WO2018033609A1 - A microfluidic device - Google Patents

A microfluidic device Download PDF

Info

Publication number
WO2018033609A1
WO2018033609A1 PCT/EP2017/070891 EP2017070891W WO2018033609A1 WO 2018033609 A1 WO2018033609 A1 WO 2018033609A1 EP 2017070891 W EP2017070891 W EP 2017070891W WO 2018033609 A1 WO2018033609 A1 WO 2018033609A1
Authority
WO
WIPO (PCT)
Prior art keywords
region
membrane
sacrificial
channel
microfluidic device
Prior art date
Application number
PCT/EP2017/070891
Other languages
French (fr)
Inventor
Rohit Mishra
Jens Ducree
Original Assignee
Dublin City University
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 Dublin City University filed Critical Dublin City University
Publication of WO2018033609A1 publication Critical patent/WO2018033609A1/en

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502738—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 integrated valves
    • 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
    • B01L3/502723—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
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00—Subject matter not provided for in other groups of this subclass
    • F16K99/0001—Microvalves
    • F16K99/0003—Constructional types of microvalves; Details of the cutting-off member
    • F16K99/0015—Diaphragm or membrane valves
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00—Subject matter not provided for in other groups of this subclass
    • F16K99/0001—Microvalves
    • F16K99/0003—Constructional types of microvalves; Details of the cutting-off member
    • F16K99/003—Valves for single use only
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00—Subject matter not provided for in other groups of this subclass
    • F16K99/0001—Microvalves
    • F16K99/0034—Operating means specially adapted for microvalves
    • F16K99/0036—Operating means specially adapted for microvalves operated by temperature variations
    • F16K99/004—Operating means specially adapted for microvalves operated by temperature variations using radiation
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00—Subject matter not provided for in other groups of this subclass
    • F16K99/0001—Microvalves
    • F16K99/0034—Operating means specially adapted for microvalves
    • F16K99/0063—Operating means specially adapted for microvalves using centrifugal forces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0621—Control of the sequence of chambers filled or emptied
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0684—Venting, avoiding backpressure, avoid gas bubbles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0803—Disc shape
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0874—Three dimensional network
    • 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
    • B01L2400/0409—Moving fluids with specific forces or mechanical means specific forces centrifugal forces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0677—Valves, specific forms thereof phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers
    • 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
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0677—Valves, specific forms thereof phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers
    • B01L2400/0683—Valves, specific forms thereof phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers mechanically breaking a wall or membrane within a channel or chamber
    • 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
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0688—Valves, specific forms thereof surface tension valves, capillary stop, capillary break
    • 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
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0694—Valves, specific forms thereof vents used to stop and induce flow, backpressure valves
    • 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
    • B01L3/502707—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 manufacture of the container or its components
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00—Subject matter not provided for in other groups of this subclass
    • F16K2099/0073—Fabrication methods specifically adapted for microvalves
    • F16K2099/008—Multi-layer fabrications
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00—Subject matter not provided for in other groups of this subclass
    • F16K2099/0082—Microvalves adapted for a particular use
    • F16K2099/0084—Chemistry or biology, e.g. "lab-on-a-chip" technology
    • 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
    • Y10T137/1624—Destructible or deformable element controlled
    • Y10T137/1632—Destructible element
    • Y10T137/1692—Rupture disc

Definitions

  • a microfluidic device A microfluidic device
  • the invention relates to a microfluidic device incorporating a valve for controlling the flow of a fluid within the microfluidic device.
  • One solution to this problem proposed by the Applicant 4 5 comprises a microfluidic device comprising a fluid channel comprising a first and second region separated by a valve comprising a first sacrificial membrane.
  • the first region is upstream of the valve and the second region is downstream of the valve, the first sacrificial membrane being configured to disintegrate on contact with a liquid to provide a fluid path between the first and second regions of the fluid channel.
  • a gas pocket region is provided within the first region adjacent to the first sacrificial membrane configured to receive and retain a gas pocket against the first sacrificial membrane to prevent liquid in the first region contacting the first sacrificial membrane.
  • a force generating means for example a centrifugal force generating means
  • actuation induces flow of liquid from the first region towards the second region of the fluid channel displacing the gas pocket from the sacrificial membrane and allowing the liquid to come into contact with and effect disintegration of the membrane.
  • the valving mechanisms of Reference 5 are provided as a series of sequential events where actuation of a first valving mechanism causes liquid flow, which in-turn triggers a second valving event.
  • the Applicant has solved at least some of the problems of the microfluidic device of References 4 and 5 by providing a device according to the preamble of claim 1 , characterised in that the device incorporates an actuation channel having an pressurised upstream region and a depressurisation region separated by an actuation valve comprising a second sacrificial membrane configured to rupture in response to an optical beam directed on to the second sacrificial membrane, in which the upstream region is in fluid communication with the gas pocket region, whereby the rupture of the actuation valve depressurises the upstream region displacing the gas pocket from the sacrificial membrane and allowing the liquid to come into contact with and effect disintegration of the membrane.
  • the device of the invention solves the footprint problem of the prior art by providing a valving mechanism that is not reliant on a previous device-based liquid valving event, but on an external optical event, and as such obviates the large footprint required by the valving mechanisms of the prior art and allows the device incorporate more valving mechanisms per unit area.
  • the use of the device of the invention provides greater flexibility as regards positioning of the valves on the device.
  • the sequence of operation is also completely customizable as the opening of the valves can be defined on-demand thus neither depending on the rotational frequency of operation of the valves (as in Reference 4) nor on the previously performed function (as in Reference 5).
  • second sacrificial membranes of controllable fluid channels can be arranged in an overlapping configuration, so that they can be actuated by a single light source by changing the focal length of the light source (See Fig. 9).
  • the invention provides a microfluidic device comprising a controllable fluid channel, the controllable fluid channel comprising: a first and second region separated by a valve, the first region being upstream of the valve and the second region being downstream of the valve, the valve comprising a sacrificial membrane configured to disintegrate on contact with a liquid to provide a fluid path between the first and second regions of the fluid channel; and a gas pocket region provided within the first region adjacent to the sacrificial membrane configured to receive and retain a gas pocket against the sacrificial membrane to prevent liquid in the first region contacting the sacrificial valve, characterised in that the controllable fluid channel comprises an actuation channel having an upstream region and a depressurisation region separated by an actuation membrane configured to rupture in response to an incident focussed optical beam, in which the upstream region is pressurised and in fluid communication with the gas pocket region, whereby the rupture of the actuation valve depressurises the upstream region displacing the gas pocket from
  • the depressurisation region may be atmosphere (i.e. when the actuation membrane is positioned on an external face of the device), or may be a downstream region of the actuation channel in fluid communication with atmosphere or a depressurisation chamber (i.e. when the actuation membrane is positioned within the device, in one of the internal layers).
  • the first region of the fluid channel comprises a reservoir for liquid.
  • the reservoir is vented to atmosphere.
  • the gas pocket region is disposed above the first sacrificial membrane.
  • the gas pocket region comprises a first outlet in fluid communication with the first region of the first channel and a second outlet in fluid communication with the upstream region of the actuation channel.
  • the first and second outlets are disposed towards a top of the gas pocket region.
  • the first outlet disposed on an opposite side of the gas pocket region to the second outlet.
  • the microfluidic device comprises at least two controllable fluid channels.
  • the microfluidic device comprises at least ten controllable fluid channels.
  • the microfluidic device comprises at least twenty controllable fluid channels.
  • the microfluidic device comprises at least thirty controllable fluid channels.
  • the microfluidic device comprises at least forty controllable fluid channels.
  • At least two controllable fluid channels share a common component, for example a shared liquid reservoir, or a shared actuation valve, or a shared sacrificial membrane.
  • controllable fluid channels are disposed in a single plane.
  • controllable fluid channels may be provided in a side-by-side arrangement across a given plane of the device, as opposed to in different planes in the device.
  • controllable fluid channels are disposed in different planes.
  • controllable fluid channels may be provided on different levels the device, and in one embodiment may be stacked on top of each other.
  • at least two controllable fluid channels overlap (i.e. are stacked on top of each other along a Z-axis of the device, or along an X- or Y-axis of the device).
  • the actuation membranes of at least two controllable fluid channels overlap. In this manner, the at least two actuation membranes can be ruptured by a static light source by changing the focal point of the light source.
  • the microfluidic device comprises a layered structure having a plurality of layers.
  • different components of the controllable fluid channel are disposed in different layers.
  • the membranes are disposed in one layer.
  • the first and second regions of the fluid channel are disposed in different layers, the first regions being located above the second region.
  • the microfluidic device comprises a first layer comprising a reservoir vent, a second layer comprising at least part of an upstream region of the first channel, a third layer comprising the liquid reservoir, a fourth layer comprising one or both of the membranes, and a fifth layer comprising at least part of the second region of the fluid channel.
  • the device comprises a light path configured to transmit a focussed optical beam form a light source to one or more actuation membranes.
  • the light path comprises transparent material, or an opening, or a combination of transparent material and an opening.
  • the device has a planar structure. Examples include planar chips or disks.
  • the device is a disk.
  • the device is a circular disk.
  • the disc comprises a central aperture configured for mounting the disc on a turn-table.
  • the light path configured to transmit a focussed optical beam is typically disposed along a Z-axis of the device.
  • the Z-axis means an axis that runs substantially orthogonal to the planar aspect of the device.
  • the device may be configured such that the light path configured to transmit a focussed optical beam is typically disposed parallel to the planar aspect of the device (i.e. along an X-axis or Y-axis of the device).
  • a plurality of second actuation membranes are disposed along the light path.
  • the decompression area is the atmosphere.
  • the downstream region generally comprises a vent providing fluid communication with the atmosphere at the top of the device, the bottom of the device, or a side of the device.
  • the decompression area is a decompression chamber disposed within the device. This is generally a chamber that is sufficiently large to allow the pressurised fluid within the actuation channel decompress.
  • controllable fluid channel is configured such that upon priming the device the first region of the fluid channel, the gas pocket region, and the upstream region of the actuation channel are pneumatically pressurised.
  • first sacrificial membrane is at least partially gas permeable.
  • the first sacrificial membrane is disposed substantially parallel to a major axis of each of the first and second regions. In one embodiment, the second sacrificial membrane is disposed substantially parallel to a major axis of the upstream region of the actuation channel.
  • the device comprises a capture chamber downstream of the first sacrificial membrane configured to capture and retain debris resultant from disintegration of the first sacrificial membrane.
  • the invention also provides an apparatus comprising a microfluidic device of the invention and a light source configured to produce a focussed optical beam and direct the focussed optical beam on to the actuation membrane of the controllable fluid channel.
  • the light source is configured to allow adjustment of the focal point of the optical beam.
  • apparatus is configured to move the light source with respect to the microfluidic device.
  • the apparatus is configured to move the light source along an X-axis and Y-axis of the disk.
  • the apparatus comprises a device for subjecting the microfluidic device to centrifugal force.
  • the device comprises a turn-table for spinning the microfluidic device to generate centrifugal forces.
  • the invention also provides a method of controlling a fluid channel in a microfluidics device, which method employs a microfluidics device according to Claim 1 in a primed configuration, the method comprising the steps of directing a beam of light of appropriate wavelength on to the second sacrificial membrane to rupture the membrane, whereby the pressurised first region of the actuation channel is depressurised causing the gas pocket to dislodge and liquid in the first region of the first channel come into contact with and disintegrate the first sacrificial membrane.
  • the beam of light directed on to the second sacrificial membrane is a laser beam. In one embodiment, the beam of light directed on to the second sacrificial membrane for a period of time sufficient to rupture the membrane.
  • the invention provides a microfluidic device comprising a controllable fluid channel, the controllable fluid channel comprising:
  • the valve comprising a sacrificial membrane configured to disintegrate on contact with a liquid to provide a fluid path between the first and second regions of the fluid channel;
  • controllable fluid channel comprises an opto-pneumatic actuation channel in fluid communication with the first sacrificial membrane and adjustable between a closed-valve configuration in which the actuation channel is pressurised with gas and an open-valve configuration in which the actuation channel is depressurised.
  • the invention provides a microfluidic device comprising a controllable fluid channel, the controllable fluid channel comprising:
  • the valve comprising a sacrificial membrane configured to disintegrate on contact with a liquid to provide a fluid path between the first and second regions of the fluid channel;
  • controllable fluid channel comprises an actuation chamber having a second sacrificial membrane and is configured to provide a pressurised pneumatic chamber between the first and second sacrificial membranes, wherein the second sacrificial membrane is configured to rupture when irradiated with light of a particular wavelength in which rupturing of the second sacrificial membrane effects depressurisation of the pneumatic chamber.
  • the device of the invention, or the layers of the device may be formed from a suitable polymeric material, for example a thermoplastic resin.
  • thermoplastic resins include cyclic olefin copolymers, polymethylmethacrylate, polycarbonate, polystyrene, polyoxymethylene, perfluoralkoxy, polyvinylchloride, polypropylene, polyethylene terephthalate, polyetheretherketone, polyamide, polysulphone, and polyvinylidine chloride.
  • Microfluidic device means a device comprising at least one microfluidic channel typically having a diameter of less than 1000 microns.
  • the term includes devices configured to perform continuous flow microfluidics, droplet based microfluidics, digital microfluidics, and for application in nucleic acid arrays and immuno-assays for clinical and research applications.
  • the device comprises a plurality of microfluidic channels, one or more reservoirs for liquids, and one or more reaction chambers.
  • the microfluidic device is a passive device, in which fluid transport on the chip is effected by means of an external force (for example rotary drives applying centrifugal forces).
  • the device may comprise active micro-components such as micropumps.
  • the microfluidics device may be configured to provide for both active and passive transport of fluids within the device.
  • Microfluidics devices are well known in the literature, and are described in WO2012/164086, US6719682, US2009/166562, WO2006/044841 , and US2006/078462.
  • the microfluidic device is configured to perform an enzyme linked immunosorbent assay (ELISA).
  • ELISA enzyme linked immunosorbent assay
  • Controllable fluid channel means a channel in the microfluidics device that incorporates a valve that is actuable to open the channel to allow fluid flow in the channel. Typically, the channel is normally closed (i.e. when the device is primed) whereby actuation of the valve opens the channel.
  • at least a portion of the fluid channel is a microfluidics channel.
  • First sacrificial membrane means a membrane that separates the first and second regions of the fluid channel and that is configured to at least party disintegrate on contact with liquid.
  • the membrane comprises a thin film structure.
  • the membrane comprises a material that dissolves in a liquid, such as an aqueous liquid.
  • the membrane comprises an aqueous polymeric matrix formed from, for example, one or more of cellulose or cellulose derivatives, hydrocolloids, acrylate polymers, gums, collagen or collagen derivatives, polysaccharides, plasticisers or the like.
  • the membrane is configured to at least partly dissolve in response to pressure, for example pressure of liquid pushing against the membrane - examples of suitable membranes include pressure sensitive adhesive (PSA) films.
  • PSA pressure sensitive adhesive
  • the membrane may comprise a laminate or composite of a first liquid sensitive film, and a second pressure sensitive film.
  • Microfluidic devices including such valving arrangments may be employed in metering, mixing, separation, dilution and storage of samples and reagents.
  • Actuation channel means a fluid channel in fluid communication with the gas pocket region that can be remotely actuated using an external light source to at least partially dislodge the gas bubble in the gas pocket region resulting in liquid in the first region coming into contact with the first sacrificial membrane.
  • “Second sacrificial membrane” means a membrane that separates the upstream and downstream regions of the actuation channel and that is configured to at least party disintegrate when a beam of light of appropriate wavelength is directed on to the membrane.
  • the membrane comprises a thin film structure.
  • the membrane comprises an aqueous polymeric matrix formed from, for example, one or more of cellulose or cellulose derivatives, hydrocolloids, acrylate polymers, gums, collagen or collagen derivatives, polysaccharides, plasticisers or the like.
  • “Focussed optical beam” means a beam of light of appropriate wavelength that is focussed on to the membrane and that is capable of rupturing the membrane. In one embodiment, the optical beam of a laser beam.
  • the laser beam has a wavelength of 400-450 nm, preferably 410-420 nm.
  • Pressure as applied to the upstream region of the actuation channel means that when the device is primed a pressurised pneumatic channel exists between the first sacrificial membrane and the second sacrificial membrane. Rupturing the second sacrificial membrane releases the pressure in the pneumatic channel via a vent to a decompression area (internal chamber or vent to atmosphere), resulting in the gas pocket being dislodged (in effect the gas pocket is vented along with the gas in the pneumatic channel.
  • “Reservoir for fluid” means a chamber configured to hold a reservoir of liquid that is in fluid communication with the first region of the fluid channel.
  • the reservoir comprises a first outlet in fluid communication with the first region of the fluid channel disposed towards a base of the reservoir and a second outlet in fluid communication with atmosphere disposed towards a top of the reservoir above the level of liquid. This arrangement allows the liquid in the reservoir pass into the fluid channel once the actuation channel is actuated.
  • "Primed configuration" as applied to the microfluidic device of the invention means that a fluid path between the first and second sacrificial membranes is charged with a gas to provide a pressurised pneumatic chamber between the membranes which serves to keep liquid away from the first sacrificial membrane.
  • Suitable beam of light means a beam of light that is capable of rupturing the second sacrificial membrane when the membrane is irradiated for a sufficient period of time.
  • the beam of light is configured to rupture the membrane in a short period of time, typically less than 10 second, typically less than 5 second, and preferably less than 2 seconds.
  • the suitable beam of light is a laser.
  • the suitable beam of light is a laser having a wavelength of 400-450 nm, preferably 410-420 nm.
  • a beam of light that is suitable for rupturing the membrane depends on the configuration and material of the membrane, and it is a routine matter for the skilled person for find a workable combination of membrane and beam of light. For example, thin film membranes can be rapidly ruptured by lasers.
  • Opto-pneumatic actuation channel means a channel having a valve that can be ruptured by irradiation with light and that can be actuated from a closed-valve configuration to an open-valve configuration by irradiating the valve with light to rupture the valve.
  • Fig. 1 is a perspective view of a cross-section of part of a microfluidic device according to the invention showing a first embodiment of a controllable fluid channel in which the actuation channel is vented through the lower surface of the device;
  • Fig. 2 is a perspective view of a cross-section of part of a microfluidic device according to the invention showing a further embodiment of a controllable fluid channel in which the actuation channel is vented to a decompression chamber formed within the device;
  • Fig. 3 is a perspective view of a cross-section of part of a microfluidic device according to the invention showing a further embodiment of a controllable fluid channel in which the actuation channel is vented through the side surface of the device;
  • Fig. 4 is a perspective view of a cross-section of part of a microfluidic device according to the invention showing a further embodiment of a controllable fluid channel in which the actuation channel is vented through the top surface of the device;
  • Fig. 5A to 5D illustrate the operation of a controllable fluid channel forming part of a microfluidic device according to the invention;
  • Fig. 6 illustrates a top plan view of a segment of a layered microfluidic device of the invention depicting the small footprint given the placement of the second sacrificial membrane;
  • Fig. 7 shows the segment of the microfluidic device of Fig. 6 in an exploded view showing the eight different layers making up the device
  • Fig. 8 is a sectional view through the segment of the device of Figs. 6 and 7 showing the different layers of the device
  • Fig. 9 is sectional view of an alternative embodiment of the microfluidic device of the invention, showing how two light-actuated sacrificial membranes can be stacked on top of each other.
  • controllable fluid channel 1 forming part of a microfluidics device of the invention.
  • the controllable fluid channel 1 comprises a fluid channel having a first region (microchannel) 2 and a second region (microchannel) 3 separated by valve comprising a first sacrificial membrane 4.
  • the first region 2 of the fluid channel is in fluid communication with a reservoir 7 through a first reservoir outlet 8A located on the top of the reservoir 7.
  • the first sacrificial membrane 4 is formed from a thin-film material configured to dissolve on contact with aqueous-based liquids.
  • a gas pocket region 5 is provided in the fluid channel adjacent and upstream of the first sacrificial membrane 4, which gas pocket region 5 comprises a gas pocket (not shown) when the device is primed.
  • the gas pocket region 5 is a generally cylindrical chamber in which the first sacrificial membrane 4 forms a base of the cylinder, and a top of the cylinder comprises an outlet 8B in fluid communication with the first region 2 of the fluid channel.
  • An actuation channel configured to actuate the fluid channel 1 is provided, and comprises an upstream channel 1 1 and a depressurisation region provided in this embodiment by a downstream channel 12, separated by an actuation valve having a second sacrificial membrane 13 formed from a thin film configured to be ruptured by a focussed laser beam irradiating the membrane at a wavelength of 415 nm for about 1 second.
  • the upstream region 1 1 is in fluid communication a second outlet 14 formed in the top of the gas pocket region 5, and the downstream region 12 is in fluid communication with a decompression area, which in this embodiment comprises an outlet to atmosphere.
  • a chamber 17 is disposed above the second sacrificial membrane 13 and when primed, the channel 1 1 and chambers 17 and 5 form a pneumatic valve which prevents liquid from the reservoir 7 coming into contact with, and dissolving, the first sacrificial membrane 4.
  • the device of Fig. 1 comprises a layered structure having eight separate layers that are aligned together to form the device.
  • the top layer A comprises an inlet opening (not shown) through which liquid can be added to the reservoir.
  • the second layer B includes the microchannel 2 providing fluid communication between the top of the reservoir 7 and the gas pocket region 5, and the microchannel 1 1 providing fluid communication between the gas pocket region 5 and the chamber 17, and the top of reservoir 7.
  • the gas pocket region 5 and chamber 17 are disposed in a third layer C.
  • a layer E is provided that contains the first and second sacrificial membranes 4, 13, and a membrane support layer D is provided on top of layer E.
  • Layer F contains a first chamber 6A disposed beneath the first sacrificial membrane 4 and a second chamber 6B disposed beneath the second sacrificial membrane 13.
  • Layer G contains the second region 3 of the controllable fluid channel which is in fluid communication with the chamber 6A.
  • Layer H contains a chamber 9 disposed beneath chamber 6B and providing a depressurisation outlet from the second sacrificial membrane 13 to atmosphere.
  • controllable fluid layer 1 is actuated by irradiating the second sacrificial membrane 13 with a focussed laser beam for about 1 second.
  • a second event for example, react with a reagent
  • a controllable fluid layer 20 forming part of a microfluidics device of the invention according to an alternative embodiment of the invention, and in which parts described previously with reference to Fig. 1 are assigned the same reference numerals.
  • the depressurisation region is provided by a depressurisation chamber 21 located within the device in layer F in fluid communication with the downstream chamber 13 by means of a microchannel 22 formed in layer G.
  • the use of this embodiment is the same as that described with reference to Fig. 1 with the exception that the pneumatic chamber is vented into an internal depressurisation chamber 21 as opposed to being vented to atmosphere. This embodiment is useful where the controllable fluid channel is buried deep within a device and access to a surface of the device is difficult.
  • a controllable fluid channel 30 forming part of a microfluidics device of the invention according to an alternative embodiment of the invention, and in which parts described previously with reference to Fig. 1 are assigned the same reference numerals.
  • the depressurisation region is provided by a microchannel 31 formed in layer G that vented to atmosphere though an outlet in a side of the device.
  • a controllable fluid channel 40 forming part of a microfluidics device of the invention according to an alternative embodiment of the invention, and in which parts described previously with reference to Fig. 1 are assigned the same reference numerals.
  • the second sacrificial membrane 13 is located in on a top surface of the device in an additional layer I formed above layer A and above chamber 17.
  • An additional layer (not shown) may be included on top of layer I for reinforcing any membranes like 13. The use of this device is the same as described with reference to Fig. 1 .
  • FIG. 5A to 5D the use of a controllable fluid channel forming part of a microfluidic device of the invention is illustrated.
  • the reservoir 7 is loaded with an aqueous solution.
  • Pressurized pneumatic channels 2, 11 are created between the opto-pneumatic polymeric film tab 13 and the dissolvable film (DF) 4 which prevent the liquid from priming the exit channel and wetting of the DF.
  • DF dissolvable film
  • FIGs. 6 to 8 there is illustrated a segment of a microfluidics device of the invention, shown in plan view (Fig. 6), exploded view showing the different layers side- by-side (Fig. 7), and in cross-section for a single valving unit (Fig. 8).
  • Fig. 6 shows a segment of the device of the invention in plain view, the segment comprising a plurality of controllable fluid channels arranged across the device.
  • the illustration is a "see-through” illustration, showing the components present in all layers.
  • the segment illustrated in Fig. 6 contains nine controllable fluid channels arranged radially and circumferentially across the device, illustrating how the low footprint of the device of the invention allows for greater flexibility as regards the number and positioning of controllable fluid channels on a device.
  • the sequence of operation is also completely customizable as the opening of the valves can be defined on-demand thus neither depending on the rotational frequency of the valves nor on the previously performed function.
  • Fig.7 the device is shown as an exploded view, showing the eight different layers which are superimposed on top of each other to provide the segment shown in Fig. 6, and showing how different components of controllable fluid channel are provided in different layers.
  • layer A is a cover which contains inlets for the reservoirs
  • layer B contains the microchannels 2 and 11 and the top of the reservoir 7;
  • ⁇ layer C contains the reservoirs 7 and chambers 5 and 17;
  • layer D is the supporting/reinforcing layer for the films 4, 13 and comprises holes that align with the films;
  • layer E contains the films 4 and 13; • layer F includes the chambers 6A and 6B;
  • layer G contains the outlet microchannel 3;
  • layer H contains chamber 9. Assembly of the device involves aligning the eight layers and sealing the layers together using a suitable adhesive to provide the formed device. Priming of the device generally comprises filling the reservoir 7 with liquid, which automatically creates the pneumatic chamber in the controllable fluid channel.
  • Fig. 8 which is a cross section through the device of Fig. 1 looking in the direction of arrows VIII-VIII of Fig. 1 , the layers A to H are illustrated along with part of the pneumatic chamber (hatched lines) formed between chambers 5 and 17 and microchannel 11 , and dissolvable membrane 4 and optically addressed film 13.
  • the top layer A is formed from a light transmitting PMMA layer which allows laser light X pass through layer A and on to film 13 to rupture the film.
  • the device of the invention comprises two controllable fluid channels arranged along the Z-axis of the device (i.e. stacked on top of each other) with the light actuated films 13, aligned along the Z-axis.
  • This configuration can be either considered as the layers are in one single device or two separate devices that are stacked on top of each other.
  • the laser can be focussed onto sacrificial polymer membrane deep within the device given that all layers are accessible via transparent windows; for example the light (X 1 ) can be focussed on the top film 13 in a first operation and then refocussed light (X 2 ) can be directed on to the lower film 13
  • This is an advantage of the system as it allows for placement of the polymer membrane almost anywhere on the device (and irrespective of the axial position in case of a centrifugally driven system; as long as the footprint is reasonable). This includes any recess deep inside the layers or even on any of the surfaces of the device including the curved side surface.
  • Ferrowax valves J.-M. Park et. al. "Multifunctional microvalves control by optical illumination on nanoheaters and its application in centrifugal microfluidic devices". Lab Chip, 2007,7, 557-564.)

Abstract

A microfluidic device comprising a controllable fluid channel (1. 20, 30, 40), the controllable fluid channel comprises a first region (2) and second region (3) separated by a valve, the first region being upstream of the valve and the second region being downstream of the valve, the valve comprising a first sacrificial membrane (4) configured to disintegrate on contact with a liquid to provide a fluid path between the first and second regions of the fluid channel. A gas pocket region (5) is provided within the first region adjacent to the first sacrificial membrane configured to receive and retain a gas pocket against the first sacrificial membrane to prevent liquid in the first region contacting the first sacrificial membrane. The device incorporates an actuation channel having an upstream region (11) and a depressurisation region (12) separated by an actuation valve comprising a second sacrificial membrane (13) configured to rupture in response to a focussed optical beam incident on the membrane, in which the upstream region is pressurised and in fluid communication with the gas pocket region. The rupture of the actuation valve depressurises the upstream region displacing the gas pocket from the first sacrificial membrane and allowing the liquid to come into contact with and effect disintegration of the first sacrificial membrane.

Description

Title
A microfluidic device
Technical Field
The invention relates to a microfluidic device incorporating a valve for controlling the flow of a fluid within the microfluidic device.
Background to the Invention
The control of flow of liquids in narrow channels of a very small scale (micrometre range) is essential in modern bioanalytical devices, in particular for decentralised "point-of-care" diagnostics (e.g.: for disease diagnosis and monitoring). The sequential release of many fluids on such devices is a challenge in terms of control, cost and ease of operation. Various solutions to this problem exist, including optically actuated microfluidic valves 1 3, dissolvable film based valves in centrifugal microfluidic-based platforms 2 5, and capillary action and siphon based valving system 6. One solution to this problem proposed by the Applicant 4 5 comprises a microfluidic device comprising a fluid channel comprising a first and second region separated by a valve comprising a first sacrificial membrane. The first region is upstream of the valve and the second region is downstream of the valve, the first sacrificial membrane being configured to disintegrate on contact with a liquid to provide a fluid path between the first and second regions of the fluid channel. A gas pocket region is provided within the first region adjacent to the first sacrificial membrane configured to receive and retain a gas pocket against the first sacrificial membrane to prevent liquid in the first region contacting the first sacrificial membrane. In use, a force generating means is provided (for example a centrifugal force generating means) which upon actuation induces flow of liquid from the first region towards the second region of the fluid channel displacing the gas pocket from the sacrificial membrane and allowing the liquid to come into contact with and effect disintegration of the membrane. While this solution meets some of the requirements of microfluidic valving mechanisms, it has some limitations: for example, the valving mechanisms of Reference 5 are provided as a series of sequential events where actuation of a first valving mechanism causes liquid flow, which in-turn triggers a second valving event. This requires a considerable array of microchannels connecting a first valving mechanism to a second valving mechanism, etc, which requires a very large footprint on the device and in effect limits the number of valving mechanism that can be practically formed in a single device. While the use of purely centrifugal forces can partly overcome the footprint problem, the spread of the operational centrifugal frequencies required to actuate valves is quite large thus limiting the application of this mechanism for integration of only a limited number of microfluidic operations (thus directly impacting multiplexing and large-scale integration) It is an object of the invention to overcome at least one of the above-referenced problems.
Statements of Invention
The Applicant has solved at least some of the problems of the microfluidic device of References 4 and 5 by providing a device according to the preamble of claim 1 , characterised in that the device incorporates an actuation channel having an pressurised upstream region and a depressurisation region separated by an actuation valve comprising a second sacrificial membrane configured to rupture in response to an optical beam directed on to the second sacrificial membrane, in which the upstream region is in fluid communication with the gas pocket region, whereby the rupture of the actuation valve depressurises the upstream region displacing the gas pocket from the sacrificial membrane and allowing the liquid to come into contact with and effect disintegration of the membrane.
The device of the invention solves the footprint problem of the prior art by providing a valving mechanism that is not reliant on a previous device-based liquid valving event, but on an external optical event, and as such obviates the large footprint required by the valving mechanisms of the prior art and allows the device incorporate more valving mechanisms per unit area. In addition, the use of the device of the invention provides greater flexibility as regards positioning of the valves on the device. For multiple valves, the sequence of operation is also completely customizable as the opening of the valves can be defined on-demand thus neither depending on the rotational frequency of operation of the valves (as in Reference 4) nor on the previously performed function (as in Reference 5). In particular, second sacrificial membranes of controllable fluid channels can be arranged in an overlapping configuration, so that they can be actuated by a single light source by changing the focal length of the light source (See Fig. 9).
Thus, in one aspect, the invention provides a microfluidic device comprising a controllable fluid channel, the controllable fluid channel comprising: a first and second region separated by a valve, the first region being upstream of the valve and the second region being downstream of the valve, the valve comprising a sacrificial membrane configured to disintegrate on contact with a liquid to provide a fluid path between the first and second regions of the fluid channel; and a gas pocket region provided within the first region adjacent to the sacrificial membrane configured to receive and retain a gas pocket against the sacrificial membrane to prevent liquid in the first region contacting the sacrificial valve, characterised in that the controllable fluid channel comprises an actuation channel having an upstream region and a depressurisation region separated by an actuation membrane configured to rupture in response to an incident focussed optical beam, in which the upstream region is pressurised and in fluid communication with the gas pocket region, whereby the rupture of the actuation valve depressurises the upstream region displacing the gas pocket from the sacrificial membrane and allowing the liquid to come into contact with and effect disintegration of the sacrificial membrane.
The depressurisation region may be atmosphere (i.e. when the actuation membrane is positioned on an external face of the device), or may be a downstream region of the actuation channel in fluid communication with atmosphere or a depressurisation chamber (i.e. when the actuation membrane is positioned within the device, in one of the internal layers).
In one embodiment, the first region of the fluid channel comprises a reservoir for liquid.
In one embodiment, the reservoir is vented to atmosphere. In one embodiment, the gas pocket region is disposed above the first sacrificial membrane. In one embodiment, the gas pocket region comprises a first outlet in fluid communication with the first region of the first channel and a second outlet in fluid communication with the upstream region of the actuation channel. In one embodiment, the first and second outlets are disposed towards a top of the gas pocket region. In one embodiment, the first outlet disposed on an opposite side of the gas pocket region to the second outlet. In one embodiment, the microfluidic device comprises at least two controllable fluid channels. In one embodiment, the microfluidic device comprises at least ten controllable fluid channels. In one embodiment, the microfluidic device comprises at least twenty controllable fluid channels. In one embodiment, the microfluidic device comprises at least thirty controllable fluid channels. In one embodiment, the microfluidic device comprises at least forty controllable fluid channels.
In one embodiment, at least two controllable fluid channels share a common component, for example a shared liquid reservoir, or a shared actuation valve, or a shared sacrificial membrane.
In one embodiment, the at least two controllable fluid channels are disposed in a single plane. Thus, controllable fluid channels may be provided in a side-by-side arrangement across a given plane of the device, as opposed to in different planes in the device.
In another embodiment, the at least two controllable fluid channels are disposed in different planes. Thus, controllable fluid channels may be provided on different levels the device, and in one embodiment may be stacked on top of each other. In one embodiment, at least two controllable fluid channels overlap (i.e. are stacked on top of each other along a Z-axis of the device, or along an X- or Y-axis of the device). In one embodiment, the actuation membranes of at least two controllable fluid channels overlap. In this manner, the at least two actuation membranes can be ruptured by a static light source by changing the focal point of the light source. In one embodiment, the microfluidic device comprises a layered structure having a plurality of layers. In one embodiment, different components of the controllable fluid channel are disposed in different layers. In one embodiment, the membranes are disposed in one layer. In one embodiment, the first and second regions of the fluid channel are disposed in different layers, the first regions being located above the second region.
In one embodiment, the microfluidic device comprises a first layer comprising a reservoir vent, a second layer comprising at least part of an upstream region of the first channel, a third layer comprising the liquid reservoir, a fourth layer comprising one or both of the membranes, and a fifth layer comprising at least part of the second region of the fluid channel. In one embodiment, the device comprises a light path configured to transmit a focussed optical beam form a light source to one or more actuation membranes.
In one embodiment, the light path comprises transparent material, or an opening, or a combination of transparent material and an opening.
In one embodiment, the device has a planar structure. Examples include planar chips or disks. In one embodiment, the device is a disk. In one embodiment, the device is a circular disk. In one embodiment, the disc comprises a central aperture configured for mounting the disc on a turn-table.
In an embodiment in which the device is a planar device, the light path configured to transmit a focussed optical beam is typically disposed along a Z-axis of the device. The Z-axis means an axis that runs substantially orthogonal to the planar aspect of the device. In other embodiment, the device may be configured such that the light path configured to transmit a focussed optical beam is typically disposed parallel to the planar aspect of the device (i.e. along an X-axis or Y-axis of the device).
In one embodiment, a plurality of second actuation membranes are disposed along the light path. In one embodiment, the decompression area is the atmosphere. In this embodiment, the downstream region generally comprises a vent providing fluid communication with the atmosphere at the top of the device, the bottom of the device, or a side of the device.
In another embodiment, the decompression area is a decompression chamber disposed within the device. This is generally a chamber that is sufficiently large to allow the pressurised fluid within the actuation channel decompress.
In one embodiment, the controllable fluid channel is configured such that upon priming the device the first region of the fluid channel, the gas pocket region, and the upstream region of the actuation channel are pneumatically pressurised. In one embodiment, the first sacrificial membrane is at least partially gas permeable.
In one embodiment, the first sacrificial membrane is disposed substantially parallel to a major axis of each of the first and second regions. In one embodiment, the second sacrificial membrane is disposed substantially parallel to a major axis of the upstream region of the actuation channel.
In one embodiment, the device comprises a capture chamber downstream of the first sacrificial membrane configured to capture and retain debris resultant from disintegration of the first sacrificial membrane.
The invention also provides an apparatus comprising a microfluidic device of the invention and a light source configured to produce a focussed optical beam and direct the focussed optical beam on to the actuation membrane of the controllable fluid channel.
In one embodiment, the light source is configured to allow adjustment of the focal point of the optical beam. In one embodiment, apparatus is configured to move the light source with respect to the microfluidic device. In an embodiment in which the microfluidic device is a disk, the apparatus is configured to move the light source along an X-axis and Y-axis of the disk.
In one embodiment, the apparatus comprises a device for subjecting the microfluidic device to centrifugal force. In an embodiment in which the microfluidic device is a disk, the device comprises a turn-table for spinning the microfluidic device to generate centrifugal forces.
The invention also provides a method of controlling a fluid channel in a microfluidics device, which method employs a microfluidics device according to Claim 1 in a primed configuration, the method comprising the steps of directing a beam of light of appropriate wavelength on to the second sacrificial membrane to rupture the membrane, whereby the pressurised first region of the actuation channel is depressurised causing the gas pocket to dislodge and liquid in the first region of the first channel come into contact with and disintegrate the first sacrificial membrane.
In one embodiment, the beam of light directed on to the second sacrificial membrane is a laser beam. In one embodiment, the beam of light directed on to the second sacrificial membrane for a period of time sufficient to rupture the membrane.
In another aspect, the invention provides a microfluidic device comprising a controllable fluid channel, the controllable fluid channel comprising:
a first and second region separated by a valve, the first region being upstream of the valve and the second region being downstream of the valve, the valve comprising a sacrificial membrane configured to disintegrate on contact with a liquid to provide a fluid path between the first and second regions of the fluid channel; and
a gas pocket region provided within the first region adjacent to the sacrificial membrane configured to receive and retain a gas pocket against the sacrificial membrane to prevent liquid in the first region contacting the sacrificial valve, wherein the controllable fluid channel comprises an opto-pneumatic actuation channel in fluid communication with the first sacrificial membrane and adjustable between a closed-valve configuration in which the actuation channel is pressurised with gas and an open-valve configuration in which the actuation channel is depressurised.
In another aspect, the invention provides a microfluidic device comprising a controllable fluid channel, the controllable fluid channel comprising:
a first and second region separated by a valve, the first region being upstream of the valve and the second region being downstream of the valve, the valve comprising a sacrificial membrane configured to disintegrate on contact with a liquid to provide a fluid path between the first and second regions of the fluid channel; and
a gas pocket region provided within the first region adjacent to the sacrificial membrane configured to receive and retain a gas pocket against the sacrificial membrane to prevent liquid in the first region contacting the sacrificial valve, wherein the controllable fluid channel comprises an actuation chamber having a second sacrificial membrane and is configured to provide a pressurised pneumatic chamber between the first and second sacrificial membranes, wherein the second sacrificial membrane is configured to rupture when irradiated with light of a particular wavelength in which rupturing of the second sacrificial membrane effects depressurisation of the pneumatic chamber. The device of the invention, or the layers of the device, may be formed from a suitable polymeric material, for example a thermoplastic resin. Examples of thermoplastic resins include cyclic olefin copolymers, polymethylmethacrylate, polycarbonate, polystyrene, polyoxymethylene, perfluoralkoxy, polyvinylchloride, polypropylene, polyethylene terephthalate, polyetheretherketone, polyamide, polysulphone, and polyvinylidine chloride.
Definitions:
"Microfluidic device" means a device comprising at least one microfluidic channel typically having a diameter of less than 1000 microns. The term includes devices configured to perform continuous flow microfluidics, droplet based microfluidics, digital microfluidics, and for application in nucleic acid arrays and immuno-assays for clinical and research applications. Typically, the device comprises a plurality of microfluidic channels, one or more reservoirs for liquids, and one or more reaction chambers. In one embodiment, the microfluidic device is a passive device, in which fluid transport on the chip is effected by means of an external force (for example rotary drives applying centrifugal forces). In one embodiment, the device may comprise active micro-components such as micropumps. In one embodiment, the microfluidics device may be configured to provide for both active and passive transport of fluids within the device. Microfluidics devices are well known in the literature, and are described in WO2012/164086, US6719682, US2009/166562, WO2006/044841 , and US2006/078462. In one embodiment, the microfluidic device is configured to perform an enzyme linked immunosorbent assay (ELISA). "Controllable fluid channel" means a channel in the microfluidics device that incorporates a valve that is actuable to open the channel to allow fluid flow in the channel. Typically, the channel is normally closed (i.e. when the device is primed) whereby actuation of the valve opens the channel. In one embodiment, at least a portion of the fluid channel is a microfluidics channel.
"First sacrificial membrane" means a membrane that separates the first and second regions of the fluid channel and that is configured to at least party disintegrate on contact with liquid. In one embodiment, the membrane comprises a thin film structure. In one embodiment, the membrane comprises a material that dissolves in a liquid, such as an aqueous liquid. In one embodiment, the membrane comprises an aqueous polymeric matrix formed from, for example, one or more of cellulose or cellulose derivatives, hydrocolloids, acrylate polymers, gums, collagen or collagen derivatives, polysaccharides, plasticisers or the like. In one embodiment, the membrane is configured to at least partly dissolve in response to pressure, for example pressure of liquid pushing against the membrane - examples of suitable membranes include pressure sensitive adhesive (PSA) films. In one embodiment, the membrane may comprise a laminate or composite of a first liquid sensitive film, and a second pressure sensitive film. Microfluidic devices including such valving arrangments may be employed in metering, mixing, separation, dilution and storage of samples and reagents.
"Gas pocket region" and "gas pocket" are fully described in WO2012/164086. "Actuation channel" means a fluid channel in fluid communication with the gas pocket region that can be remotely actuated using an external light source to at least partially dislodge the gas bubble in the gas pocket region resulting in liquid in the first region coming into contact with the first sacrificial membrane.
"Second sacrificial membrane" means a membrane that separates the upstream and downstream regions of the actuation channel and that is configured to at least party disintegrate when a beam of light of appropriate wavelength is directed on to the membrane. In one embodiment, the membrane comprises a thin film structure. In one embodiment, the membrane comprises an aqueous polymeric matrix formed from, for example, one or more of cellulose or cellulose derivatives, hydrocolloids, acrylate polymers, gums, collagen or collagen derivatives, polysaccharides, plasticisers or the like. "Focussed optical beam" means a beam of light of appropriate wavelength that is focussed on to the membrane and that is capable of rupturing the membrane. In one embodiment, the optical beam of a laser beam. In one embodiment, the laser beam has a wavelength of 400-450 nm, preferably 410-420 nm. "Pressurised" as applied to the upstream region of the actuation channel means that when the device is primed a pressurised pneumatic channel exists between the first sacrificial membrane and the second sacrificial membrane. Rupturing the second sacrificial membrane releases the pressure in the pneumatic channel via a vent to a decompression area (internal chamber or vent to atmosphere), resulting in the gas pocket being dislodged (in effect the gas pocket is vented along with the gas in the pneumatic channel.
"Reservoir for fluid" means a chamber configured to hold a reservoir of liquid that is in fluid communication with the first region of the fluid channel. In one embodiment, the reservoir comprises a first outlet in fluid communication with the first region of the fluid channel disposed towards a base of the reservoir and a second outlet in fluid communication with atmosphere disposed towards a top of the reservoir above the level of liquid. This arrangement allows the liquid in the reservoir pass into the fluid channel once the actuation channel is actuated. "Primed configuration" as applied to the microfluidic device of the invention means that a fluid path between the first and second sacrificial membranes is charged with a gas to provide a pressurised pneumatic chamber between the membranes which serves to keep liquid away from the first sacrificial membrane.
"Suitable beam of light" means a beam of light that is capable of rupturing the second sacrificial membrane when the membrane is irradiated for a sufficient period of time. Typically, the beam of light is configured to rupture the membrane in a short period of time, typically less than 10 second, typically less than 5 second, and preferably less than 2 seconds. In one embodiment, the suitable beam of light is a laser. In one embodiment, the suitable beam of light is a laser having a wavelength of 400-450 nm, preferably 410-420 nm. A beam of light that is suitable for rupturing the membrane depends on the configuration and material of the membrane, and it is a routine matter for the skilled person for find a workable combination of membrane and beam of light. For example, thin film membranes can be rapidly ruptured by lasers.
"Opto-pneumatic actuation channel" means a channel having a valve that can be ruptured by irradiation with light and that can be actuated from a closed-valve configuration to an open-valve configuration by irradiating the valve with light to rupture the valve.
Brief Description of the Figures
The invention will be more clearly understood from the following description of some embodiment thereof, given by way of example only, in which:
Fig. 1 is a perspective view of a cross-section of part of a microfluidic device according to the invention showing a first embodiment of a controllable fluid channel in which the actuation channel is vented through the lower surface of the device;
Fig. 2 is a perspective view of a cross-section of part of a microfluidic device according to the invention showing a further embodiment of a controllable fluid channel in which the actuation channel is vented to a decompression chamber formed within the device; Fig. 3 is a perspective view of a cross-section of part of a microfluidic device according to the invention showing a further embodiment of a controllable fluid channel in which the actuation channel is vented through the side surface of the device;
Fig. 4 is a perspective view of a cross-section of part of a microfluidic device according to the invention showing a further embodiment of a controllable fluid channel in which the actuation channel is vented through the top surface of the device; Fig. 5A to 5D illustrate the operation of a controllable fluid channel forming part of a microfluidic device according to the invention;
Fig. 6 illustrates a top plan view of a segment of a layered microfluidic device of the invention depicting the small footprint given the placement of the second sacrificial membrane;
Fig. 7 shows the segment of the microfluidic device of Fig. 6 in an exploded view showing the eight different layers making up the device; Fig. 8 is a sectional view through the segment of the device of Figs. 6 and 7 showing the different layers of the device; and
Fig. 9 is sectional view of an alternative embodiment of the microfluidic device of the invention, showing how two light-actuated sacrificial membranes can be stacked on top of each other.
Detailed Description of the Invention The invention will now be described with reference to specific Examples. These are merely exemplary and for illustrative purposes only: they are not intended to be limiting in any way to the scope of the monopoly claimed or to the invention described. These examples constitute the best mode currently contemplated for practicing the invention. Referring to the figures, and initially to Fig. 1 , there is illustrated a controllable fluid channel 1 forming part of a microfluidics device of the invention. The controllable fluid channel 1 comprises a fluid channel having a first region (microchannel) 2 and a second region (microchannel) 3 separated by valve comprising a first sacrificial membrane 4. The first region 2 of the fluid channel is in fluid communication with a reservoir 7 through a first reservoir outlet 8A located on the top of the reservoir 7. When intact, the valve prevents movement of fluid between the first and second regions. The first sacrificial membrane 4 is formed from a thin-film material configured to dissolve on contact with aqueous-based liquids. A gas pocket region 5 is provided in the fluid channel adjacent and upstream of the first sacrificial membrane 4, which gas pocket region 5 comprises a gas pocket (not shown) when the device is primed. In this embodiment, the gas pocket region 5 is a generally cylindrical chamber in which the first sacrificial membrane 4 forms a base of the cylinder, and a top of the cylinder comprises an outlet 8B in fluid communication with the first region 2 of the fluid channel. When the device is primed, a gas pocket is disposed adjacent the membrane 4 and acts to prevent liquid from the reservoir 7 coming into contact with the membrane 4. An actuation channel configured to actuate the fluid channel 1 is provided, and comprises an upstream channel 1 1 and a depressurisation region provided in this embodiment by a downstream channel 12, separated by an actuation valve having a second sacrificial membrane 13 formed from a thin film configured to be ruptured by a focussed laser beam irradiating the membrane at a wavelength of 415 nm for about 1 second. The upstream region 1 1 is in fluid communication a second outlet 14 formed in the top of the gas pocket region 5, and the downstream region 12 is in fluid communication with a decompression area, which in this embodiment comprises an outlet to atmosphere. A chamber 17 is disposed above the second sacrificial membrane 13 and when primed, the channel 1 1 and chambers 17 and 5 form a pneumatic valve which prevents liquid from the reservoir 7 coming into contact with, and dissolving, the first sacrificial membrane 4.
In more detail, the device of Fig. 1 comprises a layered structure having eight separate layers that are aligned together to form the device. The top layer A comprises an inlet opening (not shown) through which liquid can be added to the reservoir. The second layer B includes the microchannel 2 providing fluid communication between the top of the reservoir 7 and the gas pocket region 5, and the microchannel 1 1 providing fluid communication between the gas pocket region 5 and the chamber 17, and the top of reservoir 7. The gas pocket region 5 and chamber 17 are disposed in a third layer C. A layer E is provided that contains the first and second sacrificial membranes 4, 13, and a membrane support layer D is provided on top of layer E. Layer F contains a first chamber 6A disposed beneath the first sacrificial membrane 4 and a second chamber 6B disposed beneath the second sacrificial membrane 13. Layer G contains the second region 3 of the controllable fluid channel which is in fluid communication with the chamber 6A. Layer H contains a chamber 9 disposed beneath chamber 6B and providing a depressurisation outlet from the second sacrificial membrane 13 to atmosphere. When the device is primed, the first region 2 of the first channel, the gas pocket region 5, upstream region 1 1 of the actuation channel and chamber 17 are filled with gas, forming a pressurised pneumatic chamber between the first and second sacrificial membranes 4, 13. Laser actuated rupture of the actuation valve results in depressurisation the pneumatic chamber displacing the gas pocket from the first sacrificial membrane and allowing liquid from the reservoir to come into contact with and effect disintegration of the first sacrificial membrane 4, allow liquid flow between the reservoir 7 and the outlet microchannel 3.
Once primed, the controllable fluid layer 1 is actuated by irradiating the second sacrificial membrane 13 with a focussed laser beam for about 1 second. This results in the membrane 13 rupturing, releasing the pressure in the pneumatic chamber and allowing liquid in the reservoir flow along the first region 2 of the fluid layer 1 , into the gas pocket region 5 and into contact with the first sacrificial membrane 4 where it at least party dissolves the membrane 4, thereby opening the valve in the first channel and allowing the liquid in the reservoir 7 flow along the first channel from the first region 2 to the second region 3 where the liquid can initiate a second event (for example, react with a reagent). Referring to Fig. 2, there is illustrated a controllable fluid layer 20 forming part of a microfluidics device of the invention according to an alternative embodiment of the invention, and in which parts described previously with reference to Fig. 1 are assigned the same reference numerals. In this embodiment, the depressurisation region is provided by a depressurisation chamber 21 located within the device in layer F in fluid communication with the downstream chamber 13 by means of a microchannel 22 formed in layer G. The use of this embodiment is the same as that described with reference to Fig. 1 with the exception that the pneumatic chamber is vented into an internal depressurisation chamber 21 as opposed to being vented to atmosphere. This embodiment is useful where the controllable fluid channel is buried deep within a device and access to a surface of the device is difficult.
Referring to Fig. 3, there is illustrated a controllable fluid channel 30 forming part of a microfluidics device of the invention according to an alternative embodiment of the invention, and in which parts described previously with reference to Fig. 1 are assigned the same reference numerals. In this embodiment, the depressurisation region is provided by a microchannel 31 formed in layer G that vented to atmosphere though an outlet in a side of the device. Referring to Fig. 4, there is illustrated a controllable fluid channel 40 forming part of a microfluidics device of the invention according to an alternative embodiment of the invention, and in which parts described previously with reference to Fig. 1 are assigned the same reference numerals. In this embodiment, the second sacrificial membrane 13 is located in on a top surface of the device in an additional layer I formed above layer A and above chamber 17. An additional layer (not shown) may be included on top of layer I for reinforcing any membranes like 13. The use of this device is the same as described with reference to Fig. 1 .
Referring to Figs. 5A to 5D, the use of a controllable fluid channel forming part of a microfluidic device of the invention is illustrated.
A. The reservoir 7 is loaded with an aqueous solution. Pressurized pneumatic channels 2, 11 are created between the opto-pneumatic polymeric film tab 13 and the dissolvable film (DF) 4 which prevent the liquid from priming the exit channel and wetting of the DF. B. Laser irradiation (at 415 nm for about 1 sec) releases the pressure in the pneumatic chamber via a vent to the atmosphere.
C. The siphon is immediately primed and wets the DF film 4.
D. The dissolution of the DF film releases the fluid into the lower channel 3 en- route to the next chamber and the reservoir is emptied by marginally increasing the spin frequency.
Referring to Figs. 6 to 8, there is illustrated a segment of a microfluidics device of the invention, shown in plan view (Fig. 6), exploded view showing the different layers side- by-side (Fig. 7), and in cross-section for a single valving unit (Fig. 8).
In more detail, Fig. 6 shows a segment of the device of the invention in plain view, the segment comprising a plurality of controllable fluid channels arranged across the device. The illustration is a "see-through" illustration, showing the components present in all layers. The segment illustrated in Fig. 6 contains nine controllable fluid channels arranged radially and circumferentially across the device, illustrating how the low footprint of the device of the invention allows for greater flexibility as regards the number and positioning of controllable fluid channels on a device. The sequence of operation is also completely customizable as the opening of the valves can be defined on-demand thus neither depending on the rotational frequency of the valves nor on the previously performed function.
In Fig.7, the device is shown as an exploded view, showing the eight different layers which are superimposed on top of each other to provide the segment shown in Fig. 6, and showing how different components of controllable fluid channel are provided in different layers. Starting from the right hand side (in conjunction with Figure 8):
• layer A is a cover which contains inlets for the reservoirs;
• layer B contains the microchannels 2 and 11 and the top of the reservoir 7; · layer C contains the reservoirs 7 and chambers 5 and 17;
• layer D is the supporting/reinforcing layer for the films 4, 13 and comprises holes that align with the films;
• layer E contains the films 4 and 13; • layer F includes the chambers 6A and 6B;
• layer G contains the outlet microchannel 3;
• layer H contains chamber 9. Assembly of the device involves aligning the eight layers and sealing the layers together using a suitable adhesive to provide the formed device. Priming of the device generally comprises filling the reservoir 7 with liquid, which automatically creates the pneumatic chamber in the controllable fluid channel. Referring to Fig. 8 which is a cross section through the device of Fig. 1 looking in the direction of arrows VIII-VIII of Fig. 1 , the layers A to H are illustrated along with part of the pneumatic chamber (hatched lines) formed between chambers 5 and 17 and microchannel 11 , and dissolvable membrane 4 and optically addressed film 13. In this embodiment, the top layer A is formed from a light transmitting PMMA layer which allows laser light X pass through layer A and on to film 13 to rupture the film. The chambers are then depressurized thus allowing the liquid to move in and dissolve the membrane 4 channel in layer E and exit via the chamber 6Ato an exit channel in lower layer G. Referring to Fig. 9, there is illustrated a further embodiment of the invention in which parts described previously with reference to Figs 1 and 8 are assigned the same reference numerals. In this embodiment, the device of the invention comprises two controllable fluid channels arranged along the Z-axis of the device (i.e. stacked on top of each other) with the light actuated films 13, aligned along the Z-axis. This configuration can be either considered as the layers are in one single device or two separate devices that are stacked on top of each other. This allows two controllable fluid channels be actuated without movement of the laser with respect to the device, whereby adjustment of the focal length of the laser allows actuation of multiple films along the Z-axis, thus allowing reaching any deep recessed valve in the system. It is possible to actuate multiple valves on Z axis of the device simply by changing the focal length of the laser. This allows for stacking of valves on the same axis allowing further integration. The laser can be focussed onto sacrificial polymer membrane deep within the device given that all layers are accessible via transparent windows; for example the light (X1) can be focussed on the top film 13 in a first operation and then refocussed light (X2) can be directed on to the lower film 13 This is an advantage of the system as it allows for placement of the polymer membrane almost anywhere on the device (and irrespective of the axial position in case of a centrifugally driven system; as long as the footprint is reasonable). This includes any recess deep inside the layers or even on any of the surfaces of the device including the curved side surface.
Equivalents The foregoing description details presently preferred embodiments of the present invention. Numerous modifications and variations in practice thereof are expected to occur to those skilled in the art upon consideration of these descriptions. Those modifications and variations are intended to be encompassed within the claims appended hereto.
REFERENCES
1 . Ferrowax valves (J.-M. Park et. al. "Multifunctional microvalves control by optical illumination on nanoheaters and its application in centrifugal microfluidic devices". Lab Chip, 2007,7, 557-564.) Patent: Publication number: US201 10262321 A1 . Application number: US 13/157,816.
2. Dissolvable-film based Event-triggered formations (D. J. Kinahan et al. "Event- triggered logical flow control for comprehensive process integration of multi-step assays on centrifugal microfluidic platforms". Lab Chip, 2014,14, 2249-2258). 3. Laser printer based ablation valve. Garcia-Cordero JL et al. Optically addressable single-use microfluidic valves by laser printer lithography. Lab Chip. 2010 Oct 21 ;10(20):2680-7.
4. International (PCT) Patent Application Publication No: WO2012/164086.
5. UK Patent Application No: GB25151 16
6. Robert Gorkin et al. "Centrifugal microfluidics for biomedical applications". Lab Chip. 2010 Jul 21 ;10(14):1758-73.

Claims

Claims
1 . A microfluidic device comprising a controllable fluid channel (1 ), the controllable fluid channel comprising:
a first and second region (2, 3) separated by a valve, the first region (2) being upstream of the valve and the second region (3) being downstream of the valve, the valve comprising a first sacrificial membrane (4) configured to disintegrate on contact with a liquid to provide a fluid path between the first and second regions of the fluid channel; and
a gas pocket region (5) provided within the first region (2) adjacent to the first sacrificial membrane (4) configured to receive and retain a gas pocket against the first sacrificial membrane to prevent liquid in the first region contacting the first sacrificial membrane,
characterised in that the device incorporates an actuation channel (10) having an upstream region (1 1 ) and a depressurisation region separated by an actuation valve comprising a second sacrificial membrane (13) configured to rupture in response to a focussed optical beam incident on the membrane, in which the upstream region (1 1 ) is pressurised and in fluid communication with the gas pocket region (5), whereby the rupture of the second sacrificial membrane depressurises the upstream region (1 1 ) displacing the gas pocket from the first sacrificial membrane (4) and allowing the liquid to come into contact with and effect disintegration of the first sacrificial membrane (4).
2. A microfluidic device according to Claim 1 having at least two controllable fluid channels, in which the actuation membranes of the at least two controllable fluid channels overlap, whereby the at least two actuation membranes can be ruptured by the same static light source by changing the focal point of the static light source.
3. A microfluidic device according to Claim 2, in which the actuation membranes of the at least two controllable fluid channels are stacked on top of each other along a Z-axis of the device.
4. A microfluidic device according to Claim 2 in which the at least two controllable fluid channels are disposed in a single plane.
55. A microfluidic device according to Claim 3 in which the at least two controllable fluid channels are disposed in different planes.
6. A microfluidic device according to any preceding Claim and comprising a path configured to transmit a focussed optical beam.
10
7. A microfluidic device according to Claim 6 in which the path comprises translucent material (18).
8. A microfluidic device according to any preceding Claim having a layered structure.
15
9. A microfluidic device according to any preceding Claim and having a planar structure.
10. A microfluidic device according to Claim 9 having a circular disk structure.
201 1 .A microfluidic device according to any preceding Claim in which the depressurisation regionis the atmosphere, and in which the device comprises a downstream region comprises a vent providing fluid communication with the atmosphere.
12. A microfluidic device according to any of Claims 1 to 10 in which the depressurisation 25 region is a decompression chamber disposed within the device.
13. An apparatus comprising a microfluidic device of any of Claims 1 to 12 and a light source configured to produce a focussed optical beam and direct the focussed optical beam on to the second sacrificial membrane of the controllable fluid channel.
30
14. An apparatus as claimed in Claim 13 in which the light source is configured to alter the focal point of the optical beam along a major axis of the optical beam.
15. A method of controlling fluid flow in a fluid channel in a microfluidics device, which method employs a microfluidics device according to Claim 1 in a primed configuration having a pressurised upstream region of the actuation channel, the method comprising the steps of directing a suitable beam of light on to the second sacrificial membrane 5 to rupture the membrane, whereby the pressurised upstream region of the actuation channel is depressurised causing the gas pocket to dislodge and liquid in the first region of the first channel come into contact with and disintegrate the first sacrificial membrane. io16. A method according to Claim 15 in which the beam of light directed on to the second sacrificial membrane is a laser beam.
17. A method according to Claim 15 or 16 in which the beam of light directed on to the second sacrificial membrane for a period of time sufficient to rupture the membrane.
15
18. A method of controlling fluid flow in a fluid channel in a microfluidics device, which method employs a microfluidics device according to Claim 2 in a primed configuration in which the at least two controllable fluid channels each have a pressurised upstream region of the actuation channel, the method comprising the steps of (a) directing a
20 beam of light of a first focal length on to a first of the second sacrificial membranes to rupture the membrane and actuate a first of the controllable fluid channels, and then (b) adjusting the focal length of the beam of light such that it is directed on to a second of the second sacrificial membranes to rupture the membrane and actuate a second of the controllable fluid channels
25
19. A method according to Claim 18 in which the beam of light directed on to the second sacrificial membranes is a laser beam.
20. A method according to Claim 18 or 19 in which the beam of light directed on to the 30 second sacrificial membrane for a period of time sufficient to rupture the membrane.
PCT/EP2017/070891 2016-08-19 2017-08-17 A microfluidic device WO2018033609A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB1614182.2A GB2553100A (en) 2016-08-19 2016-08-19 A microfluidic device
GB1614182.2 2016-08-19

Publications (1)

Publication Number Publication Date
WO2018033609A1 true WO2018033609A1 (en) 2018-02-22

Family

ID=57045572

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2017/070891 WO2018033609A1 (en) 2016-08-19 2017-08-17 A microfluidic device

Country Status (2)

Country Link
GB (1) GB2553100A (en)
WO (1) WO2018033609A1 (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114341538A (en) * 2019-07-12 2022-04-12 好奇诊断有限责任公司 Micro-fluidic chip and valve, production method and application
CN114950584A (en) * 2022-04-27 2022-08-30 厦门大学 Three-dimensional micro-channel chip structure for generating liquid drops and manufacturing method
WO2023064815A1 (en) * 2021-10-12 2023-04-20 University Of Virginia A microfluidic strucure for differential extraction

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19858443A1 (en) * 1998-12-17 2000-07-06 Inst Mikrotechnik Mainz Gmbh Method for dispensing a fluid, fluidic component and device for handling such components
WO2009112030A1 (en) * 2008-03-12 2009-09-17 Fluimedix Aps Controlled liquid handling
GB2515116A (en) * 2013-06-14 2014-12-17 Univ Dublin City Microfluidic Device

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070092409A1 (en) * 2005-10-21 2007-04-26 Beatty Christopher C Reconfigurable valve using optically active material
KR101422572B1 (en) * 2006-09-05 2014-07-30 삼성전자주식회사 Centrifugal force-based microfluidic device for nucleic acid detection and microfluidic system comprising the device
KR101305976B1 (en) * 2007-02-12 2013-09-12 삼성전자주식회사 Centrifugal force based microfluidic device for serial dilution and microfluidic system comprising the same
WO2010084190A1 (en) * 2009-01-23 2010-07-29 Dublin City University Fluidic single use valve and microfluidic systems incorporating said valve
GB2467298A (en) * 2009-01-23 2010-07-28 Univ Dublin City Multilayer microfluidic device
KR101439483B1 (en) * 2012-12-05 2014-09-15 매쓰파워 주식회사 A thin film valve apparatus using a hole closing membrane
EP2781263A3 (en) * 2013-03-19 2017-11-22 Samsung Electronics Co., Ltd. Microfluidic Device and Control Method Thereof
TWI545323B (en) * 2014-10-31 2016-08-11 紹興普施康生物科技有限公司 Centrifugal magnetic bead operating apparatus and operating method thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19858443A1 (en) * 1998-12-17 2000-07-06 Inst Mikrotechnik Mainz Gmbh Method for dispensing a fluid, fluidic component and device for handling such components
WO2009112030A1 (en) * 2008-03-12 2009-09-17 Fluimedix Aps Controlled liquid handling
GB2515116A (en) * 2013-06-14 2014-12-17 Univ Dublin City Microfluidic Device

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114341538A (en) * 2019-07-12 2022-04-12 好奇诊断有限责任公司 Micro-fluidic chip and valve, production method and application
CN114341538B (en) * 2019-07-12 2023-01-20 好奇诊断有限责任公司 Micro-fluidic chip and valve, production method and application
WO2023064815A1 (en) * 2021-10-12 2023-04-20 University Of Virginia A microfluidic strucure for differential extraction
CN114950584A (en) * 2022-04-27 2022-08-30 厦门大学 Three-dimensional micro-channel chip structure for generating liquid drops and manufacturing method

Also Published As

Publication number Publication date
GB201614182D0 (en) 2016-10-05
GB2553100A (en) 2018-02-28

Similar Documents

Publication Publication Date Title
EP1567796B1 (en) Devices and methods for programmable microscale manipulation of fluids
CA2679395C (en) Serial siphon valves for fluidic or microfluidic devices
JP4700004B2 (en) Packaging for microfluidic devices
KR102039515B1 (en) Microfluidic device
US20070095393A1 (en) Devices and methods for programmable microscale manipulation of fluids
WO2018033609A1 (en) A microfluidic device
US20080152546A1 (en) Enhanced sample processing devices, systems and methods
EP1899064A2 (en) Dosimeter for programmable microscale manipulation of fluids
JPWO2006077695A1 (en) Liquid feeding device and liquid feeding method
US10099218B2 (en) Method for manufacturing and/or packaging a chip
EP2920464B1 (en) Micro-reagent handler and cartridge assembly
WO2010084190A1 (en) Fluidic single use valve and microfluidic systems incorporating said valve
GB2467298A (en) Multilayer microfluidic device
JP4819945B2 (en) Substrate having flow path part including chamber, and method of transferring liquid using the same
EP1930635A2 (en) Devices and methods for programmable microscale manipulation of fluids
GB2468111A (en) Multilayer Fluidic Device
Garcia-Cordero et al. Low-cost microfluidic single-use valves and on-board reagent storage using laser-printer technology

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 17764763

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 17764763

Country of ref document: EP

Kind code of ref document: A1