EP2679307A1 - Micro-enregistreur, notamment pour l'intégration dans une cellule d'écoulement microfluidique - Google Patents

Micro-enregistreur, notamment pour l'intégration dans une cellule d'écoulement microfluidique Download PDF

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Publication number
EP2679307A1
EP2679307A1 EP20120173976 EP12173976A EP2679307A1 EP 2679307 A1 EP2679307 A1 EP 2679307A1 EP 20120173976 EP20120173976 EP 20120173976 EP 12173976 A EP12173976 A EP 12173976A EP 2679307 A1 EP2679307 A1 EP 2679307A1
Authority
EP
European Patent Office
Prior art keywords
actuator element
memory according
barrier
micro memory
outlet channel
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP20120173976
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German (de)
English (en)
Other versions
EP2679307B1 (fr
Inventor
Lutz Weber
Michel Neumeier
Stefan Keck
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.)
Thinxxs Microtechnology GmbH
Original Assignee
Thinxxs Microtechnology 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 Thinxxs Microtechnology GmbH filed Critical Thinxxs Microtechnology GmbH
Priority to EP12173976.7A priority Critical patent/EP2679307B1/fr
Priority to US13/917,284 priority patent/US9108192B2/en
Publication of EP2679307A1 publication Critical patent/EP2679307A1/fr
Application granted granted Critical
Publication of EP2679307B1 publication Critical patent/EP2679307B1/fr
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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/50273—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
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/12—Specific details about materials
    • B01L2300/123—Flexible; Elastomeric
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T137/00—Fluid handling
    • Y10T137/8593—Systems

Definitions

  • the invention relates to a micro-accumulator, in particular for integration into a microfluidic flow cell, with a fluid-containing storage space which communicates with an outlet channel for the fluid, in which a liftable barrier for the fluid is formed.
  • Micro memory of such kind are from the WO 2009/071078 A1 known.
  • the storage space and the outlet channel of this known micro memory form two arranged on a plate-shaped substrate films which are welded together under the limitation of the storage space and the outlet channel and / or glued.
  • the film facing away from the substrate has a dome-like shape.
  • a line-shaped transversely to the outlet channel extending welding or / and bonding of the films serves as the storage space hermetically sealing barrier.
  • the storage space forms a deep-drawn expansion of the film facing away from the substrate. In order to open the storage space, it is compressed with deformation of the film until such a pressure builds up at the intended as a predetermined breaking point lock that ruptures the predetermined breaking point.
  • the one-piece substrate forms part of a fluid processing device (flow cell) which, in addition to one or more micro-accumulators, may comprise further fluid-conveying elements. These include elements for supplying liquid or gaseous samples, mixing elements, pumps, valves, filters for separating components of a fluid, temperature chambers, detection chambers, lateral flow test strips, transport channels and waste chambers, which individually or in combination for the analysis and / or synthesis of Fluids for medical and pharmaceutical purposes or for analytical processes such as immunoassays or genetic assays.
  • the fluid pressure required to remove the barrier causes the fluid to shoot out of the storage space at the first moment after the exit channel has been opened at a high flow rate.
  • a subset of the stored fluid leaves in this way uncontrolled and undosed the memory space. If the flow cell is intended for reactions which require defined flow rates of supplied reagents, this subset is lost and thus the contents of the micro memory are not fully usable.
  • the invention has for its object to provide a new micro store of the type mentioned above, which allows a controlled from the beginning and metered removal of the stored fluid.
  • the problem solving micro memory according to the invention is characterized by means for lifting the lock without pressurization of the barrier by pressure of the fluid.
  • the lock can be canceled while leaving the entire amount of memory in the memory space. From the beginning, after the barrier has been opened, a controlled and metered removal of fluid from the reservoir can take place.
  • the means for lifting the barrier preferably comprise means for their mechanical destruction.
  • the barrier is formed by welding or / and bonding opposing boundary walls of the outlet channel and at least one of these two boundary walls consists of a flexible film.
  • the devices for the mechanical destruction of the barrier may comprise an actuator element which separates the welded or / and glued boundary walls, wherein this actuator element may be provided for the arrangement outside the outlet channel or within the outlet channel on the side facing away from the storage space of the barrier.
  • the at least one flexible film is arranged on a substrate and the actuator element can be pressed against the film through a passage opening in the substrate, thereby producing a break-off force which releases the barrier.
  • the outlet channel may be formed between two flexible films adjacent to each other and the film facing the substrate may be connected to the substrate, wherein the actuator element lifts the films apart by generating the demolition force across the channel width by expanding them with different radii.
  • the actuator element which is preferably in the form of a pin, expediently acts on the film on the side of the barrier which faces away from the storage space. In particular, this is done in an adjoining the outlet channel area in which the film is connected neither to the substrate nor another possibly existing film.
  • the actuator element can be part of a device for operating the micro-storage unit or flow cell.
  • the actuator element arranged within the outlet channel expediently has an impact element that can be extended against the barrier by deformation of the actuator element, which opens the barrier away from the side facing away from the storage space.
  • this actuator element is arc-shaped and the impact element can be extended by stretching the sheet.
  • the actuator element can be held in a form-fitting manner in an expansion of the film forming the boundary wall of the outlet channel at an end facing away from the butt end, so that essentially only the butt member of the element provided for opening the barrier is moved during the stretching of the arch.
  • the actuator element comprises a lever connected to the outside of the flexible film for producing a break-off force which releases the barrier.
  • the actuator element may comprise a rod element forming two such levers, crossing the outlet channel, the end of which is rotatable by bending the rod element around a pivot point formed by the substrate to form the tear-off force.
  • the ends of the rod could protrude beyond edges of the substrate, in a preferred embodiment two openings are provided in the substrate into which the ends are pressable under flexure of the rod member.
  • the actuator element provided within the outlet channel and / or the region of the outlet channel in the flow direction behind the barrier can be associated with a dry reagent which is resuspended when the fluid flows out.
  • the transport of the fluids out of the storage space can be carried out alternatively by deformation of a film forming the storage by application of pneumatic or / and hydraulic pressure.
  • Fig. 12 Reference is made, where in subfigures (a) to (f) conventional micro memory integrated into a microfluidic flow cell with a substrate 1 are shown.
  • the substrate is made of a plastic and is made by injection molding.
  • a storage space 2 for a fluid between the substrate 1 and a flexible film 3 welded or bonded to the substrate is formed by a depression in the film (FIG. Fig. 12a ) or in the substrate ( Fig. 12b to d ) educated.
  • a barrier 6 for the fluid is formed in the storage space 2, through which the storage space 2 is hermetically sealed.
  • Fig. 12d are two outlet channels, each with a barrier 6 or 6 'is formed, which delimits the storage space 2 against a feed channel 27 and a discharge channel 28.
  • Fig. 12e and f is the storage space 2 between the film 3 and another connected to the substrate 1 film 7.
  • the film 3 is with the film 7, in the same manner as the film 3 to the substrate 1 in Examples 12a-d, welded, or / and glued.
  • An outlet channel 4 with a barrier 6 is as in formed in the preceding examples by omitting the welding or gluing in the region of the channel.
  • the storage space 2 is formed between a depression of the film 3 and a depression of the film 7, the depression of the film 7 projecting into a depression formed in the substrate 1.
  • a channel-shaped storage space 2 is additionally provided with a filling channel 29 and a venting channel 30.
  • the fluid to be stored is entered by dispensing or by pumping into the filling channel 29 and the storage space completely filled. Air in the storage space can escape via the vent passage 30.
  • the filling channel 29 and the venting channel 30 are hermetically sealed by means of a bottom foil 31 glued or welded to the substrate 1. The bottom foil 31 simultaneously serves as a fluid-tight cover of the transport channel 5.
  • the foils 3, 7 are preferably made of a plastic, of aluminum or of a plastic-aluminum composite.
  • a plastic-aluminum composite foil e.g. PP, PE, COC, COP, PC, PMMA and PEEK come into consideration.
  • the storage space 2 is emptied by displacing the liquid or gaseous fluid contained therein by deformation of the film 3.
  • the fluid When the fluid is displaced, it penetrates into the unconnected channel area between the film 3 and the substrate 1 or between the film 3 and the other film 7 and is under pressure to the barrier 6 at. If the fluid pressure is sufficiently high, the barrier 6 breaks and the fluid continues to penetrate, with the opening of a channel cross-section, until the fluid flow reaches the channel 5.
  • FIG. 1 An in Fig. 1 shown, the example of Fig. 12a corresponding micro memory with a substrate 1 and a storage space 2, which is formed by a welded to the substrate 1 and / or bonded film 3 between the film 3 and the substrate 1, then points to an outlet channel 4, which penetrates the substrate 1 Channel 5 ends, a further region 8, in which the film 3 is not welded as in the outlet channel 4 with the substrate 1 and / or glued.
  • This region 8 is aligned with a passage opening 9 in the substrate 1.
  • an elastic, welded to the substrate 1 and / or bonded membrane 11 is inserted.
  • a film 12 covers the substrate on the opposite side of the storage space 2 under closure of a portion of the channel 5 from.
  • Operating equipment to be used comprises, in addition to an actuator 13 for deforming the film 3 in the region of the storage space 2, a pin-shaped actuator element 14 which is inserted into the opening 9 in the substrate 1 and against the elastic membrane 11 under deformation of the membrane 11 can be pressed. With the deformation of the membrane 11, the film 3 is raised in the adjoining the channel 4 unconnected region 8, wherein this increase continues into the channel 4 into it. This creates a tearing force which breaks the barrier 6.
  • the storage space 2 can now be emptied dosed by means of the actuator 13.
  • the film 3, which bears against the substrate 1 before the emptying of the storage space 2 is raised by the penetration of the fluid to form a channel cross-section. From the beginning, a metered delivery of fluid from the storage space 2 is possible using the entire storage contents.
  • a further actuator element 15 which can be attached to the film 3 by the side of the micro-memory that is opposite the actuator element 14, presses after opening the barrier 6, the film 3 against the substrate 1, so that fluid from the channel 4 can not penetrate into the unconnected region 8.
  • the pin-shaped, arranged outside the outlet channel 4 actuator element 14 goes out of the Fig. 4 to 7 a memory of Fig. 12e corresponding embodiment with a disposed within an outlet channel 4 actuator element 16 forth.
  • This in Fig. 5 separately shown actuator element 16 is accommodated in a molding 17 of the film 3, wherein the molding 17 is made together with the provided for forming the storage space 2 molding by deep drawing.
  • the actuator element 16 is arcuately formed with an expiring to a bow end towards impact wedge 18.
  • the actuator element 16 has a groove on its upper or lower side, in the present case on its upper side, the channel 26.
  • the channel forms a channel region in the pressed-on and stretched state, through the actuator element 16 and the pressed-on film 3 or film 7 is limited and through which the fluid from the storage space 2 can get into the channel 5.
  • the actuator element 16 is preferably made of plastic, in particular of the same plastic as the substrate, and is produced by injection molding.
  • the actuator element 16 may be made of a shape memory alloy or a bimetal, wherein in these cases, the stretching of the actuator element takes place by supplying heat.
  • an operator device comprises an actuator 13 for deforming the film 3 in the region of the storage space 2, a further actuator 19, through which the arcuate actuator element 16 compresses and stretch, so that the impact wedge 18 pierces the barrier 6, while the other end the arcuate actuator element is held positively in the formation 17.
  • the barrier 3 can be transferred from the storage space 2 into the channel 5 with the aid of the actuator 13 dosed fluid.
  • the actuator 19 can be rigidly connected to a clamping device which is part of a device for operating the flow cell.
  • a clamping device which is part of a device for operating the flow cell.
  • the actuator element 16 receiving formation 17, which is located in the channel 4 can be used to receive next to the actuator element 16, a reagent, in particular dry reagent is at a in Fig. 8a
  • the molding 17 is laid essentially in a region which adjoins the end of the channel 4, in which the films 3 and 4 are not welded or glued together.
  • Fig. 8b two outlet channels with a lock 6 and 6 'are provided, which can be destroyed by an actuator element 16 or 16'. After destruction of both locks, the memory can be emptied by pneumatic or hydraulic pressure without deformation of the storage space limiting film.
  • a through hole 20 may be formed in the substrate 1, in which a film 7 in the region of the channel 4 expanding actuator element 21 is inserted, wherein the expanded film 7, the film 3 near the barrier (in Fig. 9a not shown) and generates a tearing force.
  • one of the passage opening 20 corresponding opening 20 'for an actuator element 21' in the flow direction may also be provided in front of the barrier 6.
  • One in the 10 and 11 Micro memory shown has a rod-shaped actuator element 22, which crosses the region of the outlet channel 4, in which the film 3 is not connected to the substrate 1, and bonded to the outside of the film 3 at 23 and / or welded.
  • Through holes 24 and 25 in the substrate 1 allow a bending of the actuator element by pressing its ends in the Through holes 24,25, wherein the lock 6 canceling tear-off force is generated.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Dispersion Chemistry (AREA)
  • Micromachines (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
EP12173976.7A 2012-06-28 2012-06-28 Micro-enregistreur, notamment pour l'intégration dans une cellule d'écoulement microfluidique Active EP2679307B1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP12173976.7A EP2679307B1 (fr) 2012-06-28 2012-06-28 Micro-enregistreur, notamment pour l'intégration dans une cellule d'écoulement microfluidique
US13/917,284 US9108192B2 (en) 2012-06-28 2013-06-13 Micro reservoir, particularly for integration in a microfluidic flow cell

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP12173976.7A EP2679307B1 (fr) 2012-06-28 2012-06-28 Micro-enregistreur, notamment pour l'intégration dans une cellule d'écoulement microfluidique

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EP2679307A1 true EP2679307A1 (fr) 2014-01-01
EP2679307B1 EP2679307B1 (fr) 2015-08-12

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US (1) US9108192B2 (fr)
EP (1) EP2679307B1 (fr)

Cited By (4)

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Publication number Priority date Publication date Assignee Title
EP2962758A1 (fr) * 2014-07-01 2016-01-06 ThinXXS Microtechnology AG Cellule d'écoulement dotée d'une zone de stockage et d'un canal de transport pouvant s'ouvrir à un point de rupture
EP3912721A1 (fr) 2020-05-22 2021-11-24 Thinxxs Microtechnology Ag Cellule d'écoulement comprenant un dispositif de blocage à rupture
DE102022211171A1 (de) 2022-10-21 2024-05-02 Robert Bosch Gesellschaft mit beschränkter Haftung Versiegelung für eine mikrofluidische Kammer
DE102022211170A1 (de) 2022-10-21 2024-05-02 Robert Bosch Gesellschaft mit beschränkter Haftung Kompartiment mit Versiegelung

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JP1628116S (fr) 2012-10-24 2019-04-01
US20140322706A1 (en) 2012-10-24 2014-10-30 Jon Faiz Kayyem Integrated multipelx target analysis
AU2014235532B2 (en) 2013-03-15 2018-08-09 Genmark Diagnostics, Inc. Systems, methods, and apparatus for manipulating deformable fluid vessels
GB2516672B (en) 2013-07-29 2015-05-20 Atlas Genetics Ltd A system and method for expelling liquid from a fluidic cartridge
GB2516675A (en) 2013-07-29 2015-02-04 Atlas Genetics Ltd A valve which depressurises, and a valve system
GB2516666B (en) 2013-07-29 2015-09-09 Atlas Genetics Ltd Fluidic cartridge for nucleic acid amplification and detection
GB2516667A (en) * 2013-07-29 2015-02-04 Atlas Genetics Ltd An improved cartridge, cartridge reader and method for preventing reuse
GB2516669B (en) 2013-07-29 2015-09-09 Atlas Genetics Ltd A method for processing a liquid sample in a fluidic cartridge
US9498778B2 (en) 2014-11-11 2016-11-22 Genmark Diagnostics, Inc. Instrument for processing cartridge for performing assays in a closed sample preparation and reaction system
USD881409S1 (en) 2013-10-24 2020-04-14 Genmark Diagnostics, Inc. Biochip cartridge
CN105980058A (zh) 2014-01-07 2016-09-28 达克雷诊断器材有限公司 流体输送装置、系统和方法
US9598722B2 (en) 2014-11-11 2017-03-21 Genmark Diagnostics, Inc. Cartridge for performing assays in a closed sample preparation and reaction system
US10005080B2 (en) 2014-11-11 2018-06-26 Genmark Diagnostics, Inc. Instrument and cartridge for performing assays in a closed sample preparation and reaction system employing electrowetting fluid manipulation
US10377538B2 (en) 2015-12-01 2019-08-13 Illumina, Inc. Liquid storage and delivery mechanisms and methods
GB201615452D0 (en) * 2016-09-12 2016-10-26 Fluidic Analytics Ltd Improvements in or relating to valves for microfluidics devices
US10046322B1 (en) 2018-03-22 2018-08-14 Talis Biomedical Corporation Reaction well for assay device
US11008627B2 (en) 2019-08-15 2021-05-18 Talis Biomedical Corporation Diagnostic system
CN118414607A (zh) * 2021-11-01 2024-07-30 康维达无线有限责任公司 实现应用之间的感知和协调

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US4592493A (en) * 1984-10-15 1986-06-03 Unette Corporation Reclosable dispenser
DE10336850A1 (de) * 2003-08-11 2005-03-10 Thinxxs Gmbh Mikrospeicher
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US11364501B2 (en) 2014-07-01 2022-06-21 Thinxxs Microtechnology Ag Reagent reservoir for fluids
WO2016000998A1 (fr) * 2014-07-01 2016-01-07 Thinxxs Microtechnology Ag Cellule d'écoulement comprenant une zone de stockage et un canal de transport pouvant être ouvert en un point de rupture de consigne
WO2016000999A1 (fr) * 2014-07-01 2016-01-07 Thinxxs Microtechnology Ag Réservoir de réactif pour fluides
US10173215B2 (en) 2014-07-01 2019-01-08 Thinxxs Microtechnology Ag Flow cell comprising a storage zone and a duct that can be opened at a predetermined breaking point
US10183293B2 (en) 2014-07-01 2019-01-22 Thinxxs Microtechnology Ag Reagent reservoir for fluids
US11291996B2 (en) 2014-07-01 2022-04-05 Thinxxs Microtechnology Ag Reagent reservoir for fluids
US11364500B2 (en) 2014-07-01 2022-06-21 Thinxxs Microtechnology Ag Reagent reservoir for fluids
EP2962758A1 (fr) * 2014-07-01 2016-01-06 ThinXXS Microtechnology AG Cellule d'écoulement dotée d'une zone de stockage et d'un canal de transport pouvant s'ouvrir à un point de rupture
US11642673B2 (en) 2014-07-01 2023-05-09 Thinxxs Microtechnology Gmbh Flow cell comprising a storage zone and a duct that can be opened at a predetermined breaking point
EP3912721A1 (fr) 2020-05-22 2021-11-24 Thinxxs Microtechnology Ag Cellule d'écoulement comprenant un dispositif de blocage à rupture
WO2021233862A1 (fr) 2020-05-22 2021-11-25 Thinxxs Microtechnology Ag Cuve à circulation avec barrière de rupture prédéterminée
DE102022211171A1 (de) 2022-10-21 2024-05-02 Robert Bosch Gesellschaft mit beschränkter Haftung Versiegelung für eine mikrofluidische Kammer
DE102022211170A1 (de) 2022-10-21 2024-05-02 Robert Bosch Gesellschaft mit beschränkter Haftung Kompartiment mit Versiegelung

Also Published As

Publication number Publication date
EP2679307B1 (fr) 2015-08-12
US20140000735A1 (en) 2014-01-02
US9108192B2 (en) 2015-08-18

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