EP2834005B1 - Dispositif capillaire pour récipient pour réactif et l'utilisation - Google Patents

Dispositif capillaire pour récipient pour réactif et l'utilisation Download PDF

Info

Publication number
EP2834005B1
EP2834005B1 EP13705186.8A EP13705186A EP2834005B1 EP 2834005 B1 EP2834005 B1 EP 2834005B1 EP 13705186 A EP13705186 A EP 13705186A EP 2834005 B1 EP2834005 B1 EP 2834005B1
Authority
EP
European Patent Office
Prior art keywords
capillary
liquid
capillary structure
force
pressure
Prior art date
Legal status (The legal status 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 status listed.)
Active
Application number
EP13705186.8A
Other languages
German (de)
English (en)
Other versions
EP2834005A1 (fr
Inventor
Martina Daub
Guenter Roth
Nils Paust
Juergen Steigert
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Robert Bosch GmbH
Original Assignee
Robert Bosch GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Robert Bosch GmbH filed Critical Robert Bosch GmbH
Publication of EP2834005A1 publication Critical patent/EP2834005A1/fr
Application granted granted Critical
Publication of EP2834005B1 publication Critical patent/EP2834005B1/fr
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5021—Test tubes specially adapted for centrifugation purposes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0406—Moving fluids with specific forces or mechanical means specific forces capillary forces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0409—Moving fluids with specific forces or mechanical means specific forces centrifugal forces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0688—Valves, specific forms thereof surface tension valves, capillary stop, capillary break

Definitions

  • the invention relates to a revolver component for a reagent vessel. Likewise, the invention relates to a reagent vessel. Furthermore, the invention relates to a method for centrifuging a material and to a method for pressure-treating a material.
  • the device constructed in the format of a standard centrifuge tube may comprise various turrets which are arranged axially one above the other.
  • the turrets may include channels, cavities, reaction chambers, and other structures for performing fluidic unit operations.
  • An integrated ballpoint pen mechanism allows the turrets to be rotated with respect to their positions relative to one another, as a result of which the structures of the revolvers can be switched to one another.
  • An update of the ballpoint pen mechanism is triggered after inserting the device in a centrifuge by means of a centrifugal force caused by the operation of the centrifuge. At the same time, liquids can be transferred along the force vector of the centrifugal force produced.
  • a rotor assembly with a rotatable plate described.
  • sample chambers are formed, which are connected to each other via channels.
  • a transfer mechanism should be feasible, by means of which a sample, such as a blood sample, and at least one chemical reacting therewith should be transferable between the different sample chambers.
  • a capillary system for controlling an ink flow in an ink cartridge of a printer described.
  • the ink cartridge has two interconnected chambers, of which a first chamber is filled with the liquid ink and a second chamber with an ink-absorbent material.
  • the invention provides a revolver component for a reagent container having the features of claim 1, a reagent container for a centrifuge and / or for a pressure varying apparatus having the features of claim 8, a method for centrifuging a material having the features of claim 9 and a method for pressure treatment a material having the features of claim 11.
  • the capillary force brought about by the at least one capillary structure can be used to transfer the at least one liquid within the at least one vessel structure out of the at least one vessel structure and / or into the at least one vessel structure of the revolver component.
  • a liquid transport against a centrifugal force caused by the operation of a centrifuge and / or against a pressure force caused by an operation of a pressure-varying device can be realized.
  • the capillary force of the at least one capillary structure can also be advantageously used to temporarily store the at least one liquid.
  • the at least one capillary structure in and / or on the revolver component is thus an advantageous control component for controlling a liquid transport of the at least one liquid and / or storing the at least one liquid.
  • the at least one capillary structure can also be used as a passive valve structure and / or passive mixing component for mixing liquids.
  • the at least one capillary structure and / or in the revolver component can thus be used for a variety of uses.
  • the at least one capillary structure has an average diameter in a range between 0.1 ⁇ m to 1 mm.
  • the at least one average diameter can be in particular in a range between 1 .mu.m to 100 .mu.m. This ensures a sufficiently high capillary force of at least one Capillary structure, by means of which the at least one liquid (optionally) can be sucked into the internal volume of the at least one capillary structure.
  • the at least one capillary structure can be formed from glass, silica, a polymer, a fabric material and / or a gel.
  • the at least one capillary structure is thus relatively simple and inexpensive executable.
  • the at least one capillary structure is coated on its at least one inner wall with proteins, antigens, antibodies, enzymes, DNA partial strands, RNA partial strands and / or epoxy resin.
  • proteins, antigens, antibodies, enzymes, DNA partial strands, RNA partial strands and / or epoxy resin are used as a transfer of the at least one liquid through the at least one Capillary structure and / or a buffering of the at least one liquid in the at least one capillary structure.
  • biochemical / molecular biological reactions can be carried out targeted.
  • the at least one capillary structure is thus versatile.
  • the capillary force which can be exerted by means of the at least one capillary structure is greater than a weight force of the at least one liquid which can be filled or filled into the at least one vessel structure.
  • the at least one capillary structure can thus be used to transfer the at least one liquid counter to the weight force and / or to buffer it in spite of the weight force.
  • the revolver component has a revolver outer wall, which is designed such that the revolver component can be inserted in a reagent vessel for a centrifuge and / or for a pressure-varying device.
  • the turret component can be used in an insert part housing of a reagent vessel insertion part, which is designed such that the reagent vessel insertion part can be inserted in a reagent vessel for a centrifuge and / or for a pressure-varying device.
  • the revolver component can thus be advantageously used during centrifuging, applying an overpressure and / or applying a negative pressure.
  • the at least one liquid sucked into the at least one capillary structure by means of the capillary force can be pressed out of the capillary structure in a simple manner.
  • the pressing out of the at least one liquid can be carried out by means of the centrifugal force and / or by means of the compressive force, without the (at least) changing the shape of at least one capillary structure, the suction process and / or the pressing process can be repeated as often as desired (reversible).
  • the at least one capillary structure is therefore both a passive valve structure for switching Liquids, as well as a passive mixing component for mixing liquids.
  • the at least one vessel structure comprises in each case at least one first chamber with a filling and / or pressure compensation opening and a second chamber which is air-tight and / or liquid-tight except for a liquid exchange opening to the first chamber, wherein the at least one Capillary structure is formed in a formed as a spongy mass capillary system, which is arranged in the second chamber.
  • a reagent vessel insertion part which has an insertion part housing which is designed such that the reagent vessel insertion part can be inserted in a reagent vessel for a centrifuge and / or for a pressure-varying device, and which at least one having in the Einskyeilgetude arranged turret component according to the technology of the invention.
  • a reagent vessel for a centrifuge and / or for a pressure varying device with at least one turret component arranged in the reagent vessel according to the technology according to the invention.
  • the method has the additional steps: at least one temporary reduction of the current rotational speed to a second desired rotational speed, which causes a second centrifugal force less than the capillary force of the at least one capillary structure, whereby the material to be centrifuged and / or the other Liquid are at least partially sucked into the at least one capillary structure, and increasing the current rotational speed to a third target rotational speed, which causes a third centrifugal force greater than the capillary force of the at least one capillary structure.
  • the method may have the additional steps: At least one adjustment of the lower or Overpressure in the direction of the atmospheric pressure to a second desired pressure, which causes a second pressure force less than the capillary force of the at least one capillary structure, whereby the material and / or the other liquid are at least partially sucked into the at least one capillary structure, and reinforcing the or excess pressure away from the atmospheric pressure to a third target pressure which causes a third pressure force greater than the capillary force of the at least one capillary structure.
  • Fig. 1a and 1b show schematic representations of a first embodiment of the revolver component.
  • the revolver component 10 may have a turret outer wall 12, which is designed so that the revolver component 10 can be inserted in a reagent vessel for a centrifuge and / or for a pressure-varying device.
  • the turret component 10 may be insertable in an insert part housing of a reagent vessel insert which is adapted for insertion of the reagent vessel insert into a reagent vessel for a centrifuge and / or pressure varying device.
  • the applicability of the turret member 10 / of the reagent vial inserter to the subject reagent vial for a centrifuge and / or a pressure varying device may be interpreted as meaning that the turret outer wall 12 / an outer wall of the insert member housing corresponds to an inner wall of the reagent vial.
  • the turret outer wall 12 / the outer wall of the Einassieilgephinuses contacted the inner wall of the reagent vessel such that even during operation of the centrifuge and / or the Druckvariiervorraum a reliable hold of the turret member 10 / the Reagenzgefäß insertion is ensured in the relevant reagent vessel.
  • the reagent vessel can be understood to mean a (standard) test tube / test tube. Further embodiments are centrifuge tubes, 1.5 ml Eppendorf tubes, 2 ml Eppendorf tubes, 5 ml Eppendorf tubes and microtiter plates, such as 20 ⁇ l microtiter plates (per well).
  • the reagent vessel can be a test carrier or a disposable cartridge, which are designed as a lab-on-a-chip system on a plastic-plastic-sized plastic substrate.
  • the formability of the reagent vessel is not limited to the examples listed here.
  • the dimensions of the reagent vessel are predetermined only due to a desired usability of the reagent vessel in the centrifuge and / or in the Druckvariiervoriques. The feasibility of the technologies according to the invention described below however, does not prescribe any external shape of the reagent vessel.
  • the reagent vessel can be designed to receive samples in an amount which can be chosen optionally from a range of a few ⁇ L up to 1L.
  • the technology according to the invention can be used by means of any centrifuge, by means of which a (minimum) centrifugal force can be exerted from 20 g.
  • the technology according to the invention can be used for any pressure-varying device, by means of which an underpressure and / or overpressure can be applied.
  • the revolver component 10 can be understood in particular a turret for a reagent vessel.
  • the turret component 10 may be designed, for example, such that it can be rotated about an axis of rotation 11 by means of a suitable mechanism which can be arranged on the turret component 10 or separately from the turret component 10.
  • the axis of rotation 11 may, in particular, run centrally through the revolver component 10 and / or be aligned perpendicular to the at least one vessel bottom.
  • the revolver component 10 / the reagent vessel insertion part can also be designed for interaction with a ballpoint pen mechanism or comprise a ballpoint pen mechanism.
  • the turret member 10 / reagent vial insert may hold a volume less than 5 milliliters.
  • the revolver component 10 can thus be designed in particular such that it can be integrated in a stack of further revolvers and / or reaction chambers.
  • turrets, reaction chambers and / or cavities axially stacked one above the other
  • azimuthally relative to one another With regard to a possible execution of the ballpoint pen mechanism is on the DE 2010 003 223 A1 directed.
  • At least one vessel structure 14, into which at least one liquid 16 can be filled or filled, is formed on the revolver component 10.
  • the at least one liquid 16 may be, for example, a material / sample material to be examined and / or at least one chemical.
  • the turret component 10 described below is not limited to the use of certain liquids.
  • a plurality of vessel structures 14 may be formed on the turret component 10, which extend from the axis of rotation 11 radially to the turret outer wall 12.
  • the practicability of the revolver component 10 is not limited to a specific shape of the at least one vessel structure 14 and / or a certain number of vessel structures 14 of the turret component 10.
  • the revolver component 10 has at least one capillary structure 18 arranged on and / or arranged in the at least one vessel structure 14, by means of which a capillary force can be exerted on the at least one liquid 16.
  • the at least one liquid 16 is at least partially sucked into an internal volume 20 of the at least one capillary structure 18.
  • the at least one capillary structure 18 allows at least temporary storage of the at least one liquid 16 sucked therein.
  • the at least one capillary structure 18 can thus result in liquid transport of the at least one liquid 16 within the at least one vessel structure 14, out of the at least one vessel structure 14, and or in which at least one vessel structure 14 are used.
  • the at least one capillary structure 18 is an advantageous storage component for storing / buffering the at least one liquid 16, even without the at least one capillary structure 18 having a mechanical / adjustable element.
  • the at least one capillary structure 18 has an average diameter which lies in a range between 0.1 ⁇ m to 1 mm.
  • the average diameter of the at least one capillary structure 18 may be in a range between 1 ⁇ m to 500 ⁇ m, preferably between 1 ⁇ m and 100 ⁇ m. This can also be described in such a way that the at least one capillary structure 18 has a pore size in a range between 0.1 ⁇ m to 1 mm.
  • the at least one capillary structure 18 may be formed, for example, of glass, silica, a polymer such as polyester, polypropylene, polytetrafluoroethylene, nylon, and / or polyvinylidene fluoride, a fabric cloth, and / or a gel.
  • the at least one capillary structure 18 may be formed in particular as a glass filter.
  • the designability of the at least one capillary structure 18 is not limited to the materials listed here.
  • the at least one capillary structure 18 may also be formed from a turret material of the turret component 10.
  • the manufacturability of the at least one capillary structure is not on the one-piece forming the at least one Capillary structure 18 is limited to the turret component 10 by means of a casting process or an injection molding process.
  • the revolver component 10 can also first be formed without the at least one capillary structure 18 and then be equipped with the at least one capillary structure 18.
  • the at least one capillary structure 18 can also have a continuous, discontinuous and / or defined geometry.
  • the at least one capillary structure 18 may have, for example, a round channel cross section, a quadrangular channel cross section and / or a polygonal channel cross section.
  • the at least one capillary structure 18 can be used individually or as a bundle.
  • the revolver component can also have a capillary system of flow, filter, columnar and sponge-like capillary structures 18.
  • the turret member 10 may be made in one piece by means of a casting method or an injection molding method despite its advantageous usability.
  • the turret component 10 is thus inexpensive to produce.
  • the internal volume of the turret member 10 / reagent vial insert may be at least partially made of a polymer, e.g. from COP, COC, PC, PA, PU, PP, PET and / or PMMA. Other materials are also suitable for forming the interior volume of the turret member 10 / reagent vial insert.
  • the at least one capillary structure 18 is coated on its at least one inner wall 22 with proteins, antigens, antibodies, enzymes, DNA partial strands, RNA partial strands and / or epoxy resin. This can also be described as an immobilization of the at least one inner wall 22 of the at least one capillary structure 18 with biological probes.
  • proteins, antigens, antibodies, enzymes, DNA partial strands, RNA partial strands and / or epoxy resin This can also be described as an immobilization of the at least one inner wall 22 of the at least one capillary structure 18 with biological probes.
  • enzymatic reactions and / or or DNA hybridizations are performed during insertion of the at least one capillary structure 18 for transferring / transporting, buffering, storing, retaining and / or mixing the at least one liquid 16 biochemical / molecular biological reactions, in particular specific protein and / or DNA bonds.
  • enzymatic reactions and / or or DNA hybridizations are performed.
  • unspecific bindings can be prevented
  • the at least one inner wall 22 of the at least one capillary structure 18 may also be coated / modified such that its wetting properties and / or its contact angle cause a particularly high capillary force on the at least one liquid 16.
  • the at least one inner wall 22 of the at least one capillary structure 18 may be highly hydrophilic due to its coating / modification.
  • the at least one inner wall 22 of the at least one capillary structure 18 can have a comparatively high roughness for this purpose.
  • the capillary force exerted by means of the at least one capillary structure 18 (on the at least one liquid 16) is greater than a weight of the at least one liquid 16 which can be filled or filled in the at least one vessel structure 14.
  • the at least one at least partially sucked into the at least one capillary structure 18 Liquid 16 can be effected by means of a centrifugal force which can be effected during operation of the centrifuge, in whose rotor device the reagent vessel is arranged with the revolver component 10 inserted therein, and / or by means of a centrifugal force during operation of the pressure varying device in which the reagent vessel with the revolver component 10 inserted therein is arranged; be effected compressive force from the at least one capillary 18 out transferable.
  • the capillary force which can be exerted on the at least one liquid 16 by means of the at least one capillary structure 18, corresponds to a centrifugal acceleration of at most 1000 g, at most 500 g, in particular at most 200 g.
  • the at least one liquid 16 sucked into the at least one capillary structure 18 can be pressed out again in a simple manner. In this way, the at least one liquid 16 temporarily stored in the at least one capillary structure 18 can easily be transferred out of this again.
  • the at least one capillary structure 18 is formed as a curved capillary.
  • the at least one capillary structure 18 has an intake opening 24 and an outlet opening 26, wherein the outlet opening 26 is set back relative to a direction of action 28 of a centrifugal force which can be effected by means of a centrifuge and / or a compressive force which can be effected by means of a pressure varying device. If no centrifugal force and / or pressure force greater than the capillary force is exerted on the liquid 16 sucked into the at least one capillary structure 18, the inner volume 20 of the at least one capillary structure 18 is with the filled at least one liquid 16.
  • the at least one capillary structure 18 makes it possible to suck the at least one liquid 16 against a direction of action 28 of the centrifugal force which can be effected by means of a centrifuge and / or the pressure force which can be effected by means of a pressure-varying device.
  • the actuation force which can be effected as a centrifugal force and / or pressure force, is smaller than the capillary force, the at least one liquid 16 can be reliably sucked into the at least one capillary structure 18.
  • the advantageous shape of the at least one capillary structure 18 effects a first liquid flow 30 of a first quantity of liquid emerging from the respective suction opening 24 the at least one capillary structure 18 is pressed out, and a second fluid flow 32 of a second fluid quantity, which leaves the at least one capillary structure 18 through the respective outlet opening 26.
  • the first quantity of liquid corresponds to a first partial volume of the at least one capillary structure 18, which extends from the respective intake opening 24 to a (virtual) parting plane 34.
  • the respective separating plane 34 intersects the associated capillary structure 18 at a point 36 which is directed furthest towards the direction of action 28 and which can also be rewritten as a high point of the respective capillary structure 18.
  • the second liquid quantity is defined by a second partial volume of the at least one capillary structure 18, which extends from the respective outlet opening 26 to the parting plane 34.
  • the first subvolume and the second subvolume may together provide the interior volume 20 of the at least one capillary structure 18.
  • the embodiment described here of the at least one capillary structure 18 provided that the second quantity of liquid flowing out of the outlet opening 26 is again introduced into a common vessel with the first quantity of liquid emerging from the suction opening 24, can be used as a mixer. It is pointed out in particular that the at least one advantageous capillary structure 18 permits a passive mixing of the at least one liquid 16 even without a mechanical / adjustable element or without a movable part.
  • the at least one capillary structure 18 can also be used for measuring a defined amount of liquid and for transporting the defined amount of liquid into a desired target volume. Since the volume and / or the shape of the at least one capillary structure can be used to precisely define the first quantity of liquid and the second quantity of liquid, it is thus possible by means of FIGS Fig. 1a and 1b illustrated embodiment, liquid volumes (exactly) measured and, if desired, be directed into separate chambers.
  • the at least one capillary structure 18 designed as a riser capillary can also have a plurality of outlets in order to meter off a plurality of partial volumes in parallel. (By means of such a riser capillary also a mixing efficiency can be increased).
  • At least one channel, at least one cavity and / or at least one reaction chamber may be formed in the revolver component 10 / a reagent vessel insertion part equipped therewith.
  • Process steps and structures, such as, for example, sedimentation structures, channel structures or siphon structures for forwarding and switching at least one liquid contained in the revolver component 10 / the reagent vessel insertion part can be integrated in the inner volume of the revolver component 10 / of the reagent vessel insertion part.
  • At least one further subunit of the inner volume of the revolver component 10 / of the reagent vessel insertion part can be filled with at least one liquid as a "storage container" which contains at least one chemical reaction and / or with a subsequently filled, to be processed and / or examined material / sample material performs a biochemical / molecular biological process.
  • the at least one "reservoir” may e.g. with chemicals (e.g., buffers), enzymes, lyphilisates, beads, dyes, antibodies, antigens, receptors, proteins, DNA strands, and / or RNA strands.
  • the turret member 10 / reagent vial insert may also be equipped with additional components such as valves and / or pumps.
  • the technology according to the invention can also interact with a multiplicity of conventional actuation, detection and / or control units.
  • Fig. 2a to 2c show schematic representations of a second embodiment of the revolver component.
  • turret component 10 shown schematically has a capillary system 40 instead of a limited number of capillary structures in which a plurality of capillary structures is formed.
  • the capillary system 40 may be formed, for example, as a filter.
  • Fig. 2a shows the turret component 10 immediately after filling the at least one liquid 16 through a filling opening 42 of the at least one vessel structure 14 of the turret component 10. The at least one liquid 16 contacts the capillary system 40, which is formed in the respective vessel structure 14 chamber 44 from the filling opening 42 demarcates.
  • the at least one liquid 16 is then sucked into the capillary system 40, wherein the capillary force prevents leakage of the at least one liquid 16 into the chamber 44 (despite a weight force of the at least one liquid 16) Fig. 2b ).
  • the at least one liquid 16 is thus incubable, the capillary system 40 being usable as incubation chamber / reaction chamber.
  • the capillary force which can be exerted by means of the capillary system 40 can be greater than the weight force of the at least one aspirated liquid 16.
  • the achievable capillary force may be greater than a centrifugal force and / or compressive force below a predetermined threshold.
  • 40 incubation times can be maintained by means of the capillary system, which can optionally have a duration of a few milliseconds to minutes or hours. Only an actuation force Fa which is greater than the capillary force which can be effected by the capillary system 40 on the at least one aspirated liquid 16 results in the at least one liquid 16 exiting the capillary system 40, whereby the at least one liquid 16 is transferred into the chamber 44 ( Fig. 2c ).
  • the capillary system 40 thus enables a sequential (optional) switching of a liquid flow, which is directed from the filling opening 42 into the chamber 44.
  • the at least one liquid for a definable / defined holding time which may be in the range of a few milliseconds to hours, are temporarily stored in the capillary system 40.
  • the storage mechanism of the capillary system can be used without a mechanical opening or closing mechanism. Therefore, due to its cost-effective manufacturability, the capillary system 40 is an advantageous alternative to a mechanical opening or closing mechanism.
  • the capillary system 40 can also be used as a pressure and / or flow restrictor with increased fluidic resistance.
  • Fig. 3a and 3b show schematic representations of a third embodiment of the revolver component.
  • turret component 10 is filled after sucking the at least one first liquid 16 into the capillary system 40 through the at least one filling opening 42 with at least one second liquid 46. Due to the increased hydrostatic pressure which is exerted on the at least one first liquid 16 by means of the at least one second liquid 46, the at least one first liquid 16 can be displaced from the capillary system 40, which is filled with the at least one second liquid 46.
  • a centrifugal force / pressure force can be used to assist.
  • the at least one second liquid 46 is preferably selected so that the capillary force which can be exerted thereon by means of the capillary system 40 is greater than the comparatively small centrifugal force / pressure force. Thus, penetration of the at least one second liquid 46 into the chamber 44, into which the at least one first liquid 16 is filled, can be prevented.
  • Fig. 4a to 4c show schematic representations of a fourth embodiment of the revolver component.
  • Revolver component 10 (shown at least partially) has at least one vessel structure 14, which in each case comprises at least one first chamber 50 with a filling and / or pressure equalization opening 52 and a second chamber 54, the second chamber 54 except for a liquid exchange opening 56, via which is hydraulically connected to the first chamber 50, air and / or liquid-tight is completed.
  • the at least one capillary structure 18 is formed in a capillary system 40 formed as a sponge-like mass, which is arranged in the second chamber 54.
  • Fig. 4a shows the turret component 10 immediately after filling the at least one liquid 16, for example by the filling and / or pressure equalization opening 52.
  • the at least one liquid 16 is sucked up relatively quickly by the capillary 40 after its filling. This can lead to (almost) complete filling of the second chamber 54. For example, in this way, the first chamber 50 (almost) completely emptied.
  • the turret member 10 is insertable (in a reaction vessel) so that the liquid exchange port 56 during operation of the centrifuge / Pressure Variation device connects a directed in the direction of the Aktuationskraft Fa portion of the first chamber 50 with an aligned in the direction of the Aktuationskraft Fa portion of the second chamber 54.
  • the advantage described below is also ensured if the first chamber 50 is aligned with respect to the second chamber 55 in the direction of the actuation force Fa.
  • orientation of a partial region in the direction of the actuation force Fa can be understood to mean that the partial region is aligned relative to a remaining region of the associated chamber 50 or 54 to the tip of a vector representing the actuation force Fa
  • the vector reproducing the actuation force Fa extends from the second chamber 54 to the first chamber 50.
  • an actuation force Fa less than the capillary force Fk of the capillary system 40 which can be exerted on the at least one liquid 16 sucked into the capillary system 40 by means of an operation of a centrifuge and / or a pressure-varying device, does not emptying the capillary system 40 starting from an actuation force Fa greater than the capillary force Fk, the at least one liquid 16 previously sucked in by the capillary system 40 is ejected (see FIG Fig. 4c ). In this way, by means of the interaction of the forces Fa and Fk fluidic unit operations can be realized.
  • the capillary system 40 can be used as a valve controlled in a closed state.
  • the valve can be controlled in its open state. Reducing the actuation force Fa again below the capillary force Fk can lead to (reversible) control / switching of the valve into its closed state.
  • the threshold value at which the valve can be controlled from a closed state to an open state is optionally comparatively low or comparatively high.
  • a threshold value of 20 g can be set by means of a spongy capillary system 40. By applying a coating / modification on the inner walls of the capillary system 40, this threshold can be increased to 5000 g.
  • Fig. 5a to 5c show schematic representations of a fifth embodiment of the revolver component.
  • Revolver component 10 (partially) shown partially schematically has a further third chamber 58 as a development compared to the previous embodiment, which is air-tight and / or liquid-tight except for a liquid exchange opening 60, via which third chamber 58 is hydraulically connected to first chamber 50 is completed.
  • a further capillary system 40 which may be formed according to the embodiments described above, also arranged.
  • the turret component 10 described here has an obstacle structure 62, which is arranged between the filling and / or pressure equalization opening 52 and the two liquid exchange openings 56 and 60.
  • the obstacle structure 62 may be formed, for example, as a sieve.
  • the at least one liquid 16 After filling at least one liquid 16 in the first chamber 50 through the filling and pressure equalizing opening 52 (see Fig. 5a ), the at least one liquid 16 is sucked into the two capillary systems 40. If no actuation force Fa is exerted on the at least one liquid 16, which is greater than the capillary force Fk of the capillary systems 40, the in Fig. 5b schematically reproduced suction 64 performed continuously and the at least one sucked liquid 16 is stored in the two capillary 40. However, if the actuation force Fa exerted on the at least one aspirated liquid 16 exceeds the capillary force Fk of the two capillary systems, the at least one liquid 16 is ejected from the capillary systems 40 into the first chamber 50.
  • the capillary 40 can be reliably used as a long-term storage of at least one liquid 16. This can be used, for example, when loading the turret component 10 with different liquids.
  • a sample may be aspirated in the second chamber 54 while the remainder of the process liquid is stored as a waste liquid in the third chamber 58. Since process liquids are typically highly wetting, contamination of the sample can be reliably prevented by preventing backflow of the waste liquid from the chamber 58 by aspirating the waste liquid into the capillary system 40 disposed therein.
  • the capillary system 40 of the chamber 58 therefore functions similarly to a suction sponge or superabsorber.
  • the capillary system 40 can be designed to be elastic.
  • the capillary system 40 may be compressible.
  • the at least one aspirated liquid 16 can not only be ejected out of it by means of deforming / compressing the at least one capillary system 40, but can also be actively pressed out. This effect can be amplified by attaching at least one additional mass to one end of the capillary system 40 opposite the direction of the actuation force Fa / radially inward end.
  • the squeezing out of the liquid 16 aspirated by the at least one capillary system 40 can also take place actively by an additional integration of further actuators or actuation mechanisms, which are designed, for example, magnetically, electromagnetically, electrostatically, piezoelectrically, pneumatically and / or hydraulically.
  • further actuators or actuation mechanisms which are designed, for example, magnetically, electromagnetically, electrostatically, piezoelectrically, pneumatically and / or hydraulically.
  • the at least one Obstacle structure 62 Due to the periodic loading and ejection and / or squeezing out of the capillary system 40 and the resulting liquid stream 66, at least two liquids 16 can be mixed.
  • the mixing efficiency can be further increased.
  • the at least one obstacle structure 62 may be both fixed in the revolver component 14 and movable.
  • Fig. 6 shows a schematic representation of an embodiment of the Reagenzgefäß insert part.
  • the reagent vessel insertion part 70 shown schematically has an insertion part housing 72, which is designed so that the reagent vessel insertion part 70 can be inserted in a reagent vessel for a centrifuge and / or for a pressure-varying device.
  • the applicability of the reagent vessel insertion part 70 into the relevant reagent vessel for a centrifuge and / or a pressure-varying device can be interpreted such that an outer wall 74 of the insertion part housing 72 corresponds to an inner wall of the reagent vessel.
  • the outer wall 74 of the Einassieilgephases 72 contacts the inner wall of the reagent vessel such that even during operation of the centrifuge and / or Druckvariiervorraum a reliable hold of the Reagenzgefäß-inserting part 70 is ensured in the relevant reagent vessel.
  • the reagent vessel cooperating with the reagent vessel insertion part 70 is not limited to these.
  • the reagent vessel insertion part 70 includes at least one turret member 10a, 10b, and 10c disposed in the insertion part housing 72.
  • the at least one revolver component 10 a, 10 b and 10 c is designed so that it is rotatable about the axis of rotation 11.
  • at least one turret component 10a, 10b and 10c is also adjustable along the axis of rotation 11 (lateral). In this way, a distance between adjacent turret components 10a, 10b and 10c can be varied.
  • the lateral adjustability of the at least one turret component 10a, 10b and 10c is, for example, by means of a ball-point pen mechanism 76, which in FIG Fig. 6 is shown only schematically, effected.
  • a ball-point pen mechanism 76 which in FIG Fig. 6 is shown only schematically, effected.
  • Components of the ballpoint pen mechanism may for example be formed as part of the first turret component 10a and / or the second turret component 10b.
  • a deformable polymer / elastomer can be used to provide a restoring force, which causes a return of the at least one turret component 10a, 10b and 10c in a predetermined initial position / initial position.
  • a compressible material such as a polymer
  • a stretchable material which generates a tensile force which, as the restoring force, causes the at least one turret component 10a, 10b and 10c to be returned to a starting position / starting position.
  • a reagent vessel insertion part according to the technology according to the invention also apply to a reagent vessel for a centrifuge and / or a pressure varying device, which is designed in accordance with the described reagent vessel insertion parts.
  • the advantageous reagent vessel has an outer wall which is designed so that the reagent vessel can be used in a centrifuge and / or in a pressure-varying device.
  • the reagent vessel is designed so that a reliable hold of the reagent vessel is ensured in the operated centrifuge and / or in the operated Druckvariiervorraum.
  • a reagent vessel for a centrifuge and / or a pressure variegating device can thus be understood to mean a reagent vessel which, due to its (outer) shape, lends itself well to operation of the centrifuge with a comparatively high rotational speed and / or for application of a pressure deviating greatly from the atmospheric pressure - And / or negative pressure by means of Druckvariiervoriques.
  • the advantageous reagent vessel may include vascular structures, such as channels, reaction chambers, storage chambers, and / or active components, such as e.g. Have valves and / or pumps.
  • the reaction vessel may comprise actuation, detection and control units.
  • FIG. 10 is a flow chart for explaining an embodiment of the method for centrifuging a material.
  • a method step S1 the material to be centrifuged is introduced into a reagent vessel with a turret component inserted therein.
  • the revolver component which can also be introduced into the reagent vessel after the material has been introduced, is equipped with the advantageous technology.
  • the turret components described above may be used to carry out the method. The feasibility of the method described here is not limited to the onset of these turret components.
  • a centrifuge is operated at a current rotational speed corresponding to a first desired rotational speed which causes a first centrifugal force on the material to be centrifuged and / or another liquid filled in the reagent vessel, which is greater than the capillary force of the at least one capillary structure , As a result, the material to be centrifuged and / or the other liquid are at least partially transferred out of the at least one capillary structure.
  • the method also includes the method steps S2 and S3, which are each carried out at least once.
  • the current rotational speed is temporarily reduced to a second desired rotational speed, which causes a second centrifugal force smaller than the capillary force of the at least one capillary structure, whereby the material to be centrifuged and / or the other fluid at least partially into the at least one capillary structure be sucked in.
  • the current rotational speed is increased to a third desired rotational speed, which causes a third centrifugal force greater than the capillary force of the at least one capillary structure.
  • a repeated execution of the method steps S2 and S3 can be used for mixing a plurality of liquids and / or for pumping liquid against the centrifugal force.
  • FIG. 10 is a flow chart for explaining an embodiment of the method for pressure-treating a material.
  • the material to be treated by means of an underpressure or an overpressure for example a sample material, is introduced into a reagent vessel with a turret component inserted therein (process step S10).
  • a turret component inserted therein (process step S10).
  • the turret components described above may be used to carry out the method.
  • the feasibility of the method described here is not limited to the onset of these turret components.
  • a negative pressure or superatmospheric pressure corresponding to a first desired pressure is applied, which causes a first pressure force on the material and / or another liquid filled into the reagent vessel, which is greater than the capillary force of the at least one capillary structure.
  • the material and / or the other liquid are at least partially transferred out of the at least one capillary structure.
  • the method also has the method steps S12 and S13, which can be repeated as often as desired.
  • the underpressure or overpressure is adjusted in the direction of the atmospheric pressure to a second desired pressure, which causes a second pressure force smaller than the capillary force of the at least one capillary structure, for which reason the material and / or the other liquid at least partially into the be sucked at least one capillary structure.
  • the negative or positive pressure can be increased away from the atmospheric pressure to a third desired pressure which causes a third pressure force greater than the capillary force of the at least one capillary structure.
  • a complete mechanical and / or fluidic functionality can be formed, which can be used for the automation of complex chemical processes and / or biochemical / molecular biological processes.
  • the automation can also be used for the detection of substances.
  • valve operations and / or mixing operations may also be performed by the methods. It should also be understood that the methods may also be used to include at least one liquid without a mechanical element and / or a movable one Part against an actuation force Fa, such as a centrifugal force and / or a compressive force to transport.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Claims (12)

  1. Composant de revolver (10, 10a, 10b, 10c) pour un récipient pour réactifs, qui présente une paroi extérieure de revolver (12) qui est réalisée de telle sorte que la paroi extérieure de revolver (12) corresponde à une paroi intérieure d'un récipient pour réactifs pour une centrifugeuse et/ou pour un dispositif de variation de pression et que le composant de revolver (10, 10a, 10b, 10c) puisse être inséré dans le récipient pour réactifs ;
    le composant de revolver (10, 10a, 10b, 10c) inséré dans le récipient pour réactifs pouvant tourner autour d'un axe de rotation (11) et pouvant être réglé le long de l'axe de rotation (11) au moyen d'un mécanisme à stylo (76) ;
    et au moins une structure de récipient (14) étant réalisée sur le composant de revolver (10, 10a, 10b, 10c), dans laquelle est introduit ou peut être introduit au moins un liquide (16) ; caractérisé par
    au moins une structure capillaire (18, 40) disposée sur et/ou dans l'au moins une structure de récipient (14), au moyen de laquelle une force capillaire (Fk) peut être exercée sur l'au moins un liquide (16), de sorte que l'au moins un liquide (16) puisse être aspiré au moins en partie dans un volume intérieur (20) de l'au moins une structure capillaire (18, 40).
  2. Composant de revolver (10, 10a, 10b, 10c) selon la revendication 1, dans lequel l'au moins une structure capillaire (18, 40) présente un diamètre moyen compris dans une plage de 0,1 µm à 1 mm.
  3. Composant de revolver (10, 10a, 10b, 10c) selon la revendication 1 ou 2, dans lequel l'au moins une structure capillaire (18, 40) est formée de verre, de silice, d'un polymère, d'un matériau tissé et/ou d'un gel.
  4. Composant de revolver (10, 10a, 10b, 10c) selon l'une quelconque des revendications précédentes, dans lequel l'au moins une structure capillaire (18, 40) est revêtue au niveau de son au moins une paroi intérieure (22) de protéines, d'antigènes, d'anticorps, d'enzymes, de brins partiels d'ADN, de brins partiels d'ARN et/ou de résine époxy.
  5. Composant de revolver (10, 10a, 10b, 10c) selon l'une quelconque des revendications précédentes, dans lequel la force capillaire (Fk) pouvant être exercée au moyen de l'au moins une structure capillaire (18, 40) est supérieure à une force de pesanteur de l'au moins un liquide (16) pouvant être introduit ou étant introduit dans l'au moins une structure de récipient (14).
  6. Composant de revolver (10, 10a, 10b, 10c) selon l'une quelconque des revendications précédentes, dans lequel l'au moins un liquide (16) aspiré au moins en partie dans l'au moins une structure capillaire (18, 40) peut être transféré hors de l'au moins une structure capillaire (18, 40) au moyen d'une force centrifuge pouvant être provoquée lors d'un fonctionnement de la centrifugeuse, dans le dispositif de rotor de laquelle est disposé le récipient pour réactifs avec le composant de revolver (10, 10a, 10b, 10c) introduit dans celui-ci, et/ou au moyen d'une force de pression pouvant être provoquée dans le cas d'un fonctionnement du dispositif de variation de pression dans lequel le récipient pour réactifs est disposé avec le composant de revolver (10, 10a, 10b, 10c) inséré dans celui-ci.
  7. Composant de revolver (10, 10a, 10b, 10c) selon l'une quelconque des revendications précédentes, dans lequel l'au moins une structure de récipient (14) comprend à chaque fois au moins une première chambre (50) avec une ouverture de remplissage et/ou d'équilibrage de la pression (52) et une deuxième chambre (54), qui est fermée de manière étanche à l'air et/ou aux liquides à l'exception d'une ouverture d'échange de liquide (56) vers la première chambre (50), et l'au moins une structure capillaire (40) étant formée dans un système capillaire (40) réalisé sous forme de masse spongieuse, qui est disposé dans la deuxième chambre (54).
  8. Récipient pour réactifs pour une centrifugeuse et/ou pour un dispositif de variation de pression, comprenant :
    au moins un composant de revolver (10, 10a, 10b, 10c) selon l'une quelconque des revendications 1 à 7 disposé dans le récipient pour réactifs.
  9. Procédé de centrifugation d'une substance, comprenant les étapes suivantes :
    introduction de la substance à centrifuger dans un récipient pour réactifs avec un composant de revolver (10, 10a, 10b, 10c) selon l'une quelconque des revendications 1 à 7, introduit dans celui-ci, ou dans un récipient pour réactifs selon la revendication 8 (S1) ; et
    au moins entraînement d'une centrifugeuse avec une vitesse de rotation effective correspondant à une première vitesse de rotation de consigne qui applique une première force centrifuge sur la substance à centrifuger et/ou sur un autre liquide (16) introduit dans le récipient pour réactifs, qui est supérieure à la force capillaire (Fk) de l'au moins une structure capillaire (18, 40), de sorte que la substance à centrifuger et/ou l'autre liquide (16) soit transféré(e) au moins en partie hors de l'au moins une structure capillaire (18, 40) (S2).
  10. Procédé selon la revendication 9, comprenant les étapes supplémentaires suivantes :
    une fois au moins réduction temporaire de la vitesse de rotation effective à une deuxième vitesse de rotation de consigne qui provoque une deuxième force centrifuge inférieure à la force capillaire (Fk) de l'au moins une structure capillaire (18, 40), de sorte que la substance à centrifuger et/ou l'autre liquide (16) soient aspirés au moins en partie dans l'au moins une structure capillaire (18, 40) (S3), et augmentation de la vitesse de rotation effective à une troisième vitesse de rotation de consigne qui provoque une troisième force centrifuge supérieure à la force capillaire (Fk) de l'au moins une structure capillaire (18, 40) (S4).
  11. Procédé de traitement par pression d'une substance, comprenant les étapes suivantes :
    introduction de la substance à traiter dans un récipient pour réactifs avec un composant de revolver (10, 10a, 10b, 10c) selon l'une quelconque des revendications 1 à 7, introduit dans celui-ci, ou dans un récipient pour réactifs selon la revendication 8 (S10) ; et
    une fois au moins application d'une dépression ou d'une surpression correspondant à une première pression de consigne, qui applique une première force de pression à la substance et/ou à un autre liquide (16) introduit dans le récipient pour réactifs, qui est supérieure à la force capillaire (Fk) de l'au moins une structure capillaire (18, 40), de sorte que la substance et/ou l'autre liquide (16) soient au moins en partie transférés hors de l'au moins une structure capillaire (18, 40) (S11).
  12. Procédé selon la revendication 11, comprenant les étapes supplémentaires suivantes :
    une fois au moins, équilibrage de la dépression ou de la surpression dans le sens de la pression atmosphérique à une deuxième pression de consigne, qui provoque une deuxième force de pression inférieure à la force capillaire (Fk) de l'au moins une structure capillaire (18, 40), de sorte que la substance et/ou l'autre liquide (16) soient aspirés au moins en partie dans l'au moins une structure capillaire (18, 40) (S12), et amplification de la dépression ou de la surpression depuis la pression atmosphérique à une troisième pression de consigne qui provoque une troisième force de pression supérieure à la force capillaire (Fk) de l'au moins une structure capillaire (18, 40) (S13).
EP13705186.8A 2012-04-04 2013-02-21 Dispositif capillaire pour récipient pour réactif et l'utilisation Active EP2834005B1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102012205511A DE102012205511A1 (de) 2012-04-04 2012-04-04 Revolverbauteil für ein Reagenzgefäß
PCT/EP2013/053406 WO2013149761A1 (fr) 2012-04-04 2013-02-21 Élément capillaire pour récipient à réactifs et son utilisation

Publications (2)

Publication Number Publication Date
EP2834005A1 EP2834005A1 (fr) 2015-02-11
EP2834005B1 true EP2834005B1 (fr) 2019-05-08

Family

ID=47740974

Family Applications (1)

Application Number Title Priority Date Filing Date
EP13705186.8A Active EP2834005B1 (fr) 2012-04-04 2013-02-21 Dispositif capillaire pour récipient pour réactif et l'utilisation

Country Status (3)

Country Link
EP (1) EP2834005B1 (fr)
DE (1) DE102012205511A1 (fr)
WO (1) WO2013149761A1 (fr)

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4835106A (en) * 1987-07-17 1989-05-30 Martin Marietta Energy Systems, Inc. Rotor for processing liquids using movable capillary tubes
US5173262A (en) * 1987-07-17 1992-12-22 Martin Marietta Energy Systems, Inc. Rotor assembly and method for automatically processing liquids
CA2100977C (fr) * 1992-07-24 2000-02-08 Noribumi Koitabashi Reservoir a encre, encre et appareil d'enregistrement a jet d'encre utilisant ce reservoir
US5789259A (en) * 1996-09-27 1998-08-04 Robert A. Levine Method and apparatus for mixing samples in a capillary tube
ITMI20062272A1 (it) * 2006-11-27 2008-05-28 Genedia S R L Reattore per lo svolgimento di processi biochimici particolarmente di estrazione purificazione arricchimento sedimentazione
EP3108949A1 (fr) * 2009-03-02 2016-12-28 Dignity Health Dispositifs diagnostiques et procédés d'utilisation
DE102010003223B4 (de) 2010-03-24 2014-09-18 Albert-Ludwigs-Universität Freiburg Vorrichtung zum Einsetzen in einen Rotor einer Zentrifuge, Zentrifuge und Verfahren zum fluidischen Koppeln von Kavitäten

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
None *

Also Published As

Publication number Publication date
DE102012205511A1 (de) 2013-10-10
WO2013149761A1 (fr) 2013-10-10
EP2834005A1 (fr) 2015-02-11

Similar Documents

Publication Publication Date Title
DE112013003342B4 (de) Patrone zur biochemischen Verwendung und biochemische Verarbeitungsvorrichtung
EP1886146B1 (fr) Microdistributeur et procede correspondant pour l'utiliser
EP2413138B1 (fr) Dispositif et procédé de séparation de composants d'un liquide d'échantillon
EP1743700B1 (fr) Dispositif de pipetage
DE10319045A1 (de) Vorrichtung und Verfahren zur Aufbereitung Biopolymerhaltiger Flüssigkeiten
WO2013034469A2 (fr) Soupape d'admission pour des systèmes de chambres et récipients à échantillons ainsi que systèmes de chambres dotés de récipients à échantillons dotés de telles soupapes d'admission
EP2536507A1 (fr) Dispositif, centrifugeuse et procédé pour l'accouplement fluidique de cavités
DE10010208C2 (de) Mikrodosiervorrichtung zur definierten Abgabe kleiner in sich geschlossener Flüssigkeitsvolumina
EP2428272B1 (fr) Procédé de revêtement hyrophobe d'embouts de pipette
EP2535108A1 (fr) Système microfluidique et son procédé de d'utilisation
EP3538267A1 (fr) Dispositif microfluidique et procédé pour l'analyse d'acides nucléiques
EP2647436A2 (fr) Composant de revolver pour un flacon de réactif
EP2647433B1 (fr) Pièce d'insertion de flacon de réactif et flacon de réactif
EP2692440A1 (fr) Pièce d'insertion de flacon de réactif, flacon de réactif, procédé de centrifugation d'au moins un matériau et procédé de traitement sous pression d'au moins un matériau
EP1161995A2 (fr) Procédé et dispositif pour absorber un milieu dans un dispositif capillaire
WO2014019826A1 (fr) Élément revolver pour un récipient à réactifs, partie de récipient à réactifs et récipient à réactifs pour une centrifugeuse et/ou pour un dispositif à variation de pression
EP2156890B1 (fr) Agencement et procédé de production, de manipulation et d'analyse de compartiments
DE102009001257A1 (de) Vorrichtung und Verfahren zur Handhabung von Flüssigkeiten
EP1533035A1 (fr) Porte-échantillon
EP2834005B1 (fr) Dispositif capillaire pour récipient pour réactif et l'utilisation
WO2013149762A1 (fr) Élément enceinte pour récipient à réactifs et son utilisation
EP1353752A1 (fr) Dispositif et proc d pour transf rer des echantillons fluides
DE102015203779A1 (de) Vorrichtung zur automatisierten Prozessierung von Flüssigkeiten
DE202006019795U1 (de) Mikrodispenser
EP1340543A1 (fr) Système microfluidique

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20141104

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

AX Request for extension of the european patent

Extension state: BA ME

DAX Request for extension of the european patent (deleted)
GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: GRANT OF PATENT IS INTENDED

INTG Intention to grant announced

Effective date: 20190103

GRAS Grant fee paid

Free format text: ORIGINAL CODE: EPIDOSNIGR3

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE PATENT HAS BEEN GRANTED

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

REG Reference to a national code

Ref country code: GB

Ref legal event code: FG4D

Free format text: NOT ENGLISH

REG Reference to a national code

Ref country code: CH

Ref legal event code: EP

Ref country code: AT

Ref legal event code: REF

Ref document number: 1129336

Country of ref document: AT

Kind code of ref document: T

Effective date: 20190515

REG Reference to a national code

Ref country code: DE

Ref legal event code: R096

Ref document number: 502013012776

Country of ref document: DE

Ref country code: IE

Ref legal event code: FG4D

Free format text: LANGUAGE OF EP DOCUMENT: GERMAN

REG Reference to a national code

Ref country code: NL

Ref legal event code: MP

Effective date: 20190508

REG Reference to a national code

Ref country code: LT

Ref legal event code: MG4D

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: FI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20190508

Ref country code: AL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20190508

Ref country code: NO

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20190808

Ref country code: HR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20190508

Ref country code: PT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20190908

Ref country code: SE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20190508

Ref country code: NL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20190508

Ref country code: ES

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20190508

Ref country code: LT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20190508

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LV

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20190508

Ref country code: BG

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20190808

Ref country code: RS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20190508

Ref country code: GR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20190809

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: CZ

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20190508

Ref country code: RO

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20190508

Ref country code: SK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20190508

Ref country code: DK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20190508

Ref country code: EE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20190508

REG Reference to a national code

Ref country code: DE

Ref legal event code: R097

Ref document number: 502013012776

Country of ref document: DE

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: IT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20190508

Ref country code: SM

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20190508

PLBE No opposition filed within time limit

Free format text: ORIGINAL CODE: 0009261

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: TR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20190508

26N No opposition filed

Effective date: 20200211

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: PL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20190508

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20190508

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: DE

Payment date: 20200421

Year of fee payment: 8

REG Reference to a national code

Ref country code: CH

Ref legal event code: PL

GBPC Gb: european patent ceased through non-payment of renewal fee

Effective date: 20200221

REG Reference to a national code

Ref country code: BE

Ref legal event code: MM

Effective date: 20200229

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LU

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20200221

Ref country code: MC

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20190508

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: CH

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20200229

Ref country code: LI

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20200229

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: GB

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20200221

Ref country code: FR

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20200229

Ref country code: IE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20200221

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: BE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20200229

REG Reference to a national code

Ref country code: AT

Ref legal event code: MM01

Ref document number: 1129336

Country of ref document: AT

Kind code of ref document: T

Effective date: 20200221

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: AT

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20200221

REG Reference to a national code

Ref country code: DE

Ref legal event code: R119

Ref document number: 502013012776

Country of ref document: DE

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: DE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20210901

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20190508

Ref country code: CY

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20190508

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20190508

Ref country code: IS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20190908