WO2005002729A1 - Utilisation d'un contenant a usage unique, dispositif microfluidique et procede de traitement de molecules - Google Patents

Utilisation d'un contenant a usage unique, dispositif microfluidique et procede de traitement de molecules Download PDF

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Publication number
WO2005002729A1
WO2005002729A1 PCT/EP2003/007645 EP0307645W WO2005002729A1 WO 2005002729 A1 WO2005002729 A1 WO 2005002729A1 EP 0307645 W EP0307645 W EP 0307645W WO 2005002729 A1 WO2005002729 A1 WO 2005002729A1
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WO
WIPO (PCT)
Prior art keywords
connection
channel
disposable container
liquid
piston
Prior art date
Application number
PCT/EP2003/007645
Other languages
German (de)
English (en)
Inventor
Jürgen SCHÜLEIN
Björn GRASSL
Jürgen KRAUSE
Roland Barten
Dirk Kuhlmeier
Jörg HASSMANN
Hans Kosak
Original Assignee
november Aktiengesellschaft Gesellschaft für Molekulare Medizin
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 november Aktiengesellschaft Gesellschaft für Molekulare Medizin filed Critical november Aktiengesellschaft Gesellschaft für Molekulare Medizin
Priority to US10/563,279 priority Critical patent/US20070048194A1/en
Priority to EP03817332A priority patent/EP1641564B1/fr
Priority to AU2003250952A priority patent/AU2003250952A1/en
Priority to DE50308515T priority patent/DE50308515D1/de
Publication of WO2005002729A1 publication Critical patent/WO2005002729A1/fr

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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
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/50273—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means or forces applied to move the fluids
    • 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
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502715—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02—Adapting objects or devices to another
    • B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
    • B01L2200/027—Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/14—Process control and prevention of errors
    • B01L2200/141—Preventing contamination, tampering
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/16—Reagents, handling or storing thereof
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/02—Identification, exchange or storage of information
    • B01L2300/021—Identification, e.g. bar codes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/02—Identification, exchange or storage of information
    • B01L2300/021—Identification, e.g. bar codes
    • B01L2300/022—Transponder chips
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0478—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure pistons

Definitions

  • the invention relates to the use of a disposable container, a microfluidic device and a method for processing molecules.
  • Automatic analyzers for carrying out chemical and biochemical reactions are generally known from the prior art. Solutions required for the reaction are removed from a storage container by means of a suction pump and fed to a sample room.
  • automatic analysis devices are also known, in which the solutions required for the reaction are supplied, for example, by means of a piston pump. - In the known devices, the solutions can be contaminated disadvantageously. The required solutions are usually presented in a certain volume. In this respect, there is a risk of inaccurate filling by the user.
  • Automatic analyzers must be carefully cleaned after each analysis. This is time consuming. Apart from this, even with careful cleaning, a residue can remain in the device. Such a backlog leads to falsification of results in later analyzes.
  • Tl disposable syringes From the field of medicine, e.g. B. known from DE 33 90 336 Tl disposable syringes. Such disposable syringes are e.g. T. filled up. A piston guided in a cylinder is designed such that the liquid received in the cylinder can be pressed out manually by means of the piston. Ampoules for taking liquid medicines are also known from the medical field. Such drugs can be injected, for example, using a syringe. It is therefore not possible to fill an exact volume in the ⁇ l range.
  • microfluidic devices for the detection of predetermined biochemical molecules are also known from the prior art. Such devices work with small volumes. This is a detection of biochemical molecules, for. B. of DNA possible. Such a device is known for example from EP 0 397 424 A2 or EP 0 189 316 B1.
  • the object of the invention is to eliminate the disadvantages of the prior art.
  • a use, a microfluidic device and a method are to be specified which enable a simplified and as accurate as possible automated implementation of sample preparation for carrying out chemical detection reactions and / or chemical detection reactions.
  • a simplified automated preparation of samples for the detection of biochemical molecules, such as DNA is to be made possible.
  • a disposable container which has a cylinder with a piston displaceably guided therein and a connection provided at a first end of the cylinder opposite the piston, for generating a pressure difference in a Microfluidic device and for providing a means for processing molecules and / or as a reaction vessel.
  • Such a disposable container can be manufactured inexpensively. It can be filled with a predetermined volume using suitable machines. The filling process can be carried out in such a way that contamination is excluded.
  • the disposable container can not only serve as a storage container for the agent for processing molecules, but also as a reaction vessel. For this, e.g. B. first a means for processing molecules in a microfluidic device and then a solution in the disposable container are pressed or sucked out of the microfluidic device.
  • the disposable containers are easy to handle. Operation of microfluidic devices is thus quick, simple and easy to carry out.
  • a “microfluidic device” is understood to mean a compact and handy device for carrying out an analysis, synthesis, purification, modification and / or increasing the concentration of molecules.
  • a microfluidic device can form a closed system with respect to the environment.
  • a sample taken up in the microfluidic device is moved to carry out the respective reaction via at least one channel provided therein and, if necessary, brought into contact with a liquid presented in the microfluidic device.
  • the channel is designed in such a way that the liquid can be displaced exactly over a predetermined section and thus moved precisely to a predetermined location of the device.
  • the means for processing is a liquid, a gel or a solid or a combination thereof.
  • the solid can comprise at least one of the following constituents: soluble or suspendable particles, lyophilisate, chromatographic material, preferably an ion exchanger or an affinity matrix.
  • the processing agent can also be selected from the following group: lysis liquid, elution liquid, buffer solution, beads, enzymes, primers, reactants, reagents.
  • the proposed disposable containers are preferably kept ready as a kit.
  • a kit can be pre-assembled for certain analysis or diagnostic purposes. It can contain, for example, solutions required for cell disruption as well as adsorbents for DNA.
  • the disposable containers are designed differently depending on the type of agent for processing molecules presented therein, for example in their diameter or in their length. This can prevent a disposable container from being accidentally connected to an incorrect connection of a microfluidic system. In this case, a recording of a microfluidic device is carried out in such a way that only the correct disposable container can be used in it. Of course, it is also possible to avoid a mix-up or a corresponding print
  • the processing of the molecules can involve analysis, synthesis, purification and / or increasing the concentration of the molecules. Such reactions always take place in vitro.
  • the disposable container is expediently completely filled with the processing agent.
  • the means for processing is a liquid, a paste, in gel or the like.
  • a complete filling is understood to mean an essentially bubble-free filling in which the proportion of gas bubbles is ⁇ 5.0% by volume. is expediently ⁇ 1.0% by volume, preferably ⁇ 0.1% by volume, particularly preferably ⁇ 0.01% by volume.
  • Liquids are expediently degassed before the disposable container is filled. Filling is preferably carried out under sterile conditions. It is also possible to sterilize the disposable container after it has been filled. This increases the durability of the processing agent contained in the disposable container.
  • the piston can be made of an elastic material, preferably rubber or plastic. It can have at least one circumferential seal which is symmetrical in cross section. This enables the piston to be pushed back and forth repeatedly, with a complete sealing effect being guaranteed at all times.
  • the piston is designed to correspond to the connection, so that a complete emptying of the cylinder and possibly the connection is possible when the piston rests on the first end. This enables a particularly precise procedure; there are no residual volumes left in the disposable container. If the connection has a volume, this volume is also emptied.
  • the piston has a means for engaging a pushing and / or towing means.
  • the means for engagement can be a recess provided centrally in the piston, e.g. B. a hemispherical or conical recess to a thread, a bayonet or a snap lock or the like .
  • a pushing and / or towing device is attached to the piston. It can be a rod or a cylinder.
  • the pushing and / or towing means has a means for engaging in a pushing and / or towing device at the free end.
  • the means for engagement can be an opening, radially protruding projections, a flange or the like.
  • the means for engagement is expediently designed such that it can be connected to a push and / or towing rod of a push and / or towing device by inserting it.
  • the cylinder is made of a transparent material. This allows a simple visual inspection. It can immediately be determined whether the cylinder is correct, e.g. H. is bubble-free, filled.
  • the cylinder can also be made of an opaque material, in particular for receiving light-sensitive reagents.
  • the cylinder is preferably made of a material that is inert for the means for processing contained therein.
  • the cylinder is expediently made of an elastic plastic, preferably polypropylene. Polyethylene or polycarbonate are also suitable for manufacturing the cylinder. A particularly good sealing effect is achieved when using an elastic material.
  • the connection is closed with a closure means.
  • the closing means can be a rubber or plastic membrane, a ball, a cone or a closing cylinder.
  • the ball, the cone and / or the locking cylinder are made of a plastic or glass which is inert to the received means for processing.
  • a radially inwardly projecting projection that blocks a displacement of the piston out of the cylinder is provided on a second end of the cylinder opposite the connection. This makes removal of the piston impossible. Unwanted manipulation of the disposable container is avoided.
  • a further projection projecting radially inwards and opposing a displacement of the piston in the direction of the connection can be provided.
  • the further projection is expediently designed such that the piston can only be moved in the direction of the first end by applying a predetermined force.
  • the force is expediently chosen such that the connection is brought into a correct connection position with the connection piece before the piston is displaced. As soon as this is the case, a further axial displacement of the disposable container is no longer possible.
  • the force acting on the further projection is then so great that the resistance thus formed can be overcome and the piston can be displaced in the direction of the first end.
  • the provision of the further projection in addition to ensuring a proper and tight connection of the disposable container to the microfluidic device, has the further advantage that an undesired leakage of liquid received in the disposable container prior to the Position of a completely sealed connection is avoided.
  • the piston can only be moved after a tight connection has been made.
  • the further projection is expediently designed to be radially symmetrical. This prevents uneven wear or damage to the piston when the further projection is overcome.
  • a means for automatically reading out information about the means for processing received in the disposable container is provided.
  • the means can be a barcode, a transponder, a chip or a specific shape.
  • a barcode can, for example, be printed on the outside of the cylinder or applied by means of a label.
  • a transponder or a suitable chip can be cast in at a suitable location on the disposable container.
  • the cylinder has a specific shape, for example projections or recesses provided on the outside, which contain the information in codified form.
  • a microfluidic device for processing molecules is provided with a device having at least one channel for conveying a sample, at least two connecting pieces being provided on the channel for connecting two disposable containers, each of the disposable containers having a cylinder which is displaceably guided therein Piston and a connection provided at a first end of the cylinder opposite the piston, and wherein the disposable containers with the connection provided thereon can each be connected to one of the connection pieces, so that liquid can be conveyed through the channel by displacing one of the pistons.
  • the proposed microfluidic device is particularly simple. The use of micro pumps and the like can be dispensed with. A pressure to move the liquid in the channel of the microfluidic device is generated by moving the pistons.
  • the disposable containers not only serve to provide means for processing molecules, but can also serve as a reaction space. If at least two disposable containers are connected to the microfluidic device, it is possible, for example, to purify or disrupt biological material by moving a liquid back and forth between the disposable containers.
  • the proposed microfluidic device is surprisingly simple. It is easy to handle. The use of the proposed disposable containers eliminates the need to manually supply exact volumes, for example of liquids required to carry out reactions. Contamination is practically impossible. With the proposed microfluidic devices, exact results can be achieved quickly and reliably.
  • the channel is a channel system composed of a plurality of channels connected to one another.
  • the channel or the channel system can be meandering at least in sections.
  • the device can have a microfluidic mixing chamber and / or a microfluidic reaction space and / or a microfluidic detection space and / or a bubble trap.
  • the channel can have a diameter of at most 2 mm, preferably less than 1.5 mm.
  • the device can also have at least one agent selected from the following group: sensor, electrode, temperature control unit, sieve, filter, membrane, affinity matrix, substance or magnet.
  • a connecting channel connecting the connecting piece to the channel can be provided.
  • an inlet opening connected to the channel preferably closable by means of a first valve
  • an outlet opening connected to the channel preferably closable by means of a second valve
  • the proposed designs of the facility enable a differentiated and automated process management.
  • the arrangement and design of the channel are expediently chosen so that the desired reaction can be carried out simply and quickly.
  • liquid can be conveyed into the other disposable container by moving the pistons.
  • the piston can be pushed back into other disposable containers. It may also be the case that the piston in the other container is pulled back by a tow bar.
  • each connection piece has a pipe socket, preferably a hollow needle, for opening a closure means closing the connection.
  • the connector or the pipe socket can be closed with a further closure means. It can be a rubber or plastic branch or the like. This prevents contamination of the device and / or of a liquid placed therein.
  • the disposable container can expediently be a disposable container with the features described above.
  • Each of the disposable containers can have a connection corresponding to the connection pieces. This enables simple and tight connection of the disposable containers to the connector.
  • the connection can be closed with a closure means, for example a plastic or rubber membrane, a metal foil or the like.
  • the device has a means for fixing the disposable container in a position that is fixed relative to the connector. This prevents undesired loosening of the connection from the connection piece. Leakages cannot occur, in particular when a liquid moves from the disposable container into the device or from the device into the disposable container.
  • the means for fixing can be, for example, a thread, a bayonet catch or the like.
  • the connector can have an internal thread and the connector an external thread. Contamination of the agent for processing the molecules contained in the disposable container is avoided.
  • the device has at least one, preferably cylindrical, recess corresponding to the outer diameter of the disposable container for guiding the connection of the disposable container into an engagement position with the connecting piece.
  • the proposed microfluidic device is compact, stable and robust. Due to its design, it can easily be inserted into a device for the automatic movement of the pistons. Another advantage of the compact design of the microfluidic device is that it can be transported, packaged and stored is particularly simple. A faulty, possibly insufficiently tight connection is prevented.
  • the means for fixing can have a means for holding the disposable container that is fully inserted into the recess and engages in the connector in a fixed position. This prevents unwanted loosening of the connector from the connector.
  • the means for holding can be, for example, at least one first latching means which surrounds the second end of the disposable container.
  • a distance between the first latching means and the connection piece is selected such that the disposable container can be inserted into the recess without opening a closure means provided thereon.
  • the device can be delivered pre-assembled with the disposable containers suitable for the respective purpose.
  • Such a prefabricated device which can be designed, for example, in the manner of a cassette, then only has to be inserted into a suitable device for the automatic movement of the pistons and filled with the sample to be processed. Incorrect operation and contamination are practically excluded with such a pre-assembled device.
  • Second locking means can be provided on the cylinder of the disposable container and / or on the inner wall of the recess.
  • the second rest means can be designed so that the disposable container, for. B. by pressure on the piston, is displaceable into a latching position in which the connector closes the connector liquid-tight.
  • Such an embodiment is expedient if the connection piece or the pipe socket are not closed with a second connection means.
  • the second locking means can also be designed such that the disposable container can be moved from the first to a second locking position, in which the connection closes the connection piece in a liquid-tight manner and the pipe socket pierces the closing means. In the second latching position, a connection is first established between the disposable container and the channel. It is then possible, for example, to push a liquid from the disposable container into the channel.
  • the channel is advantageously filled with liquid. This enables a bubble-free liquid column to be easily produced in the entire device. This enables the liquid to be moved particularly precisely in the channel.
  • several recesses can be provided on one side of the device. This simplifies and reduces the cost of building a device for the automatic movement of the pistons of the disposable containers.
  • a device only has to be equipped with a plurality of push rods which are suitable for pressing down the pistons and which are moved according to a predetermined program.
  • the parallel arrangement of the recesses contributes to a particularly compact embodiment of the device according to the invention.
  • the device is advantageously made in one piece from plastic.
  • the cost of manufacturing the proposed facility is not particularly high.
  • the device can be manufactured, for example, by means of injection molding.
  • the device combined from the device with the disposable containers can be manufactured overall without great effort. It can be kept ready in the manner of a disposable device.
  • the device can have a means for automatically reading out information about means for processing included in the device.
  • the means can be a barcode, a transponder, a chip or a specific shape of the device.
  • the microfluidic device can be designed as a kit that includes the device and several of the disposable containers according to the invention.
  • the disposable containers can already be captively inserted into the recesses, the closure means of which are of course still closed.
  • Such a kit or microfluidic device is particularly easy to store, transport and operate by the user.
  • a method for processing molecules is provided with the following steps:
  • Provision of at least two disposable containers each of which has a cylinder with one which is displaceably guided therein
  • Piston and has a connection provided on a first end of the cylinder opposite the piston, Providing a microfluidic device with at least one channel, at least two connecting pieces being provided on the channel for connecting the disposable containers,
  • the proposed method enables a particularly simple processing of molecules.
  • the pressure for moving or conveying the liquid in the channel of the device is generated by moving the pistons in the disposable containers. In this way, the liquid can be easily transported from one place to another in the facility. In particular, no micropumps and the like are required.
  • the exact positioning of the liquid in the device can reduce the number of valves required.
  • the liquid is expediently contained in one of the disposable containers. It is also possible that liquid is present in the channel. This enables the simple production of a bubble-free liquid column in the facility.
  • the device can be kept as a disposable part. The liquid can be transferred from one container to the other.
  • the piston accommodated therein is expediently displaced by the liquid pressure. In this case, it is not necessary to tow the piston by means of a special towing device in order to convey the liquid into the disposable container.
  • a liquid in the channel can be preferably meandering section of the channel and / or a microfluidic mixing chamber and / or a microfluidic reaction space and / or a microfluidic detection space and / or a bubble trap. Moving the pistons enables an exact
  • the liquid can be processed according to a predetermined program at certain points on the channel.
  • the predetermined section of the channel can have a meandering channel and / or microfluidic detection space.
  • at least one valve provided therein can also be opened and / or closed according to a predetermined program.
  • the pistons also move according to the specified program, so that the liquid in the channel or in the disposable containers is moved according to specified reaction steps.
  • the disposable containers are inserted into recesses provided on the device. This enables the connections provided on the disposable containers to be guided precisely to the connection pieces of the device.
  • the disposable container is expediently fixed relative to the connector.
  • a means for fixing can be provided. The fixation is expediently only when the connection is properly connected to the connector. In this way, the establishment of a leaky connection can be avoided.
  • the disposable container can be moved into a first latching position in the recess provided on the device, so that the connection closes the connection piece in a liquid-tight manner. Furthermore, can the disposable container can be moved from the first into a second latching position, so that the connection closes the connector in a liquid-tight manner and the pipe socket pierces the closure means. In the second latching position, a connection is only established between the disposable container and the channel.
  • the liquid is conveyed in the device by moving the pistons in such a way that the steps required to carry out at least one of the following methods are carried out: washing, purification, PCR, detection.
  • the aforementioned methods are particularly suitable for the detection of DNA from different samples.
  • FIG. 1 is a schematic sectional view of a first disposable container
  • FIG. 2 shows a schematic partial sectional view of a first microfluidic device
  • FIG. 3 shows the partial sectional view according to FIG. 2 with a disposable container inserted
  • FIG. 4 shows the partial sectional view according to FIG. 3 with a push rod
  • FIG. 5 shows the partial sectional view according to FIG. 4 with the piston partially pressed in
  • FIG. 6 is a schematic sectional view of a second disposable container
  • FIG. 7 shows a schematic sectional view of a microfluidic device with the second disposable container according to FIG. 6,
  • FIG. 8 shows the arrangement according to FIG. 7, the second disposable container being connected to the microfluidic device
  • FIG. 9 shows the arrangement according to FIG. 8, further disposable containers being connected
  • FIG. 10 shows the arrangement according to FIG. 9, with a sample container being connected
  • FIG. 11 shows the arrangement according to FIG. 10, the sample container having been emptied
  • FIG. 12 shows the arrangement according to FIG. 11, wherein the second disposable container has been emptied
  • Fig. 1 shows a schematic sectional view of a first
  • Disposable container In a suitably made of a transparent plastic, such as polyethylene or polypropylene, cylinder 1 is slidably a, for. B. Piston 2 made of plastic or rubber slidably guided. A connection 3 is provided at a first end E1 of the cylinder 1 opposite the piston 2. The connection 3 is closed with a closure means 4, here for example in the form of a glass ball. A liquid F is taken up in the volume formed by the cylinder 1 and the piston 2 located therein. This can be, for example, a lysis liquid, an elution liquid, a buffer solution or the like. The piston 2 is formed on its side facing the first end E1 of the cylinder 1 corresponding to the first end E1 of the cylinder 1.
  • a transparent plastic such as polyethylene or polypropylene
  • Piston 2 made of plastic or rubber slidably guided.
  • a connection 3 is provided at a first end E1 of the cylinder 1 opposite the piston 2.
  • the connection 3 is closed with a closure means 4, here for example in the
  • the projection 5 has a projection 5 corresponding to the shape of the connection 3. If the piston 2 is pressed completely to the first end E1, the projection 5 fulfills the connection 3, so that a complete emptying of the liquid F from the cylinder 1 and the volume formed by the connection 3 is possible.
  • a central recess 7 On the side of the piston 2 opposite the projection 5, a central recess 7, a central projection 5 or the like can be provided for the engagement of a push rod and / or towing bar.
  • a second end of the cylinder 1 opposite the first end E1 is designated by the reference symbol E2.
  • FIG. 2 shows a sectional view of a microfluidic device 13, specifically a receptacle 6 for the disposable container shown in FIG. 1.
  • the receptacle 6 has a cylindrical recess 7 corresponding to the diameter of the cylinder 1.
  • the recess 7 is designed such that the disposable container can be inserted therein.
  • the connection 3 is guided in such a way that it arrives correctly in an engagement position of a connection piece 8.
  • the connecting piece 8 can comprise a hollow needle 9 with which the closure means 4 pierce or pressed into the cylinder 1 and thus a connection of the cylinder 1 with the microfluidic device 13 is achieved.
  • FIG. 3 shows the disposable container connected to the connector 8 using the receptacle 6.
  • the piston 2 can be pressed in the direction of the connecting piece 8 by means of a push rod 10. This situation is shown in Figs. 4 and 5.
  • Fig. 6 shows in cross section a second disposable container.
  • the cylinder 1 has a retaining means 11 pointing radially inwards. With the retaining means 11, a displacement of the piston 2 beyond the second end E2 is prevented.
  • the piston 2 has on its side facing away from the connection 3 an engagement means 12 for connection 3 to a push rod and / or towing rod.
  • the engagement means 12 can be designed, for example, in the form of a stamp. Of course, other suitable configurations are also possible.
  • the closure means 4 is designed as a membrane. It can be a plastic and rubber membrane. It is expedient to have a plastic film formed in one piece with the cylinder 1.
  • the cylinder 1 can be produced together with the plastic film in one piece, for example by means of injection molding. As shown in FIG. 6, particles P can be suspended in the liquid F.
  • FIG. 7 shows in cross section a microfluidic device 13 which has a plurality of further connecting pieces 14 lying next to one another.
  • the further connecting pieces 14 are closed with a further closure means 15, so that one Contamination of the microfluidic device 13 is excluded.
  • the further closure means 15 can also be a plastic film, a rubber membrane or the like.
  • Each of the further connecting pieces 14 is connected via a connecting channel 16 to a channel 17 connecting the connecting channels 16.
  • the channel 17 is also connected via a first valve 18 to an inlet opening 19 and via a second valve 20 to an outlet opening 21.
  • the connecting channels 16 and the channel 17 expediently have a diameter in the range from 1 to 2 mm. They are incorporated in a base plate 22 made of transparent plastic.
  • Each of the connecting pieces 8, 14 has a hollow needle 9 for piercing the closure means 4.
  • connection 3 shows the microfluidic device 13, the second disposable container having the connection 3 being connected to the further connection piece 14.
  • the hollow needle 9 penetrates the connection 3, so that a tight connection is established.
  • the liquid F can now be moved through the hollow needle 9 into the connecting channel 16 and into the channel 17 by moving the piston 2 in the direction of the connection 3.
  • FIG. 9 shows a sectional view of the microfluidic device 13 according to FIG. 8, second disposable containers being connected to all further connection pieces 14 here.
  • the diameter of the second disposable container can be designed differently. If necessary, recesses 7 provided on the microfluidic device 13 can thus be made such that only certain disposable containers can be used therein. For example, incorrect operation can be caused by connecting a disposable container to a wrong further connector 14 can be prevented.
  • the other disposable containers shown in FIG. 9 are otherwise identical to the second disposable container.
  • FIG. 10 shows the microfluidic device 13 according to FIG. 9, a syringe 23 in which sample liquid PF is received being connected to the inlet opening 19 here.
  • the sample liquid PF can be pressed, for example, into the opposing second disposable container by means of the syringe 23. To do this, it is necessary to open the first valve 20 and to hold down another piston 24 of a further disposable container 25. In this case, the sample liquid PF is pressed via the connecting channel 16 into the disposable container opposite the syringe 23. A piston 24 located therein is displaced by the applied pressure (see FIG. 11).
  • the transferred sample liquid PF can then be mixed with the liquid F contained in the cylinder 1, for example by depressing the piston 2.
  • the first and / or second valve can be a simply designed one-way valve which has, for example, a spring-loaded ball or a spring-loaded cone as the valve body.
  • a one-way valve is arranged such that a liquid flow in the direction of the channel is possible under pressure and the valve body is pressed into its closed position by a pressure generated in the channel. By moving the valve body away from its closed position, the valve can be emptied.
  • the first and / or second valve it can also be a simply designed reusable valve, e.g. B. a diaphragm valve act.
  • the sample liquid PF can be acted upon in succession with several different liquids. It can be mixed intensively with the liquids. For example, a simple disruption of cells contained in the sample liquid PF is possible. As soon as the cells are disrupted, DNA molecules contained therein can be separated by magnetic beads containing liquids in the disposable containers and can be sent to a further detection method for analysis.
  • FIG. 13 shows a further exemplary embodiment of a microfluidic device 13.
  • the microfluidic device 13 shown in FIGS. 7 to 12 it has cutouts 7 on one side, preferably in a parallel arrangement, for inserting disposable containers (not shown here) ) on.
  • the recesses 7 have first latching means 26 at their ends opposite the connector 8. The first latching means 26 serve to ensure that a disposable container once inserted into the recess 7 can no longer be easily removed from the recess 7.
  • the disposable container can therefore be presented captively with the microfluidic device. To start up the device according to the invention, it is only necessary to remove the To move the disposable container in the direction of the connector 8 and thus to connect it to the microfluidic device 13.
  • FIGS. 14a to 14c show an advantageous embodiment of the connection of the disposable container to the microfluidic device 13.
  • Second latching means provided in the recess 7 in the vicinity of the connector 8 are designated by 27.
  • third locking means 28 are provided on the cylinder 1, which are designed to correspond to the second locking means 25.
  • the hollow needle 9 is with a, for. B. executed as a 0-ring, sealant 29.
  • the disposable container In the first position shown in FIG. 14 a, the disposable container is pushed into the recess 7 of the microfluidic device 13. There is no sealing connection between the connection 3 and the sealing means 29 provided on the hollow needle 9. The closure means 4 is closed.
  • the disposable container In the second position shown in FIG. 14b, the disposable container is in a first latching position. In this position, the connection 3 overlaps the sealant 29. The connection 3 thus closes the opening formed by the hollow needle 9 in a liquid-tight manner.
  • the disposable container is in a second latching position.
  • the hollow needle 9 penetrates the locking device 4 (not shown here).
  • the proposed microfluidic device can be easily equipped with a wide variety of combinations of reagents, agents, buffers and the like.
  • the proposed device can be used for a wide variety of assays. It is only necessary to fill the disposable containers with the necessary reagents, agents and the like.
  • the disposable containers themselves and the microfluidic device do not have to be changed. Nevertheless, they can be made extremely inexpensively from injection molded plastic. This makes it possible to design the disposable containers as well as the microfluidic device as a disposable part.
  • Control of the movements of the pistons 2, 24 of the disposable containers can be carried out relatively easily and inexpensively. Such a device does not require a particularly high level of maintenance, since liquids do not escape from the proposed device.
  • the proposed disposable containers allow simple and flexible storage, assembly and manufacture of the proposed device. LIST OF REFERENCE NUMBERS

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
  • Devices For Use In Laboratory Experiments (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

L'invention concerne l'utilisation d'un contenant à usage unique présentant un cylindre (1) dans lequel un piston (2, 24) est guidé en déplacement et un raccordement (3) situé à une première extrémité (E1) du cylindre (1), cette extrémité étant opposée au piston (2, 24), pour générer une différence de pression dans un dispositif microfluidique (13) et recevoir (6) un moyen (F, P) destiné au traitement de molécules et/ou pour faire office de récipient de réaction.
PCT/EP2003/007645 2003-07-04 2003-07-15 Utilisation d'un contenant a usage unique, dispositif microfluidique et procede de traitement de molecules WO2005002729A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
US10/563,279 US20070048194A1 (en) 2003-07-04 2003-07-15 Use of a disposable container, microfluidic device and method for processing molecules
EP03817332A EP1641564B1 (fr) 2003-07-04 2003-07-15 Utilisation d'un contenant a usage unique, dispositif microfluidique et procede de traitement de molecules
AU2003250952A AU2003250952A1 (en) 2003-07-04 2003-07-15 Use of a disposable container, microfluidic device and method for processing molecules
DE50308515T DE50308515D1 (de) 2003-07-04 2003-07-15 Verwendung eines einwegbehälters, mikrofluidische vorrichtung und verfahren zur bearbeitung von molekülen

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
DE10330409.6 2003-07-04
DE10330409 2003-07-04
DE10331975.1 2003-07-14
DE10331975 2003-07-14

Publications (1)

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WO2005002729A1 true WO2005002729A1 (fr) 2005-01-13

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EP (1) EP1641564B1 (fr)
AT (1) ATE376882T1 (fr)
AU (1) AU2003250952A1 (fr)
DE (1) DE50308515D1 (fr)
WO (1) WO2005002729A1 (fr)

Cited By (5)

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DE102005008224B3 (de) * 2005-02-23 2006-06-14 Directif Gmbh Vorrichtung und Verfahren zur automatischen Betätigung einer mikrofluidischen Einrichtung
WO2007101653A1 (fr) * 2006-03-06 2007-09-13 Directif Gmbh Procédé de réalisation d'une réaction de multiplication d'un acide nucléique
DE202006020469U1 (de) 2006-03-06 2008-10-16 Directif Gmbh Vorrichtung zum Nachweis biochemischer Zielmoleküle
WO2012041479A1 (fr) * 2010-09-30 2012-04-05 INSTITUT FüR MIKROTECHNIK MAINZ GMBH Puce microfluidique pourvue de plusieurs ensembles cylindre-piston
WO2016062788A1 (fr) 2014-10-24 2016-04-28 Ait Austrian Institute Of Technology Gmbh Puce microfluidique pour analyse biologique

Families Citing this family (5)

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CN104722342B (zh) 2009-03-24 2017-01-11 芝加哥大学 滑动式芯片装置和方法
US9447461B2 (en) 2009-03-24 2016-09-20 California Institute Of Technology Analysis devices, kits, and related methods for digital quantification of nucleic acids and other analytes
US10196700B2 (en) 2009-03-24 2019-02-05 University Of Chicago Multivolume devices, kits and related methods for quantification and detection of nucleic acids and other analytes
US9464319B2 (en) 2009-03-24 2016-10-11 California Institute Of Technology Multivolume devices, kits and related methods for quantification of nucleic acids and other analytes
DE102015001999B3 (de) * 2015-02-20 2016-02-04 Friz Biochem Gesellschaft Für Bioanalytik Mbh Doppelspritze für die Zuführung einer Flüssigkeit in ein Mikrofluidiksystem

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WO1982002211A1 (fr) * 1980-12-22 1982-07-08 Chandler Howard Milne Dispositif et procede de detection d'antigenes et d'anticorps
US6143252A (en) * 1999-04-12 2000-11-07 The Perkin-Elmer Corporation Pipetting device with pipette tip for solid phase reactions
WO2003015922A1 (fr) * 2001-08-20 2003-02-27 Biomicro Systems, Inc. Dispositif d'interface a microreseaux stratifie

Patent Citations (3)

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Publication number Priority date Publication date Assignee Title
WO1982002211A1 (fr) * 1980-12-22 1982-07-08 Chandler Howard Milne Dispositif et procede de detection d'antigenes et d'anticorps
US6143252A (en) * 1999-04-12 2000-11-07 The Perkin-Elmer Corporation Pipetting device with pipette tip for solid phase reactions
WO2003015922A1 (fr) * 2001-08-20 2003-02-27 Biomicro Systems, Inc. Dispositif d'interface a microreseaux stratifie

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102005008224B3 (de) * 2005-02-23 2006-06-14 Directif Gmbh Vorrichtung und Verfahren zur automatischen Betätigung einer mikrofluidischen Einrichtung
WO2007101653A1 (fr) * 2006-03-06 2007-09-13 Directif Gmbh Procédé de réalisation d'une réaction de multiplication d'un acide nucléique
DE102006010958A1 (de) * 2006-03-06 2007-09-13 Directif Gmbh Verfahren zur Durchführung einer Reaktion zur Vervielfältigung einer Nukleinsäure
DE202006020469U1 (de) 2006-03-06 2008-10-16 Directif Gmbh Vorrichtung zum Nachweis biochemischer Zielmoleküle
WO2012041479A1 (fr) * 2010-09-30 2012-04-05 INSTITUT FüR MIKROTECHNIK MAINZ GMBH Puce microfluidique pourvue de plusieurs ensembles cylindre-piston
US9278352B2 (en) 2010-09-30 2016-03-08 Fraunhofer-Gesellschaft Zur Forderung Der Angewandten Forshung E.V. Microfluidic chip comprising several cylinder-piston arrangements
WO2016062788A1 (fr) 2014-10-24 2016-04-28 Ait Austrian Institute Of Technology Gmbh Puce microfluidique pour analyse biologique

Also Published As

Publication number Publication date
EP1641564B1 (fr) 2007-10-31
AU2003250952A1 (en) 2005-01-21
ATE376882T1 (de) 2007-11-15
EP1641564A1 (fr) 2006-04-05
DE50308515D1 (de) 2007-12-13

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