EP2729251B1 - Microfluid structure with cavities - Google Patents
Microfluid structure with cavities Download PDFInfo
- Publication number
- EP2729251B1 EP2729251B1 EP12732642.9A EP12732642A EP2729251B1 EP 2729251 B1 EP2729251 B1 EP 2729251B1 EP 12732642 A EP12732642 A EP 12732642A EP 2729251 B1 EP2729251 B1 EP 2729251B1
- Authority
- EP
- European Patent Office
- Prior art keywords
- cavity
- region
- liquid
- indentation
- microfluidic
- 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.)
- Not-in-force
Links
- 230000007704 transition Effects 0.000 claims description 12
- 239000012530 fluid Substances 0.000 claims description 8
- 238000007373 indentation Methods 0.000 claims 9
- 239000007788 liquid Substances 0.000 description 57
- 239000000523 sample Substances 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 7
- 239000008280 blood Substances 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 238000001514 detection method Methods 0.000 description 3
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000005429 filling process Methods 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000009736 wetting Methods 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000013060 biological fluid Substances 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
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
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502746—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means for controlling flow resistance, e.g. flow controllers, baffles
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502738—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by integrated valves
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/06—Fluid handling related problems
- B01L2200/0642—Filling fluids into wells by specific techniques
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/06—Fluid handling related problems
- B01L2200/0684—Venting, avoiding backpressure, avoid gas bubbles
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0809—Geometry, shape and general structure rectangular shaped
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0848—Specific forms of parts of containers
- B01L2300/0858—Side walls
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
- B01L2300/0864—Configuration of multiple channels and/or chambers in a single devices comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
-
- 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
- B01L2400/08—Regulating or influencing the flow resistance
- B01L2400/084—Passive control of flow resistance
-
- 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
- B01L2400/08—Regulating or influencing the flow resistance
- B01L2400/084—Passive control of flow resistance
- B01L2400/086—Passive control of flow resistance using baffles or other fixed flow obstructions
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502723—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by venting arrangements
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502753—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation
Definitions
- the invention relates to a microfluidic structure, comprising at least one cavity with at least one inlet opening and at least one outlet opening, wherein the cavity can be filled with a liquid or flowed through by a liquid and within the cavity at least one element is provided which the liquid in the flow within the cavity stops at least temporarily and / or at least partially deflects.
- Microfluidic structures are components of microfluidic platforms or microfluidic components and essentially comprise cavities and / or channels in which sample liquids to be examined or manipulated can be taken up and transported by suitable means (for example capillary forces, generated pressure differences) to correspondingly provided reaction sites ,
- the present invention encompasses microfluidic platforms such as, for example, sample carriers, test strips, biosensors, or the like, which may serve to perform individual tests or measurements.
- biological fluids eg blood, urine or saliva
- pathogens eg blood, urine or saliva
- cholesterol blood fat
- corresponding detection reactions or entire reaction cascades take place on the microfluidic platforms.
- the biological sample liquid is transported to the appropriate reaction site or the reaction sites by suitable means.
- a transport of the sample liquid can take place, for example, by means of passive capillary forces (by means of appropriate capillary systems or microchannels) or else by means of an active actuator.
- active actuators syringe or diaphragm pumps are used, for example, which can be located outside of the microfluidic platform or on this and build up within a micro-fluidic structure consisting of micro channels and micro cavities in particular a corresponding pressure.
- microfluidic platforms have a sample task on the order of a few millimeters to give up a sample liquid amount on the order of a few microliters, the sample liquid (for example, blood) must be transported via a micro-channel or via a micro-channel system to corresponding cavities, in which, for example chemical reactants are in dried form.
- sample liquid for example, blood
- a disadvantage of this structure is that volume actually consumed within the cavity is consumed by the web-like elements.
- a microfluidic structure or a microfluidic platform for air bubble free filling known. Concretely, there is provided a cavity, with an inlet opening and an outlet opening. In the area of the inlet opening, the Cavity microstructure elements in the form of columns on. This area forms a site with increased capillary force. Due to the increased capillary force, first a complete and air bubble-free wetting of the entrance area of the cavity with sample liquid takes place. Only then is a wetting of the outlet opening facing part of the cavity.
- EP 0 153 110 A2 shows a microfluidic structure with ribs.
- a ramp is provided in the cavity, which raises the level of the cavity floor to the level of the outlet opening.
- Such an arrangement is unsatisfactory for the filling of large, in particular (transverse to the inflow or throughflow direction of the liquid) wide and irregularly shaped cavities.
- the invention is therefore based on the object to improve a microfluidic structure according to the preamble of claim 1 such that an improved, in particular substantially air bubble-free filling, in particular of large cavities is made possible. This object is achieved with the characterizing features of claim 1.
- Advantageous developments of the invention can be taken from the subclaims.
- the invention is therefore based on a microfluidic structure, comprising at least one cavity having at least one inlet opening and at least one outlet opening, wherein the cavity can be filled with a liquid or flowed through by a liquid and within the cavity at least one element is provided, which at the liquid whose flow within the cavity at least temporarily stops and / or at least partially deflects.
- the at least one element is formed by a depression formed in a wall of the cavity, which has at least one first region at which the liquid is stopped and / or at least partially deflected at least temporarily and at least one second region at which the liquid preferably flows into the depression.
- the liquid runs immediately upon reaching the second region, that is, without a significant stop into the depression and pulls from a certain filling level the well also in the first area of the well first stopped liquid into the recess.
- the liquid in the cavity can be controlled so that the cavity is filled evenly and substantially free of air bubbles.
- This is also possible with large, in particular wide and irregularly shaped cavities which, for example, have a filling volume of the order of magnitude of about 10 ⁇ l to 10 ml.
- said wall of the cavity may be, for example, a bottom of the cavity. But there are also any other walls of the cavity conceivable.
- the second region is formed by a ramp-like transition, which, starting from a bottom level of the cavity, passes over to a bottom level of the depression.
- This ramp-like transition ensures in a simple manner that the sample liquid at this point runs into the depression without a stop and fills it.
- the ramp-like transition starting from a boundary edge of the recess with a bottom plane of the cavity forms an angle of about 10 degrees to 60 degrees, more preferably of about 45 degrees.
- the second region could also be formed by a "smooth" transition, for example by a convex or concave rounding.
- a notch-like structure (seen in plan view of the depression) is conceivable.
- the first region is expediently formed by a boundary edge of the depression on which the converging, forming the boundary edge Walls occupy an angle which is less than 120 degrees, preferably approximately between 95 degrees and 70 degrees, more preferably at about 90 degrees.
- the first region forms a capillary stop in a very reliable manner, at which the inflowing liquid is first stopped or deflected.
- the at least one recess is elongated, wherein the at least one first region facing an inflowing liquid and the at least one second region of an inflowing liquid is remote.
- the inflowing liquid can be controlled such that it initially reaches the first area, is stopped there, deflected and preferably reaches the second area (without a noteworthy stop) into the depression and fills it.
- the recess may be formed in plan view, for example, approximately rectangular. But it can also be different in plan view, for example, be arcuate. This may be expedient, for example, if the cavity to be filled is likewise curved in its longitudinal extension.
- a further advantageous embodiment of the inventive idea provides that a plurality of depressions are provided, which are arranged starting from side walls of the cavity, mutually.
- the at least one first region extends approximately over the entire length of one longitudinal side of the at least one depression and the at least one second region only over a portion of the length of another longitudinal face.
- the invention also relates to a microfluidic platform with at least one microfluidic structure according to at least one of claims 1 to 7.
- a microfluidic platform can be produced inexpensively and meets high demands on a process-reliable, in particular air bubble-free filling of the existing cavities.
- the microfluidic structure 1 comprises a cavity 10, which has a filling volume of about 15 ⁇ l.
- the cavity 10 is unevenly shaped and provided with an inlet opening 11, which connects the cavity 10 with a filling channel 16.
- the filling channel 16 itself may be connected to an unspecified numbering filling opening (for example, a sample task area).
- the cavity 10 is provided with an outlet opening 12 which, for example, releases the fluidic connection to a ventilation channel 17.
- a capillary stop 24 is also provided in the usual way.
- the cavity 10 may be connected via an outlet opening to a further microchannel 18 (indicated by dashed lines) if a liquid is to be transported through the cavity 10, for example into a further cavity (not shown).
- the cavity 10 is a comparatively large cavity having dimensions of about 12 mm in width, 36 mm in length and about 1.5 mm in depth.
- Each recess 13 has in plan view approximately a rectangular appearance with a length L and a width B.
- the recesses 13, starting from longitudinal sides of the cavity 10, are mutually arranged.
- each depression 13 has a first region 14 which faces an inflowing liquid F (cf. Fig. 4 ) and at which the inflowing liquid F is at least temporarily stopped and / or at least partially deflected.
- each depression 13 is provided with a second region 15, at which an incoming liquid F runs into the depression 13 without stopping.
- the cavity 10 is closed by a cover 21 (for example, a glued foil) and has a bottom 19.
- a cover 21 for example, a glued foil
- Each recess 13 has a bottom 20.
- the first region 14 (capillary stop) is formed by a boundary edge 22 of the recess 13, at which the converging, the boundary edge 22 forming walls occupy an angle ⁇ , which is 90 degrees. Deviating from the embodiment, of course, other angles are conceivable, which may be greater or less than 90 degrees.
- the second region 15 is formed by a ramp-like transition R, which, starting from the bottom level 19 of the cavity 10, to a bottom level 20 of the recess 13 passes.
- the ramp-like transition R starting from a boundary edge 23 of the recess 13 with the bottom plane 19 of the cavity 10 forms an angle ⁇ of approximately 45 degrees. Again, angles greater or less than 45 degrees are conceivable.
- the second area 15 does not necessarily have to be formed by a ramp-like transition, but other configurations are also conceivable. So is in Fig. 3 indicated that the second area, for example, by a “smooth" transition, such as by a concave (15 ") or convex (15"') rounding can be formed.
- the liquid F is first stopped at the first region 14 or the boundary edge 22 and deflected ( Fig. 4b ).
- the liquid F continues to the first region 14 of the second recess 13 and thereby also to the second region 15 of the first recess 13, whereby the liquid F via the second region 15, the first recess 13 fills (see dashed lines indicated arrow in FIG Fig. 4c ).
- the liquid F is then stopped and deflected again at the first region 14 of the second depression 13 and a complete filling of the cavity 10 takes place, first leaving the second depression 13 (see FIG Fig. 4d ).
- the second depression 13 is also filled via the second region 15 (ramp-like transition R).
- the liquid front of the liquid F now extends to the first region 14 of the last depression 13 (FIG. Fig. 4e ).
- the liquid F is again initially stopped and deflected until it subsequently reaches the second region 15 of the last depression 13 and, starting there, fills it.
- the filling process extends to the capillary stop 24 in the region of the outlet opening 12 and essentially takes place without air inclusions (air bubbles) (cf. Fig. 4f ).
- the second region 15 does not extend over the entire length L of a depression 13, but only constitutes part of this length. Furthermore, the region 15 also assumes a width which is significantly smaller than the width B of the entire depression 13. In particular, the width of the region 15 is preferably less than half the width B of the depression 13. This makes it possible, with sufficient filling function Area 15 well exploit the volume of the recess 13.
- the regions 15 are positioned on the longitudinal sides of the depressions 13 facing away from the inflowing liquid F, it is also conceivable to provide such regions at least partially on the transverse sides of the depressions 13 (cf. dashed lines 15 'in FIG Fig. 1 ). It is also conceivable to provide several such areas at one depression (see also paragraphs 43 in FIG Fig. 6 ).
- a second embodiment 3 for a microfluidic structure of a microfluidic component 4 is shown.
- the microfluidic structure 3 comprises a cavity 30, with Each recess 31 is in turn equipped with a first region 32 in the form of a stop edge (capillary stop), which faces the flow direction S of an inflowing liquid.
- a second region 33 in the form of a ramp is again provided on the longitudinal side of the depression 31 facing away from an inflowing liquid, the region 33 extending over an entire length L of the depression 31.
- the width of the region 33 is in turn only about a maximum of half a width B of the recess 31.
- a meandering flow of an incoming liquid is modeled by the mutual arrangement of the recesses 31.
- a microfluidic structure 5 can be seen on a microfluidic component 6, which (in contrast to the preceding exemplary embodiments) has a curved cavity 40 viewed in the inflow direction S of a liquid.
- each recess 41 has a longitudinal extent L and extends over this length L curved. Furthermore, it can be seen that each depression 41 is in turn provided with a first region 42 in the form of a stop edge (comparable to region 14 of the first embodiment) and on the longitudinal side facing away from an inflowing liquid, each having two regions 43 in the form of a ramp (comparable to FIG the area 15 in the first embodiment).
- a microfluidic structure 7 of a microfluidic component 8 can be seen, in which, within a cavity 50 unlike the embodiments according to the invention, no depressions, but webs 51 are attached.
- the webs 51 starting from longitudinal sides of the cavity 50, are mutually arranged and intended to meander a flow of an inflowing liquid (not shown) and thus enable a largely bubble-free filling of the cavity 50.
- the webs 51 extend from a bottom 53 of the cavity 50 starting up to a cavity 50 upwards final cover 52 zoom.
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Dispersion Chemistry (AREA)
- Analytical Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Hematology (AREA)
- Clinical Laboratory Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Automatic Analysis And Handling Materials Therefor (AREA)
- Physical Or Chemical Processes And Apparatus (AREA)
- Micromachines (AREA)
Description
Die Erfindung betrifft eine mikrofluidische Struktur, umfassend wenigstens eine Kavität mit wenigstens einer Einlassöffnung und wenigstens einer Auslassöffnung, wobei die Kavität mit einer Flüssigkeit befüllbar oder von einer solchen durchströmbar ist und innerhalb der Kavität wenigstens ein Element vorgesehen ist, welches die Flüssigkeit bei deren Strömung innerhalb der Kavität zumindest zeitweise abstoppt und/oder zumindest bereichsweise umlenkt.The invention relates to a microfluidic structure, comprising at least one cavity with at least one inlet opening and at least one outlet opening, wherein the cavity can be filled with a liquid or flowed through by a liquid and within the cavity at least one element is provided which the liquid in the flow within the cavity stops at least temporarily and / or at least partially deflects.
Mikrofluidische Strukturen sind Bestandteile von mikrofluidischen Plattformen bzw. mikrofluidischen Bauteilen und umfassen im Wesentlichen Kavitäten und/oder Kanäle, in denen zu untersuchende oder zu manipulierende Probenflüssigkeiten aufgenommen werden und durch geeignete Mittel (bspw. Kapillarkräfte, erzeugte Druckunterschiede) zu entsprechend vorgesehenen Reaktionsorten transportiert werden können.Microfluidic structures are components of microfluidic platforms or microfluidic components and essentially comprise cavities and / or channels in which sample liquids to be examined or manipulated can be taken up and transported by suitable means (for example capillary forces, generated pressure differences) to correspondingly provided reaction sites ,
Inbesondere werden von der vorliegenden Erfindung mikrofluidische Plattformen wie beispielsweise Probenträger, Teststreifen, Biosensoren oder dergleichen umfasst, welche zur Durchführung einzelner Tests oder Messungen dienen können. Beispielsweise können biologische Flüssigkeiten (z. B. Blut, Urin oder Speichel) zum einen auf Krankheitserreger, Unverträglichkeiten und zum anderen aber auch auf ihr Gehalt beispielsweise Glukose (Blutzucker) oder Cholesterol (Blutfett) untersucht werden. Dazu finden auf den mikrofluidischen Plattformen entsprechende Nachweisreaktionen oder ganze Reaktionskaskaden statt.In particular, the present invention encompasses microfluidic platforms such as, for example, sample carriers, test strips, biosensors, or the like, which may serve to perform individual tests or measurements. For example, biological fluids (eg blood, urine or saliva) can be examined for pathogens, incompatibilities and also for their content, for example glucose (blood sugar) or cholesterol (blood fat). For this purpose, corresponding detection reactions or entire reaction cascades take place on the microfluidic platforms.
Hierfür ist es erforderlich, dass die biologische Probenflüssigkeit zu dem dafür vorgesehenen Reaktionsort bzw. den Reaktionsorten mit geeigneten Mitteln transportiert wird. Ein solcher Transport der Probenflüssigkeit kann beispielsweise mittels passiver Kapillarkräfte (durch entsprechende Kapillarsysteme bzw. Mikrokanäle) erfolgen oder auch mittels einer aktiven Aktorik. Als aktive Aktorik werden beispielsweise Spritzen- oder Membranpumpen verwendet, die sich außerhalb der mikrofluidischen Plattform oder auch auf dieser befinden können und innerhalb einer mit insbesondere aus Mikrokanälen und Mikrokavitäten bestehenden mikrofluidischen Struktur einen entsprechenden Druck aufbauen.For this purpose, it is necessary that the biological sample liquid is transported to the appropriate reaction site or the reaction sites by suitable means. Such a transport of the sample liquid can take place, for example, by means of passive capillary forces (by means of appropriate capillary systems or microchannels) or else by means of an active actuator. As active actuators syringe or diaphragm pumps are used, for example, which can be located outside of the microfluidic platform or on this and build up within a micro-fluidic structure consisting of micro channels and micro cavities in particular a corresponding pressure.
Im Allgemeinen weisen mikrofluidische Plattformen einen Probenaufgabenbereich in der Größenordnung von wenigen Millimetern zur Aufgabe einer Probenflüssigkeitsmenge in der Größenordnung von einigen Mikrolitern auf, wobei die Probenflüssigkeit (beispielsweise Blut) über einen Mikrokanal bzw. über ein Mikrokanalsystem zu entsprechenden Kavitäten transportiert werden muss, in denen beispielsweise chemische Reaktionsstoffe in getrockneter Form vorliegen.In general, microfluidic platforms have a sample task on the order of a few millimeters to give up a sample liquid amount on the order of a few microliters, the sample liquid (for example, blood) must be transported via a micro-channel or via a micro-channel system to corresponding cavities, in which, for example chemical reactants are in dried form.
Damit eine Probenflüssigkeit mit den Reaktionsstoffen in einer Kavität eine einwandfreie Nachweisreaktion vollführen kann, ist eine möglichst gleichmäßige und vollständige Befüllung einer solchen Kavität erforderlich.In order for a sample liquid to be able to perform a satisfactory detection reaction with the reactants in a cavity, the most uniform and complete possible filling of such a cavity is required.
Bei der Befüllung von großen, insbesondere breiten und ungleichmäßig geformten Kavitäten, beispielsweise mit Längen- und/oder Breitendimensionen von jeweils mehreren Millimetern und einem daraus resultierenden Volumenbereich von beispielsweise 10 µl bis etwa 10 ml, besteht das Problem, dass sich die Kavität nicht gleichmäßig füllt und sich so Lufteinschlüsse bzw. Luftblasen in der Kavität bilden können. Dadurch steht nicht das komplette Volumen der Kavität für die Probenflüssigkeit zur Verfügung. In einer solchen Kavität beispielsweise aufbewahrte Trockensubstanzen werden so nicht ausreichend aufgelöst und es kann zu Klumpenbildung kommen, wodurch eine gewünschte Nachweisreaktion beeinträchtigt werden kann.When filling large, in particular wide and irregularly shaped cavities, for example with length and / or width dimensions of several millimeters and a resulting volume range of, for example, 10 .mu.l to about 10 ml, there is the problem that the cavity does not fill evenly and so air bubbles or air bubbles can form in the cavity. As a result, the entire volume of the cavity for the sample liquid is not available. In such a cavity, for example, stored dry substances are not sufficiently dissolved and it can lead to lump formation, whereby a desired detection reaction can be impaired.
Nach dem Stand der Technik wird hier dadurch Abhilfe geboten, indem man in der Kavität stegartige Elemente derart anordnet, dass die Flüssigkeit in der Kavität eine mäanderförmige Strömungsrichtung vollführen muss.According to the prior art, this is remedied by arranging web-like elements in the cavity such that the liquid in the cavity has to perform a meandering flow direction.
Ein Nachteil dieser Struktur ist jedoch, dass durch die stegartigen Elemente eigentlich benötigtes Volumen innerhalb der Kavität verbraucht wird.A disadvantage of this structure, however, is that volume actually consumed within the cavity is consumed by the web-like elements.
Zum Ausgleich muss daher mehr Fläche auf der mikrofluidischen Plattform bzw. dem mikrofluidischen Bauteil zur Verfügung gestellt werden. Dies soll insbesondere für mikrofluidische Plattformen wegen der damit verbundenen Zunahme der Herstellkosten vermieden werden.To compensate, therefore, more area must be provided on the microfluidic platform or the microfluidic component. This should be avoided in particular for microfluidic platforms because of the associated increase in manufacturing costs.
Aus der
Eine solche Anordnung ist zur Befüllung von großen, insbesondere (quer zur Einström- bzw. Durchströmrichtung der Flüssigkeit) breiten und ungleichmäßig geformten Kavitäten nicht zufrieden stellend.
Der Erfindung liegt daher die Aufgabe zu Grunde, eine mikrofluidische Struktur gemäß dem Oberbegriff von Anspruch 1 derart zu verbessern, dass eine verbesserte, insbesondere im Wesentlichen luftblasenfreie Befüllung, insbesondere von großen Kavitäten ermöglicht wird. Diese Aufgabe wird mit den kennzeichnenden Merkmalen von Anspruch 1 gelöst. Vorteilhafte Weiterbildungen der Erfindung sind den Unteransprüchen entnehmbar.
Die Erfindung geht daher aus von einer mikrofluidischen Struktur, umfassend wenigstens eine Kavität mit wenigstens einer Einlassöffnung und wenigstens einer Auslassöffnung, wobei die Kavität mit einer Flüssigkeit befüllbar oder von einer solchen durchströmbar ist und innerhalb der Kavität wenigstens ein Element vorgesehen ist, welches die Flüssigkeit bei deren Strömung innerhalb der Kavität zumindest zeitweise abstoppt und/oder zumindest bereichsweise umlenkt.
Erfindungsgemäß ist vorgesehen, dass das wenigstens eine Element durch eine in eine Wandung der Kavität eingebrachte Vertiefung gebildet ist, welche wenigstens einen ersten Bereich aufweist, an dem die Flüssigkeit zumindest zeitweise gestoppt und/oder zumindest bereichsweise umgelenkt wird und zumindest einen zweiten Bereich, an dem die Flüssigkeit bevorzugt in die Vertiefung hineinläuft.
Dabei läuft die Flüssigkeit bei Erreichen des zweiten Bereiches sofort, also ohne einen nennenswerten Stopp in die Vertiefung hinein und zieht ab einem bestimmten Befüllstand der Vertiefung auch noch die im ersten Bereich der Vertiefung zunächst abgestoppte Flüssigkeit mit in die Vertiefung hinein.From the
Such an arrangement is unsatisfactory for the filling of large, in particular (transverse to the inflow or throughflow direction of the liquid) wide and irregularly shaped cavities.
The invention is therefore based on the object to improve a microfluidic structure according to the preamble of
The invention is therefore based on a microfluidic structure, comprising at least one cavity having at least one inlet opening and at least one outlet opening, wherein the cavity can be filled with a liquid or flowed through by a liquid and within the cavity at least one element is provided, which at the liquid whose flow within the cavity at least temporarily stops and / or at least partially deflects.
According to the invention, it is provided that the at least one element is formed by a depression formed in a wall of the cavity, which has at least one first region at which the liquid is stopped and / or at least partially deflected at least temporarily and at least one second region at which the liquid preferably flows into the depression.
In this case, the liquid runs immediately upon reaching the second region, that is, without a significant stop into the depression and pulls from a certain filling level the well also in the first area of the well first stopped liquid into the recess.
Auf diese Weise kann die Flüssigkeit in der Kavität derart gesteuert werden, dass die Kavität gleichmäßig und im Wesentlichen luftblasenfrei gefüllt wird. Dies ist auch bei großen, insbesondere breiten und ungleichmäßig geformten Kavitäten möglich, welche beispielsweise ein Befüllvolumen in der Größenordnung von etwa 10 µl bis 10 ml aufweisen.In this way, the liquid in the cavity can be controlled so that the cavity is filled evenly and substantially free of air bubbles. This is also possible with large, in particular wide and irregularly shaped cavities which, for example, have a filling volume of the order of magnitude of about 10 μl to 10 ml.
Anzumerken ist, dass die genannte Wandung der Kavität beispielsweise ein Boden der Kavität sein kann. Es sind aber auch beliebige andere Wandungen der Kavität denkbar. So kann die Wandung, bei geeigneter Ausbildung eines die Kavität abschließenden Deckels, beispielsweise auch durch diesen selbst gebildet sein. Auch eine Kombination dieser beiden Möglichkeiten ist zum Beispiel möglich.It should be noted that said wall of the cavity may be, for example, a bottom of the cavity. But there are also any other walls of the cavity conceivable. Thus, the wall, with a suitable design of the cavity-closing lid, for example, be formed by this itself. A combination of these two options is possible, for example.
Nach einer Weiterbildung der Erfindung ist vorgesehen, dass der zweite Bereich durch einen rampenartigen Übergang gebildet ist, der, von einem Bodenniveau der Kavität ausgehend, bis auf ein Bodenniveau der Vertiefung übergeht.According to a development of the invention, it is provided that the second region is formed by a ramp-like transition, which, starting from a bottom level of the cavity, passes over to a bottom level of the depression.
Durch diesen rampenartigen Übergang wird auf einfache Weise sichergestellt, dass die Probenflüssigkeit an dieser Stelle ohne einen Stopp in die Vertiefung hineinläuft und diese befüllt.This ramp-like transition ensures in a simple manner that the sample liquid at this point runs into the depression without a stop and fills it.
Dabei hat es sich als vorteilhaft erwiesen, dass der rampenartige Übergang, ausgehend von einer Begrenzungskante der Vertiefung mit einer Bodenebene der Kavität einen Winkel von etwa 10 Grad bis 60 Grad, besonders bevorzugt von in etwa 45 Grad bildet. In Versuchen hat sich gezeigt, dass mit der Wahl derartiger geometrischer Parameter ein gewolltes Strömungsverhalten der Flüssigkeit am besten realisierbar ist.It has proven to be advantageous that the ramp-like transition, starting from a boundary edge of the recess with a bottom plane of the cavity forms an angle of about 10 degrees to 60 degrees, more preferably of about 45 degrees. Experiments have shown that with the choice of such geometric parameters a desired flow behavior of the liquid is best realized.
Allerdings wären statt rampenartiger Ausgestaltung auch andere Ausgestaltungen des zweiten Bereichs denkbar. So könnte der zweite Bereich auch durch einen "sanften" Übergang gebildet sein, bspw. durch eine konvexe oder konkave Verrundung. Auch eine (in Draufsicht auf die Vertiefung gesehen) kerbenartige Struktur ist vorstellbar.However, instead of a ramp-like design, other embodiments of the second area would also be conceivable. Thus, the second region could also be formed by a "smooth" transition, for example by a convex or concave rounding. Also, a notch-like structure (seen in plan view of the depression) is conceivable.
Der erste Bereich wird hingegen zweckmäßigerweise durch eine Begrenzungskante der Vertiefung gebildet, an der die zusammenlaufenden, die Begrenzungskante bildenden Wandungen einen Winkel einnehmen, der kleiner als 120 Grad, bevorzugt in etwa zwischen 95 Grad und 70 Grad, besonders bevorzugt bei etwa 90 Grad liegt.By contrast, the first region is expediently formed by a boundary edge of the depression on which the converging, forming the boundary edge Walls occupy an angle which is less than 120 degrees, preferably approximately between 95 degrees and 70 degrees, more preferably at about 90 degrees.
Auf diese Weise bildet der erste Bereich auf sehr zuverlässige Weise einen Kapillarstopp, an dem die einströmende Flüssigkeit zunächst gestoppt bzw. umgelenkt wird.In this way, the first region forms a capillary stop in a very reliable manner, at which the inflowing liquid is first stopped or deflected.
Es hat sich in Versuchen ferner als sehr vorteilhaft erwiesen, wenn die wenigstens eine Vertiefung länglich ausgebildet ist, wobei der wenigstens eine erste Bereich einer einströmenden Flüssigkeit zugewandt und der wenigstens eine zweite Bereich einer einströmenden Flüssigkeit abgewandt ist. So kann die einströmende Flüssigkeit derart gesteuert werden, dass diese zunächst den ersten Bereich erreicht, dort abgestoppt, umgelenkt wird und bei Erreichen des zweiten Bereiches dort bevorzugt (ohne einen nennenswerten Stopp) in die Vertiefung hinein läuft und diese befüllt. Bei einer entsprechenden Anordnung mehrerer Vertiefungen miteinander kann die gewünschte Flüssigkeitssteuerung der konkreten Länge einer Kavität angepasst werden.It has also proved to be very advantageous in experiments, if the at least one recess is elongated, wherein the at least one first region facing an inflowing liquid and the at least one second region of an inflowing liquid is remote. Thus, the inflowing liquid can be controlled such that it initially reaches the first area, is stopped there, deflected and preferably reaches the second area (without a noteworthy stop) into the depression and fills it. With a corresponding arrangement of several recesses with each other, the desired fluid control of the specific length of a cavity can be adjusted.
Die Vertiefung kann in der Draufsicht beispielsweise in etwa rechteckförmig ausgebildet sein. Sie kann aber auch in der Draufsicht andersförmig, beispielsweise bogenförmig ausgebildet sein. Dies kann beispielsweise dann zweckmäßig sein, wenn die zu befüllende Kavität in ihrer Längserstreckung ebenfalls bogenförmig ausgebildet ist.The recess may be formed in plan view, for example, approximately rectangular. But it can also be different in plan view, for example, be arcuate. This may be expedient, for example, if the cavity to be filled is likewise curved in its longitudinal extension.
Eine weitere zweckmäßige Ausbildung des Erfindungsgedankens sieht vor, dass mehrere Vertiefungen vorgesehen sind, die von Seitenwänden der Kavität ausgehend, wechselseitig angeordnet sind.A further advantageous embodiment of the inventive idea provides that a plurality of depressions are provided, which are arranged starting from side walls of the cavity, mutually.
Auf diese Weise ist es möglich, mit den Vertiefungen in der zu befüllenden Kavität einen mäanderförmigen Strömungsverlauf der Flüssigkeit nachzubilden.In this way it is possible to emulate a meandering flow pattern of the liquid with the wells in the cavity to be filled.
Es hat sich zudem als vorteilhaft erwiesen, wenn sich der wenigstens eine erste Bereich in etwa über die gesamte Länge einer Längsseite der wenigstens einen Vertiefung erstreckt und der wenigstens eine zweite Bereich lediglich über einen Teil der Länge einer anderen Längsseite.It has also proved to be advantageous if the at least one first region extends approximately over the entire length of one longitudinal side of the at least one depression and the at least one second region only over a portion of the length of another longitudinal face.
Hierdurch ist es möglich, zum einen einen Kapillarstopp auf breiter Front sicherzustellen und zum anderen dennoch einen zeitlich verzögerten Einlauf der Flüssigkeit in die Vertiefung, wobei zusätzliches Volumen an der Stelle gewonnen werden kann, wo der zweite Bereich nicht ausgebildet ist.This makes it possible, on the one hand to ensure a capillary stop on a wide front and, on the other hand, a time-delayed inlet of the liquid into the depression, wherein additional volume can be obtained at the location where the second area is not formed.
Die Erfindung betrifft aber auch eine mikrofluidische Plattform mit wenigstens einer mikrofluidischen Struktur nach wenigstens einem der Ansprüche 1 bis 7. Eine derart ausgebildete mikrofluidische Plattform kann kostengünstig hergestellt werden und genügt hohen Ansprüchen an eine prozesssichere, insbesondere luftblasenfreien Befüllung der vorhandenen Kavitäten.However, the invention also relates to a microfluidic platform with at least one microfluidic structure according to at least one of
Weitere Vorteile und Ausgestaltungen der Erfindung werden anhand von Ausführungsbeispielen deutlich, was mit Hilfe der beiliegenden Figuren näher erläutert werden soll. Dabei bedeuten
- Fig. 1
- eine mikrofluidische Struktur gemäß einem ersten, bevorzugten Ausführungsbeispiel in einer Draufsicht, prinziphaft dargestellt,
- Fig. 2
- eine Schnittdarstellung der mikrofluidischen Struktur gemäß Schnittverlauf II in
Fig. 1 , - Fig. 3
- eine Detaildarstellung III aus
Fig. 2 , - Fig. 4a bis 4f
- unterschiedliche Befüllstadien der mikrofluidischen Struktur gemäß
Fig. 1 mi einer Flüssigkeit, - Fig. 5
- eine mikrofluidische Struktur in einer Draufsicht gemäß einem zweiten Ausführungsbeispiel, prinziphaft dargestellt,
- Fig. 6
- eine mikrofluidische Struktur in einer Draufsicht gemäß einem dritten Ausführungsbeispiel, prinziphaft dargestellt,
- Fig. 7
- eine mikrofluidische Struktur gemäß dem Stand der Technik und
- Fig. 8
- eine Schnittdarstellung gemäß Schnittverlauf VIII aus
Fig. 7 .
- Fig. 1
- a microfluidic structure according to a first preferred embodiment in a plan view, shown in principle,
- Fig. 2
- a sectional view of the microfluidic structure according to section line II in
Fig. 1 . - Fig. 3
- a detail III from
Fig. 2 . - Fig. 4a to 4f
- different filling stages of the microfluidic structure according to
Fig. 1 with a liquid, - Fig. 5
- a microfluidic structure in a plan view according to a second embodiment, shown in principle,
- Fig. 6
- a microfluidic structure in a plan view according to a third embodiment, shown in principle,
- Fig. 7
- a microfluidic structure according to the prior art and
- Fig. 8
- a sectional view according to section line VIII from
Fig. 7 ,
Zunächst wird auf die
In diesen Figuren ist eine in einem mikrofluidischen Bauteil 2 eingebrachte mikrofluidische Struktur 1 ersichtlich. Die mikrofluidische Struktur 1 umfasst eine Kavität 10, welche ein Befüllvolumen von etwa 15 µl aufweist. Die Kavität 10 ist ungleichmäßig geformt und mit einer Einlassöffnung 11 versehen, welche die Kavität 10 mit einem Befüllkanal 16 verbindet. Der Befüllkanal 16 selbst kann mit einer nicht näher bezifferten Befüllöffnung (beispielsweise einem Probenaufgabenbereich) verbunden sein.These figures show a
Auf der anderen Seite ist die Kavität 10 mit einer Auslassöffnung 12 versehen, welche beispielsweise die fluidische Verbindung zu einem Entlüftungskanal 17 freigibt. Im Bereich der Auslassöffnung 12 ist zudem in üblicher Weise ein Kapillarstopp 24 vorgesehen.On the other side, the
Zusätzlich oder alternativ kann die Kavität 10 über eine Auslassöffnung mit einem weiteren Mikrokanal 18 verbunden sein (gestrichelt angedeutet), wenn eine Flüssigkeit durch die Kavität 10 beispielsweise in eine weitere Kavität transportiert werden soll (nicht dargestellt).Additionally or alternatively, the
Die Kavität 10 ist eine vergleichsweise große Kavität mit Abmessungen von etwa 12 mm in der Breite, 36 mm in der Länge und etwa 1,5 mm in der Tiefe.The
Ferner ist zu erkennen, dass innerhalb der Kavität 10 drei Vertiefungen 13 angeordnet sind. Jede Vertiefung 13 hat in der Draufsicht dabei in etwa ein rechteckförmiges Aussehen mit einer Länge L und einer Breite B. Dabei sind die Vertiefungen 13, ausgehend von Längsseiten der Kavität 10, wechselseitig angeordnet.Furthermore, it can be seen that within the
Es ist ersichtlich, dass jede Vertiefung 13 einen ersten Bereich 14 aufweist, welcher einer einströmenden Flüssigkeit F zugewandt ist (vergleiche
Ferner ist jede Vertiefung 13 mit einem zweiten Bereich 15 versehen, an dem eine einlaufende Flüssigkeit F ohne einen Stopp in die Vertiefung 13 hineinläuft.Furthermore, each
Die Kavität 10 ist dabei durch einen Deckel 21 (beispielsweise eine aufgeklebte Folie) abgeschlossen und weist einen Boden 19 auf. Jede Vertiefung 13 weist einen Boden 20 auf.The
Insbesondere aus der Detaildarstellung gemäß
Ferner ist ersichtlich, dass der zweite Bereich 15 durch einen rampenartigen Übergang R gebildet ist, der, vom Bodenniveau 19 der Kavität 10 ausgehend, bis auf ein Bodenniveau 20 der Vertiefung 13 übergeht.Furthermore, it can be seen that the
Insbesondere ist erkennbar, dass der rampenartige Übergang R, ausgehend von einer Begrenzungskante 23 der Vertiefung 13 mit der Bodenebene 19 der Kavität 10 einen Winkel α von in etwa 45 Grad bildet. Auch hier sind Winkel größer oder kleiner 45 Grad denkbar.In particular, it can be seen that the ramp-like transition R, starting from a
Angemerkt sei, dass der zweite Bereich 15 nicht unbedingt durch einen rampenartigen Übergang gebildet sein muss, sondern auch andere Ausgestaltungen denkbar sind. So ist in
Anhand der
So strömt die einströmende Flüssigkeit F zunächst auf die Erste der Kavitäten 13 mit einer Strömungsrichtung S zu (
Thus, the inflowing liquid F first flows toward the first of the
Dabei wird die Flüssigkeit F zunächst an dem ersten Bereich 14 bzw. der Begrenzungskante 22 gestoppt und umgelenkt (
Die Flüssigkeit F gelangt weiter bis zum ersten Bereich 14 der zweiten Vertiefung 13 und dabei auch bis zum zweiten Bereich 15 der ersten Vertiefung 13, wodurch die Flüssigkeit F über den zweiten Bereich 15 die erste Vertiefung 13 befüllt (vergleiche gestrichelt angedeuteter Pfeil in
Die Flüssigkeit F wird nun an dem ersten Bereich 14 der zweiten Vertiefung 13 wiederum gestoppt und umgelenkt und es erfolgt eine komplette Befüllung der Kavität 10 zunächst unter Freilassung der zweiten Vertiefung 13 (vergleiche
Sobald die Flüssigkeit F auch den zweiten Bereich 15 der zweiten Vertiefung 13 erreicht, wird auch über den zweiten Bereich 15 (rampenartiger Übergang R) die zweite Vertiefung 13 befüllt. Die Flüssigkeitsfront der Flüssigkeit F reicht nun bis zum ersten Bereich 14 der letzten Vertiefung 13 (
An dem ersten Bereich 14 wird die Flüssigkeit F wiederum zunächst abgestoppt und umgelenkt, bis sie anschließend zum zweiten Bereich 15 der letzten Vertiefung 13 gelangt und von dort ausgehend, diese befüllt.At the
Der Befüllvorgang reicht bis zum Kapillarstopp 24 im Bereich der Auslassöffnung 12 und geht im Wesentlichen ohne Lufteinschlüsse (Luftblasen) vonstatten (vergleiche
Durch die wechselseitige Anordnung der Vertiefungen 13 erfolgt eine im Wesentlichen mäanderförmige Steuerung der Flüssigkeit F durch die Kavität 10.Due to the mutual arrangement of the
Es ist an den
Abweichend vom gezeigten Ausführungsbeispiel, bei dem die Bereiche 15 an der der einströmenden Flüssigkeit F abgewandten Längsseiten der Vertiefungen 13 positioniert sind, ist jedoch auch denkbar, derartige Bereiche zumindest teilweise an den Querseiten der Vertiefungen 13 vorzusehen (vergleiche gestrichelt angedeutet 15' in
In
Bezugnehmend auf die
In der Kavität 40 sind sieben Vertiefungen 41 vorgesehen, wobei jede Vertiefung 41 eine Längserstreckung L aufweist und über diese Länge L gekrümmt verläuft. Des Weiteren ist ersichtlich, dass jede Vertiefung 41 wiederum mit einem ersten Bereich 42 in Form einer Stoppkante (vergleichbar mit Bereich 14 des ersten Ausführungsbeispiels) versehen ist und an der einer einströmenden Flüssigkeit abgewandten Längsseite mit jeweils zwei Bereichen 43 in Form einer Rampe (vergleichbar mit dem Bereich 15 im ersten Ausführungsbeispiel).In the
Eine einströmende Flüssigkeit wird nun zunächst an den Bereichen 42 gestoppt und umgelenkt werden und nach Erreichen der Bereiche 43 mit dem Befüllvorgang einer jeden Vertiefung 41 beginnen, bis die Flüssigkeit komplett bis zur nächsten Vertiefung 41 weiterläuft. Es ist somit also auch eine schrittweise Befüllung der Kavität 40 ohne nennenswerte Lufteinschlüsse möglich.An inflowing liquid will now be stopped and deflected first at the
Schließlich soll bezugnehmend auf die
In diesen Figuren ist eine mikrofluidische Struktur 7 eines mikrofluidischen Bauteils 8 ersichtlich, bei der innerhalb einer Kavität 50 im Unterschied zu den Ausführungsbeispielen gemäß der Erfindung keine Vertiefungen, sondern Stege 51 angebracht sind. Die Stege 51 sind, ausgehend von Längsseiten der Kavität 50, wechselseitig angeordnet und sollen einen mäanderförmigen Durchfluss einer einströmenden Flüssigkeit (nicht dargestellt) und damit eine weitgehend luftblasenfreie Befüllung der Kavität 50 ermöglichen. Die Stege 51 reichen von einem Boden 53 der Kavität 50 ausgehend bis an einen die Kavität 50 nach oben hin abschließenden Deckel 52 heran.In these figures, a
Es ist ohne weiteres ersichtlich, dass durch die eingebrachten Stege 51 das Nutzvolumen der Kavität 50 deutlich eingeschränkt wird.It is readily apparent that the useful volume of the
- 11
- mikrofluidische Strukturmicrofluidic structure
- 22
- mikrofluidisches Bauteilmicrofluidic component
- 33
- mikrofluidische Strukturmicrofluidic structure
- 44
- mikrofluidisches Bauteilmicrofluidic component
- 55
- mikrofluidische Strukturmicrofluidic structure
- 66
- mikrofluidisches Bauteilmicrofluidic component
- 77
- mikrofluidische Strukturmicrofluidic structure
- 88th
- mikrofluidisches Bauteilmicrofluidic component
- 1010
- Kavitätcavity
- 1111
- Einlassöffnunginlet port
- 1212
- Auslassöffnungoutlet
- 1313
- Vertiefungdeepening
- 1414
- erster Bereich der Vertiefung (Stoppkante)first area of the depression (stop edge)
- 1515
- zweiter Bereich der Vertiefung (Rampe)second area of the depression (ramp)
- 15'15 '
- alternativ ausgebildeter zweiter Bereichalternatively trained second area
- 15"15 "
- alternativ ausgebildeter zweiter Bereich (konkave Rundung)alternatively formed second area (concave rounding)
- 15"'15 " '
- alternativ ausgebildeter zweiter Bereich (konvexe Rundung)alternatively formed second area (convex rounding)
- 1616
- Befüllkanalfilling channel
- 1717
- Entlüftungskanalvent channel
- 1818
- weiterer Mikrokanalanother microchannel
- 1919
- Boden der KavitätBottom of the cavity
- 2020
- Boden der VertiefungBottom of the depression
- 2121
- Deckelcover
- 2222
- Begrenzungskante der VertiefungBounding edge of the depression
- 2323
- Begrenzungskante der VertiefungBounding edge of the depression
- 2424
- Kapillarstopcapillary
- 3030
- Kavitätcavity
- 3131
- Vertiefungdeepening
- 3232
- erster Bereich der Vertiefung (Stoppkante)first area of the depression (stop edge)
- 3333
- zweiter Bereich der Vertiefung (Rampe)second area of the depression (ramp)
- 4040
- Kavitätcavity
- 4141
- Vertiefungdeepening
- 4242
- erster Bereich der Vertiefung (Stoppkante)first area of the depression (stop edge)
- 4343
- zweiter Bereich der Vertiefung (Rampe)second area of the depression (ramp)
- 5050
- Kavitätcavity
- 5151
- Stegweb
- 5252
- Deckelcover
- 5353
- Boden der VertiefungBottom of the depression
- αα
- Winkelangle
- ββ
- Winkelangle
- BB
- Breite der VertiefungWidth of the recess
- FF
- Flüssigkeitliquid
- LL
- Längserstreckung der VertiefungLongitudinal extension of the depression
- RR
- rampenartiger Übergangsbereichramp-like transition area
- SS
- Strömungsrichtung einer einströmenden FlüssigkeitFlow direction of an inflowing liquid
Claims (6)
- Microfluidic structure (1, 3, 5) comprising at least one cavity (10, 30, 40) with at least one inlet opening (11) and at least one outlet opening (12), wherein the cavity (10, 30, 40) is fillable with a fluid (F) or a fluid can flow through said cavity and an element (13, 31, 41) is provided inside the cavity (10, 30, 40) which at least temporarily stops and at least in sections deflects the fluid (F) upon its flow (S) inside the cavity (10, 30, 40), characterised in that the at least one element (13, 31, 41) is formed by an indentation (13, 31, 41) introduced into a wall (19) of the cavity (10, 30, 40), the indentation (13, 31, 41) having at least one first region (14, 32, 42) which is formed by a boundary edge (22) of the indentation (13), at which the converging walls forming the boundary edge (22) form an angle (β) which is smaller than 120°, particularly preferably approximately 90°, and the first region (14, 32, 42) forms a capillary stop at which the fluid (F) is at least temporarily stopped and is deflected at least in sections and the at least one element (13, 31, 41) has at least one second region (15, 15', 15", 15"', 33, 43) which is formed by a ramp-like transition (R) which, proceeding from a ground level (19) of the cavity (10), merges up to a ground level (20) of the indentation (13), at which the fluid (F) runs into the indentation (13, 31, 41).
- Microfluidic structure (1, 3, 5) according to claim 1, characterised in that the ramp-like transition (R), proceeding from a boundary edge (23) of the indentation (13), forms an angle (α) of approximately 10° to 60°, particularly preferably approximately 45°, with the ground level (19) of the cavity (10).
- Microfluidic structure (1, 3, 5) according to any one of the preceding claims 1 or 2, characterised in that the at least one indentation (13, 31, 41) is formed longitudinally, wherein the at least one first region (14, 32, 42) is facing an inflowing fluid (F) and the at least one second region (15, 33, 43) is facing away from an inflowing fluid (F).
- Microfluidic structure (1, 3) according to any one of the preceding claims 1 to 3, characterised in that a plurality of indentations (13, 31, 41) are provided which, proceeding from side walls of the cavity (10, 30, 40), are arranged alternatingly.
- Microfluidic structure (1, 5) according to any one of the preceding claims 1 to 4, characterised in that the at least one first region (14, 32, 42) extends approximately over the entire length (L) of a longitudinal side of the at least one indentation (13, 31, 41) and the at least one second region (15, 33, 43) only extends over a part of the length (L) of another longitudinal side.
- Microfluidic platform (2, 4, 6) with at least one microfluidic structure (1, 3, 5) according to at least one of claims 1 to 5.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP12732642.9A EP2729251B1 (en) | 2011-07-05 | 2012-07-02 | Microfluid structure with cavities |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP11172775 | 2011-07-05 | ||
PCT/EP2012/062863 WO2013004673A1 (en) | 2011-07-05 | 2012-07-02 | Microfluidic structure having recesses |
EP12732642.9A EP2729251B1 (en) | 2011-07-05 | 2012-07-02 | Microfluid structure with cavities |
Publications (2)
Publication Number | Publication Date |
---|---|
EP2729251A1 EP2729251A1 (en) | 2014-05-14 |
EP2729251B1 true EP2729251B1 (en) | 2018-11-14 |
Family
ID=44773214
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP12732642.9A Not-in-force EP2729251B1 (en) | 2011-07-05 | 2012-07-02 | Microfluid structure with cavities |
Country Status (4)
Country | Link |
---|---|
US (2) | US20140227148A1 (en) |
EP (1) | EP2729251B1 (en) |
JP (1) | JP6098020B2 (en) |
WO (1) | WO2013004673A1 (en) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP6240785B2 (en) * | 2013-12-20 | 2017-11-29 | スリーエム イノベイティブ プロパティズ カンパニー | System and method for sample concentration and detection |
WO2015184343A1 (en) * | 2014-05-30 | 2015-12-03 | Absolute Exhibits, Inc. | Thermoset in-mold finishing film |
TWI499637B (en) * | 2014-06-20 | 2015-09-11 | Ind Tech Res Inst | Foam body and light emitting device with thereof |
GB201617869D0 (en) | 2016-10-21 | 2016-12-07 | Blacktrace Holdings Limited | A microfluidic device |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4271119A (en) * | 1979-07-23 | 1981-06-02 | Eastman Kodak Company | Capillary transport device having connected transport zones |
US4618476A (en) | 1984-02-10 | 1986-10-21 | Eastman Kodak Company | Capillary transport device having speed and meniscus control means |
DE10313201A1 (en) * | 2003-03-21 | 2004-10-07 | Steag Microparts Gmbh | Microstructured separator and microfluidic process for separating liquid components from a liquid containing particles |
DE10360220A1 (en) | 2003-12-20 | 2005-07-21 | Steag Microparts Gmbh | Fine structure arrangement in fluid ejection system, has predetermined region in transitional zone between inlet and discharge ports, at which capillary force is maximum |
DE102004027422A1 (en) * | 2004-06-04 | 2005-12-29 | Boehringer Ingelheim Microparts Gmbh | Device for receiving blood and separating blood components |
EP1616619A1 (en) * | 2004-07-17 | 2006-01-18 | Tecan Trading AG | Device and method to influence air bubbles in a hybridizaion chamber |
ATE503578T1 (en) * | 2005-01-27 | 2011-04-15 | Boehringer Ingelheim Micropart | USE OF A DEVICE FOR EXAMINING SAMPLE FLUID |
DE102005017653A1 (en) * | 2005-04-15 | 2006-10-19 | Boehringer Ingelheim Microparts Gmbh | Device and method to control liquid flow has two sections of channel whereby liquid flows from one to the other and can be held at first section using capillary stop and said stop can be bypassed if wished by moving sections |
JP4685611B2 (en) * | 2005-12-02 | 2011-05-18 | 株式会社エンプラス | Microfluidic device |
-
2012
- 2012-07-02 JP JP2014517765A patent/JP6098020B2/en active Active
- 2012-07-02 US US14/127,341 patent/US20140227148A1/en not_active Abandoned
- 2012-07-02 WO PCT/EP2012/062863 patent/WO2013004673A1/en active Application Filing
- 2012-07-02 EP EP12732642.9A patent/EP2729251B1/en not_active Not-in-force
-
2015
- 2015-05-22 US US14/719,503 patent/US9409171B2/en not_active Expired - Fee Related
Non-Patent Citations (1)
Title |
---|
None * |
Also Published As
Publication number | Publication date |
---|---|
US9409171B2 (en) | 2016-08-09 |
US20150251182A1 (en) | 2015-09-10 |
JP2014521056A (en) | 2014-08-25 |
US20140227148A1 (en) | 2014-08-14 |
JP6098020B2 (en) | 2017-03-22 |
WO2013004673A1 (en) | 2013-01-10 |
EP2729251A1 (en) | 2014-05-14 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP1440732B1 (en) | Microfluidic configuration for dosing liquids | |
EP1441131B1 (en) | Use of a microfluidic switch to temporarily stop a flow of liquid | |
EP3052233B1 (en) | Device and method for aliquoting a liquid | |
DE102012202775B4 (en) | FLUIDIKMODUL, DEVICE AND METHOD FOR PUMPING A LIQUID | |
EP2308589B1 (en) | Microfluid structure | |
WO1999046045A1 (en) | Sample support | |
EP2576065A1 (en) | Flow cell with cavity and diaphragm | |
EP2729251B1 (en) | Microfluid structure with cavities | |
EP2455162A1 (en) | Microfluidic element for analysing a fluid sample | |
EP2308597B1 (en) | Micro-fluidic structure and method for measuring and/or positioning a liquid volume | |
DE102011078770B4 (en) | Microfluidic device, microfluidic system and method of transporting fluids | |
EP2406495B1 (en) | Pump having a filter arrangement | |
EP2552586B1 (en) | Component of a biosensor and method for producing same | |
DE102009001257A1 (en) | Apparatus and method for handling liquids | |
EP2624954B1 (en) | Method for washing a microfluid cavity | |
EP2522427B1 (en) | Micro-fluid device and method for manufacturing the same | |
EP2754495A2 (en) | Microfluidic channel system with bubble capture device and method for the removal of gas bubbles | |
WO2012041479A1 (en) | Microfluidic chip comprising several cylinder-piston arrangements | |
EP2688670B1 (en) | Fluidic system for bubbble-free filling of a microfluidic filter chamber | |
DE102009045403B4 (en) | Device for separating gas and liquid and uses thereof | |
DE102008004139B3 (en) | Liquid moving device for moving liquid back and forth over sensor surface of analytic sensor utilized in bio analytics field, has channel designed in such manner that counter pressure difference opposite to pressure difference is produced | |
EP2624955A1 (en) | Microfluidic platform |
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: 20140205 |
|
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 |
|
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: 20180803 |
|
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: CH Ref legal event code: EP Ref country code: AT Ref legal event code: REF Ref document number: 1064183 Country of ref document: AT Kind code of ref document: T Effective date: 20181115 |
|
REG | Reference to a national code |
Ref country code: DE Ref legal event code: R096 Ref document number: 502012013820 Country of ref document: DE |
|
REG | Reference to a national code |
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: 20181114 |
|
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: 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: 20181114 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: 20181114 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: 20190214 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: 20181114 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: 20190214 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: 20181114 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: 20190314 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: 20181114 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
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: 20181114 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: 20190215 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: 20181114 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: 20181114 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: 20190314 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: 20181114 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
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: 20181114 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: 20181114 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: 20181114 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: 20181114 |
|
REG | Reference to a national code |
Ref country code: DE Ref legal event code: R097 Ref document number: 502012013820 Country of ref document: DE |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
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: 20181114 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: 20181114 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: 20181114 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: 20181114 |
|
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 |
|
26N | No opposition filed |
Effective date: 20190815 |
|
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: 20181114 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
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: 20181114 |
|
REG | Reference to a national code |
Ref country code: CH Ref legal event code: PL |
|
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: 20181114 |
|
REG | Reference to a national code |
Ref country code: BE Ref legal event code: MM Effective date: 20190731 |
|
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: 20190702 Ref country code: BE Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20190731 Ref country code: CH Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20190731 Ref country code: LI Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20190731 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: IE Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20190702 |
|
REG | Reference to a national code |
Ref country code: AT Ref legal event code: MM01 Ref document number: 1064183 Country of ref document: AT Kind code of ref document: T Effective date: 20190702 |
|
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: 20190702 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
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: 20181114 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: HU Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT; INVALID AB INITIO Effective date: 20120702 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: 20181114 |
|
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: 20181114 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: GB Payment date: 20220720 Year of fee payment: 11 Ref country code: DE Payment date: 20220620 Year of fee payment: 11 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: FR Payment date: 20220720 Year of fee payment: 11 |
|
REG | Reference to a national code |
Ref country code: DE Ref legal event code: R119 Ref document number: 502012013820 Country of ref document: DE |
|
GBPC | Gb: european patent ceased through non-payment of renewal fee |
Effective date: 20230702 |
|
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: 20240201 Ref country code: GB Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20230702 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: FR Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20230731 |