsi que dispositif permettant la manipulation desdits elements
WO2000051720A3 (fr) * 1999-03-03 2001-04-05 Symyx Technologies Inc Microsystemes de traitement chimique, microreacteurs a diffusion mixte et procedes de preparation et d'utilisation associes
WO2001066242A3 (fr) * 2000-03-07 2002-05-02 Meinhard Knoll Dispositif et procede pour realiser des syntheses, des analyses ou des processus de transport
WO2001070402A3 (fr) * 2000-03-22 2002-05-16 Dewalch Technologies Inc Procede et appareil destines a traiter des substances dans un conteneur unique
JP2003527953A (ja) * 2000-03-22 2003-09-24 デワルチ テクノロジーズ、インコーポレイテッド 単一容器内での物質の処理方法および器具
WO2001089694A1 (fr) * 2000-05-22 2001-11-29 Biorobotics Limited Dispositif pour transfert de liquides
JP2011221030A (ja) * 2003-06-19 2011-11-04 Abbott Laboratories 分析用の流体を取り扱う装置および方法
DE10336850A1 (de) * 2003-08-11 2005-03-10 Thinxxs Gmbh Mikrospeicher
DE10336850B4 (de) * 2003-08-11 2006-10-26 Thinxxs Gmbh Mikrospeicher
US7964161B2 (en) 2003-09-24 2011-06-21 Klaus Kadel Microstructured device for removable storage of small amounts of liquid and a process for removal of liquid stored in this device
DE10344229A1 (de) * 2003-09-24 2005-05-19 Steag Microparts Gmbh Mikrostruktuierte Vorrichtung zum entnehmbaren Speichern von kleinen Flüssigkeitsmengen und Verfahren zum Entnehmen der in dieser Vorrichtung gespeicherten Flüssigkeit
WO2008006746A3 (fr) * 2006-07-11 2008-03-27 Tecan Trading Ag Récipient pour amener et transférer des liquides
EP2480896A2 (fr) 2009-09-21 2012-08-01 Akonni Biosystems Cartouche intégrée
EP2480896A4 (fr) * 2009-09-21 2015-12-02 Akonni Biosystems Cartouche intégrée

Also Published As

Publication number Publication date
DE19828995A1 (de) 1999-02-11
DE19828995B4 (de) 2006-01-12

Similar Documents

Publication Publication Date Title
WO1999001221A1 (fr) Cuve de microreaction, systeme de cuves de microreaction et procede pour delivrer un liquide contenu dans des cuves de microreaction
DE10030871C2 (de) Tintenstrahlaufzeichnungskopf
EP2687290B1 (fr) Dispositif de stockage microfluidique pour le stockage préalable d'un fluide, son procédé de fabrication et une utilisation de celui-ci
DE69512115T2 (de) Tintenstrahldruckkopf mit eingebauter Filterstruktur
DE60207708T2 (de) Mikrofluidik-Systeme zum Kombinieren diskreter Fluidvolumen
DE3873019T2 (de) Eine silikon-ventileinrichtung zur kontrolle des durchflusses.
DE3011674C2 (de) Tastatur
EP1171232B1 (fr) Dispositif de manipulation de fluide a conversion de format
DE69824019T2 (de) Tröpfchen-niederschlagvorrichtung
EP1212133B1 (fr) Dispositif et procede pour deposer une pluralite de microgouttelettes sur un substrat
EP1161994B2 (fr) Plaque de microtitrage
DE10133013A1 (de) Verschluss, der mit einem elektrischen Strom geöffnet werden kann
DE102015226417A1 (de) Mikrofluidische Vorrichtung, Verfahren zum Herstellen und Verfahren zum Betreiben einer mikrofluidischen Vorrichtung
DE2629995C3 (de) Ladeelektrode
WO2013170281A1 (fr) Tampon encreur, cartouche et procédé permettant d'imprégner d'encre un corps de stockage d'encre
DE19515406A1 (de) Tintenstrahl-Schreibkopf und Herstellungsverfahren für den Tintentstrahl-Schreibkopf
WO1987007217A1 (fr) Tete d'ecriture a l'encre avec membrane a excitation piezoelectrique
EP1200223B1 (fr) Puce d'impression pour tete d'impression fonctionnant selon le principe d'impression a encre
DE19858443A1 (de) Verfahren zum Abgeben eines Fluids, fluidisches Bauteil sowie Vorrichtung zur Handhabung solcher Bauteile
WO2002057015A2 (fr) Dispositif et procede de dosage de petites quantites de liquide
WO2007090418A1 (fr) Feuille de recouvrement conçue pour une plaque de microtitrage
DE102006038362A1 (de) Flaches galvanisches Element und Verfahren zur Herstellung flacher galvanischer Elemente
DE102004038152B4 (de) Abdeckfolie für eine Mikrotiterplatte
DE602005006019T2 (de) Verfahren zur herstellung einer in volumen miniaturisierten vorrichtung
DE19823876B4 (de) Mit unterschiedlichen Verbindungen beladenes Bauteil (Biochip) sowie Verfahren zu dessen Herstellung

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): CA CN 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
NENP Non-entry into the national phase

Ref country code: JP

Ref document number: 1999506303

Format of ref document f/p: F

122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: CA