EP2688670B1 - Fluidic system for bubbble-free filling of a microfluidic filter chamber - Google Patents

Fluidic system for bubbble-free filling of a microfluidic filter chamber Download PDF

Info

Publication number
EP2688670B1
EP2688670B1 EP12703472.6A EP12703472A EP2688670B1 EP 2688670 B1 EP2688670 B1 EP 2688670B1 EP 12703472 A EP12703472 A EP 12703472A EP 2688670 B1 EP2688670 B1 EP 2688670B1
Authority
EP
European Patent Office
Prior art keywords
channel
filter
microfluidic
venting
valve
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
EP12703472.6A
Other languages
German (de)
French (fr)
Other versions
EP2688670A1 (en
Inventor
Peter Rothacher
Jochen Rupp
Christian Dorrer
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Robert Bosch GmbH
Original Assignee
Robert Bosch GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Robert Bosch GmbH filed Critical Robert Bosch GmbH
Publication of EP2688670A1 publication Critical patent/EP2688670A1/en
Application granted granted Critical
Publication of EP2688670B1 publication Critical patent/EP2688670B1/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502753Containers 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
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502723Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by venting arrangements
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06Fluid handling related problems
    • B01L2200/0684Venting, avoiding backpressure, avoid gas bubbles
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/06Auxiliary integrated devices, integrated components
    • B01L2300/0681Filter
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0809Geometry, shape and general structure rectangular shaped
    • B01L2300/0816Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0874Three dimensional network
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0887Laminated structure
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0403Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0406Moving fluids with specific forces or mechanical means specific forces capillary forces
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/06Valves, specific forms thereof
    • B01L2400/0633Valves, specific forms thereof with moving parts
    • B01L2400/0655Valves, specific forms thereof with moving parts pinch valves

Definitions

  • the subject of the present invention is a microfluidic filter chamber with an adjustable venting channel and its use.
  • the invention also relates to a fluidic system for the bubble-free filling of a microfluidic filter chamber and for filtering liquids, a method for the bubble-free filling of a microfluidic filter chamber and a method for filtering liquids.
  • Purpose may be, for example, the accumulation of bacteria or the purification of DNA fragments.
  • filter mats or particle fillings made of glass, silicates, oxides, polymers, etc. are used as filters.
  • tubes plastic tubes
  • pressed filters are commercially available, eg QIAquick Purification Kit from Qiagen ®, such filters are known from the DE10218554A1 , These filters are manually filled by pipetting and then centrifuged.
  • the invention relates to a microfluidic filter chamber, comprising a filter, a vent channel, an inlet channel and an outlet channel, wherein the filter is inserted between inlet channel and outlet channel, wherein the vent channel branches off from the inlet channel, wherein the flow through the microfluidic filter chamber by means of a valve in the vent channel is adjustable, and wherein the venting channel opens into the outlet channel and the inlet channel and the outlet channel has a channel extension in the form of a variable funnel-shaped cross-sectional area with a larger cross-section towards the filter and wherein the channel extension in front of the filter has a venting channel, which opens into the outlet channel.
  • the microfluidic filter chamber according to the invention and microfluidic systems which contain this filter chamber have the following advantageous properties:
  • the microfluidic filter chamber can be filled without bubbles. There are no air bubbles trapped during filling. Clogging of the filter is thus prevented.
  • the filter is flowed homogeneously. Liquid flows can be regulated precisely. The complete rinsing of the filter is guaranteed. There is no clogging of components or undesirable reactions. The mixing of liquids is facilitated. Foaming is prevented.
  • the fluidic resistance of the system is kept constant. Reagents contained in the filter chamber can be exchanged in a controlled manner.
  • the microfluidic filter chamber comprises a valve for controllable passage through the vent passage. This serves to regulate the passage of liquid or gas.
  • the microfluidic filter chamber is characterized in that the inlet channel is widened before and / or after the filter.
  • the inlet channel in front of the filter is widened to ensure a homogeneous flow of the filter with liquids.
  • the outlet channel after the filter is also extended.
  • the invention also relates to a fluidic system as defined in claim 2, comprising at least one microfluidic filter chamber according to the invention.
  • the invention relates to a fluidic system comprising a multi-layer structure comprising at least two layers and a microfluidic filter chamber.
  • the invention also relates to a fluidic system comprising a multilayer construction of at least two layers and a microfluidic filter chamber comprising a filter, a venting channel, an inlet channel and an outlet channel, wherein the filter is inserted into the inlet channel, and wherein before the filter from the inlet channel branches off the venting channel and wherein the flow through the vent passage can be regulated, namely by a valve.
  • one or more layers are structured planes.
  • a particular embodiment of the invention relates to a fluidic system comprising a cover, a first structured plane and a second structured plane, an inlet channel, an extension of the inlet channel, a filter, a valve and an outlet channel.
  • the fluidic system may further include a duct passage.
  • a further particular embodiment of the invention relates to a fluidic system, characterized in that an elastic film is located between the one and the other layer or an elastic film is located between the first structured plane and the second structured plane.
  • the fluidic system for bubble-free filling of a microfluidic filter chamber still comprises at least one further valve.
  • the invention further provides a method as defined in claim 4 for the bubble-free filling of a microfluidic filter chamber comprising a filter, a vent passage and a valve disposed on the vent passage, wherein a fluid is pumped through the inlet passage to the filter while the valve is opened in the vent channel, whereby the filter is filled capillary and the channel region in front of the filter and a part of the venting channel are filled, in which case the channel region is filled after the filter, and then the valve is closed.
  • the invention also provides a method as defined in claim 5, for filtering a liquid with a microfluidic filter chamber, wherein first the microfluidic filter chamber is filled bubble-free with a liquid according to the aforementioned method by pumping a liquid through the inlet channel to the filter, while the valve is open in the vent channel, then the filter is filled capillary, then the channel area in front of the filter, then the vent channel and then the channel area after the filter is filled, and then the valve is closed, and then the liquid to be filtered through the Inlet channel flows in and then flows through the filter into the outlet channel.
  • the filter may be a fabric filter or a silica filter.
  • fabric mats or particle beds made of glass, silicates, oxides or polymers are used as filters.
  • all filters can be used which are suitable for fluidic systems, in particular for microfluidic systems.
  • the radius of the filter is adjusted to the size of the microfluidic filter chamber. It can be between 1 and 25 mm. Preferably, the radius of the filter is 2 to 5 mm, more preferably 3.5 mm.
  • the venting channel is adjustable, i. the flow of liquid or gas through the vent channel can be regulated.
  • the venting channel is regulated by a valve.
  • the valve can be opened, partially opened or closed.
  • Valves serve to regulate the fluid flows in a fluidic filter chamber and in the fluidic systems.
  • an elastic film located between two layers may act as a valve.
  • Other examples of valves are rotary valves or external solenoid valves.
  • the microfluidic filter chamber may be part of a fluidic system.
  • the fluidic system may be a microfluidic system.
  • the microfluidic filter chamber is in a layer.
  • the microfluidic filter chamber is realized in a multi-layer structure.
  • it is a multi-layer structure consisting of several different layers.
  • it is a multi-layer structure, which is composed of several identical layers.
  • a multi-layer structure includes, for example, two to twenty or more layers.
  • the microfluidic filter chamber can only be in one layer or extend over several layers.
  • the microfluidic filter chamber extends to two or three or more layers.
  • the layer may be, for example, a polymer.
  • the layer may consist, for example, of polycarbonate, polypropylene, polyethylene, polystyrene or a cyclic polyolefin.
  • the layer can also consist of glass or silicon.
  • the layer may be structured, for example by means of injection molding, hot stamping, milling, sandblasting or etching.
  • Individual layers can be deformable.
  • a layer may be a film, particularly preferably an elastic film, for example an elastomer or a thermoplastic elastomer, in particular a polyurethane-based thermoplastic elastomer.
  • individual layers are 0.05 to 10 mm thick.
  • individual Layers a thickness of 0.1 mm, 0.5 mm, 1 mm, 1.5 mm, 2 mm, 2.5 mm, 3 mm, 3.5 mm, 4 mm, 4.5 mm, 5 mm.
  • the fluidic channels are widened at certain locations, i. they have a larger cross section or diameter compared to the inlet channel or outlet channel.
  • the inlet channel is extended immediately in front of the filter to achieve a homogeneous flow.
  • the exhaust duct is extended immediately after the filter.
  • the inlet channel or outlet channel is expanded before or after the filter, for example over a length of 5 mm to 10 mm.
  • transversal flow for example, before or after the filter is a cavity having a height between 0.5 mm and 2 mm, for example of 1 mm, and in diameter between 0.5 mm and 3 mm, for example 2 mm, smaller than the diameter of the filter.
  • phaseguides in the extensions of the fluidic channels are called phaseguides, i. Structures (e.g., edges) that control the filling of the channel extension by pinning effects.
  • Such structures may be located, for example, in the extension of the inlet channel to control the filling of the channel extension and to ensure a uniform filling.
  • the channel leading to the filter is expanded before and after the filter in order to achieve a homogeneous flow of the filter in these systems.
  • This extension is preferably achieved by a cross section of the channels leading to the filter. These channels are funnel-shaped open towards the filter.
  • the microfluidic filter chamber can be used in all fluidic systems in which a filter is used, for example in polymer lab-on-chip (LOC) and micro-total-analysis ( ⁇ TA) systems for molecular diagnostics.
  • LOC polymer lab-on-chip
  • ⁇ TA micro-total-analysis
  • FIG. 1b shows a schematic view of a microfluidic filter chamber 10 according to the invention in a second embodiment with inlet channel 1, channel extensions 2 and 13, filter 3, vent channel 4, valve 5, outlet channel 6, wherein the vent channel 4 after the filter 3 opens into the outlet channel 6.
  • the inlet channel 1, the channel extension 2 in front of the filter 3, the filter 3, the channel extension 13 after the filter 3 and the outlet channel 6 are arranged such that the inlet channel is funnel-shaped into the channel extension 2 in front of the filter 3 Filter 3 leads, and the channel extension 13 after the filter 3 opens into the outlet channel 6.
  • the vent channel 4 is connected to both the channel extension 2 before the filter 3 and with the channel extension 13 to the filter 3.
  • the venting channel 4 has a valve 5. Through the valve 5, the flow through the vent channel 4 from the channel extension 2 before the filter 3 and the channel extension 13 to the filter 3 can be controlled.
  • the second embodiment i. the embodiment in which venting channel 4 opens after the filter 3 in the outlet channel 6, thus also has the advantage that the channel extension 13 is completely filled after the filter 3 through the vent channel 4. Since the flow resistance of the venting channel 4 is significantly lower than that of the filter 3, this filling process is bubble-free and much faster than through the filter.
  • FIG. 2 shows a possible embodiment which does not fall under the claimed subject matter.
  • the microfluidic filter chamber 10 is part of a microfluidic system.
  • the microfluidic filter chamber 10 is realized in a multi-layer structure consisting of three polymer substrates 9, 14, 11 and an elastic film 12 which is located between the first, structured layer 11 and the second, structured layer 14.
  • the three layers are arranged one above the other, wherein the third layer 9 is arranged above the second layer 14, and the second layer 14 is arranged above the first layer 11.
  • FIG. 3 shows the same embodiment of the invention as FIG. 2 but in plan view.
  • the microfluidic filter chamber 10 is part of a microfluidic system.
  • FIG. 3 1 shows an inlet channel 1 with channel extension 2, filter 3, ventilation channel 4, valve 5, outlet channel 6, channel bushing 7, additional valve 8, radius R1 of the channel extension 2, radius R2 of the filter 3 and width w2 of the outlet channel 6.
  • FIG. 4 shows the inlet channel 1, with channel extension 2, filter 3, ventilation channel 4, valve 5, outlet channel 6, channel passage 7 and additional valve. 8
  • R1 2.5mm
  • R2 3.5mm
  • w1 0.5mm
  • w2 0.3mm
  • t1 0.3mm
  • t2 1.5mm
  • t3 1.5mm
  • t4 1.5mm.

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)
  • Life Sciences & Earth Sciences (AREA)
  • Molecular Biology (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)

Description

Gegenstand der vorliegenden Erfindung ist eine mikrofluidische Filterkammer mit einem regulierbaren Entlüftungskanal und deren Verwendung. Die Erfindung betrifft auch ein fluidisches System zur blasenfreien Befüllung einer mikrofluidischen Filterkammer und zum Filtern von Flüssigkeiten, ein Verfahren zum blasenfreien Befüllen einer mikrofluidischen Filterkammer und ein Verfahren zum Filtern von Flüssigkeiten.The subject of the present invention is a microfluidic filter chamber with an adjustable venting channel and its use. The invention also relates to a fluidic system for the bubble-free filling of a microfluidic filter chamber and for filtering liquids, a method for the bubble-free filling of a microfluidic filter chamber and a method for filtering liquids.

Stand der TechnikState of the art

In der Molekularbiologie und der molekularen Diagnostik werden oftmals Filtrierungs- oder Festphasen-Extraktionsschritte durchgeführt. Zweck kann z.B. die Akkumulation von Bakterien oder die Aufreinigung von DNA-Fragmenten sein. Je nach Anwendung kommen als Filter Gewebematten oder Partikelschüttungen aus Glas, Silikaten, Oxiden, Polymeren etc. zum Einsatz. Als Bestandteil von Kits sind in Kunststoffröhrchen (sogenannte Tubes) eingepresste Filter kommerziell erhältlich, z.B. QIAquick Purification Kit der Firma Qiagen ®, solche Filter sind bekannt aus der DE10218554A1 . Diese Filter werden manuell durch Pipettieren befüllt und dann zentrifugiert.In molecular biology and molecular diagnostics, filtration or solid phase extraction steps are often performed. Purpose may be, for example, the accumulation of bacteria or the purification of DNA fragments. Depending on the application, filter mats or particle fillings made of glass, silicates, oxides, polymers, etc. are used as filters. As a component of kits in plastic tubes (so-called tubes) pressed filters are commercially available, eg QIAquick Purification Kit from Qiagen ®, such filters are known from the DE10218554A1 , These filters are manually filled by pipetting and then centrifuged.

Neuerdings wird verstärkt versucht, molekularbiologische Abläufe (sogenannte Assays) in mikrofluidische Systeme zu integrieren. Ein derartiges System wird auch als Lab-on-Chip (LOC) oder Micro-Total-Analysis-System (µTAS) bezeichnet. Zu den Besonderheiten eines LOC-Systems gehören: Die Zeitersparnis bei der Durchführung des Assays. Es werden nur geringere Mengen an Reagenzien und Proben benötigt. Der Arbeitsaufwand für den Bediener wird reduziert. Es gibt weniger Möglichkeiten für den Bediener, Fehler zu machen. Das System kann portabel ausgeführt werden.More recently, attempts have been made to integrate molecular biological processes (so-called assays) into microfluidic systems. Such a system is also referred to as Lab-on-Chip (LOC) or Micro-Total-Analysis-System (μTAS). The specifics of a LOC system include: The time savings in performing the assay. Only smaller amounts of reagents and samples are needed. The workload for the Operator is reduced. There are fewer opportunities for the operator to make mistakes. The system can be portable.

Anwendungen für LOC-Systeme finden sich in der molekularen Diagnostik, in der Umweltanalytik, etc. Eine Möglichkeit, einen Filter in ein mikrofluidisches LOC-System zu integrieren, ist in der US2002/0185431A1 beschrieben. Ein weiterer Aufbau einer Pumpeinheit mit eingebautem Filter ist beispielsweise in der US 6,416,293 B1 angegeben.Applications for LOC systems can be found in molecular diagnostics, in environmental analysis, etc. One way to integrate a filter in a microfluidic LOC system is in the US2002 / 0185431A1 described. Another structure of a pump unit with built-in filter is for example in the US Pat. No. 6,416,293 B1 specified.

Offenbarung der ErfindungDisclosure of the invention

Gegenstand der Erfindung ist eine mikrofluidische Filterkammer, umfassend einen Filter, einen Entlüftungskanal, einen Einlasskanal und einen Auslasskanal, wobei der Filter zwischen Einlasskanal und Auslasskanal eingefügt ist, wobei der Entlüftungskanal vom Einlasskanal abzweigt, wobei der Durchfluss durch die mikrofluidische Filterkammer mittels eines Ventils im Entlüftungskanal regulierbar ist, und wobei der Entlüftungskanal in den Auslasskanal mündet und der Einlasskanal und der Auslasskanal eine Kanalerweiterung in Form einer variablen trichterförmigen Querschnittsfläche mit einem größeren Querschnitt zum Filter hin aufweisen und wobei die Kanalerweiterung vor dem Filter einen Entlüftungskanal aufweist, welcher in den Auslasskanal mündet.The invention relates to a microfluidic filter chamber, comprising a filter, a vent channel, an inlet channel and an outlet channel, wherein the filter is inserted between inlet channel and outlet channel, wherein the vent channel branches off from the inlet channel, wherein the flow through the microfluidic filter chamber by means of a valve in the vent channel is adjustable, and wherein the venting channel opens into the outlet channel and the inlet channel and the outlet channel has a channel extension in the form of a variable funnel-shaped cross-sectional area with a larger cross-section towards the filter and wherein the channel extension in front of the filter has a venting channel, which opens into the outlet channel.

Die erfindungsgemäße mikrofluidische Filterkammer und mikrofluidische Systeme, die diese Filterkammer enthalten, weisen folgende vorteilhafte Eigenschaften auf: Die mikrofluidische Filterkammer kann blasenfrei befüllt werden. Es werden beim Befüllen keine Luftblasen eingeschlossen. Ein Verstopfen des Filters wird somit verhindert. Der Filter wird homogen angeströmt. Flüssigkeitsströme können genau reguliert werden. Das vollständige Ausspülen des Filters ist gewährleistet. Es kommt nicht zur Verstopfung von Komponenten oder zum Ablauf unerwünschter Reaktionen. Das Mischen von Flüssigkeiten wird erleichtert. Die Schaumbildung wird verhindert. Der fluidische Widerstand des Systems wird konstant gehalten. In der Filterkammer enthaltene Reagenzien können kontrolliert ausgetauscht werden.The microfluidic filter chamber according to the invention and microfluidic systems which contain this filter chamber have the following advantageous properties: The microfluidic filter chamber can be filled without bubbles. There are no air bubbles trapped during filling. Clogging of the filter is thus prevented. The filter is flowed homogeneously. Liquid flows can be regulated precisely. The complete rinsing of the filter is guaranteed. There is no clogging of components or undesirable reactions. The mixing of liquids is facilitated. Foaming is prevented. The fluidic resistance of the system is kept constant. Reagents contained in the filter chamber can be exchanged in a controlled manner.

Erfindungsgemäß umfasst die mikrofluidische Filterkammer ein Ventil zum kontrollierbaren Durchlass durch den Entlüftungskanal. Dies dient dazu, den Durchlass von Flüssigkeit oder Gas zu regulieren.According to the invention, the microfluidic filter chamber comprises a valve for controllable passage through the vent passage. This serves to regulate the passage of liquid or gas.

Erfindungsgemäß ist die mikrofluidische Filterkammer dadurch gekennzeichnet, dass der Einlasskanal vor und/oder nach dem Filter erweitert ist. Der Einlasskanal vor dem Filter ist erweitert, um ein homogenes Anströmen des Filters mit Flüssigkeiten zu gewährleisten. Der Auslasskanal nach dem Filter ist ebenfalls erweitert.According to the invention, the microfluidic filter chamber is characterized in that the inlet channel is widened before and / or after the filter. The inlet channel in front of the filter is widened to ensure a homogeneous flow of the filter with liquids. The outlet channel after the filter is also extended.

Die Erfindung betrifft auch ein fluidisches System, wie in Anspruch 2 definiert, mit mindestens einer erfindungsgemäßen mikrofluidischen Filterkammer. In einer besonderen Ausführungsform betrifft die Erfindung ein fluidisches System umfassend einen Mehrschichtaufbau aus mindestens zwei Schichten und eine mikrofluidische Filterkammer. Die Erfindung betrifft auch ein fluidisches System umfassend einen Mehrschichtaufbau aus mindestens zwei Schichten und eine mikrofluidische Filterkammer umfassend einen Filter, einen Entlüftungskanal, einen Einlasskanal und einen Auslasskanal, wobei der Filter in den Einlasskanal eingefügt ist, und wobei vor dem Filter vom Einlasskanal der Entlüftungskanal abzweigt und wobei der Durchfluss durch den Entlüftungskanal reguliert werden kann, nämlich durch ein Ventil. In einer besonderen Ausführungsform der Erfindung sind eine oder mehrere Schichten strukturierte Ebenen.The invention also relates to a fluidic system as defined in claim 2, comprising at least one microfluidic filter chamber according to the invention. In a particular embodiment, the invention relates to a fluidic system comprising a multi-layer structure comprising at least two layers and a microfluidic filter chamber. The invention also relates to a fluidic system comprising a multilayer construction of at least two layers and a microfluidic filter chamber comprising a filter, a venting channel, an inlet channel and an outlet channel, wherein the filter is inserted into the inlet channel, and wherein before the filter from the inlet channel branches off the venting channel and wherein the flow through the vent passage can be regulated, namely by a valve. In a particular embodiment of the invention, one or more layers are structured planes.

Eine besondere Ausführungsform der Erfindung betrifft ein fluidisches System umfassend einen Deckel, eine erste strukturierte Ebene und eine zweite strukturierte Ebene, einen Einlasskanal, eine Erweiterung des Einlasskanals, einen Filter, ein Ventil und einen Auslasskanal. Gegebenenfalls kann das fluidische System außerdem eine Kanaldurchführung umfassen.A particular embodiment of the invention relates to a fluidic system comprising a cover, a first structured plane and a second structured plane, an inlet channel, an extension of the inlet channel, a filter, a valve and an outlet channel. Optionally, the fluidic system may further include a duct passage.

Eine weitere besondere Ausführungsform der Erfindung betrifft ein fluidisches System, dadurch gekennzeichnet, dass sich zwischen der einen und der anderen Schicht eine elastische Folie befindet oder zwischen der ersten strukturierten Ebene und der zweiten strukturierten Ebene eine elastische Folie befindet.A further particular embodiment of the invention relates to a fluidic system, characterized in that an elastic film is located between the one and the other layer or an elastic film is located between the first structured plane and the second structured plane.

In einer besonderen Ausführungsform umfasst das fluidische System zur blasenfreien Befüllung einer mikrofluidischen Filterkammer noch mindestens ein weiteres Ventil.In a particular embodiment, the fluidic system for bubble-free filling of a microfluidic filter chamber still comprises at least one further valve.

Gegenstand der Erfindung ist weiterhin ein Verfahren, wie in Anspruch 4 definiert, zur blasenfreien Befüllung einer mikrofluidischen Filterkammer, die einen Filter, einen Entlüftungskanal und ein an dem Entlüftungskanal angeordnetes Ventil umfasst, wobei eine Flüssigkeit durch den Einlasskanal zum Filter gepumpt wird, während das Ventil im Entlüftungskanal geöffnet ist, wodurch der Filter kapillar befüllt wird und der Kanalbereich vor dem Filter und ein Teil des Entlüftungskanals befüllt werden, wobei dann der Kanalbereich nach dem Filter befüllt wird, und anschließend das Ventil geschlossen wird.The invention further provides a method as defined in claim 4 for the bubble-free filling of a microfluidic filter chamber comprising a filter, a vent passage and a valve disposed on the vent passage, wherein a fluid is pumped through the inlet passage to the filter while the valve is opened in the vent channel, whereby the filter is filled capillary and the channel region in front of the filter and a part of the venting channel are filled, in which case the channel region is filled after the filter, and then the valve is closed.

Gegenstand der Erfindung ist auch ein Verfahren, wie in Anspruch 5 definiert, zum Filtern einer Flüssigkeit mit einer mikrofluidischen Filterkammer, wobei zuerst die mikrofluidische Filterkammer blasenfrei mit einer Flüssigkeit nach dem vorgenannten Verfahren befüllt wird, indem eine Flüssigkeit durch den Einlasskanal zum Filter gepumpt wird, während das Ventil im Entlüftungskanal offen ist, dann der Filter kapillar befüllt wird, dann der Kanalbereich vor dem Filter, dann der Entlüftungskanal und dann der Kanalbereich nach dem Filter befüllt wird, und anschließend das Ventil geschlossen wird, und danach die zu filternde Flüssigkeit durch den Einlasskanal einströmt und dann durch den Filter in den Auslasskanal strömt.The invention also provides a method as defined in claim 5, for filtering a liquid with a microfluidic filter chamber, wherein first the microfluidic filter chamber is filled bubble-free with a liquid according to the aforementioned method by pumping a liquid through the inlet channel to the filter, while the valve is open in the vent channel, then the filter is filled capillary, then the channel area in front of the filter, then the vent channel and then the channel area after the filter is filled, and then the valve is closed, and then the liquid to be filtered through the Inlet channel flows in and then flows through the filter into the outlet channel.

Der Filter kann ein Gewebefilter oder ein Silikafilter sein. Beispielsweise kommen als Filter Gewebematten oder Partikelschüttungen aus Glas, Silikaten, Oxiden oder Polymeren zum Einsatz Grundsätzlich können alle Filter verwendet werden, die sich für fluidische Systeme, insbesondere für mikrofluidische Systeme eignen. Der Radius des Filters wird an die Abmessung der mikrofluidischen Filterkammer angepasst. Er kann zwischen 1 und 25 mm liegen. Vorzugsweise ist der Radius des Filters 2 bis 5 mm, besonders bevorzugt 3,5 mm.The filter may be a fabric filter or a silica filter. For example, fabric mats or particle beds made of glass, silicates, oxides or polymers are used as filters. In principle, all filters can be used which are suitable for fluidic systems, in particular for microfluidic systems. The radius of the filter is adjusted to the size of the microfluidic filter chamber. It can be between 1 and 25 mm. Preferably, the radius of the filter is 2 to 5 mm, more preferably 3.5 mm.

Fluidische Kanäle sind Kanäle, durch die die Flüssigkeit in einem mikrofluidischen System strömen kann. Die Abmessungen der fluidischen Kanäle werden an die betreffenden Anforderungen angepasst. Zu den fluidischen Kanälen gehören der Einlasskanal, der Auslasskanal, der Entlüftungskanal und die Kanalerweiterung. Zu den fluidischen Kanälen gehört auch die Kanaldurchführung. Die fluidischen Kanäle haben beispielsweise einen Durchmesser bzw. eine Breite von 0,05 bis 2 mm, vorzugsweise von 0,2 bis 1 mm, besonders bevorzugt 0.3 oder 0.5 mm, und eine Tiefe von 0,05 bis 1.5 mm, vorzugsweise von 0,2 bis 1 mm, besonders bevorzugt 0.3 oder 0.5 mm.Fluidic channels are channels through which the fluid can flow in a microfluidic system. The dimensions of the fluidic channels are adapted to the respective requirements. The fluidic channels include the inlet channel, the outlet channel, the vent channel and the channel extension. The ducting also belongs to the fluidic channels. The fluidic channels have, for example, a diameter or a width of 0.05 to 2 mm, preferably of 0.2 to 1 mm, particularly preferably 0.3 or 0.5 mm, and a depth of 0.05 to 1.5 mm, preferably of 0, 2 to 1 mm, more preferably 0.3 or 0.5 mm.

Der Entlüftungskanal ist regulierbar, d.h. der Durchfluss von Flüssigkeit oder Gas durch den Entlüftungskanal kann reguliert werden. Der Entlüftungskanal wird über ein Ventil reguliert. Das Ventil kann geöffnet, teilweise geöffnet oder verschlossen sein.The venting channel is adjustable, i. the flow of liquid or gas through the vent channel can be regulated. The venting channel is regulated by a valve. The valve can be opened, partially opened or closed.

Ventile dienen der Regulation der Flüssigkeitsströme in einer fluidischen Filterkammer und in den fluidischen Systemen. Beispielsweise kann eine elastische Folie, die sich zwischen zwei Schichten befindet, als Ventil fungieren. Weitere Beispiele für Ventile sind Drehventile oder externe Magnetventile.Valves serve to regulate the fluid flows in a fluidic filter chamber and in the fluidic systems. For example, an elastic film located between two layers may act as a valve. Other examples of valves are rotary valves or external solenoid valves.

Die mikrofluidische Filterkammer kann Bestandteil eines fluidischen Systems sein. Das fluidische System kann ein mikrofluidisches System sein. In einer besonderen Ausführungsform befindet sich die mikrofluidische Filterkammer in einer Schicht. In einer anderen besonderen Ausführungsform ist die mikrofluidische Filterkammer in einem Mehrschichtaufbau realisiert. In einer besonderen Ausführungsform handelt es sich um einen Mehrschichtaufbau, der aus mehreren unterschiedlichen Schichten besteht. In einer anderen besonderen Ausführungsform handelt es sich um einen Mehrschichtaufbau, der aus mehreren gleichen Schichten aufgebaut ist. Ein Mehrschichtaufbau umfasst beispielsweise zwei bis zwanzig oder mehr Schichten. Dabei kann sich die mikrofluidische Filterkammer nur in einer Schicht befinden oder sich über mehrere Schichten erstrecken. In einer besonderen Ausführungsform erstreckt sich die mikrofluidische Filterkammer auf zwei oder drei oder mehr Schichten. Die Schicht kann beispielsweise ein Polymer sein. Die Schicht kann beispielsweise aus Polykarbonat, Polypropylen, Polyethylen, Polystyrol oder einem zyklischen Polyolefin bestehen. Die Schicht kann auch aus Glas oder Silizium bestehen. Die Schicht kann strukturiert sein, beispielsweise mittels Spritzguss, Heißprägen, Fräsen, Sandstrahlen oder Ätzen. Einzelne Schichten können deformierbar sein. Beispielsweise kann eine Schicht eine Folie sein, besonders bevorzugt eine elastische Folie, beispielsweise ein Elastomer oder ein thermoplastisches Elastomer, insbesondere ein Polyurethan-basiertes thermoplastisches Elastomer. In bevorzugten Ausführungsformen der Erfindung sind einzelne Schichten 0,05 bis 10 mm dick. Vorzugsweise haben einzelne Schichten eine Dicke von 0,1 mm, 0,5 mm, 1 mm, 1,5 mm, 2 mm, 2,5 mm, 3 mm, 3,5 mm, 4 mm, 4,5 mm, 5 mm.The microfluidic filter chamber may be part of a fluidic system. The fluidic system may be a microfluidic system. In a particular embodiment, the microfluidic filter chamber is in a layer. In another particular embodiment, the microfluidic filter chamber is realized in a multi-layer structure. In a particular embodiment, it is a multi-layer structure consisting of several different layers. In another particular embodiment, it is a multi-layer structure, which is composed of several identical layers. A multi-layer structure includes, for example, two to twenty or more layers. In this case, the microfluidic filter chamber can only be in one layer or extend over several layers. In a particular embodiment, the microfluidic filter chamber extends to two or three or more layers. The layer may be, for example, a polymer. The layer may consist, for example, of polycarbonate, polypropylene, polyethylene, polystyrene or a cyclic polyolefin. The layer can also consist of glass or silicon. The layer may be structured, for example by means of injection molding, hot stamping, milling, sandblasting or etching. Individual layers can be deformable. For example, a layer may be a film, particularly preferably an elastic film, for example an elastomer or a thermoplastic elastomer, in particular a polyurethane-based thermoplastic elastomer. In preferred embodiments of the invention, individual layers are 0.05 to 10 mm thick. Preferably, individual Layers a thickness of 0.1 mm, 0.5 mm, 1 mm, 1.5 mm, 2 mm, 2.5 mm, 3 mm, 3.5 mm, 4 mm, 4.5 mm, 5 mm.

In besonders bevorzugten Ausführungsformen der Erfindung sind die fluidischen Kanäle an bestimmten Stellen erweitert, d.h. sie weisen dort einen im Vergleich zum Einlasskanal beziehungsweise Auslasskanal größeren Querschnitt oder Durchmesser auf. Der Einlasskanal ist unmittelbar vor dem Filter erweitert um eine homogene Anströmung zu erreichen. Auch ist der Auslasskanal unmittelbar nach dem Filter erweitert. Bei lateraler Anströmung ist der Einlasskanal oder Auslasskanal vor bzw. nach dem Filter beispielsweise über eine Länge von 5 mm bis 10 mm erweitert. Bei transversaler Anströmung befindet sich beispielsweise vor bzw. nach dem Filter eine Kavität, die eine Höhe zwischen 0.5 mm und 2 mm, beispielsweise von 1 mm, hat und im Durchmesser zwischen 0.5 mm und 3 mm, beispielsweise 2 mm, kleiner ist als der Durchmesser des Filters. In einer besonderen Ausführungsform der Erfindung befinden sich in den Erweiterungen der fluidischen Kanäle sogenannte Phaseguides, d.h. Strukturen (z.B. Kanten), die durch Pinning-Effekte die Befüllung der Kanalerweiterung steuern. Solche Strukturen können sich beispielsweise in der Erweiterung des Einlasskanals befinden, um die Befüllung der Kanalerweiterung zu steuern und eine gleichmäßige Befüllung zu gewährleisten.In particularly preferred embodiments of the invention, the fluidic channels are widened at certain locations, i. they have a larger cross section or diameter compared to the inlet channel or outlet channel. The inlet channel is extended immediately in front of the filter to achieve a homogeneous flow. Also, the exhaust duct is extended immediately after the filter. In the case of lateral flow, the inlet channel or outlet channel is expanded before or after the filter, for example over a length of 5 mm to 10 mm. In transversal flow, for example, before or after the filter is a cavity having a height between 0.5 mm and 2 mm, for example of 1 mm, and in diameter between 0.5 mm and 3 mm, for example 2 mm, smaller than the diameter of the filter. In a particular embodiment of the invention, in the extensions of the fluidic channels are called phaseguides, i. Structures (e.g., edges) that control the filling of the channel extension by pinning effects. Such structures may be located, for example, in the extension of the inlet channel to control the filling of the channel extension and to ensure a uniform filling.

Insbesondere bei der Integration der erfindungsgemäßen mikrofluidischen Filterkammern in ein mikrofluidisches System wird der zum Filter führende Kanal vor und nach dem Filter erweitert, um in diesen Systemen ein homogenes Anströmen des Filters zu erreichen. Diese Erweiterung wird bevorzugt durch einen Querschnitt der zum Filter führenden Kanäle erreicht. Diese Kanäle sind trichterförmig zum Filter hin geöffnet.In particular, in the integration of the microfluidic filter chambers according to the invention in a microfluidic system, the channel leading to the filter is expanded before and after the filter in order to achieve a homogeneous flow of the filter in these systems. This extension is preferably achieved by a cross section of the channels leading to the filter. These channels are funnel-shaped open towards the filter.

Bei der erfindungsgemäßen mikrofluidischen Filterkammer wird zuerst der Kanalbereich vor dem Filter vollständig befüllt. Die Luftblasen können durch den regulierbaren Entlüftungskanal entweichen, wenn das Ventil geöffnet ist. Dadurch ist eine blasenfreie Befüllung des Filters und der Filterkammer möglich. Es wird dadurch vermieden, dass sich bei der Befüllung der Filter schnell kapillar füllt und so das Entweichen der sich vor dem Filter in der Kanalerweiterung befindenden Luft verhindert wird. Kann die Luft nicht entweichen, bleiben vor und gegebenenfalls auch nach dem Filter Luftblasen eingeschlossen. Diese Luftblasen stören die homogene Anströmung des Filters und können außerdem zum kompletten oder teilweisen Verstopfen des Filters und/oder zu Schaumbildung führen, wodurch das vollständige Ausspülen des Filters unmöglich wird. Erfindungsgemäß mündet der Entlüftungskanal in den Kanalbereich nach dem Filter. Dadurch wird auch dieser Bereich blasenfrei befüllt und ein zusätzlicher fluidischer Anschluss wird eingespart.In the case of the microfluidic filter chamber according to the invention, first the channel region in front of the filter is completely filled. The air bubbles can escape through the adjustable vent channel when the valve is open. As a result, a bubble-free filling of the filter and the filter chamber is possible. It is thereby avoided that when filling the filter quickly filled capillary and thus the escape of the air located in front of the filter in the channel extension is prevented. If the air can not escape, air bubbles remain in front of and, if necessary, after the filter. These Air bubbles disturb the homogeneous flow of the filter and can also lead to complete or partial clogging of the filter and / or foaming, whereby the complete rinsing of the filter is impossible. According to the invention, the venting channel opens into the channel region downstream of the filter. As a result, this area is also filled bubble-free and an additional fluidic connection is saved.

Die mikrofluidische Filterkammer ist in allen fluidischen Systemen einsetzbar, in denen ein Filter eingesetzt wird, beispielsweise in polymeren Lab-on-Chip (LOC)- und Micro-Total-Analysis-Systemen (µTA-Systemen) zur molekularen Diagnostik.The microfluidic filter chamber can be used in all fluidic systems in which a filter is used, for example in polymer lab-on-chip (LOC) and micro-total-analysis (μTA) systems for molecular diagnostics.

Weitere Vorteile und vorteilhafte Ausgestaltungen der erfindungsgemäßen Gegenstände werden durch die Zeichnungen veranschaulicht und in der nachfolgenden Beschreibung erläutert. Dabei ist zu beachten, dass die Zeichnungen nur beschreibenden Charakter haben und nicht dazu gedacht sind, die Erfindung in irgendeiner Form einzuschränken. Es zeigen

Fig. 1a
Schematische Darstellung einer mikrofluidischen Filterkammer 10 Ausführungsform 1.
Fig. 1b
Schematische Darstellung einer mikrofluidischen Filterkammer 10 Ausführungsform 2.
Fig. 2
Schematische Darstellung eines fluidischen Systems (Querschnitt).
Fig. 3
Schematische Darstellung eines fluidischen Systems (Draufsicht).
Fig. 4
Schematische Darstellung eines fluidischen Systems (Seitenansicht).
Further advantages and advantageous embodiments of the subject invention are illustrated by the drawings and explained in the following description. It should be noted that the drawings have only descriptive character and are not intended to limit the invention in any way. Show it
Fig. 1a
Schematic representation of a microfluidic filter chamber 10 Embodiment 1.
Fig. 1b
Schematic representation of a microfluidic filter chamber 10 Embodiment 2.
Fig. 2
Schematic representation of a fluidic system (cross section).
Fig. 3
Schematic representation of a fluidic system (top view).
Fig. 4
Schematic representation of a fluidic system (side view).

Figur 1a zeigt eine schematische Ansicht einer nicht erfindungsgemäßen mikrofluidischen Filterkammer 10 in einer ersten Ausführungsform mit Einlasskanal 1, Kanalerweiterungen 2 und 13, Filter 3, Entlüftungskanal 4, Ventil 5 und Auslasskanal 6, wobei der Entlüftungskanal 4 entweder an die Atmosphäre führt oder in ein separates Reservoir führt. Der Einlasskanal 1 ist zum Filter 3 hin führend zur vor dem Filter 3 liegenden Kanalerweiterung 2 erweitert. An die Kanalerweiterung bzw. innerhalb des Kanals schließt sich der Filter 3 an. An den Filter 3 schließt sich die Kanalerweiterung 13 nach dem Filter 3 an. Die Kanalerweiterung 13 ist in ihrem Querschnitt gegenüber dem Auslasskanal 6 erweitert. Die Kanalerweiterung 2 vor dem Filter 3 und die Kanalerweiterung 13 nach dem Filter 3 sind jeweils trichterförmig ausgebildet. Die trichterförmige Ausbildung ist derart, dass der größere Querschnitt der trichterförmigen Ausbildung zum Filter 3 angeordnet ist. Die Kanalerweiterung 2 vor dem Filter 3weist einen Entlüftungskanal 4 auf. Der Entlüftungskanal 4 weist ein Ventil 5 auf. Das Ventil 5 regelt den Durchfluss von Flüssigkeit oder Gas durch den Entlüftungskanal 4. FIG. 1a shows a schematic view of a non-inventive microfluidic filter chamber 10 in a first embodiment with inlet channel 1, channel extensions 2 and 13, filter 3, vent channel 4, valve 5 and outlet channel 6, wherein the vent channel 4 either leads to the atmosphere or leads into a separate reservoir , The inlet channel 1 is extended to the filter 3 leading to lying in front of the filter 3 channel extension 2. At the channel extension or within the channel, the filter 3 connects. The filter 3 is followed by the channel extension 13 after the filter 3. The Channel extension 13 is widened in its cross-section relative to the outlet channel 6. The channel extension 2 in front of the filter 3 and the channel extension 13 after the filter 3 are each funnel-shaped. The funnel-shaped design is such that the larger cross-section of the funnel-shaped design is arranged to the filter 3. The channel extension 2 in front of the filter 3 has a venting channel 4. The venting channel 4 has a valve 5. The valve 5 regulates the flow of liquid or gas through the vent channel 4.

Figur 1b zeigt eine schematische Ansicht einer erfindungsgemäßen mikrofluidischen Filterkammer 10 in einer zweiten Ausführungsform mit Einlasskanal 1, Kanalerweiterungen 2 und 13, Filter 3, Entlüftungskanal 4, Ventil 5, Auslasskanal 6, wobei der Entlüftungskanal 4 nach dem Filter 3 in den Auslasskanal 6 mündet. FIG. 1b shows a schematic view of a microfluidic filter chamber 10 according to the invention in a second embodiment with inlet channel 1, channel extensions 2 and 13, filter 3, vent channel 4, valve 5, outlet channel 6, wherein the vent channel 4 after the filter 3 opens into the outlet channel 6.

Entsprechend der ersten Ausführungsform sind auch bei der zweiten Ausführungsform der Einlasskanal 1, die Kanalerweiterung 2 vor dem Filter 3, der Filter 3, die Kanalerweiterung 13 nach dem Filter 3 und der Auslasskanal 6 so angeordnet, dass der Einlasskanal trichterförmig in die Kanalerweiterung 2 vor dem Filter 3 führt, und die Kanalerweiterung 13 nach dem Filter 3 in den Auslasskanal 6 mündet. In der zweiten Ausführungsform ist der Entlüftungskanal 4 sowohl mit der Kanalerweiterung 2 vor dem Filter 3 als auch mit der Kanalerweiterung 13 nach dem Filter 3 verbunden. Der Entlüftungskanal 4 weist ein Ventil 5 auf. Durch das Ventil 5 kann der Durchfluss durch den Entlüftungskanal 4 aus der Kanalerweiterung 2 vor dem Filter 3 und der Kanalerweiterung 13 nach dem Filter 3 geregelt werden.According to the first embodiment, also in the second embodiment, the inlet channel 1, the channel extension 2 in front of the filter 3, the filter 3, the channel extension 13 after the filter 3 and the outlet channel 6 are arranged such that the inlet channel is funnel-shaped into the channel extension 2 in front of the filter 3 Filter 3 leads, and the channel extension 13 after the filter 3 opens into the outlet channel 6. In the second embodiment, the vent channel 4 is connected to both the channel extension 2 before the filter 3 and with the channel extension 13 to the filter 3. The venting channel 4 has a valve 5. Through the valve 5, the flow through the vent channel 4 from the channel extension 2 before the filter 3 and the channel extension 13 to the filter 3 can be controlled.

Der Einlasskanal 1 vor dem Filter 3 und der Auslasskanal 6 sind nach dem Filter 3 gegenüber dem Querschnitt des übrigen Einlasskanals 1 und Auslasskanals 6 erweitert.The inlet channel 1 in front of the filter 3 and the outlet channel 6 are extended after the filter 3 with respect to the cross section of the remaining inlet channel 1 and outlet channel 6.

Die Funktionsweise der mikrofluidischen Filterkammer 10 in der ersten Ausführungsform ist wie folgt:

  1. 1. Eine erste Flüssigkeit, z.B. Lösung oder Suspension, wird durch den Einlasskanal 4 zum Filter 3 gepumpt. Das Ventil 5 ist geöffnet.
  2. 2. Der Filter 3 befüllt sich kapillar. Im Bereich der Kanalerweiterung 2 befindet sich zunächst noch Luft.
  3. 3. Da der Flusswiderstand des Filters 3 deutlich größer ist als der des Entlüftungskanals 4, wird nun zunächst die Kanalerweiterung 2 vor dem Filter 3 und ein Teil des Entlüftungskanals 4 befüllt.
  4. 4. Das Ventil 5 wird geschlossen.
  5. 5. Das System ist komplett befüllt und der Filtrierungsvorgang beginnt.
The operation of the microfluidic filter chamber 10 in the first embodiment is as follows.
  1. 1. A first liquid, eg solution or suspension, is pumped through the inlet channel 4 to the filter 3. The valve 5 is open.
  2. 2. The filter 3 fills up capillary. In the area of the canal extension 2 is still first air.
  3. 3. Since the flow resistance of the filter 3 is significantly greater than that of the venting channel 4, the channel extension 2 is first filled in front of the filter 3 and a part of the venting channel 4.
  4. 4. The valve 5 is closed.
  5. 5. The system is completely filled and the filtration process begins.

Die Funktionsweise der mikrofluidischen Filterkammer 10 in der erfindungsgemäßen also zweiten Ausführungsform ist wie folgt:

  1. 1. Eine erste Flüssigkeit, z.B. Lösung oder Suspension, wird durch den Einlasskanal 1 zum Filter 3 gepumpt. Das Ventil 5 ist geöffnet.
  2. 2. Der Filter 3 befüllt sich kapillar. Im Bereich der Kanalerweiterung 2 befindet sich zunächst noch Luft.
  3. 3. Da der Flusswiderstand des Filters 3 deutlich größer ist als der des Entlüftungskanals 4, wird nun zunächst die Kanalerweiterung 2 vor dem Filter 3 und der Entlüftungskanal 4 befüllt.
  4. 4. Durch den Entlüftungskanal 4 wird die Kanalerweiterung 13 nach dem Filter 3 befüllt.
  5. 5. Das Ventil 5 wird geschlossen.
  6. 6. Das System ist komplett befüllt und der Filtrierungsvorgang beginnt.
The mode of operation of the microfluidic filter chamber 10 in the second embodiment according to the invention is as follows:
  1. 1. A first liquid, eg solution or suspension, is pumped through the inlet channel 1 to the filter 3. The valve 5 is open.
  2. 2. The filter 3 fills up capillary. In the area of the canal extension 2 is still first air.
  3. 3. Since the flow resistance of the filter 3 is significantly greater than that of the venting channel 4, the channel extension 2 is now first filled in front of the filter 3 and the venting channel 4.
  4. 4. Through the vent channel 4, the channel extension 13 is filled after the filter 3.
  5. 5. The valve 5 is closed.
  6. 6. The system is completely filled and the filtration process begins.

Die zweite Ausführungsform, d.h. die Ausführungsform, bei der Entlüftungskanal 4 nach dem Filter 3 in den Auslasskanal 6 mündet, hat somit zudem den Vorteil, dass durch den Entlüftungskanal 4 die Kanalerweiterung 13 nach dem Filter 3 vollständig befüllt wird. Da der Flusswiderstand des Entlüftungskanals 4 deutlich geringer ist als der des Filters 3, erfolgt dieser Befüllungsvorgang blasenfrei und deutlich schneller als durch den Filter.The second embodiment, i. the embodiment in which venting channel 4 opens after the filter 3 in the outlet channel 6, thus also has the advantage that the channel extension 13 is completely filled after the filter 3 through the vent channel 4. Since the flow resistance of the venting channel 4 is significantly lower than that of the filter 3, this filling process is bubble-free and much faster than through the filter.

Es ist möglich, die Filterkammer 10 nach Ablauf der Filtrierung mit einer zweiten Flüssigkeit zu befüllen und dabei die erste Flüssigkeit zu ersetzen. Dazu wird im einfachsten Fall die zweite Flüssigkeit über den Filter 3 gepumpt. Bei dieser Verfahrensweise besteht jedoch die Gefahr, dass in den Kanalerweiterungen (2, 13) vor und nach dem Filter 3 Rückstände der ersten Flüssigkeit zurückbleiben, die später ablaufende Reaktionen stören können. Diese Rückstände können entfernt werden, indem der Entlüftungskanal 4 nochmals kurz geöffnet und mit Flüssigkeit 2 gespült wird.It is possible to fill the filter chamber 10 after the filtration with a second liquid and thereby replace the first liquid. For this purpose, the second liquid is pumped through the filter 3 in the simplest case. In this procedure, however, there is a risk that left in the channel extensions (2, 13) before and after the filter 3 residues of the first liquid, which can interfere with later occurring reactions. These residues can be removed by the venting channel 4 is briefly opened again and rinsed with liquid 2.

Figur 2 zeigt eine mögliche Ausführungsform welche nicht unter den beanspruchten Gegenstand fällt. Dabei ist die mikrofluidische Filterkammer 10 Bestandteil eines mikrofluidischen Systems. Die mikrofluidische Filterkammer 10 ist dabei in einem Mehrschichtaufbau aus drei Polymersubstraten 9, 14, 11 und einer elastischen Folie 12, die sich zwischen der ersten, strukturierten Schicht 11 und der zweiten, strukturierten Schicht 14 befindet, realisiert. Die drei Schichten sind übereinander angeordnet, dabei ist die dritte Schicht 9 über der zweiten Schicht 14 angeordnet, und die zweite Schicht 14 ist über der ersten Schicht 11 angeordnet. FIG. 2 shows a possible embodiment which does not fall under the claimed subject matter. In this case, the microfluidic filter chamber 10 is part of a microfluidic system. In this case, the microfluidic filter chamber 10 is realized in a multi-layer structure consisting of three polymer substrates 9, 14, 11 and an elastic film 12 which is located between the first, structured layer 11 and the second, structured layer 14. The three layers are arranged one above the other, wherein the third layer 9 is arranged above the second layer 14, and the second layer 14 is arranged above the first layer 11.

Figur 2 zeigt einen Einlasskanal 1, mit Kanalerweiterung 2, Filter 3, Kanaldurchführung 7, zusätzlichem Ventil 8, Durchmesser w1 der Kanaldurchführung 7, Tiefe t1 des fluidischen Einlasskanals 1, Dicke t2 der dritten Schicht 9, Dicke t3 der zweiten Schicht 14, Dicke t4 der dritten Schicht 11. FIG. 2 shows an inlet channel 1, with channel extension 2, filter 3, channel bushing 7, additional valve 8, diameter w1 of the channel bushing 7, depth t1 of the fluidic inlet channel 1, thickness t2 of the third layer 9, thickness t3 of the second layer 14, thickness t4 of the third Layer 11.

Figur 3 zeigt dieselbe Ausführung der Erfindung wie Figur 2, aber in der Draufsicht. Die mikrofluidische Filterkammer 10 ist Bestandteil eines mikrofluidischen Systems. FIG. 3 shows the same embodiment of the invention as FIG. 2 but in plan view. The microfluidic filter chamber 10 is part of a microfluidic system.

Figur 3 zeigt einen Einlasskanal 1, mit Kanalerweiterung 2, Filter 3, Belüftungskanal 4, Ventil 5, Auslasskanal 6, Kanaldurchführung 7, zusätzliches Ventil 8, Radius R1 der Kanalerweiterung 2, Radius R2 des Filters 3 und Breite w2 des Auslasskanals 6. FIG. 3 1 shows an inlet channel 1 with channel extension 2, filter 3, ventilation channel 4, valve 5, outlet channel 6, channel bushing 7, additional valve 8, radius R1 of the channel extension 2, radius R2 of the filter 3 and width w2 of the outlet channel 6.

Figur 4 zeigt dieselbe Ausführung wie Figur 2 und 3, aber in der Seitenansicht. Die mikrofluidische Filterkammer 10 ist Bestandteil eines mikrofluidischen Systems. Sie ist in einem Mehrschichtaufbau aus drei Polymersubstraten 9, 14, 11 und einer elastischen Folie 12, die sich zwischen der ersten, strukturierten Ebene 11 und der zweiten, strukturierten Ebene 14 befindet, realisiert. FIG. 4 shows the same execution as FIGS. 2 and 3 but in the side view. The microfluidic filter chamber 10 is part of a microfluidic system. It is realized in a multi-layer structure consisting of three polymer substrates 9, 14, 11 and an elastic film 12, which is located between the first, structured plane 11 and the second, structured plane 14.

Figur 4 zeigt den Einlasskanal 1, mit Kanalerweiterung 2, Filter 3, Belüftungskanal 4, Ventil 5, Auslasskanal 6, Kanaldurchführung 7 und zusätzlichem Ventil 8. FIG. 4 shows the inlet channel 1, with channel extension 2, filter 3, ventilation channel 4, valve 5, outlet channel 6, channel passage 7 and additional valve. 8

Die Funktionsweise der in den Figuren 2, 3 und 4 gezeigten Ausführungsform ist wie folgt:

  1. 1. Flüssigkeit strömt durch den Einlasskanal 1 ein. Das Ventil 5 ist geöffnet.
  2. 2. Die Flüssigkeit wird durch eine Durchführung 7 in die zweite, strukturierte Ebene 14 gelenkt und erreicht die Kanalerweiterung 2.
  3. 3. Der Filter 3 wird kapillar benetzt.
  4. 4. Die Flüssigkeit strömt durch den Belüftungskanal 4, der eine weitere Durchführung und ein Ventil 5 beinhaltet, in die erste, strukturierte Ebene 11 zurück und erreicht die Rückseite des Filters 3.
  5. 5. Die an der Rückseite des Filters 3 gelegene Kanalerweiterung wird befüllt.
  6. 6. Das Ventil 5 wird geschlossen.
  7. 7. Die Flüssigkeit strömt durch den Filter 3 in den Auslasskanal 6.
The functioning of the in the FIGS. 2, 3 and 4 embodiment shown is as follows:
  1. 1. Liquid flows in through the inlet channel 1. The valve 5 is open.
  2. 2. The liquid is directed through a passage 7 in the second, structured plane 14 and reaches the channel extension second
  3. 3. The filter 3 is wetted capillary.
  4. 4. The liquid flows back through the ventilation channel 4, which includes a further passage and a valve 5, in the first, structured plane 11 and reaches the back of the filter third
  5. 5. The channel extension located on the back of Filter 3 will be filled.
  6. 6. The valve 5 is closed.
  7. 7. The liquid flows through the filter 3 into the outlet channel 6.

Beispiele für typische Abmessungen des in den Figuren 2, 3 und 4 gezeigten fluidischen Systems sind:
R1 = 2.5 mm, R2 = 3.5 mm, w1 = 0.5 mm, w2 = 0.3 mm, t1 = 0.3 mm, t2 = 1.5 mm, t3 = 1.5 mm, t4 = 1.5 mm.
Examples of typical dimensions of the in FIGS. 2, 3 and 4 shown fluidic system are:
R1 = 2.5mm, R2 = 3.5mm, w1 = 0.5mm, w2 = 0.3mm, t1 = 0.3mm, t2 = 1.5mm, t3 = 1.5mm, t4 = 1.5mm.

Claims (5)

  1. Microfluidic filter chamber (10) comprising a filter (3), a venting channel (4), an inlet channel (1) and an outlet channel (6), wherein the filter (3) is inserted between the inlet channel (1) and the outlet channel (6),
    wherein the venting channel (4) branches off from the inlet channel (1),
    wherein the flow through the microfluidic filter chamber (10) is able to be regulated by means of a valve (5) in the venting channel (4),
    wherein the venting channel (4) opens into the outlet channel (6), and the inlet channel (1) and the outlet channel (6) have a widened channel portion (2) in the form of a variable funnel-like cross-sectional surface, which has a larger cross section towards the filter, and wherein the widened channel portion (2) before the filter (3) has a venting channel (4) which opens into the outlet channel (6).
  2. Fluidic system having a microfluidic filter chamber (10) according to Claim 1, characterized by a multilayer structure composed of at least two layers (9, 11, 14).
  3. Fluidic system according to Claim 2, characterized in that an elastic film (12) is situated between two layers (11, 14) and acts as a valve (5).
  4. Method for the bubble-free filling of a microfluidic filter chamber (10) which comprises a filter (3), a venting channel (4) and a valve (5) arranged at the venting channel (4), wherein the venting channel (4) opens into the outlet channel (6), and the inlet channel (1) and the outlet channel (6) have a widened channel portion in the form of a variable funnel-like cross-sectional surface, which has a larger cross section towards the filter, and wherein the widened channel portion (2) before the filter (3) has a venting channel (4) which opens into the outlet channel (6), wherein a liquid is pumped through the inlet channel (1) to the filter (3) while a valve (5) in the venting channel (4) is open, whereby the filter (3) is filled by capillary action and the channel region (2) before the filter (3) and a part of the venting channel (4) are filled, wherein then the channel region (13) after the filter (3) is filled via the venting channel (4), and
    wherein subsequently the valve (5) is closed.
  5. Method for filtering a liquid by way of a microfluidic filter chamber (10), wherein firstly the microfluidic filter chamber (10) is filled in a bubble-free manner according to the method according to Claim 4, and subsequently the liquid to be filtered flows in through the inlet channel (1) and then flows through the filter (3) into the outlet channel (6).
EP12703472.6A 2011-03-23 2012-01-23 Fluidic system for bubbble-free filling of a microfluidic filter chamber Active EP2688670B1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102011005932.6A DE102011005932B4 (en) 2011-03-23 2011-03-23 Fluidic system for bubble-free filling of a microfluidic filter chamber and method for bubble-free filling and method for filtering a liquid with such a system
PCT/EP2012/050948 WO2012126647A1 (en) 2011-03-23 2012-01-23 Fluidic system for bubbble-free filling of a microfluidic filter chamber

Publications (2)

Publication Number Publication Date
EP2688670A1 EP2688670A1 (en) 2014-01-29
EP2688670B1 true EP2688670B1 (en) 2019-08-07

Family

ID=45581838

Family Applications (1)

Application Number Title Priority Date Filing Date
EP12703472.6A Active EP2688670B1 (en) 2011-03-23 2012-01-23 Fluidic system for bubbble-free filling of a microfluidic filter chamber

Country Status (4)

Country Link
EP (1) EP2688670B1 (en)
DE (1) DE102011005932B4 (en)
ES (1) ES2753534T3 (en)
WO (1) WO2012126647A1 (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102018220898B4 (en) 2018-12-04 2022-10-13 Robert Bosch Gmbh Microfluidic device and method for filtering a fluid
DE102021212645A1 (en) 2021-11-10 2023-05-11 Robert Bosch Gesellschaft mit beschränkter Haftung Device and method for carrying out microfluidic process steps
DE102022203627A1 (en) 2022-04-11 2023-10-12 Robert Bosch Gesellschaft mit beschränkter Haftung Microfluidic device

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6416293B1 (en) * 1999-07-20 2002-07-09 Deka Products Limited Partnership Pumping cartridge including a bypass valve and method for directing flow in a pumping cartridge

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6867049B1 (en) * 2000-09-27 2005-03-15 Becton, Dickinson And Company Method for obtaining increased particle concentration for optical examination
US6811695B2 (en) 2001-06-07 2004-11-02 Nanostream, Inc. Microfluidic filter
WO2003089104A2 (en) * 2002-04-19 2003-10-30 Cuno Incorporated Encapsulated filter cartridge
DE10218554A1 (en) 2002-04-25 2003-11-06 Qiagen Gmbh Syringe for purifying liquid or isolating substances from it, especially nucleic acids or proteins from blood, plasma or urine, has filter above its inlet, on which purifying agent is placed
DE10345818A1 (en) 2003-09-30 2005-04-28 Boehringer Ingelheim Micropart Method and device for separating and removing gas bubbles from liquids
US20070031283A1 (en) * 2005-06-23 2007-02-08 Davis Charles Q Assay cartridges and methods for point of care instruments
US20070125942A1 (en) 2005-07-06 2007-06-07 The Regents Of The University Of California Apparatuses, systems and methods for isolating and separating biological materials
US20090188856A1 (en) * 2007-10-20 2009-07-30 Robb Benson Externally Centering Filter Element or Cartridge and Housing and System Utilizing the Same
BRPI0915278A2 (en) * 2008-11-13 2019-09-24 Koninl Philips Electronics Nv microfluidic system and method for filling a capillary channel

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6416293B1 (en) * 1999-07-20 2002-07-09 Deka Products Limited Partnership Pumping cartridge including a bypass valve and method for directing flow in a pumping cartridge

Also Published As

Publication number Publication date
DE102011005932B4 (en) 2022-07-14
ES2753534T3 (en) 2020-04-13
EP2688670A1 (en) 2014-01-29
WO2012126647A1 (en) 2012-09-27
DE102011005932A1 (en) 2012-09-27

Similar Documents

Publication Publication Date Title
EP2072131B1 (en) Microfluid element for mixing a fluid into a reagent
DE102012202775B4 (en) FLUIDIKMODUL, DEVICE AND METHOD FOR PUMPING A LIQUID
DE102013203293B4 (en) Apparatus and method for conducting a liquid through a first or second outlet channel
DE102013219929B4 (en) Fluidic module, apparatus and method for aliquoting a fluid
DE60035611T2 (en) MICRO FLUID ANALYSIS DEVICE
EP2560756B1 (en) Device for plasma separation by means of a central channel structure
DE102016207845B4 (en) Fluid handling device and method of fluid handling
EP3592463B1 (en) Method for centrifugo-pneumatic switching of liquid
WO2006069757A1 (en) Novel microfluidic sample holder
EP2586511A1 (en) Filter assembly
DE102011078770B4 (en) Microfluidic device, microfluidic system and method of transporting fluids
EP2688670B1 (en) Fluidic system for bubbble-free filling of a microfluidic filter chamber
WO2015189280A1 (en) Fluidic module, apparatus and method for handling a liquid
EP2406495B1 (en) Pump having a filter arrangement
WO2013072110A1 (en) Microfluidic filter element for separating sample components from a biological sample fluid
DE102009001257A1 (en) Apparatus and method for handling liquids
EP2729251B1 (en) Microfluid structure with cavities
EP2624954B1 (en) Method for washing a microfluid cavity
WO2023016923A1 (en) Negative-pressure-switching of liquid
DE102018204633A1 (en) Microfluidic device and method for processing a fluid
DE102018220898B4 (en) Microfluidic device and method for filtering a fluid
EP3740313B1 (en) Method for providing a solution of the substance in a microfluidic device
DE102020210536A1 (en) Microfluidic Device
DE102018215467A1 (en) Microfluidic device for processing a fluid, in particular for a lab-on-chip system, and method for processing a fluid in a microfluidic device
DE102012220250A1 (en) FLUIDIKMODUL FOR A CENTRIFUGAL FILTRATION AND METHOD FOR FILTERING A SAMPLE

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: 20131023

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

Free format text: STATUS: EXAMINATION IS IN PROGRESS

17Q First examination report despatched

Effective date: 20170206

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: 20190417

GRAS Grant fee paid

Free format text: ORIGINAL CODE: EPIDOSNIGR3

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

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

Free format text: STATUS: THE PATENT HAS BEEN GRANTED

AK Designated contracting states

Kind code of ref document: B1

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

REG Reference to a national code

Ref country code: GB

Ref legal event code: FG4D

Free format text: NOT ENGLISH

REG Reference to a national code

Ref country code: CH

Ref legal event code: EP

Ref country code: AT

Ref legal event code: REF

Ref document number: 1162997

Country of ref document: AT

Kind code of ref document: T

Effective date: 20190815

REG Reference to a national code

Ref country code: DE

Ref legal event code: R096

Ref document number: 502012015120

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: SE

Ref legal event code: TRGR

REG Reference to a national code

Ref country code: NL

Ref legal event code: MP

Effective date: 20190807

REG Reference to a national code

Ref country code: LT

Ref legal event code: MG4D

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

Ref country code: FI

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

Effective date: 20190807

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: 20190807

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: 20191107

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: 20190807

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: 20191209

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: 20191107

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: 20190807

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

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: 20191108

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: 20190807

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: 20191207

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: 20190807

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: 20190807

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: 20190807

REG Reference to a national code

Ref country code: ES

Ref legal event code: FG2A

Ref document number: 2753534

Country of ref document: ES

Kind code of ref document: T3

Effective date: 20200413

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

Owner name: ROBERT BOSCH GMBH

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: 20190807

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: 20190807

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: 20190807

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: 20190807

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

Ref country code: IT

Payment date: 20200122

Year of fee payment: 9

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

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: 20190807

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: 20200224

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: 20190807

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: 20190807

REG Reference to a national code

Ref country code: DE

Ref legal event code: R097

Ref document number: 502012015120

Country of ref document: DE

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

PG2D Information on lapse in contracting state deleted

Ref country code: IS

26N No opposition filed

Effective date: 20200603

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: 20190807

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: 20190807

REG Reference to a national code

Ref country code: CH

Ref legal event code: PL

REG Reference to a national code

Ref country code: BE

Ref legal event code: MM

Effective date: 20200131

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: 20200123

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

Ref country code: BE

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

Effective date: 20200131

Ref country code: CH

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

Effective date: 20200131

Ref country code: LI

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

Effective date: 20200131

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: 20200123

REG Reference to a national code

Ref country code: AT

Ref legal event code: MM01

Ref document number: 1162997

Country of ref document: AT

Kind code of ref document: T

Effective date: 20200123

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: 20200123

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 NON-PAYMENT OF DUE FEES

Effective date: 20210123

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: 20190807

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: 20190807

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: 20190807

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

Ref country code: FR

Payment date: 20230123

Year of fee payment: 12

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

Ref country code: SE

Payment date: 20230123

Year of fee payment: 12

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

Ref country code: ES

Payment date: 20240216

Year of fee payment: 13

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

Ref country code: DE

Payment date: 20240322

Year of fee payment: 13

Ref country code: GB

Payment date: 20240124

Year of fee payment: 13