WO2005002729A1 - Use of a disposable container, microfluidic device and method for processing molecules - Google Patents

Use of a disposable container, microfluidic device and method for processing molecules Download PDF

Info

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
Authority
WO
WIPO (PCT)
Prior art keywords
means
connection
disposable container
channel
liquid
Prior art date
Application number
PCT/EP2003/007645
Other languages
German (de)
French (fr)
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
Priority to DE10330409.6 priority Critical
Priority to DE10330409 priority
Priority to DE10331975 priority
Priority to DE10331975.1 priority
Application filed by november Aktiengesellschaft Gesellschaft für Molekulare Medizin filed Critical november Aktiengesellschaft Gesellschaft für Molekulare Medizin
Priority claimed from US10/563,279 external-priority patent/US20070048194A1/en
Publication of WO2005002729A1 publication Critical patent/WO2005002729A1/en

Links

Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers 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
    • B01L3/50273Containers 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
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers 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
    • B01L3/502715Containers 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
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02Adapting objects or devices to another
    • B01L2200/026Fluid interfacing between devices or objects, e.g. connectors, inlet details
    • B01L2200/027Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/14Process control and prevention of errors
    • B01L2200/141Preventing contamination, tampering
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/16Reagents, handling or storing thereof
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/02Identification, exchange or storage of information
    • B01L2300/021Identification, e.g. bar codes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/02Identification, exchange or storage of information
    • B01L2300/021Identification, e.g. bar codes
    • B01L2300/022Transponder chips
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0475Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0478Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure pistons

Abstract

The invention relates to the use of a disposable container comprising a cylinder (1) containing a plunger (2, 24) that is displaceably guided in said cylinder and a connection (3) that is provided on a first end (E1) of the cylinder (1) lying opposite the plunger (2, 24), said container being designed to create a difference in pressure in a microfluidic device (13), to hold (6) an agent (F, P) for processing molecules and/or to act as a reaction vessel.

Description


    <Desc / Clms Page number 1>
 



  Use of a disposable container, microfluidic device and method for processing molecules 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. In addition, 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. It 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.



  From the field of medicine, e.g. B. known from DE 33 90 336 T1 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.

  <Desc / Clms Page number 2>

 



  Ampoules for taking liquid medicines are also known from the medical field. Such drugs can be injected, for example, using a syringe.



  It is not possible to fill an exact volume in the go area.



  So-called microfluidic devices for detecting predetermined biochemical molecules are also known from the prior art. Such devices work with small volumes. This is a proof of biochemical molecules, eg. 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. In particular, a use, a microfluidic device and a method are to be specified which enable a simplified and, if possible, precise automated implementation of sample preparation for carrying out chemical detection reactions and / or chemical detection reactions. In particular, a simplified automated preparation of samples for the detection of biochemical molecules, such as DNA, is to be made possible.



  This object is solved by the features of claims 1, 22 and 50. Appropriate configurations result from the features of claims 2 to 21, 23 to 49 and 51 to 59.



  According to the invention, the use of a disposable container is provided, 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

  <Desc / Clms Page number 3>

 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 is pressed or sucked out of the microfluidic device into the disposable container. The disposable containers are easy to handle. Operation of microfluidic devices is thus quick, simple and easy to carry out.



  In the sense of the present invention, 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. Such 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 shifted exactly over a predetermined section and thus moved precisely to a predetermined location of the device.

  <Desc / Clms Page number 4>

 



  According to one embodiment, it is provided that 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. Such a kit can be pre-assembled for certain analysis or diagnostic purposes. For example, it can contain solutions necessary for cell disruption as well as adsorbents for DNA. Advantageously, 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 provide appropriate printing or coloring on the disposable container to avoid confusion.



  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.

  <Desc / Clms Page number 5>

 



  The disposable container is expediently completely filled with the processing agent. In this case, the agent 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 <5.0 vol.%, Expediently <1.0% by volume, preferably <0.1 vol.%, 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 shelf life 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.



  According to a further embodiment, the piston is designed to correspond to the connection, so that a complete emptying of the cylinder and, if appropriate, 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.



  According to a further embodiment, the piston has a means for engaging a pushing and / or towing means. This enables the disposable container to be easily connected

  <Desc / Clms Page number 6>

 a device for moving the piston. The means for engagement can be a recess provided centrally in the piston, e.g. B. a hemispherical or conical recess, a thread, a bayonet or a snap lock or the like. It may also be the case that a pushing and / or towing means is attached to the piston. It can be a rod or a cylinder. In this case, 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.



  According to a further embodiment, 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 holding 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.

  <Desc / Clms Page number 7>

 



  According to a further embodiment, the connection is closed with a closure means. The sealing means can be a rubber or plastic membrane, a ball, a cone or a sealing cylinder. The ball, the cone and / or the locking cylinder are advantageously made of a plastic or glass that is inert to the absorbed agent for processing.



  According to a further particularly advantageous embodiment, 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. Furthermore, at the second end 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 correct 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

  <Desc / Clms Page number 8>

 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.



  According to a further embodiment, 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 point on the disposable container. Furthermore, it may be that the cylinder has a specific shape, for example projections or recesses provided on the outside, which contain the information in codified form.



  According to a further requirement of the invention, a microfluidic device for processing molecules with at least one channel for conveying a sample is provided, at least two connecting pieces being provided on the channel for connecting two single-use containers, each of the single-use containers Cylinder with a piston guided therein and a connection provided at a first end of the cylinder opposite the piston, and the disposable containers with the connection provided thereon can each be connected to one of the connecting pieces, so that one of the pistons can be moved Liquid can be transported through the channel.

  <Desc / Clms Page number 9>

 



  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. When 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.



  According to one embodiment, 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. In connection with the channel, 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.

  <Desc / Clms Page number 10>

 



  The device can also have at least one agent selected from the following group: sensor, electrode, temperature unit, sieve, filter, membrane, affinity matrix, substance or magnet. Furthermore, a connecting channel connecting the connecting piece to the channel can be provided. In addition, an inlet opening that is connected to the channel and can preferably be closed by means of a first valve can be provided. Furthermore, an outlet opening connected to the channel, preferably closable by means of a second valve, can be provided. The proposed configurations of the device enable a differentiated and automated process control. The arrangement and design of the channel are expediently chosen such that the desired reaction can be carried out simply and quickly.



  Advantageously, 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.



  In a particularly advantageous embodiment, 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 membrane 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.

  <Desc / Clms Page number 11>

 



  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 connection piece. The connection can be closed with a closure means, for example a plastic or rubber membrane, a metal foil or the like.



  According to a particularly advantageous embodiment, 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. For example, the connector can have an internal thread and the connector can have an external thread. Contamination of the agent for processing the molecules contained in the disposable container is avoided.



  Advantageously, the device has at least one, preferably cylindrical, recess corresponding to the outside diameter of the disposable container for guiding the connection of the disposable container into an engagement position with the connection piece. This makes it easier to connect the disposable container. 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

  <Desc / Clms Page number 12>

 is particularly simple. A faulty, possibly insufficiently tight connection is prevented.



  Furthermore, the means for fixing can have a means for holding the disposable container which is completely pushed into the recess and engages in the connector in a fixed position. This prevents undesired detachment of the connection from the connection piece. The means for holding can be, for example, at least one first latching means which surrounds the second end of the disposable container.



  According to a further embodiment, 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.



  This makes it possible to insert the disposable container into one of the specified recesses by the manufacturer. This prevents the disposable containers from being inserted incorrectly by the user. The device can be supplied pre-assembled by the manufacturer 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.



  The disposable container is expediently received in the recess with an unopened closure means. 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

  <Desc / Clms Page number 13>

 means can be designed so that the disposable container, for. B. by pressure on the piston, can be moved 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 connector in a liquid-tight manner and the pipe socket pierces the locking means. In the second rest 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.



  According to a further embodiment, 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. In this case, such a device only has to be equipped with a large number of push rods which are suitable for depressing the pistons and which are moved according to a predetermined program. In addition, the parallel arrangement of the recesses contributes to a particularly compact design of the device according to the invention.

  <Desc / Clms Page number 14>

 



  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.



  According to a further embodiment, the device can have a means for automatically reading out information about means for processing incorporated 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 inserted captively 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.



  According to a further measure of the invention, a method for processing molecules is provided with the following steps: providing at least two disposable containers, each of which has a cylinder with a piston which is displaceably guided therein and a first end of the cylinder which is opposite the piston provided connection,

  <Desc / Clms Page number 15>

 Providing a microfluidic device with at least one channel, at least two connection pieces being provided on the channel for connecting the disposable containers, connecting the disposable containers with the connections provided thereon on the connection pieces, displacing one of the pistons so that a liquid in the channel is promoted.



  The proposed method enables particularly simple processing of molecules. The pressure to move or



  Transport of 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. When filling one of the disposable containers, the piston accommodated therein is expediently displaced by the liquid pressure. In this case, it is not necessary to drag the piston by means of a special towing device in order to convey the liquid into the disposable container. By moving one of the pistons, a liquid in the channel can be

  <Desc / Clms Page number 16>

 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 the liquid to be moved exactly.

   The liquid can be processed according to a predetermined program at certain points on the channel. For this purpose, the predetermined section of the channel can have a meandering channel and / or microfluidic detection space. To control the movement of the liquid in the channel, at least one valve provided therein can also be opened and / or closed according to a predetermined program. The pistons are also moved according to the specified program, so that the liquid in the channel or in the disposable containers is moved in accordance with the specified reaction steps.



  According to a further embodiment, the disposable containers are inserted into recesses provided on the device.



  This enables the connections provided on the disposable containers to be routed precisely to the fittings of the facility. When the connector is connected to the connector, the disposable container is expediently fixed relative to the connector. For this purpose, a means for fixing can be provided. The fixation expediently takes place only when the connection is properly connected to the connection piece. In this way, the establishment of a leaky connection can be avoided.



  According to a further embodiment, 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,

  <Desc / Clms Page number 17>

 the disposable container is shifted from the first into a second latching position, so that 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.



  Advantageously, the liquid is conveyed through the displacement of the pistons in the device 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.



  Exemplary embodiments of the invention are explained in more detail below with reference to the drawings. 1 shows a schematic sectional view of a first one
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 inserted disposable container, FIG. 4 shows the partial sectional view according to FIG. 3 with push rod, FIG. 5 shows the partial sectional view according to 4 with the piston partially pushed in,

  <Desc / Clms Page number 18>

 Fig. 6 is a schematic sectional view of a second
Disposable container, Fig. 7 is a schematic sectional view of a microfluidic device with the second
Disposable containers according to FIG. 6, FIG. 8 the arrangement according to FIG. 7, the second
Disposable container is connected to the microfluidic device, Fig.

   9 shows the arrangement according to FIG. 8, with further disposable containers connected, FIG. 10 shows the arrangement according to FIG. 9, with a sample container connected, FIG. 11 shows the arrangement according to FIG. 10, with the sample container emptied 12, the arrangement according to FIG. 11, the second
Disposable container has been emptied, FIG. 13 is a sectional view of a further microfluidic device, and FIGS. 14a-c are sectional views of the connection and the connection piece in different latching positions.



  Fig. 1 shows a schematic sectional view of a first disposable container. In a cylinder 1 which is expediently made of a transparent plastic, for example polyethylene or polypropylene, a cylinder, for example B.

  <Desc / Clms Page number 19>

 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 received 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. In particular, it 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. 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 engaging a push rod and / or a tow bar. A second end of the cylinder 1 opposite the first end E1 is identified 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

  <Desc / Clms Page number 20>

 pierce or pressed into the cylinder 1 and thus a connection of the cylinder 1 with the microfluidic device 13 is achieved.



  3 shows the disposable container connected to the connection piece 8 using the receptacle 6. To transfer the liquid F, 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. At the second end E2, 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. On its side facing away from the connection 3, the piston 2 has an engagement means 12 for connection 3 to a push rod and / or towing rod. As shown here, the engagement means 12 can be designed, for example, in the form of a stamp. Of course, other suitable configurations are also possible. In the present exemplary embodiment, the closure means 4 is designed as a membrane.



  It can be a plastic and rubber membrane. It is expedient to use 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.



  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 connection pieces 14 are closed with a further closure means 15, so that one

  <Desc / Clms Page number 21>

 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.



  FIG. 8 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 here to all further connecting pieces 14.



  As can be seen from Fig. 9, 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 in each case. Incorrect operation can be caused by connecting a disposable container to one

  <Desc / Clms Page number 22>

 wrong further connector 14 can be prevented. The other disposable containers shown in FIG. 9 are otherwise identical to the second disposable container.



  10 shows the microfluidic device 13 according to FIG.



  9, a syringe 23 in which sample liquid PF is accommodated being connected to the inlet opening 19. 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. For this purpose, it is necessary to depress the piston 2 and again to hold the second piston 24 in position, and to keep the first 18 and the second valve 20 closed (see FIG. 12). 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. Such 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 from the outside, the valve can be emptied. The first

  <Desc / Clms Page number 23>

 and / or second valve, it can also be a simply designed reusable valve, e.g. B. a diaphragm valve act.



  By means of a program-controlled, predetermined movement of the pistons 2, 24 of the disposable containers, the sample liquid PF can be acted upon successively 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 in them can be separated by magnetic beads containing liquids in the disposable containers and sent to another detection method for analysis.



  13 shows a further exemplary embodiment of a microfluidic device 13. In contrast to 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 (here not shown). 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.

   A distance A between the first latching means 26 and the connection piece 8 is selected such that a disposable container can be pushed completely into the recess 7 without a closure means 4 provided at its connection 3 being pierced by the hollow needle 9 becomes. The disposable container can therefore be presented captively with the microfluidic device. To start up the device according to the invention, all that is required is the

  <Desc / Clms Page number 24>

 To move the disposable container in the direction of the connection piece 8 and thus to connect it to the microfluidic device 13.



  The sectional views FIGS. 14a to 14c show an advantageous embodiment of the connection of the disposable container to the microfluidic device 13. The second latching means provided in the recess 7 in the vicinity of the connector 8 are designated by 27. In the area of the connection 3 of the disposable container, 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. designed as an O-ring, sealant 29 provided.



  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.



  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.



  14c, the disposable container is in a second latching position. The hollow needle 9 penetrates the closure means 4 (not shown here). A fluid connection is established between the hollow needle 9 and the disposable container.

  <Desc / Clms Page number 25>

 



  It is readily apparent from the exemplary embodiments that 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. All that is required is 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. Nevertheless, extremely precise reaction management is achieved.

   Defined concentrations and volumes can easily be kept in the disposable containers. Since the proposed system is completely closed, contamination is avoided.



  The proposed device is outstandingly suitable for the automated detection of DNA or similar biochemical molecules. A device to be provided for this purpose for automatically controlling the movements of the pistons 2, 24 of the disposable containers can be carried out relatively simply 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.

  <Desc / Clms Page number 26>

 



  1 cylinder 2 piston 3 connection 4 closure means 5 projection 6 receptacle 7 recess 8 connection piece 9 hollow needle 10 push rod 11 retaining means 12 engagement means 13 microfluidic device 14 further connection piece 15 further closure means 16 connecting channel 17 channel 18 first valve 19 inlet opening 20 second valve 21 outlet opening 22 base plate 23 syringe 24 further plunger 25 further disposable container 26 first locking means 27 second locking means 28 third locking means A distance

  <Desc / Clms Page number 27>

 F liquid P particle PF sample liquid

Claims

1. Use of a disposable container which has a cylinder (1) with a piston (2,24) slidably guided therein and a connection (3) provided on a first end (E1) of the cylinder (1) opposite the piston (2,24) ), for generating a pressure difference in a microfluidic device (13) and for providing a means (F, P) for processing molecules and / or as a reaction vessel.
2. Use according to claim 1, wherein the means (F, P) for processing is a liquid, a gel or a solid or a combination thereof.
3. Use according to claim 1 or 2, wherein the solid comprises at least one of the following constituents: soluble or suspendable particles, lyophilisate, chromatographic material, preferably an ion exchanger or an affinity matrix.
4. Use according to one of the preceding claims, wherein the agent (F, P) for processing is selected from the following group: lysis liquid, elution liquid, buffer solution, beads, enzymes, primers, reactants, agents.
5. Use according to one of the preceding claims, wherein the processing is an analysis, synthesis, purification, modification and / or increasing the concentration of the molecules.
6. Use according to one of the preceding claims, wherein the disposable container is completely filled with the processing means.  <Desc / Clms Page number 29>  
7. Use according to one of the preceding claims, wherein the piston (2,24) is made of an elastic material, preferably of rubber or plastic.
8. Use according to one of the preceding claims, wherein the piston (2,24) has at least one circumferential seal with a symmetrical cross section.
9. Use according to one of the preceding claims, wherein the piston (2, 24) is designed to correspond to the connection (3), so that when the piston (2, 24) is in contact with the first end (E1), the Cylinder (1) and possibly the connection (3) is possible.
10. Use according to one of the preceding claims, wherein the piston (2, 24) has a means (12) for engaging a pushing and / or towing means.
11. Use according to one of the preceding claims, wherein a pushing and / or towing means (10) is attached to the piston (2,24).
12. Use according to one of the preceding claims, wherein the pushing and / or towing means (10) has a means at the free end for engaging in a pushing and / or towing device.
13. Use according to one of the preceding claims, wherein the cylinder (1) is made of a transparent or an opaque material.  <Desc / Clms Page number 30>  
14. Use according to one of the preceding claims, wherein the cylinder (1) is made of an elastic plastic, preferably polypropylene.
15. Use according to one of the preceding claims, wherein the connection (3) is closed with a closure means (4).
16. Use according to one of the preceding claims, wherein the sealing means (4) is a rubber or plastic membrane, a ball, a cone or a sealing cylinder.
17. Use according to one of the preceding claims, wherein the ball, the cone and / or the locking cylinder are made of an inert plastic or of glass.
18. Use according to one of the preceding claims, wherein at a second end (E2) of the cylinder (1) opposite the connection (3) a radially inwardly projecting, a displacement of the piston (2, 24) the cylinder (1) blocking projection (11) is provided.
19. Use according to one of the preceding claims, wherein at the second end (E2) a radially inwardly projecting, a displacement of the piston (2,24) in the direction of the connection (3) is provided with a further resistance.
20. Use according to one of the preceding claims, wherein a means for automatically reading out information about the means (F, P) accommodated in the disposable container is provided for processing.  <Desc / Clms Page number 31>  
21. Use according to one of the preceding claims, the means being a bar code, a transponder, a chip or a specific shape.
22. Microfluidic device for processing molecules with a device (13) having at least one channel (16, 17) for conveying a sample (PF), with at least two connecting pieces (8, 14) on the channel (16, 17) Connection of two disposable containers is provided, each of the disposable containers having a cylinder (1) with a piston (2,24) slidably guided therein and a first end (E1) of the cylinder (1) opposite the piston (2,24). has provided connection (3), and wherein the disposable containers with the connection (3) provided thereon are each connected to one of the connection pieces (8, 14), so that by moving one of the pistons (2, 24) liquid (F) can be conveyed through the channel (16, 17).
23. The apparatus of claim 22, wherein the channel (16, 17) is a channel system of a plurality of interconnected channels.
24. The apparatus of claim 22 or 23, wherein the channel (16, 17) or the channel system is at least partially meandering.
25. Device according to one of claims 22 to 24, wherein the device (13) in connection with the channel (16, 17) a microfluidic mixing chamber and / or a microfluidic  <Desc / Clms Page number 32>  reaction space and / or a microfluidic detection space and / or a bubble trap.
26. Device according to one of claims 22 to 25, wherein the channel (16, 17) has a diameter of at most 2 mm, preferably less than 1.5 mm. 27. Device according to one of claims 22 to 26, wherein the Device (13) has at least one agent selected from the following group: sensor, electrode, temperature unit, sieve, filter, membrane, affinity matrix, substance introduced, magnet.
28. Device according to one of claims 22 to 27, wherein a connecting channel (16) is provided connecting the connecting piece (8, 14) with the channel (17).
29. Device according to one of claims 22 to 28, wherein an inlet opening (19) which is connected to the channel (17) and is preferably closable by means of a first valve (18) is provided.
30. Device according to one of claims 22 to 29, wherein an outlet opening (21) which is connected to the channel (18) and is preferably closable by means of a second valve (20) is provided.
31. The device according to any one of claims 22 to 30, wherein liquid (F) can be conveyed into the other disposable container by displacing one of the pistons (2,24).
32. Device according to one of claims 22 to 31, wherein each connecting piece (8, 14) a pipe socket, preferably  <Desc / Clms Page number 33>  a hollow needle (9) for opening a closure means (4) closing the connection (3).
33. Device according to one of claims 22 to 32, wherein the connecting piece (8) and / or the pipe socket is closed with a further closure means (15).
34. Device according to one of claims 22 to 33, wherein the disposable container is a disposable container according to one of claims 1 to 20.
35. Device according to one of claims 22 to 34, wherein each of the disposable containers has a connection (3) corresponding to the connection pieces (8, 14).
36. Device according to one of claims 22 to 35, wherein the device (17) has at least one, preferably cylindrical, recess (7) corresponding to the outside diameter of the disposable container for guiding the connection (3) of the disposable container into an engagement position with the connection piece ( 8, 14).
37. Device according to one of claims 22 to 36, wherein the device further comprises a means for fixing the disposable container in a position that is fixed relative to the connection piece.
38. Device according to one of claims 22 to 37, wherein the means for fixing means for holding the disposable container fully inserted into the recess (7) and engaging in the connector (8, 14) in a fixed position having.  <Desc / Clms Page number 34>  
39. Device according to one of claims 22 to 38, wherein the means for holding is at least one first latching means (26) which surrounds the second end (E2) of the disposable container.
40. Device according to one of claims 22 to 39, wherein a distance (A) between the first latching means (26) and the connecting piece (8) is selected such that the disposable container can be inserted into the recess (7) without one provided closure means (4) is opened.
41. Device according to one of claims 22 to 40, wherein the one-way container (s) with unopened closure means (4) is / are received in the recess (7).
42. Device according to one of claims 22 to 41, wherein second locking means (27) are provided on the cylinder (1) of the disposable container and / or on the inner wall of the recess (7).
43. Device according to one of claims 22 to 42, wherein the second latching means (27) are designed such that the disposable container can be moved into a first latching position in which the connector (3) closes the connector (8) in a liquid-tight manner.
44. Device according to one of claims 22 to 43, wherein the second locking means (27) are designed such that the disposable container can be moved from the first into a second locking position, in which the connection (3) the connection piece (8) is liquid-tight closes and the pipe socket (9) pierces the closure means (4).  <Desc / Clms Page number 35>  
45. Device according to one of claims 22 to 44, wherein liquid is placed in the channel.
46. Device according to one of claims 22 to 45, wherein a plurality of recesses (7) are provided on one side of the device (13).
47. Device according to one of claims 22 to 46, wherein the device is made in one piece from plastic.
48. Device according to one of claims 22 to 47, wherein the device (13) has a means for automatically reading out information about means (F, P) recorded in the device (13) for processing.
49. The apparatus of claim 48, wherein the means is a bar code, a transponder, a chip or a specific shape.
50. Method for processing molecules with the following steps: providing at least two disposable containers, each of which has a cylinder (1) with a piston (2, 24) slidably guided therein and one on a piston (2, 24) Has the connection (3) provided over the first end (E1) of the cylinder (1), providing a microfluidic device (13) with at least one channel (16, 17), at least two connection pieces (8 , 14) are provided for connecting the disposable containers,  <Desc / Clms Page number 36>  Connect the disposable container with the connections (3) provided on it to the connection pieces (8,14), move one of the pistons (2,24) so that a liquid (F) in the channel (16,
   17) is promoted.
51. The method of claim 50, wherein the liquid (F) is contained in one of the disposable containers.
52. The method according to claim 50 or 51, wherein the liquid (F) is conveyed from one to the other disposable container.
53. The method according to any one of claims 50 to 52, wherein when one of the disposable containers is filled, the piston (2, 24) accommodated therein is displaced by the liquid pressure.
54. The method according to any one of claims 50 to 53, wherein by moving one of the pistons (2,24) a liquid located in the channel (16, 17) into a predetermined, preferably meandering section of the channel (16, 17) and / or a microfluidic mixing chamber and / or a microfluidic reaction space and / or a microfluidic detection space and / or a bubble trap is shifted.
55. The method according to any one of claims 50 to 54, wherein at least one valve (18, 20) provided therein is opened and / or closed to control the movement of the liquid in the channel (16, 17) according to a predetermined program.  <Desc / Clms Page number 37>  
56. The method according to any one of claims 50 to 55, wherein the disposable container is inserted into a recess (7) provided on the microfluidic device.
57. The method according to any one of claims 50 to 56, wherein the disposable container in the recess (7) is moved into a first latching position, so that the connector (3) closes the connector (8) in a liquid-tight manner.
58. The method according to any one of claims 50 to 57, wherein the disposable container is moved from the first into a second latching position, so that the connector (3) closes the connector (8) in a liquid-tight manner and the pipe socket (9) pierces the closure means (4) ,
59. The method according to any one of claims 50 to 58, wherein the liquid (F) by the displacement of the piston (2,24) is conveyed in the device (13) such that the steps required to carry out at least one of the following methods are carried out : Washing, purification, PCR, detection.
PCT/EP2003/007645 2003-07-04 2003-07-15 Use of a disposable container, microfluidic device and method for processing molecules WO2005002729A1 (en)

Priority Applications (4)

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

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
EP20030817332 EP1641564B1 (en) 2003-07-04 2003-07-15 Use of a disposable container, microfluidic device and method for processing molecules
US10/563,279 US20070048194A1 (en) 2003-07-04 2003-07-15 Use of a disposable container, microfluidic device and method for processing molecules
DE2003508515 DE50308515D1 (en) 2003-07-04 2003-07-15 Use of a disposable vessel, microfluidic device and process for processing molecules
AU2003250952A AU2003250952A1 (en) 2003-07-04 2003-07-15 Use of a disposable container, microfluidic device and method for processing molecules

Publications (1)

Publication Number Publication Date
WO2005002729A1 true WO2005002729A1 (en) 2005-01-13

Family

ID=33566020

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2003/007645 WO2005002729A1 (en) 2003-07-04 2003-07-15 Use of a disposable container, microfluidic device and method for processing molecules

Country Status (5)

Country Link
EP (1) EP1641564B1 (en)
AT (1) AT376882T (en)
AU (1) AU2003250952A1 (en)
DE (1) DE50308515D1 (en)
WO (1) WO2005002729A1 (en)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102005008224B3 (en) * 2005-02-23 2006-06-14 Directif Gmbh Apparatus for automatically activating microfluid device, for carrying out biochemical purifications and assays, having activator controlled on the basis of measurements of exerted force
WO2007101653A1 (en) * 2006-03-06 2007-09-13 Directif Gmbh Method of carrying out a reaction for replicating a nucleic acid
DE202006020469U1 (en) 2006-03-06 2008-10-16 Directif Gmbh Device for detecting biochemical target molecules
WO2012041479A1 (en) * 2010-09-30 2012-04-05 INSTITUT FüR MIKROTECHNIK MAINZ GMBH Microfluidic chip comprising several cylinder-piston arrangements
WO2016062788A1 (en) 2014-10-24 2016-04-28 Ait Austrian Institute Of Technology Gmbh Microfluidic chip for biological analysis

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2756463C (en) 2009-03-24 2019-01-22 University Of Chicago Slip chip device and methods
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
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
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 (en) * 2015-02-20 2016-02-04 Friz Biochem Gesellschaft Für Bioanalytik Mbh Double syringe for feeding a fluid into a microfluidic system

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1982002211A1 (en) * 1980-12-22 1982-07-08 Chandler Howard Milne Device and method for detecting antigens and antibodies
US6143252A (en) * 1999-04-12 2000-11-07 The Perkin-Elmer Corporation Pipetting device with pipette tip for solid phase reactions
WO2003015922A1 (en) * 2001-08-20 2003-02-27 Biomicro Systems, Inc. Laminated microarray interface device

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1982002211A1 (en) * 1980-12-22 1982-07-08 Chandler Howard Milne Device and method for detecting antigens and antibodies
US6143252A (en) * 1999-04-12 2000-11-07 The Perkin-Elmer Corporation Pipetting device with pipette tip for solid phase reactions
WO2003015922A1 (en) * 2001-08-20 2003-02-27 Biomicro Systems, Inc. Laminated microarray interface device

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102005008224B3 (en) * 2005-02-23 2006-06-14 Directif Gmbh Apparatus for automatically activating microfluid device, for carrying out biochemical purifications and assays, having activator controlled on the basis of measurements of exerted force
WO2007101653A1 (en) * 2006-03-06 2007-09-13 Directif Gmbh Method of carrying out a reaction for replicating a nucleic acid
DE102006010958A1 (en) * 2006-03-06 2007-09-13 Directif Gmbh Method for carrying out a reaction for the amplification of a nucleic acid
DE202006020469U1 (en) 2006-03-06 2008-10-16 Directif Gmbh Device for detecting biochemical target molecules
WO2012041479A1 (en) * 2010-09-30 2012-04-05 INSTITUT FüR MIKROTECHNIK MAINZ GMBH Microfluidic chip comprising several cylinder-piston arrangements
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 (en) 2014-10-24 2016-04-28 Ait Austrian Institute Of Technology Gmbh Microfluidic chip for biological analysis

Also Published As

Publication number Publication date
AU2003250952A1 (en) 2005-01-21
EP1641564A1 (en) 2006-04-05
DE50308515D1 (en) 2007-12-13
AT376882T (en) 2007-11-15
EP1641564B1 (en) 2007-10-31

Similar Documents

Publication Publication Date Title
EP0609431B1 (en) Sealable vessel for containing and processing analytical samples
US6482362B1 (en) Membrane filtered pipette tip
US5666967A (en) Fluid sample collection and introduction device
TWI475230B (en) Open platform automated sample processing system
US5871699A (en) Apparatus and method for drawing liquid samples and dispensing them into a plurality of test tubes
CN1495420B (en) Automatic resealed container cap
US9364394B2 (en) Compounder apparatus
AU748070B2 (en) Collection container assembly
US5945070A (en) Reaction vessel filter for combinatorial chemistry or biological use
DE102005063368B4 (en) Chemical reaction cartridge
US9724690B2 (en) Blood collection device, method, and system for using the same
US7578205B2 (en) Sterile sampling device
US20050059165A9 (en) Universal sample collection and testing system
EP1548420B1 (en) Disposable, pre-sterilized fluid receptacle sampling device
CA2304017C (en) Apparatuses and methods for isolating nucleic acid
US5882601A (en) Deflected septum seal access port
US7932082B2 (en) Device and method for extracting a smear sample
EP0872279B1 (en) Dosing device for dispensing small amounts of liquid
US20110212517A1 (en) Method and device for preparing a sample of biological origin in order to determine at least one constituent contained therein
JP4513085B2 (en) Sample container
EP0159342A4 (en) Multiple chamber container having leak detection compartment.
US5078970A (en) Apparatus for withdrawing a liquid sample from a sample vessel and transferring it
EP1210575A1 (en) Improved method and apparatus for aspirating and dispensing liquids
EP0273548A2 (en) Apparatus and method for dispensing liquids
US20060011539A1 (en) Apparatus for processing a fluid sample

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

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
WWE Wipo information: entry into national phase

Ref document number: 2003817332

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 2003817332

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 10563279

Country of ref document: US

Ref document number: 2007048194

Country of ref document: US

WWP Wipo information: published in national office

Ref document number: 10563279

Country of ref document: US

NENP Non-entry into the national phase in:

Ref country code: JP

WWG Wipo information: grant in national office

Ref document number: 2003817332

Country of ref document: EP