EP3154692A1 - Module fluidique, dispositif et procédé de manipulation de fluide - Google Patents

Module fluidique, dispositif et procédé de manipulation de fluide

Info

Publication number
EP3154692A1
EP3154692A1 EP15731267.9A EP15731267A EP3154692A1 EP 3154692 A1 EP3154692 A1 EP 3154692A1 EP 15731267 A EP15731267 A EP 15731267A EP 3154692 A1 EP3154692 A1 EP 3154692A1
Authority
EP
European Patent Office
Prior art keywords
compression chamber
fluid
channel
rotational frequency
outlet
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.)
Granted
Application number
EP15731267.9A
Other languages
German (de)
English (en)
Other versions
EP3154692B1 (fr
Inventor
Frank Schwemmer
Steffen ZEHNLE
Nils Paust
Daniel Mark
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.)
Hahn-Schickard-Gesellschaft fur Angewandte Forsch
Original Assignee
Hann-Schickard-Gesellschaft fuer Angewandte Forschung eV
Albert Ludwigs Universitaet Freiburg
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 Hann-Schickard-Gesellschaft fuer Angewandte Forschung eV, Albert Ludwigs Universitaet Freiburg filed Critical Hann-Schickard-Gesellschaft fuer Angewandte Forschung eV
Priority to PL15731267T priority Critical patent/PL3154692T3/pl
Publication of EP3154692A1 publication Critical patent/EP3154692A1/fr
Application granted granted Critical
Publication of EP3154692B1 publication Critical patent/EP3154692B1/fr
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/50273—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means or forces applied to move the fluids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502746—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
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0621—Control of the sequence of chambers filled or emptied
    • 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
    • B01L2300/0803—Disc shape
    • 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
    • B01L2300/087—Multiple sequential chambers
    • 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
    • B01L2400/08—Regulating or influencing the flow resistance
    • B01L2400/084—Passive control of flow resistance

Definitions

  • Fluidic module apparatus and method for handling fluid
  • the present invention relates to a fluidic module, apparatus and method for handling liquid which are particularly suitable for handling such as retaining and releasing or pumping liquid in a centrifugal micro-fluidic system.
  • Centrifugal microfluidics deals with the handling of liquids in the pl to ml range in rotating systems.
  • Such systems are mostly disposable polymer cartridges used in or in place of centrifuge rotors, with the intention of enabling completely novel processes that are not reproducible by manual processes or pipetting robots due to the required precision or volume, or to automate laboratory processes.
  • Standard laboratory processes such as pipetting, centrifuging, mixing or aliquoting can be implemented in a micro fluidic cartridge.
  • the cartridges contain channels for the fluid guidance, as well as chambers for the collection of liquids.
  • the cartridges are subjected to a predefined sequence of rotational frequencies, the frequency protocol, so that the fluids in the cartridges can be guided by inertial forces into corresponding chambers.
  • Centrifugal microfluidics is mainly used in laboratory analysis and mobile diagnostics.
  • centrifugal microfluidic disks known for example under the names “Lab-on-a-disk”, “Lab-Disk”, and “Lab-on-CD”, which are disclosed in US Pat
  • Other formats such as a microfluidic centrifuge tube, known as the "LabTube”, can be used in rotors of existing standard laboratory equipment.
  • the liquid in the first fluid chamber is retained, compressing a volume of gas trapped in the first fluid chamber, and as the rotational frequency decreases, the trapped gas volume expands again, displacing some of the fluid into a curved siphon channel the siphon apex arises too additional centrifugal pressure which causes the liquid to be transferred from the first to the second fluid chamber.
  • a volume of gas trapped by the process liquid in the first fluid chamber is compressed to use in the second phase the corresponding expansion of the gas volume for the return of the liquid.
  • a certain threshold of the rotational frequency (threshold frequency) must be exceeded in order to retain the fluid in the first fluid chamber.
  • the same threshold frequency must subsequently be exceeded in order to return the liquid via the siphon vertex and to start the fluid transfer from the first fluid chamber into the second fluid chamber. So that the filling of the siphon is independent of capillary forces, the threshold frequency should be as high as possible.
  • 5142 - 5145 describe a method for centrifugal-dynamic inward pumping, which makes it possible to retain liquid in a first phase at defined, high rotational frequencies (usually several 10 Hz) in a first fluid chamber to subsequently in a second phase with rapidly decreasing rotational frequency Fluid is transferred from a reservoir into a first fluid chamber as the rotational frequency increases, and the fluid is retained in the first fluid chamber at an increased rotational frequency, with a volume of gas trapped in the first fluid chamber With rapidly decreasing rotation frequency, the trapped gas volume expands again and displaces the G Rough part of the liquid through that channel, which has the lower flow resistance.
  • high rotational frequencies usually several 10 Hz
  • a volume of gas trapped by the process liquid in the first chamber is compressed to utilize in the second phase the energy of the compressed gas for the radial inward pumping of the liquid.
  • a corresponding method is described in DE 10 2012 202 775 AI.
  • the threshold frequency in pneumatic pumping should be as high as possible to minimize the influx of capillary forces.
  • the siphon is usually filled even at high rotational frequencies (even if the deceleration rate is several 10 Hz / s).
  • the inventors have realized that this entails disadvantages.
  • the inclusion of air bubbles and thus the malfunction of the siphon can be the result.
  • This effect could be minimized in a siphon with a small cross-sectional area, but this would increase the dependence on capillary forces, as well as the fluidic resistance and thus the time required for the fluid transfer.
  • the object of the present invention is to provide a fluidic module, a device and a method for handling, in particular pumping, a liquid, which allow a time-controlled and decoupled from the centrifuge dynamics pumping over a certain radial distance.
  • Embodiments of the invention provide a fluidic module rotatable about a center of rotation, comprising: a first compression chamber having a fluid inlet and a fluid outlet; a second compression chamber having a fluid inlet; a first fluid passage connected to the first compression chamber via the fluid inlet of the first compression chamber; and a second fluid passage connecting the fluid outlet of the first compression chamber to the fluid inlet of the second compression chamber, wherein rotation of the fluidic module enables fluid to be centrifugally driven through the first fluid passage into the first compression chamber and into the second fluid passage, and thereby a compressible medium the second compression chamber can be enclosed and compressed, wherein fluid can be driven from the second fluid channel into the first compression chamber, from the first compression chamber into an outlet channel and through the outlet channel by lowering the rotational frequency and consequent expansion of the compressible medium, wherein at least one of the the following features are fulfilled: the second fluid channel has a higher flow resistance than the outlet channel, and the fluid inlet of the second compression chamber is located radially further outward with respect to the
  • Embodiments of the invention provide an apparatus for handling, in particular pumping, fluid with a fluidic module as described herein and a drive apparatus configured to apply rotations to the fluidic module at different rotational frequencies.
  • the drive device is configured to, in a first phase, pressurize the fluidic module with rotation at a rotational frequency at or above a first rotational frequency at which fluid is centrifugally driven through the first fluid channel into the first compression chamber, at which first compression chamber is filled with the liquid and is driven at the liquid from the first compression chamber into the second fluid passage, thereby to enclose and compress the compressible medium in the second compression chamber.
  • the drive device is further configured to lower the rotational frequency in a second phase after the first phase below a second rotational frequency at which the force exerted on the fluid by the compressed medium in the second compression chamber outweighs the centrifugal force exerted by the fluid, so that expands the compressible medium and thereby fluid is driven from the second fluid channel into the first compression chamber, from the first compression chamber into the outlet channel and through the outlet channel.
  • Embodiments of the invention provide a method of handling fluid with a fluidic module as described herein.
  • the fluidic module is rotated with rotation at a rotational frequency at or above a first rotational frequency to centrifugally drive liquid through the first fluid channel into the first compression chamber to fill the first compression chamber with the fluid and to remove fluid from the first compression chamber driving the first compression chamber into the second fluid channel to thereby enclose and compress the compressible medium in the second compression chamber.
  • the rotational frequency is lowered below a second rotational frequency at which the force exerted on the fluid by the compressed medium in the second compression chamber outweighs the centrifugal force exerted by the fluid so that the compressible medium expands and thereby Fluid is driven from the second fluid channel into the first compression chamber, from the first compression chamber into the outlet channel and through the outlet channel.
  • Embodiments of the invention thus relate to fluidic modules, devices and methods suitable for controlled release and controlled passage of liquid through a channel, and more particularly to such fluidic modules, devices and methods suitable for timed pumping of a liquid in centrifuge rotors.
  • Embodiments of the invention are based on the realization that it is possible by providing a first compression chamber, a second compression chamber and a second fluid channel, which fluidly connects the first and the second compression chamber, and a corresponding design of the course and the dimensions of the second fluid channel. the dynamics of the pumping action through the exhaust passage during and after the reduction of the rotational frequency passive, that is to control without further change of the rotational frequency.
  • the second fluid channel may have a higher flow resistance than the outlet channel.
  • the cross section of the second fluid channel may be small enough to represent a flow resistance for the liquid that is higher than the flow resistance of the outlet channel.
  • the viscosity of the liquid e.g., water
  • the viscosity of the compressible medium e.g., air
  • the pumping process takes place through the outlet channel at a much higher flow rate, which is not limited by the flow resistance in the second fluid channel. Due to the delay of the pumping process, the conduction of the liquid through the outlet channel thus at any rotational frequency, especially at standstill, take place.
  • the end of the second fluid channel may be located radially further out than the beginning of the second fluid channel, such that expansion of the compressible medium in the second compression chamber and the second fluid channel causes the centrifugal back pressure to be applied to the second fluid channel during emptying expansible compressible medium significantly decreases due to this course of the second fluid channel.
  • this drop in the centrifugal counter-pressure is brought about by only a smaller change in the volume of the compressible medium, which means that the almost constant overpressure of the compressible medium is offset by a significant change in the centrifugal counter-pressure. This pressure change is compensated by the liquid in the first compression chamber with ho flow rate is pumped into the outlet channel.
  • embodiments of the invention provide high dynamics in draining the liquid from the first compression chamber. Due to the strong change in the centrifugal back pressure during emptying, but also during the filling of the second fluid channel not only the dynamics of the emptying of the first compression chamber, or the dynamics of the filling of the second compression chamber is affected, but also the rotational frequency, in which - the liquid levels are in equilibrium - the emptying of the first compression chamber takes place. Thus, embodiments of the invention allow adjustment of the switching frequencies due to the different radial positions of the fluid outlet of the first compression chamber and the fluid inlet of the second compression chamber.
  • the outlet channel may be at least partially formed by the first fluid channel.
  • the first channel is the outlet channel.
  • the outlet channel includes a portion of the first fluid channel and a third fluid channel branching from the first fluid channel.
  • the outlet channel is a fluid channel separate from the first fluid channel, which opens at a radially outer portion or the radially outer end thereof into the first compression chamber.
  • the outlet channel has a lower flow resistance than the first fluid channel.
  • the outlet channel has a siphon, wherein an outlet end of the siphon with respect to the rotation center is arranged radially further out than the position at which the outlet channel opens into the first compression chamber.
  • Embodiments of the invention are centrifugal-pneumatic delay switches.
  • there is first a delay of emptying a first compression chamber whereupon dynamic emptying can take place without further change of the rotational frequency.
  • FIGS. 1A to 1D are schematic plan views of fluidic structures of an embodiment of a fluidic module, wherein a fluid inlet of the second compression chamber is disposed radially further out than a fluid outlet of the first compression chamber.
  • Fig. 2 is a diagram for explaining underlying effects of the embodiment shown in Figs. 1A to 1D;
  • FIG. 3 shows a schematic plan view of fluidic structures according to an exemplary embodiment of a fluidic module, in which the second fluid channel has a greater fluid resistance than the outlet channel;
  • FIG. 4 shows a schematic plan view of fluidic structures according to an exemplary embodiment of a fluidic module, in which the first channel also forms the outlet channel;
  • FIG. 5 is a schematic plan view of fluidic structures according to an exemplary embodiment of a fluidic module, in which the outlet channel has a siphon;
  • 6 and 7 are schematic side views for explaining embodiments of devices for handling liquid.
  • radial is meant to be radial with respect to the center of rotation about which the fluidic module or rotor is rotatable.
  • a radial direction is radially sloping away from the center of rotation and a radial direction toward the center of rotation is radially increasing.
  • a fluid channel, the beginning of which is closer to the center of rotation than the end is thus radially sloping, while a fluid channel, the beginning of which is farther from the center of rotation than its end, is radially increasing.
  • a channel which has a radially rising section thus has directional components which rise radially or extend radially inwards. It is clear that such a channel does not have to run exactly along a radial line, but can run at an angle to the radial line or bent.
  • compression chamber is meant herein a chamber that allows the compression of a compressible medium.
  • this may be a non-vented chamber.
  • it may be a chamber, which indeed has a vent, the vent but for the compressible medium has such a high flow resistance, that still occurs by an inflowing liquid compressing the compressible medium and that by a by such a vent occurring pressure reduction in the compression chamber (in the relevant period) is negligible.
  • the first and second compression chambers described herein could also be considered as a compression chamber having two regions connected via the second fluid channel.
  • the compression chambers, with the exception of the inlets and outlets described no further fluid openings.
  • the compression chamber may be coupled to additional compression volume via one or more optional additional channels.
  • one or more compression chambers may include a closable vent.
  • different flow resistances (hydraulic resistances) of respective fluid channels can be achieved via different flow cross sections.
  • different flow resistances may also be achieved by other means, such as different channel lengths, obstacles integrated in the channels, and the like.
  • a fluid channel means a structure whose length dimension is greater from a fluid inlet to a fluid outlet, for example more than 5 times or more than 10 times greater than the dimension defining the flow area or define.
  • a fluid channel has a flow resistance for flowing through it from the fluid inlet to the fluid outlet.
  • a fluid chamber is a chamber having dimensions such that a relevant flow resistance does not occur in the same.
  • FIG. 6 shows a device with a fluidic module 10 in the form of a rotational body, which has a substrate 12 and a cover 14.
  • the substrate 12 and the cover 14 may be circular in plan view, with a central opening through which the rotary body 10 may be attached via a conventional fastening means 16 to a rotating part 18 of a drive device 20.
  • the rotating part 18 is rotatably supported on a stationary part 22 of the drive device 20.
  • the drive device 20 may be, for example, a conventional adjustable-speed centrifuge or a CD or DVD drive.
  • a control device 24 may be provided, which is designed to control the drive device 20 in order to act on the rotation body 10 with rotations with different rotational frequencies.
  • controller 24 may be implemented by, for example, a suitably programmed computing device or custom integrated circuit.
  • the controller 24 may further be configured to control the drive device 20 upon manual inputs by a user to effect the required rotations of the rotating body. In either case, the controller 24 may be configured to control the drive device 20 to apply the required rotational frequencies to the rotating body
  • Embodiments of the invention as described herein are to be implemented.
  • drive device 20 a conventional centrifuge with only one direction of rotation can be used.
  • the rotary body 10 has the required fluidic structures.
  • the required fluidic structures may be formed by cavities and channels in the lid 14, the substrate 12 or in the substrate 12 and the lid 14.
  • fluidic structures may be imaged in the substrate 12 while fill openings and vents are formed in the lid 14.
  • the patterned substrate (including fill openings and vents) is located at the top and the lid is located at the bottom.
  • fluidic modules 32 are inserted into a rotor 30 and together with the rotor 30 form the rotary body 10.
  • the fluidic modules 32 can each have a substrate and a lid, in which corresponding fluidic structures can again be formed.
  • the rotational body 10 formed by the rotor 30 and the fluidic modules 32 in turn can be acted upon by a drive device 20, which is controlled by the control device 24, with a rotation.
  • R a center of rotation about which the fluidic module or the rotational body is rotatable.
  • the fluidic module or the rotational body which has the fluidic structures can be formed from any suitable material, for example a plastic, such as PMMA (polymethyl methacrylate), PC (polycarbonate), PVC (polyvinyl chloride) or PDMS (polydimethylsiloxane), glass or the like.
  • a plastic such as PMMA (polymethyl methacrylate), PC (polycarbonate), PVC (polyvinyl chloride) or PDMS (polydimethylsiloxane), glass or the like.
  • the rotary body 10 may be considered as a centrifugal-micro fluidic platform.
  • FIGS. 1A to 1D wherein in FIGS 1D, the fluidic structures formed in a respective fluidic module are shown during different phases of operation.
  • the fluidic structures have a first fluid channel 2, which constitutes an inlet channel, a first compression chamber 3 and a second compression chamber 5, which are connected to one another via a second fluid channel 4, and a third fluid channel 1, which forms part of an outlet channel. More specifically, in the example shown in FIGS. 1A to 1D, the third fluid channel 1 branches off at a branch 50 from the first fluid channel 2, so that a part of the first fluid channel between the first compression chamber 3 and the branch 50 and the third fluid channel represent the outlet channel.
  • the third fluid channel 1 can have a lower flow resistance (that is, for example, a larger flow cross section) than the first fluid channel 2, so that a discharge of the first compression chamber 3 takes place to a greater extent through the third fluid channel 1.
  • the fluid inlet 8 of the second compression chamber 5 is located radially further outward than the fluid outlet 7 of the first compression chamber 3.
  • a portion of the second fluid channel extends between the radially innermost portion 4a and the radially outermost portion 4b of the second fluid channel with respect to the center of rotation in Fig. 1A is denoted by R, radially outward.
  • Phase 1 filling process
  • a radially inner end of the first fluid inlet channel may be fluidly coupled to an inlet chamber (not shown) for this purpose.
  • a compressible medium is enclosed, which is compressed by the liquid flowing into the first compression chamber, Fig. 1A. This builds up in the compressible medium Overpressure, which is compensated by the centrifugal pressure of the liquid in the fluid inlet channel 2 and in the fluid outlet channel 1.
  • the first compression chamber 3 is completely filled, and the liquid flows via the connecting channel 4 into the second compression chamber 5. After a sufficiently long time of filling, the system reaches the equilibrium state in which the liquid levels are not at a given rotational frequency change more. With decreasing rotational frequency, the enclosed compressed compressible medium (gas volume) expands again and liquid is pumped back through the first fluid channel 2 and the third fluid channel 1.
  • Phase 2a Discharge process with dynamics due to hysteresis behavior
  • the connecting channel 4 which causes the System again is located outside the equilibrium of centrifugal pressure and pneumatic (in the case of gas as a compressible medium) back pressure of the compressible medium. This imbalance is compensated as shown in Fig. 2 by fast ⁇ dynamic ') emptying of the first compression chamber 3 until the equilibrium state is reached again.
  • the fluid in the third fluid channel 1 can reach radially inner positions that are not attainable in the equilibrium state.
  • the second fluid channel 3 increases the dynamics of the emptying process, as a result of which higher filling levels are achieved in the first and third fluid channels 2 and 1 than in the equilibrium state.
  • the third fluid channel may be configured as a siphon, the outlet end of which is arranged radially further outward than the fluid inlet of the first compression chamber 3 in order to allow the entire liquid to drain off.
  • the liquid volumes in the fluid chambers 3 and 5 are subject to a hysteresis behavior with respect to the rotational frequency.
  • a dynamic "sudden" filling of the fluid chamber 5 occurs as the rotational frequency increases, which is indicated by + in FIG is rotational frequency / / in exceeded sinking rotational frequency which in Figure 2 by arrows with -.. is in a dynamic "abrupt" emptying the fluid chamber 3 takes place as soon as the rotational frequency ⁇ is undershot.
  • Phase 2b Discharge process with dynamics due to high flow resistance
  • Fig. 3 shows an alternative embodiment of the invention in which the fluid inlet 8 of the second compression chamber 5 is not disposed radially further out than the fluid outlet of the first compression chamber. Rather, in the embodiment shown in FIG. 3, the fluid inlet 8 of the second compression chamber 5 lies radially further inward than the fluid outlet 7 of the first compression chamber 3. It should be noted that the rotational center in the figures is above the fluidic structure, as shown in FIG. 3 in turn indicated by that designated by the reference numeral R rotation center.
  • the rotational frequency is subsequently reduced, the return flow of the fluid is limited by the high flow resistance in the second fluid channel 4.
  • the flow rate of the liquid during the backflow is so low even when the centrifuge rotor is at a standstill that the liquid fill levels in the fluid channels 1 and 2 change only slightly.
  • the rotational frequency can be significantly below the critical value / / or even zero. If the rotational frequency / / long enough undershot, so first emptied the second compression chamber 5, followed by the second fluid channel 4.
  • the high flow resistance and the hysteresis behavior can be combined.
  • the dynamics of the emptying process can be increased or maximized.
  • be designed by both a connecting channel is designed with a higher flow resistance than the outlet channel and the fluid inlet of the second compression chamber is arranged radially further outward than the fluid outlet of the first compression chamber.
  • FIG. 4 shows a further embodiment of the invention, in which the fluid inlet channel 2 also represents the fluid outlet channel.
  • the fluid inlet channel 2 also represents the fluid outlet channel.
  • the fluid outlet channel 1 is designed as a siphon 60 such that at least one region, for example an outlet end 62 of the fluid outlet channel 1, lies radially further outward than the fluid inlet 6 of the first compression chamber. This makes it possible to empty all the fluid from the fluidic structure having the described fluid channels and compression chambers.
  • the second compression chamber may be divided into a plurality of compression chambers, which are connected in series via respective fluid channels. It is thus possible that the second compression chamber is again subdivided into a plurality of chambers. This makes it possible that certain chambers are filled exclusively with the compressible medium, while other chambers are filled with both the compressible medium and with the liquid.
  • a plurality of fluids supplied sequentially via the first fluid conduit may be used for the described operation, wherein one or more of the fluids may also be compressible.
  • several of the described fluidic structures may be connected in parallel.
  • a sequential switching of the fluids to be achieved at defined times is useful for automating a wide variety of bio-chemical processes.
  • the outlet channel need not open into the first compression chamber together with the inlet channel.
  • the outlet channel can also open separately in a radially outer section, for example the radially outer end, into the first compression chamber, as long as the design ensures that the compressible medium in the compression chamber can be compressed.
  • the separate outlet channel can be designed to be closed by the liquid during the filling of the first compression chamber through the first fluid channel.
  • the connecting channel 4 may have a diameter of 20 ⁇ m to 200 ⁇ m.
  • the volume of the compression chamber 3 may be between 25 and 75 ⁇ , for example 50 ⁇ , and the volume of the compression chamber 4 may be at 150 ⁇ to 360 ⁇ .
  • the volume of the first compression chamber is smaller, for example by a factor of 2 to 6, than the volume of the second compression chamber.
  • Typical fluid volumes of the processed liquid can be 100 .mu.l, with volumes of 100 nl to 5 ml are conceivable with appropriate design of the chambers.
  • the outlet channel may have a fluidic resistance (flow resistance) that is at least a factor of 2 or at least a factor of 10 smaller than the fluidic resistance of the connection channel. As has been described, this is not required in every embodiment.
  • the viscosity of the processed liquid eg water
  • the viscosity of the processed liquid may have a viscosity of from 30 to 90 higher than the compressible medium.
  • water as the liquid to be processed has an approximately 60 times higher viscosity than air as a compressible medium.
  • the fluidic structures do not have to have the illustrated shapes.
  • the chambers need not be rectangular, but may take any shape and may typically have rounded corners.
  • the maximum volume of the connection channel may be limited to about 0.3 ⁇ to 0.5 ⁇ .
  • the minimum volume of the first compression chamber should be approximately 5 ⁇ in this case.
  • the connecting channel can also be designed with a large length, in which case also higher channel volumes would be conceivable. However, this would be associated with technical disadvantages, for example, a higher dead volume and a greater manufacturing effort.
  • a dynamic filling and emptying of a compression chamber takes place.
  • Such dynamic filling and emptying can be achieved by the first and second compression chambers connected via the connecting channel.
  • filling and emptying can be achieved, which differs from dynamic filling and emptying in compression chambers, as known in the art.
  • the equilibrium level as a function of the rotational frequency is steady, i. with a very small change in the frequency of rotation (e.g., 0.1 Hz), there is always a very small change in the level of the compression chamber (e.g., ⁇ 1%).
  • the equilibrium level is defined as the level that sets at an infinitely long lasting constant rotation frequency.
  • a dynamic filling or a dynamic emptying with a hysteresis behavior can be achieved.
  • a rotational frequency range due to the geometric arrangement of a chamber system (consisting of at least two compression chambers or pneumatic chambers) no rotational frequency in the equilibrium state, ie at infinite length of centrifugation, a defined liquid level can be assigned.
  • a first or a second equilibrium level can be set. If this rotation frequency range is left, a new equalization weight level, which deviates greatly from the current level. This large deviation can be compensated by accelerating the filling or emptying process, driven by centrifugal force or pneumatic force.
  • a dynamic filling or a dynamic emptying can be achieved by using high flow resistance.
  • the time course of the filling or emptying process can be significantly determined by channel cross sections.
  • flow rates not equal to zero can be achieved due to viscous forces even at a constant rotational frequency.
  • the replacement of different media in narrow channels and the associated changes in viscosity can lead to high flow rate changes, which can accelerate the filling and emptying even at a constant rotational frequency.
  • Embodiments of the present invention provide a fluidic module rotatable about a center of rotation, comprising: a first fluid channel; a first compression chamber fluidly coupled to the first fluid channel; a second compression chamber fluidly coupled to the first compression chamber via a second fluid channel; and a third fluid channel fluidly coupled to the first compression chamber.
  • a liquid is centrifugally drivable through the first fluid channel into the first compression chamber.
  • a compressible medium in the second compression chamber is trappable and compressible by a liquid forced by the centrifugal force through the first fluid channel into the first compression chamber, the second fluid channel, and the second compression chamber.
  • Embodiments of the invention provide a centrifugal microfluidic structure having a compression chamber divided into a first part and a second part by a fluid channel, wherein both parts can be reversibly at least partially filled with liquid and emptied.
  • embodiments of the present invention include the generation of high dynamic fluidic switching operations that do not require rapid changes in rotational frequency.
  • embodiments of the present invention have in operation the generation of highly dynamic fluidic switching operations, in which neither rapid changes of the rotational frequency, nor high fluidic resistances are required.
  • embodiments of the invention show the maintenance of the compression of a compressible medium in a centrifuge rotor over a certain minimum period of time with any variation of the rotational frequency.
  • Embodiments of the present invention allow liquids to be held in fluid chambers while any rotational frequency protocol can be used for a certain time. This allows parallel processes to be carried out while maintaining the liquid and thus automating more complex processes than are known in the prior art.
  • embodiments of the present invention also enable liquids to be maintained above a defined rotational frequency that may be well below the rotational frequency used to activate compliance with the fluid.
  • Embodiments of the present invention enable a highly dynamic release of fluid from fluid chambers even if only very low acceleration rates are available. This is especially useful for operation in standard laboratory centrifuges. Furthermore, they enable fluid transfer via a fluid outlet channel, in particular via a siphon, at low rotational frequencies. Thus, the aforementioned disadvantages of emptying at high rotational frequencies can be avoided.

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)
  • Centrifugal Separators (AREA)
  • Reciprocating Pumps (AREA)

Abstract

L'invention concerne un module fluidique, qui est apte à tourner autour d'un centre de rotation, qui comprend une première chambre de compression comportant une entrée de fluide et une sortie de fluide, une seconde chambre de compression comportant une entrée de fluide, un premier canal de fluide, qui est lié avec la première chambre de compression par l'intermédiaire de l'entrée de fluide de la première chambre de compression, et un second canal de fluide, qui relie la sortie de fluide de la première chambre de compression avec l'entrée de fluide de la seconde chambre de compression. Par une rotation du module fluidique, un fluide est apte à être entraîné de manière centrifuge à travers le premier canal de fluide dans la première chambre de compression et dans le second canal de fluide, et ainsi un milieu compressible est apte à être introduit et comprimé dans la seconde chambre de compression. Par réduction de la fréquence de rotation et ainsi de l'expansion relative du milieu compressible, du fluide est apte à être entraîné hors du second canal de fluide dans la première chambre de compression, hors de la première chambre de compression dans un canal de sortie et à travers le canal de sortie. Le second canal de sortie comprend une résistance à l'écoulement plus élevée que le canal de sortie et/ou l'entrée de fluide de la seconde chambre de compression est disposée, par rapport au centre de rotation, radialement plus à l'extérieur que la sortie de fluide de la première chambre de compression.
EP15731267.9A 2014-06-11 2015-06-10 Module fluidique, dispositif et procédé de manipulation de fluide Active EP3154692B1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PL15731267T PL3154692T3 (pl) 2014-06-11 2015-06-10 Moduł płynowy, urządzenie i sposób stosowania płynów

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102014211121.8A DE102014211121A1 (de) 2014-06-11 2014-06-11 Fluidikmodul, vorrichtung und verfahren zum handhaben von flüssigkeit
PCT/EP2015/062956 WO2015189280A1 (fr) 2014-06-11 2015-06-10 Module fluidique, dispositif et procédé de manipulation de fluide

Publications (2)

Publication Number Publication Date
EP3154692A1 true EP3154692A1 (fr) 2017-04-19
EP3154692B1 EP3154692B1 (fr) 2018-11-14

Family

ID=53487334

Family Applications (1)

Application Number Title Priority Date Filing Date
EP15731267.9A Active EP3154692B1 (fr) 2014-06-11 2015-06-10 Module fluidique, dispositif et procédé de manipulation de fluide

Country Status (8)

Country Link
US (1) US10350598B2 (fr)
EP (1) EP3154692B1 (fr)
DE (1) DE102014211121A1 (fr)
DK (1) DK3154692T3 (fr)
ES (1) ES2711088T3 (fr)
PL (1) PL3154692T3 (fr)
TR (1) TR201901927T4 (fr)
WO (1) WO2015189280A1 (fr)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102012202775B4 (de) * 2012-02-23 2016-08-25 Hahn-Schickard-Gesellschaft für angewandte Forschung e.V. Fluidikmodul, vorrichtung und verfahren zum pumpen einer flüssigkeit
DE102016207845B4 (de) * 2016-05-06 2018-04-12 Hahn-Schickard-Gesellschaft für angewandte Forschung e.V. Fluidhandhabungsvorrichtung und Verfahren zur Fluidhandhabung
DE102016208972A1 (de) * 2016-05-24 2017-11-30 Hahn-Schickard-Gesellschaft für angewandte Forschung e.V. Fluidikmodul, Vorrichtung und Verfahren zum biochemischen Prozessieren einer Flüssigkeit unter Verwendung von mehreren Temperaturzonen
AU2020239904A1 (en) 2019-03-19 2021-11-11 Stichting Euroclonality Means and methods for accurately assessing clonal immunoglobulin (IG)/T cell receptor (TR) gene rearrangements.
CN109932523A (zh) * 2019-04-11 2019-06-25 石家庄禾柏生物技术股份有限公司 一种基于离心力的液体定量转移装置
DE102019007512A1 (de) * 2019-10-29 2021-04-29 Lilian Labs GmbH Mikrofluidische Vorrichtung zur Aufnahme von Flüssigkeiten und zugehöriges Verfahren
DE102023202639A1 (de) * 2023-03-23 2024-09-26 Hahn-Schickard-Gesellschaft für angewandte Forschung e.V. Fluidikmodul, Fluidhandhabungsvorrichtung und Verfahren mit vorübergehendem Druckausgleich in einer Pneumatikkammer

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102009050979B4 (de) * 2009-10-28 2011-09-22 Hahn-Schickard-Gesellschaft für angewandte Forschung e.V. Vorrichtung und Verfahren zum Steuern eines Flüssigkeitsflusses und Vorrichtung zum Verschließen eines Entlüftungskanals
EP2688674B1 (fr) * 2011-03-24 2015-11-04 Biosurfit, S.A. Contrôle de la sequence de flux de liquide sur un dispositif microfluidique
DE102012202775B4 (de) 2012-02-23 2016-08-25 Hahn-Schickard-Gesellschaft für angewandte Forschung e.V. Fluidikmodul, vorrichtung und verfahren zum pumpen einer flüssigkeit
DE102013203293B4 (de) * 2013-02-27 2016-01-21 Hahn-Schickard-Gesellschaft für angewandte Forschung e.V. Vorrichtung und Verfahren zum Leiten einer Flüssigkeit durch einen ersten oder zweiten Auslasskanal
DE102013210818B3 (de) * 2013-06-10 2014-05-15 Hahn-Schickard-Gesellschaft für angewandte Forschung e.V. Fluidhandhabungsvorrichtung und Verfahren zum Prozessieren einer Flüssigkeit unter Verwendung einer Diffusionsbarriere
DE102013215002B3 (de) * 2013-07-31 2014-11-06 Hahn-Schickard-Gesellschaft für angewandte Forschung e.V. Vorrichtung und Verfahren zum Bewegen von Flüssigkeit in einem zentrifugalen System unter Verwendung von Unterdruck

Also Published As

Publication number Publication date
TR201901927T4 (tr) 2019-03-21
DE102014211121A1 (de) 2015-12-17
DK3154692T3 (en) 2019-03-04
EP3154692B1 (fr) 2018-11-14
WO2015189280A1 (fr) 2015-12-17
US10350598B2 (en) 2019-07-16
US20170216837A1 (en) 2017-08-03
ES2711088T3 (es) 2019-04-30
PL3154692T3 (pl) 2019-06-28

Similar Documents

Publication Publication Date Title
EP3154692B1 (fr) Module fluidique, dispositif et procédé de manipulation de fluide
DE102012202775B4 (de) Fluidikmodul, vorrichtung und verfahren zum pumpen einer flüssigkeit
DE102013203293B4 (de) Vorrichtung und Verfahren zum Leiten einer Flüssigkeit durch einen ersten oder zweiten Auslasskanal
DE102016207845B4 (de) Fluidhandhabungsvorrichtung und Verfahren zur Fluidhandhabung
DE102013219929B4 (de) Fluidikmodul, Vorrichtung und Verfahren zum Aliquotieren einer Flüssigkeit
EP3592463B1 (fr) Procédé de commutation centrifugo-pneumatique de liquide
DE102013215002B3 (de) Vorrichtung und Verfahren zum Bewegen von Flüssigkeit in einem zentrifugalen System unter Verwendung von Unterdruck
DE102008003979B3 (de) Fluidikvorrichtung, Fluidikmodul und Verfahren zum Handhaben einer Flüssigkeit
EP2486978A1 (fr) Support de test microfluidique destiné à répartir une quantité de liquide en quantités partielles
DE102009050979B4 (de) Vorrichtung und Verfahren zum Steuern eines Flüssigkeitsflusses und Vorrichtung zum Verschließen eines Entlüftungskanals
DE102013218978B3 (de) Vorrichtung und Verfahren, die Rückschlüsse über die Viskosität einer Probe ermöglichen
EP1944084A1 (fr) Dispositif de soupape pour un système de microliquide
EP2406495B1 (fr) Pompe à système de filtres
DE102004046396A1 (de) Partikelsedimentationsvorrichtung und Verfahren zum Durchführen einer Partikelsedimentation
EP2754495A2 (fr) Système de canaux microfluidique doté d'un dispositif de collecte de bulles et procédé d'élimination de bulles de gaz
EP2688670B1 (fr) Système fluidique de remplissage sans bulles d'une chambre de filtration microfluidique
DE102023207560B3 (de) Halten und Transferieren von Flüssigkeiten
DE102012220250A1 (de) Fluidikmodul für eine zentrifugale filtration und verfahren zum filtern einer probe
DE102023202639A1 (de) Fluidikmodul, Fluidhandhabungsvorrichtung und Verfahren mit vorübergehendem Druckausgleich in einer Pneumatikkammer
DE102023202206A1 (de) Sequentielles Pumpen mittels eines Aktuators
EP3720611B1 (fr) Tambour séparateur
WO2023202862A1 (fr) Manipulation de deux volumes de liquide

Legal Events

Date Code Title Description
STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE INTERNATIONAL PUBLICATION HAS BEEN MADE

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

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

Free format text: STATUS: REQUEST FOR EXAMINATION WAS MADE

17P Request for examination filed

Effective date: 20161115

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

RIN1 Information on inventor provided before grant (corrected)

Inventor name: ZEHNLE, STEFFEN

Inventor name: PAUST, NILS

Inventor name: SCHWEMMER, FRANK

Inventor name: MARK, DANIEL

DAV Request for validation of the european patent (deleted)
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: 20180524

RAX Requested extension states of the european patent have changed

Extension state: ME

Extension state: BA

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

DAX Request for extension of the european patent (deleted)
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: 1064185

Country of ref document: AT

Kind code of ref document: T

Effective date: 20181115

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: DE

Ref legal event code: R096

Ref document number: 502015006880

Country of ref document: DE

REG Reference to a national code

Ref country code: DK

Ref legal event code: T3

Effective date: 20190225

REG Reference to a national code

Ref country code: NL

Ref legal event code: FP

REG Reference to a national code

Ref country code: LT

Ref legal event code: MG4D

REG Reference to a national code

Ref country code: SE

Ref legal event code: TRGR

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

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

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: 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: 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

REG Reference to a national code

Ref country code: ES

Ref legal event code: FG2A

Ref document number: 2711088

Country of ref document: ES

Kind code of ref document: T3

Effective date: 20190430

RAP2 Party data changed (patent owner data changed or rights of a patent transferred)

Owner name: HAHN-SCHICKARD-GESELLSCHAFT FUER ANGEWANDTE FORSCH

REG Reference to a national code

Ref country code: NO

Ref legal event code: T2

Effective date: 20181114

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

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: 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: 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

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: 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: 502015006880

Country of ref document: DE

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

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

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

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

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: 20190610

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: 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

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: 20150610

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

P01 Opt-out of the competence of the unified patent court (upc) registered

Effective date: 20230508

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

Ref country code: DE

Payment date: 20230620

Year of fee payment: 9

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

Ref country code: ES

Payment date: 20230719

Year of fee payment: 9

Ref country code: CH

Payment date: 20230702

Year of fee payment: 9

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

Ref country code: IE

Payment date: 20240617

Year of fee payment: 10

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

Ref country code: GB

Payment date: 20240620

Year of fee payment: 10

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

Ref country code: DK

Payment date: 20240620

Year of fee payment: 10

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

Ref country code: NL

Payment date: 20240619

Year of fee payment: 10

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

Ref country code: AT

Payment date: 20240617

Year of fee payment: 10

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

Ref country code: NO

Payment date: 20240618

Year of fee payment: 10

Ref country code: FR

Payment date: 20240621

Year of fee payment: 10

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

Ref country code: PL

Payment date: 20240529

Year of fee payment: 10

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

Ref country code: TR

Payment date: 20240530

Year of fee payment: 10

Ref country code: SE

Payment date: 20240620

Year of fee payment: 10

Ref country code: BE

Payment date: 20240618

Year of fee payment: 10