EP2688672A2 - Dispositif et procédé pour filtrer du sang - Google Patents

Dispositif et procédé pour filtrer du sang

Info

Publication number
EP2688672A2
EP2688672A2 EP12711625.9A EP12711625A EP2688672A2 EP 2688672 A2 EP2688672 A2 EP 2688672A2 EP 12711625 A EP12711625 A EP 12711625A EP 2688672 A2 EP2688672 A2 EP 2688672A2
Authority
EP
European Patent Office
Prior art keywords
membrane
sample
filtration
carrier
receiving
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.)
Withdrawn
Application number
EP12711625.9A
Other languages
German (de)
English (en)
Inventor
Dirk Kurowski
Dirk Osterloh
Ying Yu
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.)
Boehringer Ingelheim Microparts GmbH
Original Assignee
Boehringer Ingelheim Microparts 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 Boehringer Ingelheim Microparts GmbH filed Critical Boehringer Ingelheim Microparts GmbH
Priority to EP12711625.9A priority Critical patent/EP2688672A2/fr
Publication of EP2688672A2 publication Critical patent/EP2688672A2/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/40—Concentrating samples
    • G01N1/4005—Concentrating samples by transferring a selected component through a membrane
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502715—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/50273—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means or forces applied to move the fluids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502753—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02—Adapting objects or devices to another
    • B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
    • B01L2200/027—Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0681—Filter
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0887—Laminated structure
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0406—Moving fluids with specific forces or mechanical means specific forces capillary forces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502723—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by venting arrangements

Definitions

  • the present invention relates to a device for filtering a liquid sample, in particular blood, according to the preamble of claim 1 and to a method for filtering a liquid sample, in particular blood, according to the preamble of claim 10.
  • the present invention is concerned with the filtration of a liquid sample.
  • a liquid sample This is preferably a biological sample or sample liquid, in particular blood or the like.
  • the present invention relates to the filtration of a particle-containing solution (suspension), such as blood or other human or animal body fluid.
  • the present invention is particularly concerned with fluidic devices containing or forming a microfluidic system.
  • the following statements therefore relate preferably to devices in which act capillary forces and in particular for the function are important or relevant.
  • EP 1 421 993 A1 discloses a device for blood separation, wherein a carrier made of a transport fleece, for example made of glass fibers, is provided with a separating fleece in a blood separation region.
  • the separating fleece forms a filter for the separation of blood constituents.
  • the blood separation is carried out by capillary forces, where supportive, for example, a negative pressure can be applied.
  • a technical realization for generating the negative pressure is not specified.
  • the separated blood plasma is removed from the transport fleece by pressing. If necessary, the area of the Separate carrier with the separating mat from the other carrier to prevent potential contamination of the blood plasma by blood cells.
  • the disadvantage here is that a relatively undefined and slow blood separation and forwarding of the separated blood plasma takes place in a nonwoven.
  • Another disadvantage is that a separate device for squeezing to remove the separated blood plasma is required.
  • the present invention has for its object to provide an apparatus and a method for the filtration of a liquid sample, such as blood, wherein an optimized or accelerated filtration and / or a simple structure is or are enabled.
  • One aspect of the present invention is that, when filtering a sample through a membrane, filtration is first (only) capillary driven - that is, driven by capillary forces - until the filtered sample reaches or partially fills a fluidic system associated with the membrane for discharge, and Only then is an underpressure or overpressure used to accelerate the filtration or for the further filtration, ie then a pressure-operated filtration takes place.
  • a conveying device is used which only generates or uses an underpressure or overpressure for accelerating the filtration or for the further filtration after the filtered sample has reached or partially filled the fluidic system.
  • the initially purely capillary-operated filtration allows an optimal fluidic seal against gas exchange or entry from the outside, in particular between the membrane used for filtering and the downstream fluidic system, so that in particular no airtight connection or complex connection technology for gas-tight connection of the filtration membrane with the associated Carrier or fluidic system is required.
  • the subsequent pressure-operated filtration allows an acceleration of the filtration over the purely capillary-operated filtration, so that a particularly fast filtration or high volume flows is or will be possible.
  • the pressure-operated filtration allows a better reproducibility, since the flow is determined by the pressure difference or the amount of the negative pressure or overpressure acting and can be controlled or even regulated.
  • native or untreated materials in particular also hydrophobic materials, can be used for the support or the fluidic system itself in the filtration of hydrophilic samples. This is conducive to a simple and inexpensive production.
  • the membrane rests only loosely on a support forming the fluidic system or its cover. This allows a very simple realization or production. In particular, this is possible because here an initial fluidic seal is enabled by the capillary filling in the initial capillary-driven filtration.
  • the underpressure or overpressure for pressure-operated filtration is limited to at most 100 mPa, in particular to substantially 50 mPa or less.
  • the discharge of the filtered sample on a flat side of the membrane is particularly preferably carried out via a receiving opening of the fluidic system, wherein the receiving opening is preferably arranged at least substantially centrally or centrally under the membrane. This is conducive to the preferred, in particular circumferential or annular fluidic seal by the filtered sample.
  • the membrane is at least substantially over the entire surface of the carrier and / or its cover.
  • the dead volume for the filtered sample under the membrane can be minimized or virtually avoided altogether.
  • the membrane can be connected directly to the carrier forming the fluidic system and / or received in a depression thereof, if the filtered sample is preferably perpendicular to the flat side or through the carrier, in particular through an opening of the carrier, is derived under the membrane.
  • the apparatus preferably has a sample delivery means in capillary contact with the membrane.
  • the supply device is, for example, funnel-shaped and guides the sample to be filtered, in particular via capillary forces, in direct contact with the membrane.
  • the feeding device is arranged in particular in a receiving direction for the sample or formed thereof, wherein the membrane in turn is peripherally and / or circumferentially, preferably connected to the receiving device.
  • FIG. 1 shows a schematic section of a proposed device according to a first embodiment
  • FIG. 2 shows a schematic section of a proposed device according to a second embodiment
  • FIG. 3 is a schematic plan view of a carrier of the device according to the second embodiment.
  • Fig. 4 is a schematic section of a proposed device according to a third embodiment.
  • the sample 2 is a particle-containing solution or suspension. Particularly preferably, it is a biological sample 2.
  • the representation example is, in particular, blood or another human or animal body fluid. However, other liquids or suspensions or the like can be filtered as sample 2.
  • the device 1 preferably has a membrane 3 or other separating device for the filtration of the sample 2 or separation of components or particles from the sample 2.
  • the membrane 3 is preferably constructed or formed as described in WO 2009/106331 A2, which is hereby incorporated by reference as a supplementary disclosure.
  • membrane is to be understood in particular as meaning a flat filter element which is suitable for filtering a liquid sample 2 in the sense mentioned, in particular blood or the like, for example for the separation of blood cells and / or for plasma separation.
  • the membrane 3 can also be of multilayer construction and / or more or less open-pored. It may also be a suitable composite material.
  • membranes or filter elements can be stacked directly above one another.
  • the device 1 has a carrier 4 which forms or has a fluidic system 5.
  • the fluidic system 5 is at least partially or completely formed by or in the carrier 4, possibly together with a cover 6.
  • the carrier 4 is preferably at least substantially plate-like and / or rigidly enveloped and particularly preferably made of plastic, in particular injection-molded.
  • the device 1 preferably has a cover 6 associated with the carrier 4, which preferably at least partially covers the fluidic system 5.
  • the cover 6 is preferably at least substantially smooth, flat, elastically deformable, and / or formed like a foil. In particular, it is a plastic film o. The like.
  • the cover 6 is preferably arranged or applied on a flat side of the carrier 4, for example by gluing, sealing, in particular heat-sealing, welding or the like.
  • the device 1 or the carrier 4 or the fluidic system 5 preferably has a receiving channel 7 with a receiving opening 8 for the preferably filtered sample 2 or the permeate.
  • the carrier 4 preferably has a raised region 9, which is particularly preferably in direct contact with the membrane 3 or on which the membrane 3 preferably rests directly.
  • the receiving opening 8 or the receiving channel 7 preferably opens in this raised region 9 of the carrier 4 to the membrane 3.
  • the receiving channel 7 starts in particular in the raised area 9.
  • the receiving channel 7 is preferably formed by a corresponding groove, groove or other recess in the carrier 4 and extends in the illustrated embodiment, preferably along the membrane 3 facing surface or flat side of the support 4. This allows a very simple production of the support 4, and the grooves, Grooving o. The like. In particular by injection molding.
  • the cover 6 preferably covers at least substantially the support 4 or its surface or flat side facing the membrane 3, in particular the receiving channel 7, so that the receiving channel 7 or its receiving opening 8 is at least substantially only centrally under the membrane 3 to the membrane 3 or generally opens.
  • the term "central” is to be understood here in particular as an at least substantially central arrangement. Alternatively or additionally, however, this can also be indicate that only a single receiving opening 8 is provided for discharging the filtered sample 2 or the permeate.
  • the receiving channel 7 extends from the receiving opening 8 to the left.
  • the receiving channel 7 is covered by the cover 6.
  • the cover 6 preferably extends in the illustrated embodiment to below the membrane 3, in particular from all sides or circumferentially. Particularly preferably, the cover 6 forms an annular support area around the receiving opening 8 or the raised area 9.
  • the membrane 3 is in the representation example - preferably at least substantially over the entire surface or evenly - on the raised portion 9 and the outside on the support 4 or its cover 6. Thus, a very small or almost negligible dead volume for the filtered sample 2 can be formed on the discharge side of the membrane 3.
  • Fig. 1 shows the device 1 and the sample 2 in a state prior to the start of the capillary-operated filtration or before the sample 2 flows or diffuses on and into the membrane 3.
  • the device 1 preferably has a feed device 11 for feeding the sample 2 to be filtered to the membrane 3.
  • the feeding device 11 is preferably formed like a funnel in the representation example or provided with a funnel-like area.
  • the feeding device 11 is preferably designed such that it is in capillary contact and / or direct contact with the membrane 3 in order to feed the sample 2 to the membrane 3 even if the material forming the feeding device 11 or its surface is only very poor or is virtually not wettable by the sample 2, for example, because the Zufuphreimichtung 11 and their material is hydrophobic and the sample 2, however, is hydrophilic.
  • the sample 2 is preferably conducted centrally or centrally on the membrane 3 by the feed device 11 and / or via a central or central feed opening 12 and / or a feed section extending directly into the vicinity or onto the membrane 3 to produce the preferred direct or capillary contact with the membrane 3 for the sample 2.
  • the feed section 13 can be formed, for example, by a capillary tube, a notch, a pillar structure and / or another suitable structure.
  • the device 1 preferably has a receiving device 14 for receiving the sample 2 to be filtered and / or for holding the membrane 3.
  • the membrane 3 is preferably fixed or insoluble, in particular in a peripheral edge region, connected to the receiving device 14, for example by welding, gluing, clamping and / or in any other suitable manner.
  • the receiving device 14 has, in particular, a corresponding receiving opening or depression for the membrane 3.
  • the fevolutionenirmchtung 11 is arranged in the receiving device 14 and / or formed by this or integrally formed therewith.
  • the formation of the feed device 11, so that it is in direct and / or capillary contact with the membrane 3 for the sample 2 represents a particular aspect of the present invention, which is also independent of the proposed combination of capillary force operated and pressure-operated filtration feasible ,
  • the sample 2 penetrates (only) due to capillary forces in the membrane 3 and penetrates them, in particular solid components of the sample 2, such as cells o. The like., At least for a certain size, retained by the membrane 3, ie from the Sample 2 are filtered out.
  • the sample 2 When the sample 2 is supplied, it may possibly spread on the flat feed side of the membrane 3.
  • the membrane 3 preferably has such a thickness and / or structure that the sample 2 can also flow within the membrane 3 into the surface extension of the membrane 3. This flow is also referred to as "cross flow" in the present invention.
  • the cross-flow in the membrane 3 is very important because the membrane 3 preferably rests at least substantially over the entire surface on the underlying cover 6 in the outer ring area, which leads to the preferred low dead volume, but with a lower throughput or a associated with lower filter performance and / or in particular requires said cross-flow of the sample 2 in the membrane 3.
  • the filtered sample 2 fills the preferably very small spaces between the membrane 3 and the carrier 4 or the cover 6 in the illustrated embodiment, as a result of which an air-tight seal, in particular, can be achieved with respect to the environment.
  • This seal is also referred to as "fluidic seal" in the present invention.
  • spaces u. Like., It is displaced air contained therein.
  • the annular region 10, if present, is preferably completely filled without trapping air or air bubbles.
  • the filtered sample 2 reaches the fluidic system 5, here the receiving opening 8 and the receiving channel 7, and may - depending on the acting capillary forces - possibly also the fluidic system 5 begin to fill. However, this is not essential.
  • a pressure-operated filtration is carried out by applying an underpressure or overpressure, whereby the filtration is continued and / or accelerated with respect to the capillary-operated filtration and optionally the further filtration is made possible.
  • the conveying device 15 may be, for example, a vacuum pump, a vacuum pump or the like.
  • the conveyor 15 may be a separate device. However, the conveyor 15 may also form part of the device 1 or be integrated into it.
  • An underpressure or overpressure for accelerating the filtration and / or for further filtration is preferably only generated or applied after the filtered sample 2 has reached or partially filled the fluidic system 5.
  • This can be realized, for example, by detecting the reaching or partial filling of the fluidic system 5 by the sample 2 and only then switching on or switching on the conveyor 15 or opening or closing a corresponding valve or closing a corresponding ventilation. For example, this can be done via a corresponding detection device, not shown, or in that the filtered sample 2 itself includes a ventilation opening or the like, for example after partial filling of the fluidic system 5.
  • the generation of the underpressure or overpressure for the pressure-operated filtration can also take place after a predetermined time, for example after the sample 2 has been applied to the device 1. This can be realized by a corresponding time control or the like.
  • the further filtration is pressure-operated, that is, with underpressure or overpressure, this being able to assist or accelerate the filtration or even make filtration possible in the first place.
  • the fluidic seal prevents, especially in the filtration under negative pressure, an undesirable ingress of air or other gas.
  • the membrane 3 - possibly together with the feeder 11 and / or recording device 14 only loose on the carrier 4 and the cover 6 hang up.
  • the fluidic seal then provides the desired seal against the environment.
  • an otherwise required gas-tight connection of the receiving device 14 with the carrier 4 or its cover 6 can be avoided.
  • the underpressure or overpressure which is used or acts during the filtration is preferably limited to at most 100 mPa, in particular to substantially 50 mPa or less. This can ensure that the fluidic seal is not overstressed. In particular, with such a limitation, it can be achieved or ensured that the capillary forces or diffusion forces that provide the fluidic seal are greater than the pressure forces exerted.
  • the fluidic seal is the particularly preferred direct support of the membrane 3 on the support 4 or its cover 6 conducive, since so a direct contact with the sample 2 is achieved.
  • all intermediate spaces on the discharge side or permeate side to the carrier 4 or its cover 6 are minimized and / or securely filled.
  • the membrane 3 may also be arranged somewhat, but only slightly, away from the carrier 4 or its cover 6.
  • the initially capillary filling leads to or facilitates that the filtered sample 2, in particular the plasma, is free of air bubbles and / or that air pockets in the device 1, in particular in the membrane 3 and / or in adjoining interspaces, are avoided.
  • the proposed combination allows a "loose" connection or support or for example a non-gas-tight connection between the actual sample receiving, such as the membrane 3, the feeder 11 and / or recording device 14 on the one hand and the receptacle for the filtered sample 2 and the plasma, as the carrier 4, the fluidic system 5 and / or the cover 6, on the other hand.
  • the filtration is very well reproducible, since the flow rate is largely determined by the pressure difference, ie the negative pressure or overpressure, and can be controlled or regulated as needed.
  • the total yield or total amount of filtered sample 2 or discharged blood plasma can not normally be increased as this volume is usually determined primarily or exclusively by the capacity of the membrane 3, since the membrane 3 finally "clogs" at the end of the filtration. ,
  • the proposed combination leads to a low risk of hemolysis, since especially at the beginning capillary-operated filtration avoids unwanted destruction of cells such as blood cells or the like. In further filtration, the risk of hemolysis, even with pressure-operated filtration, then no longer so great.
  • the proposed combination allows for a hydrophilic liquid, for example, only use a hydrophilic membrane 3.
  • the further structures can be produced, for example, from native or untreated or hydrophobic plastic or glass and / or in particular must not be hydrophilic. Namely, the hydrophilic or hydrophilized membrane 3 already leads to a particularly sufficient or even complete wetting of the following structures, such as the carrier 4 and / or the cover 6, in particular directly below the membrane 3, with a corresponding delivery-side support. However, at least partial hydrophilization of the other structures may also be advantageous to effect faster wetting.
  • FIG. 2 shows in a schematic section a second embodiment of the device 1 according to the invention.
  • FIG. 3 shows the device 1 according to the second embodiment in a plan view, but only the carrier 4 with the cover 6.
  • a structure 16 for supplying the filtered sample 2, ie the permeate, to the receiving opening 8 or to the receiving channel 7 or to the fluidic system 5 is preferably provided or formed below the membrane 3.
  • the structure 16 is formed in particular by the carrier 4 or in the carrier 4.
  • the structure 16 has in particular grooves, depressions, grooves, ramps or the like and / or is in particular recessed or inclined at least essentially starting from the edge of the membrane 3 and / or radially and / or towards the receiving opening 8, in particular around the filtered one Sample 2 or the permeate from outside to inside or towards the middle or to the receiving opening 8 to promote.
  • the structure 16 has a sector-like design. tion or more sector-like recesses, ramps o. The like., As can be seen in particular from the plan view of FIG. 3.
  • the structure 16 may additionally or alternatively also have other elevations, columns, projections or the like, which in particular produce a fluidic contact with the membrane 3 lying over it.
  • the feeder 11 is omitted.
  • the membrane 3 is again preferably peripherally and / or circumferentially tightly connected to the receiving device 14, in particular welded.
  • the receiving device 14 is preferably formed at least substantially annular.
  • the receiving device 14 is preferably connected to the carrier 4 or its cover 6, wherein, however, a gas-tight connection is not absolutely necessary.
  • the cover 6 preferably has a tongue-like projection 17 in particular, which extends below the diaphragm 3 toward the middle or receiving opening 8, as can be seen in particular from FIG.
  • the projection 17 covers the receiving channel 7, so that the receiving opening 8 opens at least substantially only centrally or only in the middle under the membrane 3 to the membrane 3 out.
  • annular region 10 is preferably formed circumferentially and / or along the edge of the membrane 3 under the membrane 3, in which the liquid sample 2 or the permeate is held by capillary forces. This is achieved by a corresponding contact or a small distance of the membrane 3 to the underlying support 4 or its cover 6.
  • the annular region 10 is formed very flat in cross section, so has a much larger Width or radial extent as height. This is conducive to a good fluidic seal.
  • the structure 16 leads to a better or faster discharge or larger-scale discharge of the filtered sample 2 or the permeate under the membrane 3, so that a higher filter performance and thus a higher throughput are possible.
  • this leads to a higher dead volume under the membrane 3 or between the membrane 3 and the actual fluidic system 5 or the receiving opening 8.
  • An advantage of the structure 16 or similar structures is that no cross-flow is required in the membrane 3. In particular, it is therefore also possible to use membranes 3 without crossflow or with only reduced crossflow.
  • the receiving channel 7, at least the section adjoining the receiving opening 8, extends transversely to the surface extension of the carrier 4 or the membrane 3 and / or preferably at least substantially perpendicular to the surface or flat side of the carrier 4.
  • the receiving channel 7 is formed or executed as an opening in the carrier 4, since an overlap of the receiving channel 7 or a support 4 formed in this groove or the like. Through the cover 6 on the Membrane 3 facing flat side of the support 4 is not required.
  • the membrane 3 is preferably received in a recess 19 of the carrier 3, as indicated in Fig. 4. This is particularly due to the derivation of the filtered sample 2 to the other side of the carrier 4 and / or through the course of the receiving channel 7 across to the main extension plane of the membrane 3 and / or the support 4 is possible because an overlap of the receiving channel 7 or a groove 4 formed in the support 4 o. The like.
  • the cover 6 on the membrane 3 facing flat side of the support 4 is not required ,
  • the membrane 3 may be connected, in particular welded, to the carrier 4, in particular at the edge and / or peripherally, in particular in the depression 19.
  • the membrane 3 may be at least partially covered, in particular by a cover 20, which is preferably formed by a corresponding foil or the like.
  • the lid 20 or the film is then preferably provided with a corresponding feed opening 12 for receiving the sample 2.
  • the cover 20 or the film can also fix or hold the membrane 3 on the support 4, in particular in the depression 19, and / or form a (edge-sided) (sufficient) seal in particular.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Dispersion Chemistry (AREA)
  • Hematology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Molecular Biology (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Separation Using Semi-Permeable Membranes (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)

Abstract

L'invention concerne un dispositif et un procédé pour filtrer un échantillon liquide comprenant d'abord une filtration par capillarité puis, après un remplissage initial, une filtration par pression consistant à appliquer d'une pression négative ou une pression excessive.
EP12711625.9A 2011-03-24 2012-03-23 Dispositif et procédé pour filtrer du sang Withdrawn EP2688672A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP12711625.9A EP2688672A2 (fr) 2011-03-24 2012-03-23 Dispositif et procédé pour filtrer du sang

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP11002441 2011-03-24
PCT/EP2012/055264 WO2012127050A2 (fr) 2011-03-24 2012-03-23 Dispositif et procédé pour filtrer du sang
EP12711625.9A EP2688672A2 (fr) 2011-03-24 2012-03-23 Dispositif et procédé pour filtrer du sang

Publications (1)

Publication Number Publication Date
EP2688672A2 true EP2688672A2 (fr) 2014-01-29

Family

ID=44588308

Family Applications (1)

Application Number Title Priority Date Filing Date
EP12711625.9A Withdrawn EP2688672A2 (fr) 2011-03-24 2012-03-23 Dispositif et procédé pour filtrer du sang

Country Status (4)

Country Link
US (1) US9182326B2 (fr)
EP (1) EP2688672A2 (fr)
JP (1) JP6019485B2 (fr)
WO (1) WO2012127050A2 (fr)

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012127050A2 (fr) 2011-03-24 2012-09-27 Boehringer Ingelheim Microparts Gmbh Dispositif et procédé pour filtrer du sang
DE102012015063B4 (de) * 2012-07-31 2014-10-30 Sartorius Stedim Biotech Gmbh Vorrichtung und Verfahren zur Behandlung eines Filtrationsmediums
US9386948B2 (en) 2012-12-05 2016-07-12 Theranos, Inc. Systems, devices, and methods for bodily fluid sample transport
US10248765B1 (en) 2012-12-05 2019-04-02 Theranos Ip Company, Llc Systems, devices, and methods for bodily fluid sample collection, transport, and handling
US20140323911A1 (en) * 2013-03-15 2014-10-30 Theranos, Inc. Methods and devices for sample collection and sample separation
KR20150133774A (ko) 2013-03-15 2015-11-30 테라노스, 인코포레이티드 시료 수집 및 시료 분리용 방법과 기기
MX2017001368A (es) 2014-08-01 2017-05-11 Siemens Healthcare Diagnostics Inc Separacion de plasma asistido por vacio.
EP3281009A4 (fr) 2015-04-09 2018-11-14 Axela Inc. Cartouche de test biologique jetable et procédé de réalisation de plusieurs étapes de test et d'un transfert de fluide à l'intérieur de la cartouche
US10371606B2 (en) 2015-07-21 2019-08-06 Theraos IP Company, LLC Bodily fluid sample collection and transport
WO2017044888A1 (fr) 2015-09-09 2017-03-16 Theranos, Inc. Procédés et dispositifs de collecte et de séparation d'échantillons
US20190247853A1 (en) * 2016-06-27 2019-08-15 Fluidic Analytics Limited Improvements in or relating to sample loading into a microfluidic device
US20200009568A1 (en) * 2016-12-13 2020-01-09 Koninklijke Philips N.V. Microfluidic device for accommodating, isolating, treating, and/or processing cells having an inlet chamber with a chute structure
JP7004333B2 (ja) * 2017-02-06 2022-01-21 イーエフエー―エンジニアリング フォー オール エルティーディー． 携帯用のデジタル診断デバイス
US11857966B1 (en) 2017-03-15 2024-01-02 Labrador Diagnostics Llc Methods and devices for sample collection and sample separation
CN108722504A (zh) * 2017-04-19 2018-11-02 光宝电子(广州)有限公司 检测装置及其注入口结构
US11007526B2 (en) * 2018-07-06 2021-05-18 Qorvo Us, Inc. Capless sample well port for a cartridge

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011027092A1 (fr) * 2009-09-01 2011-03-10 F. Hoffmann-La Roche Ag Structures microfluidiques

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4849340A (en) * 1987-04-03 1989-07-18 Cardiovascular Diagnostics, Inc. Reaction system element and method for performing prothrombin time assay
US6540962B1 (en) 1997-03-03 2003-04-01 Kyoto Daiichi Kagaku Co., Ltd. Testing instrument for analyzing liquid sample
US6071294A (en) * 1997-12-04 2000-06-06 Agilent Technologies, Inc. Lancet cartridge for sampling blood
US7497994B2 (en) 1998-02-24 2009-03-03 Khushroo Gandhi Microfluidic devices and systems incorporating cover layers
US20030180711A1 (en) * 2002-02-21 2003-09-25 Turner Stephen W. Three dimensional microfluidic device having porous membrane
US7524462B2 (en) * 2002-03-29 2009-04-28 Agilent Technologies, Inc. Capillary flow for a heterogenous assay in a micro-channel environment
DE10252223A1 (de) 2002-11-11 2004-05-27 Roche Diagnostics Gmbh Vorrichtung zur Separierung und Ausgabe von Plasma
DE102004027422A1 (de) 2004-06-04 2005-12-29 Boehringer Ingelheim Microparts Gmbh Vorrichtung zur Aufnahme von Blut und Abtrennung von Blutbestandteilen
JP5475692B2 (ja) 2008-02-27 2014-04-16 ベーリンガー インゲルハイム マイクロパーツ ゲゼルシャフト ミット ベシュレンクテル ハフツング 血漿の分離装置
CA2730480A1 (fr) * 2008-07-15 2010-01-21 L3 Technology Limited Dispositif et procedes de dosage
CN102481573A (zh) * 2009-09-01 2012-05-30 皇家飞利浦电子股份有限公司 流体过滤设备
WO2012127050A2 (fr) 2011-03-24 2012-09-27 Boehringer Ingelheim Microparts Gmbh Dispositif et procédé pour filtrer du sang

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011027092A1 (fr) * 2009-09-01 2011-03-10 F. Hoffmann-La Roche Ag Structures microfluidiques

Also Published As

Publication number Publication date
JP6019485B2 (ja) 2016-11-02
WO2012127050A3 (fr) 2013-01-17
JP2014517909A (ja) 2014-07-24
WO2012127050A2 (fr) 2012-09-27
US20140134595A1 (en) 2014-05-15
US9182326B2 (en) 2015-11-10

Similar Documents

Publication Publication Date Title
WO2012127050A2 (fr) Dispositif et procédé pour filtrer du sang
EP1144095B1 (fr) Dispositif de concentration et/ou de purification de macromolecules en solution et procede de fabrication d'un tel dispositif
EP2413138B1 (fr) Dispositif et procédé de séparation de composants d'un liquide d'échantillon
EP1480749B1 (fr) Systeme microfluidique
EP2687290B1 (fr) Dispositif de stockage microfluidique pour le stockage préalable d'un fluide, son procédé de fabrication et une utilisation de celui-ci
DE102011078961B4 (de) System zum Separieren von Körperflüssigkeitsbestandteilen und Verfahren zum Herstellen eines derartigen Systems
EP2268405A2 (fr) Dispositif de séparation de plasma
EP2695656A1 (fr) Procédé ainsi que dispositif de séparation destiné à séparer un filtrat d'un échantillon de liquide
EP2560756A1 (fr) Dispositif pour la séparation plasmatique au moyen d'une structure de canal centrale
WO2015044040A1 (fr) Unité d'analyse pour effectuer une réaction en chaîne par polymérase, procédé pour faire fonctionner une telle unité d'analyse et procédé de fabrication d'une telle unité d'analyse
WO2002020141A1 (fr) Dispositif et procedes pour separer des constituants non dissous contenus dans des liquides biologiques
DE102015205906B4 (de) Bevorratungseinheit, Verfahren zum Herstellen einer Bevorratungseinheit und Verfahren zum Freisetzen eines in einer Bevorratungseinheit gelagerten Fluids
DE112004000225T5 (de) Unterdruckfiltervorrichtung
DE102013215565A1 (de) Vorrichtung zum Einbringen einer flüssigen Probe in ein mikrofluidisches System
EP2754495A2 (fr) Système de canaux microfluidique doté d'un dispositif de collecte de bulles et procédé d'élimination de bulles de gaz
WO2017032845A1 (fr) Récipient d'analyse et procédé de filtration d'une suspension faisant appel à son utilisation
DE102014202342A1 (de) Vorrichtung zum Vorlagern eines Fluids in einem mikrofluidischen System, Verfahren zum Betreiben und Verfahren zum Herstellen einer solchen Vorrichtung
WO2022037912A1 (fr) Dispositif microfluidique
EP1596961B1 (fr) Chambre a echantillon pour un liquide
DE202014104510U1 (de) Vorrichtung zum Vorlagern eines Fluids in einem mikrofluidischen System
EP2598242B1 (fr) Dispositif de séparation d'éléments constitutifs d'un échantillon liquide
WO2017025506A1 (fr) Tube médical
DE10301176A1 (de) Anordnung zur Separation von Blutplasma aus Vollblutproben
DE102021211549A1 (de) Vorrichtung, insbesondere mikrofluidische Kartusche, und Verfahren mit Entnahmekammer und entfernbarer Abdeckung
WO2020161013A1 (fr) Dispositif microfluidique et procédé pour la séparation du sérum sanguin

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: 20131024

AK Designated contracting states

Kind code of ref document: A2

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)
17Q First examination report despatched

Effective date: 20170203

GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

RIC1 Information provided on ipc code assigned before grant

Ipc: B01L 3/00 20060101AFI20171010BHEP

INTG Intention to grant announced

Effective date: 20171107

GRAS Grant fee paid

Free format text: ORIGINAL CODE: EPIDOSNIGR3

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

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20181002