EP2688670B1 - Système fluidique de remplissage sans bulles d'une chambre de filtration microfluidique - Google Patents

Système fluidique de remplissage sans bulles d'une chambre de filtration microfluidique Download PDF

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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
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EP
European Patent Office
Prior art keywords
channel
filter
microfluidic
venting
valve
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Active
Application number
EP12703472.6A
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German (de)
English (en)
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EP2688670A1 (fr
Inventor
Peter Rothacher
Jochen Rupp
Christian Dorrer
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Robert Bosch GmbH
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Robert Bosch GmbH
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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502753Containers 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.

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  • 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)

Claims (5)

  1. Chambre de filtration microfluidique (10), comprenant un filtre (3), un canal de désaération (4), un canal d'entrée (1) et un canal de sortie (6),
    dans laquelle le filtre (3) est inséré entre le canal d'entrée (1) et le canal de sortie (6),
    dans laquelle le canal de désaération (4) est dérivé du canal d'entrée (1),
    dans laquelle le débit à travers la chambre de filtration microfluidique (10) peut être réglé au moyen d'une soupape (5) dans le canal de désaération (4),
    dans laquelle le canal de désaération (4) débouche dans le canal de sortie (6) et le canal d'entrée (1) et le canal de sortie (6) présentent un élargissement de canal (2) sous la forme d'une surface de section transversale variable en forme d'entonnoir avec une section transversale plus grande en direction du filtre et
    dans laquelle l'élargissement de canal (2) présente avant le filtre (3) un canal de désaération (4), qui débouche dans le canal de sortie (6).
  2. Système fluidique doté d'une chambre de filtration microfluidique (10) selon la revendication 1, caractérisé par une structure multicouche en au moins deux couches (9, 11, 14).
  3. Système fluidique selon la revendication 2, caractérisé en ce qu'il se trouve entre deux couches (11, 14.) une feuille élastique (12), qui fait office de soupape (5).
  4. Procédé pour le remplissage sans bulles d'une chambre de filtration microfluidique (10), qui comprend un filtre (3), un canal de désaération (4) et une soupape (5) disposée dans le canal de désaération (4), dans lequel le canal de désaération (4) débouche dans le canal de sortie (6) et le canal d'entrée (1) et le canal de sortie (6) présentent un élargissement de canal sous la forme d'une surface de section transversale variable en forme d'entonnoir avec une section transversale plus grande en direction du filtre et dans lequel l'élargissement de canal (2) présente avant le filtre (3) un canal de désaération (4), qui débouche dans le canal de sortie (6), dans lequel on pompe un liquide à travers le canal d'entrée (1) vers le filtre (3), tandis qu'une soupape (5) dans le canal de désaération (4) est ouverte, grâce à quoi on remplit le filtre (3) capillarité et on remplit la région de canal (2) avant le filtre (3) et une partie du canal de désaération (4), dans lequel on remplit ensuite la région de canal (13) après le filtre (3) par le canal de désaération (4), et dans lequel on ferme ensuite la soupape (5).
  5. Procédé pour la filtration d'un liquide avec une chambre de filtration microfluidique (10), dans lequel on remplit d'abord la chambre de filtration microfluidique (10) sans bulles par le procédé selon la revendication 4, puis le liquide à filtrer pénètre à travers le canal d'entrée (1) et s'écoule ensuite à travers le filtre (3) dans le canal de sortie (6).
EP12703472.6A 2011-03-23 2012-01-23 Système fluidique de remplissage sans bulles d'une chambre de filtration microfluidique Active EP2688670B1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102011005932.6A DE102011005932B4 (de) 2011-03-23 2011-03-23 Fluidisches System zur blasenfreien Befüllung einer mikrofluidischen Filterkammer sowie Verfahren zur blasenfreien Befüllung und Verfahren zum Filtern einer Flüssigkeit mit einem solchen System
PCT/EP2012/050948 WO2012126647A1 (fr) 2011-03-23 2012-01-23 Système fluidique de remplissage sans bulles d'une chambre de filtration microfluidique

Publications (2)

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

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EP12703472.6A Active EP2688670B1 (fr) 2011-03-23 2012-01-23 Système fluidique de remplissage sans bulles d'une chambre de filtration microfluidique

Country Status (4)

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EP (1) EP2688670B1 (fr)
DE (1) DE102011005932B4 (fr)
ES (1) ES2753534T3 (fr)
WO (1) WO2012126647A1 (fr)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102018220898B4 (de) 2018-12-04 2022-10-13 Robert Bosch Gmbh Mikrofluidische Vorrichtung und Verfahren zur Filterung eines Fluids
DE102021212645B4 (de) 2021-11-10 2024-08-22 Robert Bosch Gesellschaft mit beschränkter Haftung Vorrichtung und Verfahren zur Durchführung mikrofluidischer Prozessschritte
DE102022203627A1 (de) 2022-04-11 2023-10-12 Robert Bosch Gesellschaft mit beschränkter Haftung Mikrofluidische Vorrichtung

Citations (1)

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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

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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
US7081201B2 (en) * 2002-04-19 2006-07-25 3M Innovative Properties Company Encapsulated filter cartridge
DE10218554A1 (de) 2002-04-25 2003-11-06 Qiagen Gmbh Aufreinigung von Flüssigkeiten
DE10345818A1 (de) 2003-09-30 2005-04-28 Boehringer Ingelheim Micropart Verfahren und Vorrichtung zum Separieren und Abführen von Gasblasen aus Flüssigkeiten
WO2007002579A2 (fr) * 2005-06-23 2007-01-04 Bioveris Corporation Cartouches et methodes d'analyse pour instruments d'analyse delocalisee
CA2614180A1 (fr) 2005-07-06 2007-01-11 The Regents Of The University Of California Dispositifs, systemes et procedes pour isoler et separer des substances biologiques
US20090188856A1 (en) * 2007-10-20 2009-07-30 Robb Benson Externally Centering Filter Element or Cartridge and Housing and System Utilizing the Same
BRPI0915278A2 (pt) * 2008-11-13 2019-09-24 Koninl Philips Electronics Nv sistema microfluídico e método para preencher um canal capilar

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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 (de) 2022-07-14
ES2753534T3 (es) 2020-04-13
DE102011005932A1 (de) 2012-09-27
WO2012126647A1 (fr) 2012-09-27
EP2688670A1 (fr) 2014-01-29

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