WO2015150742A1 - Distribution de fluide - Google Patents
Distribution de fluide Download PDFInfo
- Publication number
- WO2015150742A1 WO2015150742A1 PCT/GB2015/050905 GB2015050905W WO2015150742A1 WO 2015150742 A1 WO2015150742 A1 WO 2015150742A1 GB 2015050905 W GB2015050905 W GB 2015050905W WO 2015150742 A1 WO2015150742 A1 WO 2015150742A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- piercing
- piercing member
- plate
- blister
- chip
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
Classifications
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502715—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/52—Containers specially adapted for storing or dispensing a reagent
- B01L3/523—Containers specially adapted for storing or dispensing a reagent with means for closing or opening
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/02—Adapting objects or devices to another
- B01L2200/025—Align devices or objects to ensure defined positions relative to each other
-
- 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
- B01L2300/04—Closures and closing means
- B01L2300/041—Connecting closures to device or container
- B01L2300/044—Connecting closures to device or container pierceable, e.g. films, membranes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/06—Auxiliary integrated devices, integrated components
- B01L2300/0672—Integrated piercing tool
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0809—Geometry, shape and general structure rectangular shaped
- B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
- B01L2300/0883—Serpentine channels
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
- B01L2400/0481—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure squeezing of channels or chambers
-
- 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
Definitions
- the apparatus includes a piercing member locatable with respect to a sealing membrane of a respective blister pouch that has a tip region which is locatable in an abutting relationship with the sealing membrane in a first mode of operation and through the sealing member in a further mode of operation for providing liquid from the blister pouch at a desired location.
- a piercing plate comprising a piercing member, together with devices, for example, bio chips and microfluidic devices, which are for use in combination with the apparatus.
- Microfluidic systems have recently emerged as powerful tools for bio-sensing, particularly in enriching and purifying molecules and cells in biological samples.
- Microfluidic technology has enabled the miniaturisation of normal sized equipment and has resulted in more readily portable devices and the sensing of increasingly small sample volumes and target analyte concentrations which have not been possible with previous technologies.
- Microfluidic devices can be laboratory-based devices for use in genomics, sequencing, high- throughput screening and separations. Additionally, microfluidic devices provide the opportunity to integrate processes and measurement systems on a single technology platform leading to the concept of the "lab on a chip". Thus, microfluidic devices are also sometimes known as "bio-chips" or lab-on-chip” systems. Microfluidic technology has found applications in chemical and system biology, point-of-care analysis, high-throughput biological screening. Advantages associated with lab-on-chip include consumption of small volumes of reagents and sample, and delivery of results in a short timescale.
- Microfluidic devices often comprise a substrate together with microstructures such as micropumps, micromixers, ports, microchannels and the like.
- fluids plays an important role in fields such as chemistry, microbiology and biochemistry.
- These fluids may include liquids or gases and may provide reagents, buffers, solvents or reactants, to chemical and/or biological processes, including processes involving microfluidic technology.
- a problem often associated with fluid delivery to microfluidic devices is the difficulty of delivering known volumes of reagents into the microfluidic flow system in a controlled manner at a steady rate.
- Existing technology often relies upon pipetting of reagents and/or samples into wells or chambers of the device.
- microfluidic technology may have resulted in portable devices being developed, there still remains the problem of how to easily transport and deliver reagents and/or samples outside a laboratory environment.
- Blister pouches include individually sealed units which store fluids or solids prior to delivery and have been used to store and subsequently deliver fluids to microfluidic devices.
- a user breaks the seal of the unit. The seal may be broken by a user manually applying a force to the seal or by way of an actuator applying pressure. Often, when the seal is broken, the release of the stored fluid is not always controlled and thus at least some of the stored fluid is not directed to the target location. Also there is a risk of fluid "surging" from the blister.
- One way of automatically providing the right reagents in the correct volume is to package the reagents into blister packages and allow the blister to release the reagents once the sample is on the chip.
- most conventional blister popper constructs lead to the blisters rupturing in the wrong place and the reagent splashing outside of the chip. This results in a waste of reagent and can lead to a reduction in accuracy if a precise amount of the fluid is required.
- Certain embodiments of the present invention aim to provide a device and/or method which delivers a fluid, e.g. a liquid, in a controlled manner to a target location. It is an aim of certain embodiments of the present invention to provide a mechanism that can selectively burst a blister pouch when desired and in a controlled way but which doesn't pose a risk (in terms of causing an undesired breach) at other times.
- a fluid e.g. a liquid
- apparatus for providing a target liquid at a desired location comprising at least one piercing member upstanding from a support surface at a height of about around 300 to 1200 microns and locatable with respect to a sealing membrane of a respective blister pouch; wherein a tip region of the piercing member is locatable in an abutting relationship with the sealing membrane in a first mode of operation and through the sealing membrane in a further mode of operation for providing liquid from the blister pouch at a desired location.
- the piercing member is upstanding from a support surface at a height of about around 300 to 1200 microns e.g. 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000, 1050, 1 100, 1 150 or 1200 microns.
- the piercing member has a height of from about 300 to 1200 microns.
- the piercing member in the first mode of operation is locatable to deform but not pierce the sealing membrane. In one embodiment, in the first mode of operation, the piercing member does not pierce the sealing membrane when an abutment force of up to about around 1 N is applied by the piercing member to the sealing membrane. In one embodiment, in the first mode of operation, the piercing member does not pierce the sealing membrane when an abutment force of up to about around 1 N, e.g. 0.80, 0.85, 0.9, 0.95 or 1 .0N, is applied by the piercing member to the sealing membrane.
- an abutment force of up to about around 1 N e.g. 0.80, 0.85, 0.9, 0.95 or 1 .0N
- the tip region comprises a rounded nose region having a generally arcuate shape with a radius of curvature of about around 50 to 1000 microns. Aptly, the radius of curvature is about around 100 to 500 microns. In one embodiment, the radius of curvature of the rounded nose region of the piercing member is approximately 100, 150, 200, 250, 300, 350, 400, 450 or 500 microns.
- the piercing member has a comparatively blunt nose region, which is used to pierce the sealing membrane of the blister pouch when desired.
- the "blunt" nose region when the sealing membrane is pierced, substantially all of the fluid held in the blister pouch flows over and through the piercing member, rather than, as is the case with many prior art fluid delivery systems, the fluid is released in an uncontrolled manner leading to a portion of the liquid not being directed into the chamber.
- the piercing member further comprises a plurality of abutment wall regions extending from the support surface to the tip region at a predetermined angle so that each wall region forms a tangent with an arc of a rounded nose region at an end of the tip region.
- each abutment wall region meets the nose region at an angle of about around 45 degrees.
- each abutment wall region meets the nose region at an angle of approximately 45 degrees e.g. 40, 41 , 42, 43, 44, 45, 46 or 47 degrees.
- each abutment wall region meets the nose region at substantially the same angle.
- each abutment wall region meets the nose region at a different angle to each other abutment wall region.
- the piercing member provides a plurality of fluid communication passageways proximate to the tip region that each communicate liquid urged from a pierced blister pouch to at least one collection chamber under the support surface.
- the piercing member comprises two or more fluid communication passageways proximate to the tip region, e.g. 2, 3, 4 or more.
- the piercing member comprises four fluid communication passageways.
- the piercing member comprises a plurality of arms extending upwards and in an inclined manner from the support surface.
- the fluid communication passageways are provided by openings in the support surface in notched regions between adjacent arms.
- the piercing member comprises two or more upwardly extending arms e.g. 2, 3, 4, or more.
- the piercing member comprises four upwardly extending arms.
- Blister pouches are often pre-filled with a required volume of liquid and thus it follows that certain embodiments of the present invention may provide a more accurate result in a method which is based on calculations involving the known volume of the liquid in the blister pouch.
- Certain embodiments of the present invention provide a piercing member which comprises a plurality of openings which allow fluid released from the blister pouch to flow into a chamber situated beneath the piercing member.
- the plurality of openings results in the fluid flowing downwardly in a plurality of flow streams which should enable the flow of fluid to be controlled more effectively.
- the first mode of operation comprises a transportation mode during which a blister pouch is transportable in an abutting relationship with the piercing member without risk of puncture.
- Certain embodiments of the present invention provide the advantage that the piercing member is capable of piercing a sealing membrane of a blister pouch when a predetermined level of force is applied to either the piercing member or the blister pouch but does not pierce the sealing member when simply in an abutting relationship with the sealing membrane.
- certain embodiments of the present invention provide an apparatus which is capable of being transported in an abutting relationship with a sealed blister pouch pre-filled with a reagent for example without the blister pouch being pierced and its contents released.
- the piercing member in the further mode of operation in which the blister pouch is urged against the piercing member, is disposed to rupture the sealing membrane at a rupture force of about around 3 to 12N.
- the piercing member is disposed to rupture the sealing membrane at a force of about 3, 4, 5, 6, 7, 8, 9, 10, 1 1 or 12 N.
- each piercing member is manufactured from a material selected from a group comprising glass, polycarbonate or polymethyl methacrylate (PMMA), cyclic olefin copolymer (COC), polystyrene (PS), polyether ether ketone (PEEK), polytetrafluoroethylene (PTFE) and polypropylene (PP).
- PMMA polycarbonate or polymethyl methacrylate
- COC cyclic olefin copolymer
- PS polystyrene
- PEEK polyether ether ketone
- PTFE polytetrafluoroethylene
- PP polypropylene
- a piercing plate securable to at least one blister pouch, comprising an apparatus for providing a target liquid at a desired location comprising at least one piercing member upstanding from a support surface at a height of about around 300 to 1200 microns and locatable with respect to a sealing membrane of a respective blister pouch; wherein a tip region of the piercing member is locatable in an abutting relationship with the sealing membrane in a first mode of operation and through the sealing member in a further mode of operation for providing liquid from the blister pouch at a desired location.
- the apparatus is as further described herein.
- the piercing plate further comprises a planar upper surface, comprising the support surface, and a planar lower surface that is securable to an upper surface of a bio chip.
- the piercing plate further comprises an adhesive layer on the lower surface.
- the piercing plate further comprises at least one alignment element that locates the piercing plate at a desired position with respect to each blister pouch.
- the alignment element comprises at least one edge of the piercing plate.
- the alignment element comprises at least one locating lug or recess that mates with a complimentary alignment element of the blister pouch.
- the piercing plate further comprises one further alignment element that locates the piercing plate at a desired position with respect to a bio chip.
- each further alignment element comprises at least one edge of the piercing plate.
- each further alignment element comprises at least one locating lug or recess that mates with a complimentary alignment element of the bio chip.
- the piercing plate further comprises a cavity under each piercing member that is locatable in fluid communication with a collection chamber of a bio chip.
- the piercing plate has a thickness of about around 200 to 1000 microns.
- the piercing plate is manufactured from a material selected from glass, polycarbonate and PMMA.
- the plate and each piercing member are integrally formed. In one embodiment, the plate and the apparatus are integrally formed. In one embodiment, the plate is retrofittable to an underside of a blister package comprising one or more blister pouches sealed with a sealing membrane.
- a blister pack comprising a plurality of blister pouches secured together via a web and a common sealing membrane; and at least one piercing plate as described herein secured to a lower surface of the sealing membrane.
- the blister pack may be fabricated using vacuum thermoforming of polymer films, for example.
- the blister pack comprises a plurality of frangible lines or perforation lines in the web.
- the frangible lines or perforation lines are provided between each blister pouch so as to enable a single blister pouch to be removed from the blister pack.
- a bio chip comprising an apparatus according to the first aspect of the invention as described herein.
- bio chip refers to a device which can be used to analyse samples having a volume of from about 10nl and 10ml.
- microfluidic device microfluidic assembly
- microfluidic systems and the like may also be used herein to indicate devices, assembly and systems wherein samples for the processing and/or analysis of samples having a volume of from about 10 nl to about 10 ml.
- the bio chip is used to analyse samples having a volume of between about 100 ⁇ and 2000 ⁇ .
- the bio-chip is a microfluidic device.
- the bio chip comprises an upper chip layer comprising one or more piercing member as an integral unit. In one embodiment, the bio chip comprises an upper chip layer comprising each piercing member as an integral unit. In an embodiment, the bio chip further comprises an upper chip layer having an upper surface on which at least one piercing plate comprising said at least one piercing member is secured.
- the bio chip comprises a lower surface of the upper chip layer and wherein the lower surface of the upper chip layer comprises a collection chamber located beneath each piercing member and at least one channel connecting a collection chamber to a respective sample chamber.
- the channel comprises a channel region that provides a serpentine pathway.
- the channel comprises an inlet end and an outlet end.
- the bio chip comprises a plurality of channels.
- the bio chip comprises a plurality of piercing members and a corresponding plurality of collection chambers.
- a collection chamber is located beneath the piercing element.
- the bio chip comprises a first collection chamber and at least one further collection chamber.
- the first collection chamber and the further collection chamber are in fluid communication via a channel region.
- the channel region comprises a T-junction region and/or a Y-junction region.
- Certain embodiments of the present invention provide a bio-chip which incorporates at least one blister pouch which is integrally formed with the bio-chip. Certain embodiments of the present invention provide an advantage that fluids may be stored on the bio-chip and delivered using the piercing member when required. Thus, certain embodiments of the present invention may result in a reduction of gas exchange with stored solutions and reagent waste, as well as cost reduction. Certain embodiments of the present invention provide a portable bio-chip device, e.g. a microfluidic device, which incorporates a blister pouch pre-filled with one or more reagents.
- Certain embodiments of the present invention provide the advantage that precise location of the piercing member relative to the sealed unit of the blister pouch is not required providing that the piercing member contacts at least a portion of the blister pouch.
- the bio chip is formed from a material selected from glass, polycarbonate, polymethyl methacrylate (PMMA), cyclic olefin copolymer (COC), polystyrene (PS), polyether ether ketone (PEEK), polytetrafluoroethylene (PTFE) and polypropylene (PP).
- PMMA polymethyl methacrylate
- COC cyclic olefin copolymer
- PS polystyrene
- PEEK polyether ether ketone
- PTFE polytetrafluoroethylene
- PP polypropylene
- the bio chip may be fabricated from a metal.
- the chip may be formed from a metal which could be readily formed into the required shapes using a range of fabrication techniques.
- the chip may be formed a technique selected from die casting, injection moulding and subtractive milling.
- the bio chip is fabricated from a ceramic material.
- the bio chip is produced using an injection moulding technique.
- the bio chip is formed from a polymer.
- the polymer is an injection moulded polymer.
- the bio chip further comprises one or more further elements.
- the bio chip comprises one or more of the following elements: one or more micropumps, one or more microvalves, a power source e.g. a battery, and/or a sensor.
- a method of delivering a target fluid to a desired location comprising locating an apparatus as described herein such that the piercing member of the apparatus abuts a sealing membrane of a respective blister pouch; wherein the fluid is located in the blister pouch; and applying a predetermined force to the sealing membrane such that the sealing membrane is pierced by the piercing member.
- the method comprises applying a force of between about 3N and about 12N to the sealing membrane.
- the method comprises: locating a biochip comprising a collection chamber as described herein underneath the piercing member prior to the piercing of the sealing membrane; and collecting the fluid from the blister pouch in the collection chamber.
- the method further comprises locating the apparatus in an abutting relationship with the sealing membrane prior to application of a predetermined force. Further details of certain embodiments are provided below.
- Figure 1 illustrates a bio chip and blister pouch according to certain embodiments of the present invention
- Figure 2 illustrates a bio chip according to certain embodiments of the present invention
- Figure 3A illustrates an apparatus according to certain embodiments of the present invention which comprises a piercing member
- Figure 3B illustrates an apparatus according to certain embodiments of the present invention which comprises a piercing member
- Figure 3C illustrates an apparatus according to certain embodiments of the present invention which comprises two piercing members
- Figure 4 illustrates a cross-sectional view of a blister pouch located above a piercing member according to certain embodiments of the present invention
- Figure 5 illustrates a cross-sectional view of a blister pouch located above a piercing member according to certain embodiments of the present invention
- Figure 6 illustrates a side view of an apparatus comprising a piercing member according to certain embodiments of the present invention
- Figure 7 illustrates a cross sectional view of section A-A as shown in Figure 6 of an apparatus comprising a piercing member according to certain embodiments of the present invention
- Figure 8 illustrates a top view of an apparatus comprising a piercing member according to certain embodiments of the present invention
- Figure 9 illustrates a bottom view of an apparatus comprising a piercing member according to certain embodiments of the present invention
- Figure 10 illustrates an exploded view of a blister pack and a piercing plate comprising a piercing member according to certain embodiments of the present invention
- Figure 1 1 illustrates a blister pouch located above a piercing member according to certain embodiments of the present invention
- Figure 12 illustrates a cross-sectional side view of a blister pouch located above a piercing member according to certain embodiments of the present invention
- Figure 1 illustrates an apparatus 100 for providing a target liquid at a desired location according to certain embodiments of the present invention.
- the desired location is situated on a device e.g. a bio-chip 1 10.
- the apparatus may be a distinct element from the bio-chip 1 10 or may be an integrally formed portion of the bio-chip. Further details of the bio chip which are not shown in the Figures are provided below.
- the bio-chip may comprise a number of other elements e.g. one or more of sensing regions, micropumps, valves, heaters, microchannels and other elements known in the art (not shown).
- the bio chip comprises one or more elements for controlling fluid flow thereon e.g. electroosmotic flow, vacuum pumps, electrokinetic pumps, membrane actuated pumps, centrifugal force, gas bubbles, ferrofluidic plugs, capillary action, electrohydrodynamic pumps, and/or magnetohydrodynamic pumps.
- fluid flow e.g. electroosmotic flow, vacuum pumps, electrokinetic pumps, membrane actuated pumps, centrifugal force, gas bubbles, ferrofluidic plugs, capillary action, electrohydrodynamic pumps, and/or magnetohydrodynamic pumps.
- pumps for microfluidics may be governed by electrokinetic principles or by the mechanism of differential pressure.
- the bio chip can be used for automating a variety of bioassay protocols, such as absorption, fluorescence, ELISA, enzyme immunoassay (EIA), light scattering, electrochemical measurement assays and chemiluminescence for testing a variety of analytes.
- bioassay protocols such as absorption, fluorescence, ELISA, enzyme immunoassay (EIA), light scattering, electrochemical measurement assays and chemiluminescence for testing a variety of analytes.
- analytes include for example proteins, nucleic acids, cells, receptors, and the like.
- the biochip can be configured and designed for whole blood, tears, sweat, serum, plasma, urine, and other biological fluid applications.
- the bio-chip is adapted to perform DNA hybridization assays, expression analysis of mRNA, certain forms of DNA detection and/or DNA sequencing.
- the bio chip may be used in one or more of the techniques described in Sensors (Basel). 2012; 12(8): 10713-10741
- the bio chip is made of elastomers or polymers such as for example, PDMS, PMMA, polyurethane, PFPE, SIFEL and parylene.
- the bio-chip is formed from a material selected from for example plastic, glass, silicon, polycarbonate, polycarbonate, polydimethylsiloxane, polymethyl methacrylate (PMMA), cyclic olefin copolymer (COC), polystyrene (PS), polyether ether ketone (PEEK), polytetrafluoroethylene (PTFE) and polypropylene (PP).
- the bio-chip may comprise a sample region.
- sample region refers to any portion of a bio-chip that provides storage, analysis, separation or that provides, conducts or is otherwise involved in any processing step on or with the sample liquid.
- the sample region is involved in the analysis of a sample liquid or components therein, and the sample region is considered a sensor (or sensor region), for example a sensor surface.
- the sample is taken from a plant, e.g. a tree, a shrub and/or a flowering plant.
- the sample is selected from a human and/or animal sample.
- the sample is whole blood, serum and/or plasma.
- the sample is urine sample, a sample taken from a swab e.g. a nasal swab, a pharyngeal swab, a vaginal swab or a rectal swab.
- the sample is taken from tears and/ or sweat. Aptly, multiple analytes or multiple samples may be detected in a very small quantity.
- the bio-chip comprises a sensor (not shown).
- the term "sensor” refers to a device that detects a change in at least one physical property and produces a signal, or induces a change in a signal, in response to the detectable change.
- the manner in which the sensor detects a change may include, for example, acousto- mechanical changes, electrochemical changes, optical changes and/or electro-optical changes.
- acousto-mechanical sensors can utilise resonant frequency, phase- shifts, piezoelectric properties.
- electrochemical sensors utilise potentiometric and amperometric measurements.
- optical sensors may utilise absorbance, fluorescence, luminescence and/or evanescent waves.
- the senor is a biosensor and comprises at least one detection moiety attached thereto.
- the detection moiety is selected from one or more of: an antibody; a nucleic acid, e.g. DNA, RNA, or PNA; a protein; a peptide; an aptamer; a cell; a charged molecule; a membrane; a vesicle; a chemical and/or electrochemical receptor.
- the detection moiety may be immobilised directly to a surface of the bio-chip.
- the detection moiety may be immobilised on a solid support e.g. latex beads or magnetic beads using techniques known in the art.
- the detection moiety may comprise a label for detection.
- the detection moiety may be directly detectable via a label free detection method.
- the bio-chip of certain embodiments of the present invention may be used to detect for example the presence or absence of a target protein, a target DNA molecule and/or a target RNA molecule.
- the target molecule for detection may be for example a hormone, a cell surface molecule, a cardiac protein, a tumour marker and/or a small molecule.
- the target molecule is a drug of abuse.
- the target molecule may be a plurality of target molecules and the bio-chip is for the detection of the presence and/or absence of one or more target molecules.
- the apparatus 100 comprises a piercing member 120 located on a support surface 130.
- the piercing member 120 is described in more detail below and illustrated in Figures 6 to 9.
- the apparatus 100 may comprise a plurality of spaced apart piercing members 120.
- the bio chip 1 10 comprises a lower chip sealing plate 140.
- the lower chip sealing plate 140 may be rectangular for example in shape.
- the chip sealing plate may have dimensions of for example a length of about 120mm and a width of about 60mm, although it will be appreciated that bio-chips of other dimensions are encompassed by certain embodiments of the present invention.
- the lower chip sealing plate 140 may comprise a rectangular glass plate. Other materials which may be suitable to fabricate the bio chip plates are described herein.
- the bio chip also comprises a chip top layer 150.
- the lower surface 160 of the chip top layer 150 can be bonded to the upper surface 170 of the lower chip sealing plate 140 by a suitable known method e.g. thermal bonding.
- the upper surface 180 of the chip top layer 150 forms an upper external surface of the bio chip and the lower surface 190 of the lower chip sealing plate 140 forms a lower external surface of the bio chip 1 10.
- the chip top layer 150 may have a thickness of for example about 3mm and the lower chip sealing plate may have a thickness of 1 mm.
- the bio chip 1 10 further comprises one or more channels.
- Figure 1 illustrates that the chip top layer comprises one or more channels 200.
- the chip top layer also comprises a sample chamber 210 which is in fluid communication with at least one channel.
- the chip top layer 150 further comprises a collection chamber 220.
- the collection chamber may be considered a fluid introduction chamber. In use, the collection chamber 220 is situated beneath a piercing member as described herein.
- the collection chamber is in fluid communication with at least one channel 200 and may provide an inlet for the channel 200.
- the channels may differ between devices.
- the channels may have a cross-sectional width of between about 0.1 mm and 5mm.
- the channels may have a depth of e.g. 20 microns and 1 mm.
- the piercing member 120 is provided on a piercing plate 230.
- the piercing plate 230 is secured to the chip top layer 150 by a layer of adhesive 240.
- the piercing plate Prior to application of the layer of adhesive, the piercing plate is positioned such that the piercing member is located above the collection chamber 220.
- the piercing plate may be about around 200 to 1000 microns thick and/or manufactured from a material e.g. glass, polycarbonate or PMMA.
- Figure 1 illustrates a blister pouch 250 located above the piercing member 120.
- the blister pouch 250 is formed from a blister forming material.
- the blister pouch comprises a reservoir 260 which may be filled with a predetermined volume of liquid e.g. a reagent.
- the reservoir is sealed by a blister sealing membrane 270.
- the liquid may be a reagent such as for example a buffer, a liquid comprising one or more detection molecule and/ or a liquid comprising a sample material. The nature of the liquid may depend on the reaction being carried out on the bio chip.
- the blister sealing membrane 270 is formed from a blister sealing material.
- the blister sealing material is capable of being pierced by the piercing member 120 when brought into contact with the piercing member with a predetermined level of force. Aptly, the piercing member does not pierce the blister sealing membrane when it is located abutting the blister membrane at a level of force which is less than about 1 N.
- FIG. 2 illustrates an embodiment in which two piercing members 120a, 120b are located in a bio chip 1 10.
- the illustrated bio chip may be generally square in shape as shown in Figure 2. In other embodiments, the bio chip may be alternative shapes e.g. rectangular, circular, hexagonal or pentagonal.
- the piercing members 120a, 120b are each provided above a respective collection chamber 220a, 220b.
- the collection chamber holds the liquid released from the blister pouch when the sealing membrane 270 is pierced by the corresponding piercing member.
- the collecting chamber helps to prevent liquid being released from the blister pouch over the surface of the bio-chip and thus away from the target location i.e. the channels of the bio-chip.
- the bio chip 1 10 of Figure 2 includes a channel 200a which is generally linear and extends between a first piercing member 120a and a second piercing member 120b.
- the channel 200a includes a T-junction intersection with a further portion of the channel 200b.
- the further portion of the channel is serpentine and is connected to a sample chamber 210.
- Figure 3 illustrates alternative embodiments of a bio chip 1 10.
- Figure 3A illustrates a bio chip 1 10 which comprises a linear channel 200.
- the linear channel is in fluid communication with the collection chamber 220 and the sample chamber 210.
- the linear channel 200 connects the collection chamber 220 and the sample chamber 210.
- the piercing member 120 located above the collection chamber 220 and is either integrally formed with the upper surface of the biochip or within a piercing plate.
- Figure 3B illustrates an alternative embodiment of a bio chip according to certain embodiments of the present invention.
- the bio chip comprises a channel 200 which follows a serpentine path between the collection chamber 220 and the sample chamber 210.
- the piercing member 120 is located above the collection chamber 220 and can be either integrally formed with the bio chip 1 10 or within a separate piercing plate 230 as described herein.
- FIG. 3C illustrates a further alternative embodiment of a bio-chip 1 10 according to certain embodiments of the present invention.
- Two piercing members 120a and 120b are located above two separate collection chambers 220a and 220b.
- One or both piercing members 120a and 120b are either integrally formed with the upper surface of the biochip or within a piercing plate 230.
- the collection chambers 220a, 220b are linked by a linear channel 200a.
- the channel 200a is intersected by and in fluid communication with a further portion of the channel 200b at an intersection point 300.
- the further portion of the channel 200b is in fluid communication with the sample chamber 210.
- the channel has a linear portion 310 extending from the intersection point 300, a middle serpentine section 320 and an end linear section 330 which is connected to the sample chamber 210.
- Figure 4 illustrates a cut through of a piercing member 120 provided on a piercing plate 230 and located above a collection chamber 220 located in a bio chip.
- the collection chamber 220 is provided in an upper chip plate 150 of the bio chip 1 10.
- the piercing plate 230 is secured to the upper surface of the upper chip plate by a layer of adhesive 240.
- a blister pouch 250 is located above the piercing member 120.
- the blister membrane 270 of the blister pouch 250 is in contact with the piercing member 120 but since the force applied to the blister sealing membrane by the piercing member does not exceed about 1 N, the blister sealing material of the blister membrane is not punctured by the piercing member. As a result, the fluid is retained in the blister pouch 250 shown in Figure 4.
- Figure 5 is an alternative view of the blister pouch 250, piercing plate 230 and bio chip shown in Figure 4.
- the piercing member 120 is shown in more detail in Figures 6 to 9.
- the piercing member illustrated in Figures 6 to 9 may be comprised in a piercing plate or a bio chip as described herein.
- Figure 6 illustrates a cross sectional view of a piercing member 120.
- the piercing member 120 is located upstanding from a support surface 130 at a height of about around 300 to 1200 microns.
- the support surface 130 may be provided as an integral surface of the bio chip.
- the support surface 130 may be provided on a piercing plate or as an integral part of the piercing plate.
- the piercing member 120 comprises a tip region 600 which has a rounded nose region 610.
- the piercing member 120 also comprises a plurality of abutment wall regions or angled struts 620, 630, 640 and 650 which extend upwardly from the support surface to the tip region 600.
- Each strut extends from the support surface 130 to the tip region at a predetermined angle so that each wall region or strut forms a tangent with an arc of the rounded nose region 610 at an end of the tip region.
- the piercing member comprises four angled struts, however, in alternative embodiments the piercing member may comprise a different number of angled struts e.g. two, three or five.
- the abutment wall regions 620, 630, 640, 650 form a cross when viewed from above with the centre of the cross being the rounded nose region 610.
- the abutment wall regions extend upwardly from the support surface at an angle of approximately 90°, as shown in Figure 6.
- the rounded nose region of the piercing member allows the piercing member to abut a blister sealing membrane without piercing it.
- This embodiment has the advantage that a blister pouch may be stored and e.g. transported in an abutting relationship with a piercing member which may be an integral part of a microfluidic device e.g. a bio-chip.
- certain embodiments of the present invention may have utility in systems which need to be easily transported e.g. lab-on-chip portable devices.
- a passageway 660, 670, 680, 690 through which fluid stored in the blister pouch can flow once the blister sealing membrane is punctured by the piercing member.
- the fluid can then flow into the collection chamber 220 located beneath the passageways formed by adjacent abutment wall regions.
- the passageways are sized such that liquid may pass through the passageway and do not pool on top of the piercing member and therefore the bio-chip. As a result, substantially all of the liquid stored in the blister pouch passes into the biochip which means that the amount of liquid used in the process taking place on the bio-chip can be accurately determined.
- Figure 7 is a cross sectional view of section A-A of Figure 6 and shows the collection chamber 220 located underneath the rounded nose region 610 of the piercing member 120.
- Figure 9 is a bottom view of the apparatus 100 showing a lower surface 900 of for example a piercing plate or a bio chip.
- Figure 10 is an exploded view illustrating a blister pack 710 which comprises two blister pouches 250a, 250b which protrude from and are supported by a backing web 720. It will be appreciated that a blister pack 710 may comprise a plurality of blister pouches 250.
- Figure 10 also illustrates a piercing plate 230 which comprises two piercing members 120a, 120b. Each blister pouch may be filled with the same type of fluid or a different type of fluid.
- the backing web 720 includes one or more interconnecting regions 730 between the blister pouches.
- the backing web 720 may be provided with frangible lines or perforations (not shown) in the interconnecting regions between blister pouches to enable a section comprising one or more blister pouches to be "snapped-off" or removed from the blister pack.
- the backing web may be formed from the same material as the blister forming material.
- the backing web is formed from a plastic, a composite material, a film material or a combination of such materials.
- the blister pack 710 may also include a sealing membrane (not shown) which extends across the backing web 720 and the otherwise open entrance of a plurality of blister pouches 250, thus sealing a plurality of blister pouches.
- the sealing membrane may comprise one or more perforations (not shown) which coincide with an outer perimeter surrounding an individual blister pouch.
- the backing web comprises frangible lines or perforations
- the sealing membrane may comprise corresponding frangible lines or perforations.
- the blister pouch may be sealed by a heat-sealing method.
- the blister pouch may be sealed by way of a cold-sealing method.
- the blister pack may comprise a plurality of sealing membranes, each sealing membrane extending across an otherwise open blister pouch thus sealing a single blister pouch.
- the sealing membrane may be heat sealed to an upper surface of the backing web.
- the blister pouch 250 is filled with a pre-determined amount of a fluid e.g. a reagent.
- a fluid e.g. a reagent.
- the blister pouch may be filled with the fluid using an automated filling process.
- the blister pouch may be filled with a liquid manually or using a semi-automated process.
- Figure 10 also illustrates a layer of adhesive or adhesive material 740 which secures the blister pack to a piercing plate or to a biochip which comprises the piercing member.
- the embodiment illustrated in Figure 10 shows the piercing members being composed in a piercing plate.
- the adhesive material 740 comprises one or more apertures 750a, 750b which are located to correspond to the location of the piercing members 120a, 120b respectively.
- the apertures 750a, 750b also provide a through passageway for fluid stored in the blister pouch to flow through the piercing member once the blister sealing membrane is pierced.
- the piercing member 120 is an integrally formed portion of a piercing plate 230.
- a piercing plate 230 can be used in conjunction with microfluidic devices of differing types.
- the piercing plate may be secured to a bio chip 1 10 by an adhesive element e.g. a layer of adhesive 240. Prior to being secured to the bio chip, the piercing plate will be aligned to the bio chip such that each piercing member is positioned above a collection chamber.
- the piercing plate can be used in combination with a variety of bio chips providing that the bio chip comprises at least one collection chamber in a position which corresponds to the positioning of at least one piercing member of the piercing plate.
- the piercing member 120 when comprised in the piercing plate 230 is upstanding from the upper surface of the piercing plate to a height of between about 300 to 1200 microns.
- the piercing member 120 when comprised in the bio chip is upstanding from the upper surface of the piercing plate to a height of between about 300 to 1200 microns.
- the piercing plate comprising one or more piercing members may be supplied in combination with a blister pack.
- the blister pack may be supplied with the piercing member abutting but not piercing the sealing membrane of a blister pouch comprised in the blister pack.
- the piercing member may pierce the blister sealing membrane only when a predetermined force is applied e.g. about 3N or greater.
- the piercing plate may include at least one alignment element (not shown) which locates the piercing plate at a desired position with respect to each blister pouch.
- the alignment element comprises at least one edge of the piercing plate.
- the alignment element comprises at least one locating lug or recess which mates with a complimentary alignment element of the blister pouch.
- Figure 1 1 illustrates an alternative view of an individual blister pouch 250.
- the blister pouch 250 comprises a continuous curved exterior wall 1 100 which define a cavity in which fluids are introduced and stored prior to use. If individual blister pouches are used, which are not an integral part of a blister pack, the blister pouch may comprise a lip region 1 1 10 which a user can grip to handle the blister pouch.
- Figure 12 illustrates a side view of a blister pouch 250 positioned over a piercing member 120 which is in turn located above a collection chamber of a device e.g. a bio chip as described herein.
- the piercing member abuts the blister sealing membrane at an abutment point 1200 and deforms the membrane but since there is insufficient force applied the sealing membrane is not pierced.
- the apparatus comprising the piercing member may be stored and/or transported packaged such that the piercing member abuts but does not pierce the sealing membrane.
- a blister pouch 250 is prefilled with a predetermined volume of a liquid.
- the liquid may be any reagent for use in a process taking place on a microfluidic device e.g. a bio chip 1 10 as defined herein.
- An open mouth of the blister pouch is subsequently sealed by a sealing membrane 270.
- the blister pouch may be one of a plurality of blister pouches in a blister pack. Alternatively, the blister pouch may be supplied as an individual pouch.
- the blister pouch is sealed in an air tight manner and as such may be suitable for long term storage of the liquid. Additionally, the blister pouch can be stored at low temperatures, e.g. in a refrigerator, if the liquid needs to be stored in this way.
- the provision of reagents in blister pouches in this way enable different liquids to be stored in their optimum conditions ready for use in a process carried out on a microfluidic device.
- a piercing member 120 is provided in an apparatus 100.
- the piercing member may be an integral element of a piercing plate 230 or an integral feature of a bio chip 1 10.
- the piercing member may be provided in an abutting relationship with the sealing membrane of the blister pouch such that it deforms but does not break the sealing membrane in a first mode of operation. Aptly, the piercing member deforms but does not pierce the sealing membrane when a force of up to about 1 N is applied.
- a predetermined amount of force is applied to the blister pouch and/or the piercing member such that the sealing membrane is punctured by the piercing member.
- the piercing member is disposed to rupture the membrane when a force of about around 3 to 12N is applied to the membrane.
- the force may be applied to the blister pouch or the piercing member manually by a user or by an actuator.
- the actuator may be adapted to apply a pressure at a predetermined rate.
- the actuator may further comprise a control element adapted to instruct the actuator to apply a force to a plurality of blister pouches at substantially the same time or at predetermined time intervals.
- the liquid stored in the blister pouch is released in a controlled manner and substantially all of the liquid flows over the piercing member and through the openings formed between the abutment wall regions.
- the liquid then collects underneath the piercing member e.g. in a collection chamber comprised in a biochip. The liquid can then be used in a process on the bio-chip.
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Clinical Laboratory Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Dispersion Chemistry (AREA)
- Analytical Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Hematology (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
Abstract
Certains modes de réalisation de la présente invention portent sur un appareil et des procédés pour fournir un liquide cible à un emplacement souhaité. Dans certains modes de réalisation, l'appareil comprend un élément de perçage pouvant être placé par rapport à une membrane d'étanchéité d'une poche blister respective qui a une région d'extrémité qui peut être placée dans une relation en butée avec la membrane d'étanchéité dans un premier mode de fonctionnement et à travers la membrane d'étanchéité dans un autre mode de fonctionnement pour fournir le liquide de la poche blister à un emplacement souhaité. La présente invention concerne également, inter alia, une plaque de perçage comprenant un élément de perçage, conjointement avec des dispositifs, par exemple, des puces biologiques et des dispositifs microfluidiques, qui sont destinés à être utilisés en combinaison avec l'appareil.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB1405808.5 | 2014-03-31 | ||
| GB201405808A GB201405808D0 (en) | 2014-03-31 | 2014-03-31 | Fluid delivery |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2015150742A1 true WO2015150742A1 (fr) | 2015-10-08 |
Family
ID=50737777
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/GB2015/050905 Ceased WO2015150742A1 (fr) | 2014-03-31 | 2015-03-26 | Distribution de fluide |
Country Status (2)
| Country | Link |
|---|---|
| GB (1) | GB201405808D0 (fr) |
| WO (1) | WO2015150742A1 (fr) |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2538846A (en) * | 2015-04-01 | 2016-11-30 | Bosch Gmbh Robert | Storage unit, method for manufacturing a storage unit and method for releasing fluid stored in a storage unit |
| DE102017118060A1 (de) | 2017-08-09 | 2019-02-14 | Presens Precision Sensing Gmbh | Sensorelement und dessen verwendung |
| EP3765195A1 (fr) * | 2018-03-29 | 2021-01-20 | Heriot-Watt University | Dispositif fluidique |
| CN112771362A (zh) * | 2019-04-01 | 2021-05-07 | 酷睿有限公司 | 非排气机体流体样品优化装置和系统 |
| EP3895802A1 (fr) * | 2020-04-18 | 2021-10-20 | CapitalBio Corporation | Dispositif de stockage de liquide et à libération contrôlée et puce de détection biologique |
| CN114324905A (zh) * | 2020-09-27 | 2022-04-12 | 青岛海尔电冰箱有限公司 | 生物检测装置及其控制方法、冰箱 |
| CN114324908A (zh) * | 2020-09-27 | 2022-04-12 | 青岛海尔电冰箱有限公司 | 生物检测装置、生物检测芯片及冰箱 |
| US20220214277A1 (en) * | 2020-03-11 | 2022-07-07 | Newton Howard | Cartridge-based automated rapid test analyzer |
| CN115734818A (zh) * | 2020-03-25 | 2023-03-03 | 京东方科技集团股份有限公司 | 检测芯片、检测装置及制备和操作检测芯片的方法 |
| US11859734B2 (en) | 2020-11-16 | 2024-01-02 | Siemens Healthcare Diagnostics Inc. | Valve for microfluidic device |
| US12138052B1 (en) | 2015-07-24 | 2024-11-12 | Kurin, Inc. | Blood sample optimization device |
| US12257051B2 (en) | 2017-02-10 | 2025-03-25 | Kurin, Inc. | Blood contaminant sequestration device with one-way air valve and air-permeable blood barrier with closure mechanism |
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| US5096669A (en) * | 1988-09-15 | 1992-03-17 | I-Stat Corporation | Disposable sensing device for real time fluid analysis |
| US20060183216A1 (en) * | 2005-01-21 | 2006-08-17 | Kalyan Handique | Containers for liquid storage and delivery with application to microfluidic devices |
| US20100291588A1 (en) * | 2005-06-24 | 2010-11-18 | The Board Of Regents Of The University Of Texas System | Systems and methods including self-contained cartridges with detection systems and fluid delivery systems |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2538846A (en) * | 2015-04-01 | 2016-11-30 | Bosch Gmbh Robert | Storage unit, method for manufacturing a storage unit and method for releasing fluid stored in a storage unit |
| US12357209B2 (en) | 2015-07-24 | 2025-07-15 | Kurin, Inc. | Blood sample optimization device |
| US12138052B1 (en) | 2015-07-24 | 2024-11-12 | Kurin, Inc. | Blood sample optimization device |
| US12257051B2 (en) | 2017-02-10 | 2025-03-25 | Kurin, Inc. | Blood contaminant sequestration device with one-way air valve and air-permeable blood barrier with closure mechanism |
| DE102017118060A1 (de) | 2017-08-09 | 2019-02-14 | Presens Precision Sensing Gmbh | Sensorelement und dessen verwendung |
| WO2019030584A1 (fr) | 2017-08-09 | 2019-02-14 | Presens Precision Sensing Gmbh | Élément de détection et son utilisation |
| DE102017118060B4 (de) | 2017-08-09 | 2021-09-02 | Presens Precision Sensing Gmbh | Sensorelement und dessen verwendung |
| EP3765195A1 (fr) * | 2018-03-29 | 2021-01-20 | Heriot-Watt University | Dispositif fluidique |
| EP3765195B1 (fr) * | 2018-03-29 | 2025-11-05 | Heriot-Watt University | Dispositif fluidique |
| US12383174B2 (en) | 2019-04-01 | 2025-08-12 | Kurin, Inc. | Non-venting bodily fluid sample optimization device and system |
| CN112771362A (zh) * | 2019-04-01 | 2021-05-07 | 酷睿有限公司 | 非排气机体流体样品优化装置和系统 |
| US20220214277A1 (en) * | 2020-03-11 | 2022-07-07 | Newton Howard | Cartridge-based automated rapid test analyzer |
| CN115734818A (zh) * | 2020-03-25 | 2023-03-03 | 京东方科技集团股份有限公司 | 检测芯片、检测装置及制备和操作检测芯片的方法 |
| US11577240B2 (en) | 2020-04-18 | 2023-02-14 | Capitalbio Corporation | Liquid storage and controlled-release device and biological detection chip |
| EP3895802A1 (fr) * | 2020-04-18 | 2021-10-20 | CapitalBio Corporation | Dispositif de stockage de liquide et à libération contrôlée et puce de détection biologique |
| CN114324908A (zh) * | 2020-09-27 | 2022-04-12 | 青岛海尔电冰箱有限公司 | 生物检测装置、生物检测芯片及冰箱 |
| CN114324908B (zh) * | 2020-09-27 | 2025-10-10 | 青岛海尔电冰箱有限公司 | 生物检测装置、生物检测芯片及冰箱 |
| CN114324905A (zh) * | 2020-09-27 | 2022-04-12 | 青岛海尔电冰箱有限公司 | 生物检测装置及其控制方法、冰箱 |
| US11859734B2 (en) | 2020-11-16 | 2024-01-02 | Siemens Healthcare Diagnostics Inc. | Valve for microfluidic device |
Also Published As
| Publication number | Publication date |
|---|---|
| GB201405808D0 (en) | 2014-05-14 |
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