EP2522427B1 - Dispositif microfluidique et son procédé de fabrication - Google Patents

Dispositif microfluidique et son procédé de fabrication Download PDF

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Publication number
EP2522427B1
EP2522427B1 EP12179918.3A EP12179918A EP2522427B1 EP 2522427 B1 EP2522427 B1 EP 2522427B1 EP 12179918 A EP12179918 A EP 12179918A EP 2522427 B1 EP2522427 B1 EP 2522427B1
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EP
European Patent Office
Prior art keywords
film
component
channel structures
opening
channel
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EP12179918.3A
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German (de)
English (en)
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EP2522427A1 (fr
Inventor
Jörg Nestler
Thomas Otto
Thomas Gessner
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Fraunhofer Gesellschaft zur Forderung der Angewandten Forschung eV
Technische Universitaet Chemnitz
Original Assignee
Fraunhofer Gesellschaft zur Forderung der Angewandten Forschung eV
Technische Universitaet Chemnitz
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    • 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
    • B01L3/502707Containers 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 manufacture of the container or its components
    • 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
    • B01L2200/025Align devices or objects to ensure defined positions relative to each other
    • 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
    • B01L2200/028Modular arrangements
    • 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
    • B01L2200/06Fluid handling related problems
    • B01L2200/0684Venting, avoiding backpressure, avoid gas bubbles
    • 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
    • B01L2200/06Fluid handling related problems
    • B01L2200/0689Sealing
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0809Geometry, shape and general structure rectangular shaped
    • B01L2300/0816Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0874Three dimensional network
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0887Laminated structure
    • 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
    • B01L2400/0481Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure squeezing of channels or chambers
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/06Valves, specific forms thereof
    • B01L2400/0633Valves, specific forms thereof with moving parts
    • B01L2400/0655Valves, specific forms thereof with moving parts pinch valves
    • 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
    • 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
    • B01L3/502723Containers 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 venting arrangements
    • 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
    • B01L3/502738Containers 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 integrated valves

Definitions

  • the present invention relates to microfluidic devices and methods of making same.
  • Microfluidic devices are used in many fields of technology, such as e.g. for diagnostic applications.
  • Microfluidic systems often consist, among other components, of one part, which is manufactured for example by means of injection molding. In this part, for example, there are channels or reservoirs.
  • injection molding technology has the advantage that very large quantities can be manufactured here at low cost. However, this is associated with high initial costs, so that a later design change is no longer readily possible.
  • a portion of such a microfluidic system may include a portion defined with its channel and reservoir system. It would be desirable to design such a system so that it would be customizable to the particular application or combination of sensors. The manufacturer costs should also remain low.
  • the US 2002 / 0187072A1 refers to multilayer microfluidic splitters.
  • a common fluid inlet fluidly communicates with a branching channel network, which evenly distributes a fluid flow to a plurality of outlets.
  • Uniform splitting is provided by maintaining substantially equal fluidic impedance across all branch channels.
  • Substantially equal fluidic impedance may be provided by maintaining a substantially equal flow path length between the common inlet and each of the outlets.
  • the WO 02/083310 A2 refers to microfluidic devices capable of measuring fluid flow. Devices and methods for stem branch measurement of fluid stoppers in which one or more branch channels of a defined volume of mass fluid are measured are described. In addition, measuring at least one separate plug is described by selecting the delivery conditions of a first and a second fluid to a microfluidic channel.
  • the first fluid may be a liquid and the second fluid may be a gas. Reduced area channel segments are provided to assist in measuring one or more separate fluid plugs.
  • a microfluidic volume is measured by filling a microfluidic chamber with fluid, sealing an inlet channel, and then extracting the fluid.
  • the document EP 1 205 670 A2 provides a distribution plate for liquids and / or gases, which consists of at least one layer, wherein in the layer or layers, a plurality of first elongated channels having a first geometric configuration formed in a first direction substantially, and also a plurality of second elongated channels is formed with a second geometric configuration substantially in a second direction.
  • Such layers in particular if they have very small dimensions and accordingly miniaturized trained channels have been prefabricated in a simple manner and cost-saving, for example made of plastic by means of molding or injection molding in large numbers and stored. If necessary, in such a layer in a simple manner by means of suitable holes in spaces between juxtaposed channels at least a first and second channel are connected to each other, with appropriate requirements can be considered by the proper use of the distributor plate in an equally simple manner.
  • the US 2002/0112961 A1 refers to multilayer microfluidic devices with folded channels and densely positioned microfluidic structures. Desired microfluidic structures which, when cut in a single device layer, would be subject to deformation may be formed from multiple non-deforming layers. Channel segments of each geometry, defined in separate layers, communicate to form continuous flow paths, which in turn form the desired microfluidic structures. Any number of device layers can be used to fabricate the microfluidic structures as desired.
  • the US 2005/0266582 shows a microfluidic system for performing chemical or biological or biochemical reactions.
  • the US 2002/0187074 shows a modular microfluidic system for performing fluidic operations, such as filtering, regulating, pressure adjusting, mixing, measuring, reacting, heating or cooling.
  • the US 2008/0262213 shows methods and systems for editing polynucleotides.
  • the object of the present invention is thus to provide a microfluidic device and a method for producing such microfluidic devices, so that low production costs can be achieved even with a high degree of design flexibility or a better relationship between production costs on the one hand and design flexibility on the other hand is achieved.
  • microfluidic device according to claim 1 and a method of manufacturing according to claim 11.
  • One finding of the present invention is that it has recognized that a foil having an opening therein can be used inexpensively for at least one component in which channel structures are formed that at least partially form a respective component surface of the at least one component are open to individualize to a respective one of a plurality of channel structure combinations.
  • the manufacturing costs for the microfluidic devices can thus be kept low, since a plurality of such at least one component, which are identical to one another, can be used to produce different microfluidic devices which differ in the connection combination of the channel structures.
  • a self-adhesive film can be used as the film, which makes the process of assembling the microfluidic device very simple
  • the channel structures are also formed in a (common) microfluidic device so as to at least partially open in the component surface of the one component, wherein the film covers the component surface of this component such that a first and a second channel structure extend laterally along the component Component surface and within the opening in the film leading path interconnected While a third channel structure is not adjacent to the opening and is at least partially closed by the film on the component surface.
  • a different microfluid device could be formed by a film covering the component surface of another identical component such that, for example, the third channel structure with one of the first or the second channel structure over a laterally along the component surface and within the opening of the last-mentioned film path connected to each other. Both microfluidic devices thus differ in the connection of the channel structures, although an identically shaped component is the basis.
  • the production costs are therefore lower, in particular because the underlying at least one component can be manufactured in large quantities in injection molding.
  • the opening on the side opposite the component is closed by a porous membrane, so that gas such as e.g. Air introduced when introducing liquids, e.g. Analytes or samples in which channel structures is displaced, can escape through the porous membrane, although the liquids are safely retained in the fluid structures.
  • gas such as e.g. Air introduced when introducing liquids, e.g. Analytes or samples in which channel structures is displaced, can escape through the porous membrane, although the liquids are safely retained in the fluid structures.
  • Fig. 1 shows the top view of a comparative example of a component with a channel structure.
  • the component is, for example, an injection molded part and, as in the embodiments described below, the reference numeral 10 is used for the component.
  • Fig. 1 shows the top view of a component surface 12 of the component 10.
  • the outer shape of the component 10 is substantially cuboid but other shapes would also be conceivable, such as parallelepiped, cylindrical or the like.
  • the component surface 12 as shown in FIG Fig. 1 is visible to one of the main sides of the component 10, and is also planar, but simply curved component surfaces would also be conceivable, for example.
  • the embodiments described below will not be discussed in more detail, but the just made statements with respect to the component 10 also apply to the embodiments described below.
  • a channel structure is formed in the component 10. It includes channels 14 and chambers 16a, 16b, 16c and 16d, of which the chambers 16b and 16d may serve as sensor sites, for example, where different sensors can perform different measurements in the respective chamber, while the chambers 16a and 16c, for example may be reservoirs or sources of fluids, such as analytes or samples.
  • the channels 14 and 16a-16d are formed in the surface of the component in the form of recesses, with a cover component covering these recesses on the component surface 12, as a result of which the inside in FIG Fig. 1 formed fluid structure, according to which the channels 14 are branched into several sections.
  • a channel section 14a-14d leads from a respective chamber 16a-16d to a common connecting section 14e.
  • the section 14e connects nodes at which the sections 14a, 14c and 14e or 14b, 14d and 14e meet.
  • Fig. 2a to 2d show the four possible combinations, according to which one of the reservoirs 16a and 16c is connected to one of the sensor sites 16b and 16d. As can be seen, only three of the channel sections would actually be needed. To realize the four different variants Fig. 2a - 2d Thus, either four different components 10 would have to be produced, or else the idea on which the exemplary embodiments described below are based is used.
  • the channels located in the same, no direct connection by means of channels to the flexible chambers for the sensor sites or sources. Rather, the connection, so the channel or channels, is interrupted at one or more points.
  • the injection molded part is then provided with a foil which has one or more openings or recesses which (in each case) form a kind of bridge between the separate channel structures, such as channel ends thereof, at the interruptions.
  • Fig. 3 shows an embodiment of a microfluidic device according to an embodiment of the present invention.
  • the microfluidic device of Fig. 3 is generally indicated with 20. It comprises a component 22, in which or in which channel structures 24a, 24b and 24c are formed which are at least partially open to a component surface 26 of the component 22.
  • the component 22 may be an injection molded part.
  • the channel structures are completely open to the component surface 26 of the component, ie they are formed in the form of depressions or recesses in the component surface 26.
  • After assembly they are at least partially covered by a film 28 of the microfluidic device 20.
  • the recesses 24a-24c include trenches 30a-30c and shafts 32a-32c which together with the film 28 form channels or chambers.
  • the component 22 of Fig. 3 formed in the form of a substrate or as a flat cuboid and the channel structures 24a - 24c all open on one main side, namely the top of the component 22.
  • the component 22 can in principle take any shape and of course as well the component surface 26.
  • channel structures 24a-24c are laterally spaced from each other. This means that the channel structures 24a-24c have no fluidic connection to one another within the component 22.
  • the fluidic connection between a subset of the channel structures 24a-24c is first produced by the film 28, as will be discussed in more detail below, wherein the subset each of the set of channel structures 24a-24c may correspond.
  • Fig. 3 there are four possibilities for channel structure connection combinations.
  • the component 22 can be an injection-molded part. It can thus be produced inexpensively in large quantities. Preferably, the component 22 is inherently stable and requires no further carrier. A flexible design would also be possible. Exemplary materials for component 22 include polycarbonate (PC), polymethylmethacrylate (PMMA), cycloolefin polymer (COP), and cycloolefin copolymer (COC).
  • PC polycarbonate
  • PMMA polymethylmethacrylate
  • COP cycloolefin polymer
  • COC cycloolefin copolymer
  • the film is preferably designed flexibly.
  • Material and film thickness or thickness may vary.
  • the film thickness is less than or equal to 1 mm or even less than or equal to 0.5 mm.
  • the material of the film 28 may be plastic, but other materials such as e.g. Metal.
  • the film 28 comprises an opening 34, ie a recess which extends over the entire thickness of the film 28, ie from a front side of the film 28 to a rear side thereof.
  • the film 28 is not yet shown in the assembled state.
  • the film 28 In the assembled state, the film 28 is on the component surface 26, as indicated by dotted lines 36.
  • the opening 34 connects the channel structures 24a and 24c. As indicated by dashed lines 38, it accomplishes this by providing in the assembled state, the channels 30a and 30c covered.
  • the channel structure 24b is closed by the film 28 on the component surface 26, so that it is not in particular fluidly connected via the opening 34 with the other two channel structures 24a and 24b.
  • the opening 34 in the film 28 thus implements one of the four channel structure connection combinations already mentioned above, wherein Fig. 7 another film 28 'is shown with a different opening 34', which leads to another of the four possible combinations in which the channel structures 24a and 24b are interconnected by the opening 34 'in the assembled state covering the trenches 30a and 30b but laterally separated from the channel structure 24c. It is readily apparent how films could look for the other two possible combinations.
  • Fig. 3 What in Fig. 3 is not shown, that the opening 34 in the film 28 and the therein of the channel structure 24a to the channel structure 24c and vice versa leading path on a side facing away from the component surface 26 is closed with a lid.
  • the lid can, as it later regarding the Fig. 4 to 5b can be a porous membrane, but can also, as it regards Fig. 6 is shown, another component, ie, a further injection molded part, in which possibly even one or more or more channel structures are formed.
  • the film is glued to the component surface 26, for example. It is advantageous if the component surface 26, as in Fig. 3 shown, flat or at least only slightly curved so that no wrinkles form during application. Corners or edges could also be present in the surface.
  • the film 28 may in particular be a self-adhesive film. So if the microfluidic device of Fig. 3 is produced, then it is sufficient for joining of the component and the film to apply the film 28 on the component surface 26, as for example, by rolling and / or pressing, with the self-adhesive side facing the component surface.
  • the self-adhesive film is, for example, an adhesive tape.
  • the film 28 may also be a self-adhesive film on both sides, such as adhesive tape provided on both sides with an adhesive layer.
  • An otherwise gluing the lid on the film 28 is also possible.
  • the components could also be clamped with a clamping device such as an extra frame which presses the film 28 against the surface 26.
  • An adhesive or an adhesive layer between the components could also be an attachment by means of melting, such as the film material 28, to the surface 26, are used.
  • the adhesive which adjoins the channel structures and, in particular, the fluid located therein may be chosen such that the abutment for the respective application is not critical. The same applies regardless of the presence or absence of the self-adhesive property also for the material of the film.
  • Fig. 3 in many respects is merely exemplary with respect to the design of the channel structures 24a-24c in the component 22. It has already been pointed out that the channel structures 24a-24c are merely exemplary in FIG Fig. 3 have only depressions. Rather, the channel structures 24a-24c could also be partially buried formed in the interior of the component 22, ie parts that are not first closed by the film 28 on the component surface 26. Furthermore, the channel structures 24a - 24c may also have holes or passages to an opposite side of the component 22.
  • Such a passage is exemplified by a dotted line in FIG Fig. 3 indicated at 40 in the bottom of the duct 32a.
  • This passage could, for example, serve as an outlet or inlet for a liquid if the channel structure 24a is to serve as a source of fluids or as an outlet.
  • the opening 40 could also be provided so that a sensor attachable to the underside of the component 22 can come into contact with the liquid in the chamber 32a to make a sensor measurement, such as electrochemical, potentiometric, amperometric, optical Measurement, a gravimetric or the like.
  • a sensor could already be installed prior to delivery of the microfluidic device 20 in the course of production or only be mounted after delivery to the customer.
  • the microfluidic device 20 it is possible for the microfluidic device 20 to be a disposable product, whereas the sensor is used multiple times.
  • the number of channel structures here is only three by way of example and may be more.
  • Fig. 4 now shows a side sectional view of the microfluidic device of Fig. 3 , As can be seen, the opening 34 in the film 28 is closed by a lid on a side opposite the component surface 26, the lid being a porous membrane 42.
  • the porous membrane 34 allows outgassing of excess air.
  • the porous membrane 42 may in particular consist of a material or have a surface which faces the opening 34 in the film 28, which with Water forms a contact angle greater than 90 ° or is water-repellent. Of course, the material could also be formed to additionally or alternatively form a contact angle greater than 90 ° with other materials.
  • the film 28 is made thin.
  • the porous membrane in addition to the reduction in size, it offers an advantage when the film is made thinner: due to the reduced in this region in contrast to the channel structures flow cross-section in the region between the membrane 42 and surface 26, locally increases the pressure , which promotes the outgassing through the membrane 42.
  • the flow area of the flow path in the area of the opening 34 is smaller than the average cross section of the channels of the channel structures (i.e., excluding the chambers), e.g. less than 80% or even less than 50% of the latter.
  • Fig. 3 shows that the film 28, the surface 26 over the whole or a part covered so that the channel structures 24a - 24c, as far as the opening to the surface 26 is concerned, are completely covered, this is not absolutely necessary.
  • the porous membrane 42 can be over the entire surface of the film 28 formed across or be attached to her, but it is of course also possible that it protrudes only slightly beyond the edge of the opening 34.
  • the film 20 may also have further openings 44.
  • aperture 44 is aligned with chamber 32c in the assembled condition.
  • Fig. 5a It is shown that the resulting upward opening can be used as an example to displace liquid contained in the chamber 32c therefrom. As in the example of Fig. 5a can be seen, this is a deformable membrane 46 provided to cover the opening 44 on a side facing away from the surface 26 of the film 28.
  • An actuator 48 is provided to urge the membrane into the opening 44 and the chamber 32c, respectively.
  • the actuator could be configured differently, such as by means of a piezoelectric element or the like, is in Fig.
  • a variant is shown, according to which the actuator 48 is mounted on a side facing away from the component 22 to the film 28 or the deformable membrane 46, so that on a side facing away from the opening 44 of the deformable membrane 46, a sealed chamber 50 is formed containing a substance, such as water, which is chemically converted from a liquid to a gaseous state by electrolysis by means of electrodes 52 located in the chamber 50, whereby the resulting density reduction and expansion is a force on the deformable membrane 46 exerts, which then bulges into the opening 44 and chamber 32 c inside and displaces liquid there.
  • the deformable membrane 46 is, for example, a flexible membrane that tends to return to its original state. As it is in Fig.
  • the actuator may be formed by a multilayer arrangement of multiple layers 54a and 54b, such as a multilayer board, such as a spacer layer 54b having a recess for the chamber 50 and a layer 54a having the electrodes 52 the spacer layer 54b is located between the layer 54a and the substrate 22.
  • a multilayer board such as a spacer layer 54b having a recess for the chamber 50 and a layer 54a having the electrodes 52 the spacer layer 54b is located between the layer 54a and the substrate 22.
  • Fig. 3 is indicated with a dashed line 56 that it is possible that the flexible membrane 46 and / or the multilayer assembly 54 is laterally located on one side only, whereas the other side of the line 56 is covered by the porous membrane 42.
  • Fig. 5b shows one to Fig. 5a alternative example.
  • the film 28 already has a sufficiently high ductility to be pressed by the actuator 48 in the direction of the chamber 32c in order to displace the liquid content located in the chamber 32c.
  • the opening 44 may be missing and the actuator 48 may be mounted directly on the film 28 on a side facing away from the component 22 thereof.
  • Fig. 6 shows an unclaimed alternative already mentioned above Fig. 3 , according to which a further component 56 is used as cover.
  • Fig. 6 shows Fig. 6 in that it is possible that the channel structures 24a-24c of a microfluidic device according to examples are not all provided in a single component 22, but that they are formed distributed in a plurality of components.
  • Fig. 6 shows by way of example therefore a modified component 22 ', which differs from the one Fig. 3 characterized in that the channel structure 24c in the component 22'mVM. Rather, this channel structure 24c is in the assembled state as shown in FIG Fig.
  • FIG. 6 is shown, mirror image of its original position in the component 22 'relative to the plane of the film 28 formed in the component 56, in a component surface 58 thereof, with which the component 56 to the component 22' opposite side of the film 28 added is.
  • the component 56 has, for example, the same dimensions as the component 42 ', that is, for example, also substrate-like or cuboid.
  • the opening 34 in the film 28 thus connects channel structures in different components 22 'and 56 respectively, namely the channel 30a with the channel 30c in the component 56.
  • FIG Fig. 6 Similar advantages with respect to the channel structure connection combinations can be achieved, as is the case in the exemplary embodiment of FIG Fig. 3 and 7, respectively, but with reference to FIG Fig. 4 has been described, the embodiment according to Fig. 3 offers the possibility of using a porous membrane, with the associated benefits in terms of outgassing, etc.
  • the channel structures 24a-24c which were to be combined in a combination manner, each had a trench 30a-30c which, at least over a section 60 (FIG. Fig. 7 ) parallel to one another, ie such that at least one channel runs parallel to another channel.
  • the individual channels project more or less into the section 60 from the two sides along the channel propagation direction 62.
  • This configuration allows elongated apertures in the film 28 having a longitudinal direction 64 transverse to the straight span direction 62 to more or less selectively interconnect the channel structures. The location of these openings 34 in the directions 62 and 64 and the length of the direction 64 of these openings then determines which channel structures are interconnected.
  • FIG. 8 An embodiment of a component 22 having five channel structures 24a-24e, each also having a trench 30a-30e extending across a portion 60 along the component surface 26, is parallel to one another, such that a plurality of channel structure combination options exist by forming an aperture 34 of the film over the component surface 26 is varied with a longitudinal direction 64 transverse to the trench extension direction 62 within the region 60 in position and length of the opening 34, as referenced in FIG Fig. 7 has been described.
  • Fig. 9a - 9d show four different combinations. Black arrows in the figures indicate channel structures which are interconnected via the respective opening 34. White arrows were used for channel structures that are kept separate from the connected channel structures.
  • trenches 30c and 30d it may be useful to collinearly guide some of the trenches of the channel structures, here trenches 30c and 30d, from opposite directions into region 60, with a gap 66 therebetween, with which they extend in the extension direction 62 from one another are spaced, wherein the gap 66 in the direction 62 is sufficiently large, for example, to accommodate the width of one of the elongated openings 34.
  • Fig. 9a - 9d Now show different layers of the opening 34 in the film 28. The openings 34 of Fig. 9a - 9d always connects three of the channel structures together, as shown in the figures.
  • Fig. 10 shows a to the embodiment of Fig. 8 - 9d similar embodiment of a microfluidic device. While in Fig. 10 the state is shown in which the film and a porous membrane are not mounted as a lid, show the Fig. 11 and 12 each state with foil, but without membrane or both.
  • Fig. 13 shows a sectional view in which the opening 34 can be seen in the film.
  • the embodiment of Fig. 10 - 13 corresponds to the embodiment of the Fig. 3 in the example / execution according to Fig. 4 and Fig. 5a and thus also shows an example such as a restriction of the lateral expansion area for the porous membrane 42 as indicated by the dashed line 56 in FIG Fig. 3 may also have been visualized.
  • Fig. 10 shows a to the embodiment of Fig. 8 - 9d similar embodiment of a microfluidic device. While in Fig. 10 the state is shown in which the film and a porous membrane are not mounted as a lid, show the Fig. 11 and
  • the film 28 extends over the entire surface on the upper side 26 of the component 22.
  • the porous membrane 42 extends only laterally in the interior of the recess in the multilayer arrangement of the actuator 48.
  • the actual actuator locations of the actuator 46 are in Fig. 10 - 13 not shown, but can for example like in Fig. 5a be designed shown.
  • a one-sided adhesive film can be used as the film, and the use of a double-sided adhesive film can be particularly advantageous.
  • a lid may be provided to close a channel open at this point.
  • This cover can also be designed in the form of a foil, as has been described above.
  • the lid can be limited laterally to the recess. He closes the recess from above.
  • the lid does not have to be completely closed here.
  • the lid may be formed by a porous membrane. This allows escape of possibly unwanted and possibly present in the duct system gas bubbles.
  • the porous membrane may also be formed of a material which is not wetted by the liquid. If the liquid is a water-based liquid, a membrane with a surface or a material with a low surface energy is particularly suitable here. Examples include fluoropolymers, such as PTFE, PVDF, etc.
  • the easy combinability of configurable fluidic connections and bubble trap represents a further advantage of some embodiments described above, since this only three parts are needed, namely the fixed component with channel system or reservoirs, the structured film and the cover membrane.
  • a liquid source which is not required to be separated.
  • a fixed microfluidic part such as e.g. one of the components 22 of the embodiments described above, contains a plurality of reservoirs, for a particular application, however, only a part thereof is needed. If, in such a case, all reservoirs were connected to each other by channels, then liquid could compress the air in these reservoirs and thus flow in the direction of these empty (because not required) reservoirs.
  • the problem can be solved in that the reservoirs are just not directly connected to the channel system, but, as described above, are first connected to each other via a "bridge" in the form of a recess with a film.
  • a "bridge" in the form of a recess with a film.
  • the chambers 32a, 32d and 32e are reservoirs and the chambers 32c and 32b are sensor sites, i. H. Places where sensors are positioned or can be positioned.
  • the above-mentioned reservoirs can also be provided with pumps.
  • Such pumps can be operated by electrolysis, as previously described.
  • the electrolysis thereby generates a gas, namely in the above-mentioned chamber 50, and deforms a membrane, namely the deformable membrane 46, which is adjacent to the respective reservoir is located.
  • the membrane can then warp into this reservoir and displace the fluid contained therein.
  • the liquid pumped from a reservoir by means of the electrolysis pump could be introduced into the empty (instead of outward / waste) container. air-shrouded) reservoir flow.
  • the only alternative to the above "separation" of the reservoir by means of suitable placement and design of the film according to the above embodiments would be only in the filling of the unused reservoirs, but this meant an additional material and manufacturing costs.
  • the membrane 46 which in this case is preferably not a porous membrane, but rather preferably a membrane which deforms plastically, for example, can be temporarily or permanently connected to two or more channels upon impact with a pressure in the direction of the fixed part or component 22 interrupt.
  • Fig. 14 shows such an alternative.
  • the deformable membrane 46 is used, above which in turn is an actuator 48.
  • the cross-section of the lateral path 70 through the opening 34 in the film 28 may be at least reduced or the path interrupted. Narrowing in the cross-section of the path 70 may often be sufficient.
  • Fig. 15 shows a further alternative to the embodiment of Fig. 14 ,
  • the component 22 "to the component of Fig. 3 formed differently, namely in that the area of the surface 26 between the channels 30a and 30c is lowered in the region of the opening 34 by a depth which is smaller than a depth of the trenches 30a - 30c, so that the flow resistance can be adjusted, which results when the membrane 46 is pressed and when the membrane 46 is not depressed.
  • an increase may be present.
  • FIGS. 14 and 15 achieve a valve effect.
  • Such a step may, for example, be done after filling a reservoir to close it.
  • the membrane 46 again dissolves from the component 22 or 22 "and the liquid can leave the reservoir in the channel system by means of the path 70 in the channel system.
  • the application of the membrane 46 with a pressure in the direction of the component 22 can also be used as an active valve, if, for example, directly or indirectly the Pressure of a gas pressure generated by the electrolysis is.
  • the interruption between the channels or the channel or the reservoir need not be complete, but may also be formed as a recess, which is, however, preferably shallower than the subsequent channel, as with reference to FIG Fig. 15 has been shown, ie by means of a flat portion in a channel of the channel structures.
  • Such a depression does not necessarily have to be present between separate channel structures in the sense of the channel structures 24a-24e of the preceding exemplary embodiments.
  • Such a depression in the trenches can also be present in the above-mentioned trenches 30a-30c within a single channel structure in order, as mentioned, to control the flow from a corresponding reservoir or into a corresponding reservoir.
  • microfluidic devices in which it was possible to form different microfluidic devices based on a fixed microfluidic part that is identical for all. It was possible, for example by two sensors and two fluid sources each one to connect via a bridge with the channel system and another liquid source. This was, for example, in the embodiments after Fig. 9a and 9d the case where unfilled arrows indicate that no liquid can flow here.
  • the above embodiments also show implementation variants, with a porous membrane as a bubble trap. Valves for closing, z. B. a reservoir may be present, as has been described above.
  • the above embodiments thus also describe a microfluidic system which has at least one part with fixed channel structures, wherein at least two channel structures in the stationary part initially have no connection to one another, the connection is instead produced by a foil which at least partially covers the channel structures, an opening connecting at least two of the unconnected channel structures in the stationary part.
  • Two channel structures not connected to one another in the stationary part can each lead to an alternatively populated position.
  • the microfluidic system may be designed such that two channel structures which are not connected to one another in the stationary part come from a different fluid source or reservoir.
  • non-interconnected channel structures there are at least four non-interconnected channel structures in the stationary part, three each of which can be connected by a recess in a foil to select one of two alternative sensor regions or two alternative liquid sources and to another liquid source connect.
  • at least five non-interconnected channel structures are present in the fixed part, of which three by means of a Recess may be connected in a film, wherein a solid fluid source is connected to one of two alternative sensor areas and one of two alternative fluid sources.
  • the film may be an adhesive tape, wherein the adhesive tape may in turn be an adhesive tape provided with an adhesive layer on both sides.
  • the recess in the film is closed with a lid. This lid has a porous membrane.
  • the material of this membrane may be made of a material or be coated with selbigem that forms a contact angle greater than 90 ° with the channel system liquid to be transported.
  • the porous membrane may be made of a water-repellent material, wherein the water-repellent material may also be a fluorine-containing polymer.
  • a membrane On the side facing away from the fixed part of the film, a membrane may be located, which can be at least partially pressed into the recess of the film by applying pressure. In this case, the necessary pressure for the deformation by electrolysis of water or at least partially water-containing liquid can be caused.
  • the above exemplary embodiments have shown a microfluid device with at least one component 22, in which or in which channel structures 24a are formed, which are at least partially open to a respective component surface 26 of the at least one component 22; and a film 28 having an opening 24; 34 ', via which at least a first and a second of the channel structures 24a, 24c; 24a, 24b are interconnected, and the at least one third of the channel structures at 24b; 24c of the respective component surface 26 at least partially closes, so that it does not over the opening 34; 34 'is connected to the first and second channel structure.
  • the first to third channel structure can be formed in the same component and at least partially open in the component surface thereof, the film covering the component surface of the same component such that the first and second channel structure extend laterally along the component surface of the same component and inside the opening in the film leading path are connected to each other, while the third channel structure is not adjacent to the opening.
  • the path leading within the opening 24 in the film can be closed on one side of the component 26 facing away from the same component 22 with a lid or with another of the at least one component.
  • the path leading through the opening in the film on a side remote from the component surface of the same component is closed by a deformable membrane as a cover.
  • the path leading through the opening 34 in the film 28 is on a side facing away from the component surface 26 of the same component 22 a porous membrane 42 is closed as a lid.
  • a porous membrane 42 is closed as a lid.
  • the path leading through the opening in the film on a side facing away from the component surface of the same component can be closed with a deformable membrane as a lid.
  • the microfluid device may further include an actuator for urging the deformable membrane into the opening.
  • the first to third channel structures 24a may have depressions in the component surface of the same component, which are at least partially covered by the film.
  • the recesses may include trenches 30a and / or wells 32a to form channels or chambers together with the foil.
  • the film is deformable, and the microfluid device further comprises an actuator for pressing the film into a recess of the at least one component on the respective component surface in which the recess is formed, wherein the recess is part of the channel structures.
  • the film 28 may be a self-adhesive film.
  • the film 28 may also be a self-adhesive film on both sides.
  • An actuator 48 may be configured to generate a force necessary for pressing by electrolysis of water or at least partially water-containing liquid.

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Claims (12)

  1. Dispositif microfluidique, avec:
    au moins un composant (22) dans lequel ou dans lesquels sont formées des structures de canal (24a) qui sont au moins partiellement ouvertes vers une surface de composant respective (26) de l'au moins un composant (22); et
    un film (28) présentant une ouverture allongée (24; 34') par l'intermédiaire de laquelle au moins une première et une deuxième des structures de canal (24a, 24c; 24a, 24b) sont connectées entre elles, dans lequel l'ouverture allongée est obturée par un couvercle d'un côté opposé à la surface du composant (26),
    dans lequel la première et la deuxième structure de canal sont formées dans le même composant et s'ouvrent, chacune, au moins partiellement dans la surface de composant, le film recouvrant la surface de composant du même composant de sorte que la première et la deuxième structure sont connectées entre elles par l'intermédiaire d'un trajet conduisant latéralement le long de la surface du même composant et à l'intérieur de l'ouverture allongée dans le film,
    dans lequel les structures de canal présentent, chacune, un segment de tranchée, et les segments de tranchée des structures de canal s'étendent parallèles entre eux au-delà d'un segment de longueur (60) le long d'une direction d'extension commune (62) dans la surface du même composant, dans lequel une direction longitudinale (64) de l'ouverture allongée (34; 34') s'étend transversalement à la direction d'extension commune (62), et dans lequel les structures de canal pénètrent d'une distance différente d'un et/ou de deux côtés dans le segment de longueur (60), de sorte qu'une variation de l'ouverture allongée (34) dans le film (28) conduise, dans sa position le long de la direction d'extension (62) et le long de la direction longitudinale (64) et dans sa longueur le long de la direction longitudinale (64), à au moins quatre combinaisons de connexions de structures de canal différentes,
    dans lequel, dans une combinaison de connexions de structures de canal, d'éventuelles troisièmes structures de canal formées dans le même composant que la première et la deuxième structure de canal, non connectées par l'intermédiaire de l'ouverture à la première et la deuxième structure de canal ne sont pas adjacentes à l'ouverture allongée,
    dans lequel les structures de canal (24a) présentent des creux dans la surface du même composant qui sont au moins partiellement recouverts par le film,
    dans lequel le film (28) est collé à la surface (26) du même composant (22);
    caractérisé par le fait que le trajet conduisant à travers l'ouverture allongée (34) dans le film (28) est obturé d'un côté opposé à la surface (26) du même composant (22) par une membrane poreuse (42) comme couvercle, et
    dans lequel le trajet conduisant à travers l'ouverture (34) dans le film (28) présente une section de flux réduite par rapport aux structures de canal, de sorte que par une augmentation de pression locale résultant de la section réduite soit favorisé le dégazage par l'intermédiaire de la membrane poreuse (42) qui n'est pas humidifiée par un liquide,
    dans lequel une épaisseur du film (28) à l'endroit de l'ouverture (34) est si faible qu'il est empêché que dans l'eau puissent passer des bulles de gaz sans contact avec la membrane poreuse (42).
  2. Dispositif microfluidique selon la revendication 1, dans lequel l'au moins un composant (22) est un composant moulé par injection.
  3. Dispositif microfluidique selon la revendication 1 ou 2, dans lequel l'épaisseur du film (28) est inférieure à 1 mm.
  4. Dispositif microfluidique selon l'une des revendications 1 à 3, dans lequel la membrane poreuse (42) est constituée d'un matériau ou présente une surface qui forme avec l'eau un angle de contact supérieur à 90°.
  5. Dispositif microfluidique selon l'une des revendications 1 à 4, dans lequel la membrane poreuse est constituée d'un polymère à teneur en fluor ou est revêtue de ce dernier.
  6. Dispositif microfluidique selon l'une des revendications 1 à 5, dans lequel la surface du même composant (22) est plane.
  7. Dispositif microfluidique selon l'une des revendications 1 à 6, dans lequel le film présente une autre ouverture (34') qui est obturée d'un côté opposé au même composant (22) par une membrane déformable (46), dans lequel le dispositif microfluidique présente par ailleurs un actionneur destiné à pousser la membrane déformable dans l'autre ouverture, dans lequel s'étend, au-dessous de l'autre ouverture, une partie plane de l'une de la première à la troisième structure de canal, de sorte que par la déformation puisse être réduit un débit de passage à travers la partie plane.
  8. Dispositif microfluidique selon l'une des revendications 1 à 5, dans lequel les creux comportent des tranchées (30a) et/ou des puits (32a) destinés à former, ensemble avec le film, des canaux ou des chambres.
  9. Dispositif microfluidique selon l'une des revendications 1 à 8, dans lequel la première à la troisième structure de canal (24a) ne présentent pas de connexion fluidique entre elles à l'intérieur au premier composant (22).
  10. Dispositif microfluidique selon l'une des revendications précédentes, dans lequel le film (28) est un film auto-adhésif.
  11. Procédé de fabrication d'un dispositif microfluidique, aux étapes suivantes consistant à:
    prévoir au moins un composant dans lequel ou dans lesquels sont formées des structures de canal qui sont ouvertes au moins partiellement vers une surface de composant respective de l'au moins un composant;
    prévoir un film présentant une ouverture;
    assembler l'au moins un composant et le film, de sorte qu'au moins une première et une deuxième des structures de canal soient connectées entre elles par l'intermédiaire de l'ouverture, et que le film obture au moins partiellement au moins une troisième des structures de canal sur la surface de composant respective, de sorte que cette dernière ne soit pas connectée par l'intermédiaire de l'ouverture avec la première et la deuxième structure de canal; et
    obturer l'ouverture allongée d'un côté opposé à la surface de composant (26) par un couvercle,
    dans lequel la prévision de l'au moins un composant est réalisée de sorte que la première à la troisième structure de canal soient formées, chacune, dans le même composant et s'ouvrent, chacune, au moins partiellement dans une surface de ce dernier, dans lequel l'assemblage présente un collage du film sur la surface du même composant, de sorte que la première et la deuxième structure de canal soient connectées entre elles par un trajet conduisant latéralement le long de la surface du même composant et à l'intérieur de l'ouverture dans le film,
    dans lequel les structures de canal présentent, chacune, un segment de tranchée, et les segments de tranchée des structures de canal s'étendent en parallèle jusqu'au-delà d'un segment de longueur (60) le long d'une direction d'extension commune (62) dans la surface du même composant, dans lequel une direction longitudinale (64) de l'ouverture allongée (34; 34') s'étend transversalement à la direction d'extension commune (62), et dans lequel les structures de canal pénètre d'un et/ou de deux côtés d'une distance différente dans le segment de longueur (60), de sorte qu'une variation de l'ouverture allongée (34) dans le film (28) conduise dans sa position le long de la direction d'extension (62) et le long de la direction longitudinale (64) et dans sa longueur le long de la direction longitudinale (64) à au moins quatre combinaisons de connexion de structures de canal différentes,
    dans lequel, dans une combinaison de connexion de structures de canal, des troisièmes structures de canal formées dans le même composant que la première et la deuxième structure de canal, éventuellement non connectées par l'intermédiaire de l'ouverture à la première et la deuxième structure de canal ne sont pas adjacentes à l'ouverture allongée,
    dans lequel les structures de canal (24a) présentent des creux dans la surface du même composant qui sont recouverts au moins partiellement par le film,
    caractérisé par le fait que le trajet conduisant à travers l'ouverture allongée (34) dans le film (28) est obturé d'un côté opposé à la surface (26) du même composant (22) par une membrane poreuse (42) comme le couvercle, et
    dans lequel le trajet conduisant à travers l'ouverture (34) dans le film (28) présente une section de flux réduite par rapport aux structures de canal, de sorte que par une augmentation de pression locale résultant de la section réduite soit favorisé le dégazage par l'intermédiaire de la membrane poreuse (42) qui n'est pas humidifiée par un liquide,
    dans lequel une épaisseur du film (28) à l'endroit de l'ouverture (34) est si faible qu'il est empêché que dans l'eau puissent passer des bulles de gaz sans contact avec la membrane poreuse (42).
  12. Procédé selon la revendication 11, dans lequel le film est un film auto-adhésif et le collage présente uniquement une application du film sur la surface du même composant.
EP12179918.3A 2010-11-24 2011-11-23 Dispositif microfluidique et son procédé de fabrication Active EP2522427B1 (fr)

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DE102020135053B4 (de) 2020-12-29 2022-12-15 Biflow Systems Gmbh Mikrofluidikvorrichtung mit Reststoffbehälter und Analysesystem

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DE102010061910A1 (de) 2012-05-24
EP2522427A1 (fr) 2012-11-14

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