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WO2023022714A1 - Fixation amovible de réceptacle microfluidique consommable à l'aide de pression négative - Google Patents

Fixation amovible de réceptacle microfluidique consommable à l'aide de pression négative Download PDF

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Publication number
WO2023022714A1
WO2023022714A1 PCT/US2021/046557 US2021046557W WO2023022714A1 WO 2023022714 A1 WO2023022714 A1 WO 2023022714A1 US 2021046557 W US2021046557 W US 2021046557W WO 2023022714 A1 WO2023022714 A1 WO 2023022714A1
Authority
WO
WIPO (PCT)
Prior art keywords
receptacle
examples
microfluidic
substrate
electrodes
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
Application number
PCT/US2021/046557
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English (en)
Inventor
Michael W. Cumbie
Viktor Shkolnikov
Napoleon J. Leoni
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Hewlett Packard Development Co LP
Original Assignee
Hewlett Packard Development Co LP
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 Hewlett Packard Development Co LP filed Critical Hewlett Packard Development Co LP
Priority to PCT/US2021/046557 priority Critical patent/WO2023022714A1/fr
Publication of WO2023022714A1 publication Critical patent/WO2023022714A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • 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
    • B01L3/502769—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 multiphase flow arrangements
    • B01L3/502784—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 multiphase flow arrangements specially adapted for droplet or plug flow, e.g. digital microfluidics
    • B01L3/502792—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 multiphase flow arrangements specially adapted for droplet or plug flow, e.g. digital microfluidics for moving individual droplets on a plate, e.g. by locally altering surface tension
    • 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
    • B01L2200/028—Modular arrangements
    • 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
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0645—Electrodes
    • 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
    • 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
    • B01L2400/0415—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic
    • B01L2400/0427—Electrowetting
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • B01L2400/049—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics vacuum

Definitions

  • Microfluidic devices are revolutionizing testing in the healthcare industry. Some microfluidic devices comprise digital microfluidic technology, which may employ circuitry to move fluids.
  • FIGS. 1A and 1 C are each a diagram including a side sectional view schematically representing an example device and/or example method to releasably secure a consumable microfluidic receptacle and an electrode control element relative to each other, such as via application of negative pressure.
  • FIG. 1 B is a diagram including a top plan view schematically representing an example electrode control element including an example array of apertures for applying negative pressure.
  • FIG. 2 is a diagram including a side sectional view schematically representing an example consumable microfluidic receptacle.
  • FIG. 3A are each a diagram including a side sectional view schematically representing an example device and/or example method to cause electrowetting movement of a liquid droplet within a consumable microfluidic receptacle via application of charges from an external electrode control element.
  • FIG. 3B and 3C are each a side view schematically representing an example electrically conductive element.
  • FIG. 4A is a diagram including a top view schematically representing an example consumable microfluidic device.
  • FIG. 4B is a diagram including an isometric view schematically representing an example two-dimensional array of individually controllable electrodes, prior to releasable contact relative to, a portion of a consumable microfluidic receptacle.
  • FIG. 5A is a diagram including a side sectional view schematically representing an example electrode control element including apertures extending through a central portion of electrodes.
  • FIG. 5B is a diagram including a top plan view schematically representing an example electrode control element of FIG. 5A.
  • FIG. 6A is a diagram including a side sectional view schematically representing an example electrode control element including apertures extending through an outer portion of electrodes.
  • FIG. 6B is a diagram including a top plan view schematically representing an example electrode control element of FIG. 6A.
  • FIG. 7A is a diagram including a side sectional view schematically representing an example electrode control element including protrusions on a contact surface of the electrodes.
  • FIG. 7B is a diagram including a top plan view schematically representing an example electrode control element of FIG. 7A.
  • FIG. 8A is a diagram including a side sectional view schematically representing an example electrode control element including compliant conductive elements on a contact surface of the electrodes.
  • FIG. 8B is a diagram including a side sectional view schematically representing an example consumable microfluidic receptacle/device including compliant conducive elements on a contact surface of the electrodes.
  • FIGS. 9A and 9C each are a diagram including a side sectional view schematically representing an example device and/or example method to releasably secure a consumable microfluidic receptacle and an electrode control element relative to each other.
  • FIG. 9B is a diagram including a top plan view schematically representing an example manifold arrangement of an anisotropic conductivity portion of an example consumable microfluidic receptacle.
  • FIG. 10A is a block diagram schematically representing an example operations engine.
  • FIGS. 10B and 10C are each a block diagram schematically representing an example control portion and an example user interface, respectively.
  • FIG. 11 is a flow diagram schematically representing an example method.
  • At least some examples of the present disclosure are directed to providing a consumable microfluidic receptacle and/or electrode control element by which digital microfluidic operations can be performed in an inexpensive manner and/or more effectively.
  • a digital microfluidic assembly may comprise an electrode control element, which comprises an array of individually controllable electrodes, a chamber, and a plurality of apertures.
  • the respective electrodes are supported on at least a first side of a substrate while the chamber is sealed relative to an opposite second side of the substrate.
  • the plurality of apertures extends through, and between the respective first and second sides of, the substrate with the apertures being in communication with the chamber.
  • the assembly comprises a support to align a consumable microfluidic receptacle with the array of electrodes to receive charges on an anisotropic conductivity portion of the receptacle to induce electrowetting movement of a liquid droplet within the receptacle.
  • the array of electrodes becomes releasably secured against the receptacle.
  • the consumable microfluidic receptacle may form part of and/or comprise a microfluidic device, such as a digital microfluidic device.
  • the consumable microfluidic receptacle may sometimes be referred to as a single use microfluidic receptacle, or as being a disposable microfluidic receptacle.
  • each droplet comprises a small, single generally spherical mass of fluid, such as may be dropped into the consumable microfluidic receptacle.
  • the entire droplet is sized to be movable via electrowetting forces.
  • dielectrophoresis may cause movement of particles within a fluid, rather than movement of an entire droplet of fluid.
  • the term “charges” as used herein refers to ions (+/-) or free electrons.
  • the electrode control element may generate and apply the charges having a first polarity and/or an opposite second polarity, depending on whether the electrode control element is to build charges on the anisotropic conductivity portion or is to neutralize charges on the plate.
  • the first polarity may be positive or negative depending on the particular goals, while the second polarity will be the opposite of the first polarity.
  • the consumable microfluidic receptacle (of a microfluidic device) may omit on-board control electrodes (e.g. electrically active electrodes) which would otherwise be used to cause microfluidic operations such as moving, merging, and/or splitting droplets within a microfluidic device.
  • on-board control electrodes e.g. electrically active electrodes
  • the consumable microfluidic receptacle may omit inclusion of a printed circuit board and circuitry (e.g. active control circuitry) typically associated with digital microfluidic devices.
  • This arrangement may significantly reduce the cost of the consumable microfluidic receptacle of the microfluidic device and/or significantly ease its recyclability.
  • some example consumable microfluidic receptacles of the present disclosure omit such electrically active control electrodes (for causing electrowetting movement) and omit complex circuitry which is typically otherwise directly connected to the control electrodes via conductive traces, the example consumable microfluidic receptacle of the present disclosure is not limited by the limited space constraints typically arising from a one-to-one correspondence between control electrodes and the complex control circuitry.
  • a greater number of target positions along the passageways of the example microfluidic receptacle may be used, which may increase the precision by which microfluidic operations are performed, with a resolution (e.g. number of target positions for a given area) of such target positions corresponding to the capabilities (e.g. resolution) by which the example electrode control element can deposit charges.
  • a resolution e.g. number of target positions for a given area
  • the capabilities e.g. resolution
  • the consumable microfluidic receptacle may be used to perform microfluidic operations to implement a lateral flow assay and therefore may sometimes be referred to as a lateral flow device.
  • the consumable microfluidic receptacle also may be used for other types of devices, tests, assays which rely on or include digital microfluidic operations, such as moving, merging, splitting, etc. of droplets within internal passages within the microfluidic device.
  • FIG. 1A is a diagram 100 including a side sectional view schematically representing an example device and/or example method including releasably securing a consumable microfluidic receptacle 102 and an electrode control element 160 relative to each other, such as via application of negative pressure.
  • a microfluidic (DMF) device assembly 107 the consumable microfluidic receptacle 102 and the electrode control element 160 may be referred to as a microfluidic (DMF) device assembly 107, in some examples.
  • the consumable microfluidic receptacle may form a portion of a microfluidic device, and according sometimes may be referred to as a microfluidic device or portion thereof.
  • a support 133 may help align and/or support the consumable microfluidic receptacle 102 and/or electrode control element 160 before, during, and/or after their releasable securement.
  • a consumable microfluidic receptacle 102 may comprise a conduit or passageway 119 within, and through, which a liquid droplet 130 is to travel via electrowetting movement, as further described later in association with at least FIGS. 3A-4B.
  • the liquid droplet 130 may comprise a polar liquid droplet (e.g. conductive droplet).
  • the consumable microfluidic receptacle 102 comprises a first plate 110 (which may comprise multiple components) and a second plate 115, which together define the conduit 119.
  • the second plate 115 may comprise an anisotropic conductivity layer or portion 120.
  • second plate 115 may comprise a structure other than the illustrated anisotropic conductive layer 120 to provide preferential conductivity to facilitate migration of charges deposited via the electrode control element 160.
  • the anisotropic conductivity layer 120 shown in FIG. 1A is generally representative of a layer exhibiting preferential conductivity, such arrangements may take forms, configurations, etc. other than depicted in FIG. 1A.
  • the anisotropic conductivity 120 may be omitted from second plate 1 15 for desired purposes.
  • the second plate 115 may comprise a multi-layered structure including layers in addition to the anisotropic conductivity layer 120.
  • the second plate 115 comprises a first surface 122 (e.g. exterior surface) and an opposite second surface 121 (e.g. interior surface), while the first plate 110 comprises an interior surface 111 and an exterior surface 112.
  • the respective first and second plates 110, 115 may sometimes be referred to as a portion, sheet, and the like.
  • At least the interior surface 111 , 121 of the respective first and second plates 110, 115 may comprise a planar or substantially planar surface. It will be further understood that a passageway 119 defined between the respective first and second plates 110, 115 may comprise side walls, which are omitted for illustrative simplicity. The passageway 119 may sometimes be referred to as a conduit, cavity, and the like.
  • first and plates 110, 115 may form part of, and/or be housed within a frame, such as the frame 405 of the microfluidic device 400 shown in FIG. 4A.
  • the interior of the passageway 119 may comprise a filler such as a dielectric oil, while in some examples, the filler may comprise air.
  • the filler may comprise other liquids which are immiscible and/or which are electrically passive relative to the droplet 130 and/or relative to the respective plates 110, 115.
  • the filler may affect the pulling forces (P), may resist droplet evaporation, and/or facilitate sliding of the droplet and maintaining droplet integrity.
  • the receptacle 102 may comprise a cover 104 (e.g. lid) including side wall 105 (e.g. shell) to contain and covers at least the first plate 110, with the cover 104 secured relative to the second plate 115.
  • cover 104 e.g. lid
  • side wall 105 e.g. shell
  • the electrode control element 160 comprises a substrate 162 which may comprise an insulative material which houses circuitry (and/or conductive elements connectable to circuitry) for controlling generation and application of charges (e.g. 144A in FIG. 3A) via each of the addressable electrodes 172A, 172B, 172C, 172D of array 170.
  • the substrate 162 may comprise an array of conductors to individually control electrodes (e.g. 172A-172D) of electrode array 170, which are connected to additional circuitry which may be located remotely from the electrodes.
  • the substrate 162 may comprise a portion of control portion (e.g. 1300 in FIG.
  • the electrode control element 160 may be implemented in the form of a printed circuit board (PCB) and/or other structure, such as a molded interconnect substrate (MIS) structure.
  • the substrate 162 may sometimes be referred to as a control circuitry portion, base, and the like.
  • each respective electrode 172A-172D of electrode control element 160 comprises a central portion 174 extending between a first end portion 171 exposed at first side 163 of substrate 162 and an opposite second end portion 173 exposed at an opposite second side 165 of substrate 162.
  • the first end portion 171 of each respective electrode e.g. 172A-172D
  • the electrode control element 160 may comprise opposite edges 167A, 167B.
  • the respective electrodes 172A-172D are spaced apart from each other laterally across (and along) substrate 162 by a distance X1 , such as between the respective first end portions 171 of adjacent respective electrodes 172A, 172B, etc.
  • the spacing between adjacent electrodes 172A, 172B may sometimes be referred to as a gap 167, as shown in FIG. 1A.
  • the first end portion 171 (and second end portion 173) of the respective electrodes 172A-172D may comprise a length X2.
  • the length X2 may correspond to a length (D1 ) of a droplet 130 while the distance X1 between adjacent electrodes 172A-172D may correspond to a minimum or other target separation between adjacent locations at (and through which) droplet 130 may move within and through passageway 119.
  • the length (D1 ) of the droplet in passageway 119 may sometimes be referred as a length scale of the droplet, or a length of a target position of a droplet.
  • the spacing or distance (X1) between adjacent electrodes 172A, 172B, etc. may sometimes be referred to as the length scale of the electrodes 1053.
  • the length scale (X1) between electrodes 172A, 172B, etc. may comprise about 50 to about 75 micrometers (e.g. 2-3 mils).
  • the application of charges via second plate 115 causes an electric field E between the second plate 115 and the first plate 110, which induces electrowetting movement (e.g. pulling forces P) of droplet 130 to a new position within passageway 119 of the receptacle 102 corresponding to the location at which charges were applied.
  • a shell 180 may be connected to, and extend from, the electrode control element 160 in order to form a chamber 184 for applying negative pressure NP.
  • the shell 180 may comprise a side wall 182 having a size and shape to provide an adequate volume of space within chamber 184 for applying negative pressure NP, with the side wall 182 comprising end portions 186A, 186B to be secured relative to second side 165 of electrode control element 160.
  • each end portion 186A, 186B may comprise a sealing element 188, gasket, or similar element such as O-ring to help seal the shell 180 relative to the electrode control element 160 to provide the sealed chamber 184.
  • the side wall 182 may comprises a sealable port 190 through which negative pressure (NP) may be applied, such as via an external negative pressure source (e.g. 149 in FIG. 1 C).
  • a multitude of consumable microfluidic receptacles 102 may be stored separately from the electrode control element 160 and be available for use. Either prior to or after collecting a liquid sample (e.g. at least one liquid droplet 130) within the consumable microfluidic receptacle 102, the consumable microfluidic receptacle 102 and electrode control element 160 may be brought into close proximity to each other within a distance X3 at gap 150 at which application of negative pressure NP would be effective to help releasably secure the respective receptacle 102 and electrode control element 160 together, as shown in FIG. 1 C.
  • a liquid sample e.g. at least one liquid droplet 130
  • negative pressure NP pulls air into and through apertures 180A (extending through the substrate 162 of electrode control element 160), into chamber 184, and out through port 190.
  • This arrangement of applying negative pressure draws the second plate 115 (including anisotropic conductivity portion 120) of consumable microfluidic receptacle 102 toward and against the first side 163 of the electrode control element 160 to cause the exterior surface 122 of the second plate 115 to become releasably secured relative to the first end portion 171 of the respective, separate electrodes 172A, 172B, 172C, 172D, as shown in the diagram 225 of FIG. 1C.
  • the exterior surface 122 of the second plate 115 is in pressing releasable contact against the side 163 of the electrode control element 160, as represented by arrow 152.
  • an exterior surface 122 of the second plate 115 (including the anisotropic conductivity layer 120) is in releasable electrical connection with, and against, the end portions 171 of each respective electrode 172A, 172B, etc.
  • the application of negative pressure may continue via apertures 180A, 180B, etc., chamber 184, and port 190 in order to maintain this established electrical connection for a selectable period of time to perform desired microfluidic operations in the receptacle 102.
  • FIG. 1 B is a top plan view schematically representing a portion of the example electrode control element 160 and the general relationship, spacing, and position of the respective electrodes 172A, 172B, etc. relative to each other and relative to the apertures 180A, 180B, etc.
  • the apertures 180A are located in the gap 167 between respective end portions 171 of adjacent electrodes 172A, 172B, etc., which are spaced apart along the first side 163 (e.g. top surface) of substrate 162 of the electrode control element 160.
  • FIG. 2 is a diagram 250 including a side sectional view schematically representing an example consumable microfluidic receptacle 102.
  • the consumable microfluidic receptacle 102 may comprise at least some of substantially the same features and attributes as, and/or an example implementation of, the consumable microfluidic receptacle 102 of FIGS. 1A, 1 C.
  • at least a portion of the first plate 110 may be grounded, i.e. electrically connected to a ground element 113, which is also later shown in other FIGS, such as element 113 in FIG. 3.
  • the first plate 110 may comprise a thickness (D3 in FIGS. 1 C, 2) of about 100 micrometers to about 3 millimeters, and may comprise a plastic or polymer material.
  • the first plate 100 may comprise a glass-coated, indium tin oxide (ITO).
  • ITO indium tin oxide
  • the thickness (D3) of first plate 110 may be implemented to accommodate fluid inlets (e.g. 421 A, 423A, etc. in FIG. 4B), to house and/or integrate sensors into the first plate 110, and/or to provide structural strength.
  • the sensors may sense properties of the fluid droplets, among other information.
  • the first plate 110 of the consumable microfluidic receptacle 102 may comprise an electrically conductive layer 266, by which the first plate 110 may be electrically connected to a ground element 113.
  • the electrically conductive layer 266 may comprise a material such an indium titanium oxide (ITO) which is transparent and may have a thickness D7 on the order of a few tens of nanometers.
  • the electrically conductive layer 266 may form a portion of (or a coating on) the first plate (e.g. 110) in any one or all of the various example consumable microfluidic receptacles (of an example microfluidic device) of the present disclosure.
  • microfluidic receptacle 102 may comprise a coating 264 which also additionally comprises a portion of first plate 110.
  • second plate 115 also may additionally comprise a second coating 262, with such coatings arranged to facilitate electrowetting movement of droplets 130 through the passageway 119 defined between the respective plates 110, 115.
  • At least one of the respective coatings 264, 262 may comprise a hydrophobic coating, while in some examples, at least one of the respective coatings 264, 262 may comprise a low contact angle hysteresis coating.
  • a low contact angle hysteresis coating may correspond to contact angle hysteresis of less than about 30, 29, 28, 27, 26, 25, 24, 23, 22, 21 , or 20 degrees.
  • the contact angle hysteresis may comprise less than about 20, 19, 18, 17, 16, or 15 degrees.
  • the previously mentioned oil filler is provided within the passageways 219A-219E, which further enhances the effect of the coatings 264, 262.
  • the coating 264 and coating 262 may have respective thicknesses of D6, D8 on the order of one micrometer, but in some examples the thicknesses D6, D8 can be less than one micrometer, such as a few tens of nanometers. In some examples, the thicknesses can be greater than one micrometer, such as a few micrometers.
  • the second plate 115 may further comprise a dielectric layer 260.
  • the combination of the coating 262 and the dielectric layer 260 may correspond to a first portion 268 of the second plate 115. Further details regarding the dielectric layer 260 are further described below in association with at least FIG. 3A.
  • the receptacle 102 may further comprise adhesive layer 270 to facilitate securing an upper assembly (shell 105 and first plate 110 including layers 266, 264) relative to the second plate (e.g. anisotropic conductivity layer 120 and layers 260, 262).
  • adhesive layer 270 to facilitate securing an upper assembly (shell 105 and first plate 110 including layers 266, 264) relative to the second plate (e.g. anisotropic conductivity layer 120 and layers 260, 262).
  • the consumable microfluidic receptacle 102 may comprise spacer element(s) 274 at periodic locations or non-periodic locations between the first plate 110 and the second plate 115 to maintain the desired spacing between the respective plates 110, 115 and/or to provide structural integrity to the microfluidic receptacle 102.
  • the spacer element(s) 274 may be formed as part of forming one or both of plates 110, 115, such as via a molding process. Whether explicitly shown or not, it will be understood that such spacer element(s) 274 may form part of any of the other example microfluidic receptacles of the present disclosure.
  • the anisotropic conductivity layer 120 comprises a conductive-resistant medium 135 (e.g. partially conductive matrix) within which an array 132 of conductive elements 134 is oriented generally perpendicular to the plane (P2) through which the entire anisotropic conductivity layer 120 generally extends.
  • the conductive- resistant medium 135 e.g. matrix
  • the conductive elements 134 may comprise a conductivity at least two orders of magnitude greater than a bulk conductivity of the conductive-resistant medium 135.
  • the resistant-conductive medium 135 of the layer 120 may comprise a plastic or polymeric materials, such as but not limited to, materials such as polypropylene, Nylon, polystyrene, polycarbonate, polyurethane, epoxies, or other plastic materials which are low cost and available in a wide range of conductivities.
  • a bulk conductivity (or bulk resistivity) within the desired range noted above may be implemented via mixing into the plastic material some conductive carbon molecules, carbon black pigments, carbon fibers, or carbon black crystal.
  • the conductive-resistant medium 135 may comprise a resistivity of less than 10 9 Ohm-cm in the perpendicular direction (direction B) to the plane P2, and a larger lateral resistivity (e.g. lateral conductivity) of at least 10 11 Ohm-cm (direction C along plane P2). Accordingly, the lateral conductivity is at least two orders of magnitude less than the conductivity of the conductive-resistant medium 135 in the direction perpendicular to the plane P2. Further details regarding the anisotropic layer 120 are later described below.
  • FIG. 3A is a diagram 300 including a side sectional view schematically representing an example device and/or example method to cause electrowetting movement of a liquid droplet 130 within the consumable microfluidic receptacle 302 via application of charges from the external electrode control element 160.
  • the consumable microfluidic receptacle 302 may comprise at least some of substantially the same features and attributes as the consumable microfluidic receptacle 102 as described in association with at least FIGS. 1A-2.
  • the electrode control element 360 may comprise at least some of substantially the same features and attributes as the electrode control element 160, as described in association with at least FIGS. 1A-2, with it being understood that FIG. 3A depicts electrode control element 360 shown in dashed lines in a simplified form for illustrative simplicity and clarity to primarily demonstrate migration of charges 144A to induce electrowetting.
  • the electrode control element 360 comprises an array 370 of electrodes 372A, 372B, etc. which are like electrodes 172A, 172B etc., except depicted without showing the apertures 180A, 180B (FIGS. 1A-1 C), the example l-shaped configuration of electrodes 172A, 172B, etc.
  • FIG. 3A simply depicts a first end portion 371 (like first end portion 171 in FIGS. 1A-2) of each electrode 372A, 372B (like electrodes 172A, 172B, etc. in FIGS. 1A-2) with it being understood that each respective electrode 372A, 372B, etc. may comprise additional portions such as in the example implementations of electrode control elements in FIGS. 1A-2C, FIGS. 5A-5B, 6A-6B, 7A-7B, 8A-8B, 9A-9B.
  • the electrode control element 160 may apply charges 144A at exterior surface 122 of the second plate 115 (which corresponds to the exterior surface 122 of the anisotropic conductivity layer 120), which may then be referred to as initially deposited charges 144A.
  • the initially deposited charges 144A exhibit a first voltage V1 , which may sometimes be referred to as an applied voltage.
  • the deposited charges 144A at exterior surface 122 of second plate 115 travel through the anisotropic conductivity portion 120 to an interface 135 (between the anisotropic conductivity portion 120 and the dielectric layer 134) to be further represented as deposited charges 144B.
  • the conductive elements 134 are aligned generally parallel to each other, in a spaced apart relationship, in an orientation generally the same as the direction (arrow B) which the charges 144A at the exterior surface 122 (of second plate 115) are to travel through anisotropic conductivity portion 120 to reach the interface 135 with the dielectric layer 260 of the second plate 115.
  • conductive elements 134 are shown as being oriented perpendicular to the plane P2, it will be understood that in some examples the conductive elements 134 may be oriented at a slight angle (i.e. slanted) which not strictly perpendicular. Further details are provided below regarding the anisotropic conductivity layer 120.
  • the charges 144B Upon such migration to interface 135, the charges 144B exhibit substantially the same voltage (e.g. V1 ) at the interface 135 as the charges 144A exhibited at exterior surface 122.
  • the deposited charges 144B are located at a target position shown in dashed lines T1 , which is immediately adjacent to the droplet 130.
  • this target position may sometimes be referred to as a virtual electrode, at least to the extent that the dimensions/shape of the area over which the charges are deposited (and the applied voltage resides) may be viewed as being analogous to the dimensions/shape of an electrode pad.
  • counter negative charges 146A develop at the first plate 110 to cause an electric field (E) between the respective first and second plates 110, 160, which creates a pulling force (P) to draw the droplet 130 forward into the target position T1.
  • at least part of this arrangement includes the liquid droplet 130 being conductive (i.e. polar) in at least some examples, such that counter-charges 146B develop within the droplet 130 relative to charges 146A (at first plate 110) and countercharges 144C develop within the droplet 130 relative to charges 144B at interface 135 (between the dielectric layer 260 and the anisotropic conductivity layer 120) within the second plate 115.
  • a pulling force is created to pull the droplet 130 from the position (e.g. TO) into the target position T 1 .
  • the droplet 130 is moved from one virtual electrode to the next/adjacent virtual electrode.
  • parameters e.g. dielectric strength, thickness, etc. associated with the dielectric layer 260 help to maintain the desired charge differential (or voltage differential) which induces the desired droplet movement.
  • the pulling force (P), which causes movement of droplet 130 upon inducing the electric field (E), may comprise electrowetting forces.
  • the electrowetting forces may result from: (1 ) modification of the wetting properties of the interior surface 121 of second plate 115 and/or surface 111 of plate 110 upon application of the electric field (E); (2) counter charges introduced in the droplet 130, which may result from electrical conductivity within the droplet 130 in some examples and/or from induced dielectric polarization within the droplet 130 in some examples; and/or (3) a minimization of the electrical potential energy due to charges in the system including as an example the minimization of the energy due to the counter charges 146A (e.g. negative) and the charges 144A (144B) (e.g. positive) in the case of a non-conductive droplet.
  • the deposited charges 144B at second plate 115 may comprise between on the order of tens of volts and on the order of a few hundred volts of charges on the second plate 115. In some examples, the deposited charges 144B may comprise 1000 Volts. In some examples, the deposited charges 144B will dissipate, e.g. discharge upon electrode control element 160 applying opposite charges (e.g. negative charges) via the second plate 115, such as at interface 135. As the droplet 130 moves into the area of the charges (i.e. the target position T1 ), the electric field E drops due to an increased dielectric constant occurring in the effective capacitor which is formed between the respective first and second plates 110, 115.
  • opposite charges e.g. negative charges
  • the charges e.g. 144B
  • the charges will be significantly discharged or at least be discharged to a level at which their voltage is significantly lower than the voltage to be applied.
  • an additional deposit of charges may be used to neutralize residual charges so as to prepare the microfluidic receptacle (e.g. portion of a microfluidic device) to receive a deposit of fresh charges in preparation of causing further electrowetting movement of the droplet 130 to a next target position (e.g. T2).
  • the electrode control element 160 may be used to discharge the charges 144B at interface 135 by applying an appropriate voltage of an opposite polarity for a period of time (e.g. 0.5 to 0.6 seconds), which results in the T1 locations of interface 135 being discharged to 0 Volts (or a minimal value).
  • an appropriate voltage of an opposite polarity e.g. 0.5 to 0.6 seconds
  • the electrode control element 160 In order to move the droplet 130 from target position T1 to T2, the electrode control element 160 generates and applies fresh charges 114A via a subsequent electrode (e.g. 372C) which is aligned with the target location T2 to create a voltage differential and electric field E to cause electrowetting movement of droplet 130 from position T1 to position T2.
  • a subsequent electrode e.g. 372C
  • the second voltage V2 remains substantially stable at least during the droplet-movement time period.
  • a velocity of droplet movement may be achieved that falls within a range between about 0.5 mm/second and 200 mm/second.
  • the velocity of droplet movement may comprise between about 1 mm/second to about 30 mm/second.
  • the velocity of droplet movement may comprise between about 5 mm/second to about 20 mm/second.
  • the velocity of droplet movement may comprise at least about 10 mm/second.
  • one example droplet- movement time period may comprise between about 0.1 and about 3 seconds. In one example, the time period may comprise about 2 seconds.
  • the dielectric layer 260 may be an insulating material, comprising a resistivity of at least 10 11 Ohm-cm, and in some examples, at least 10 13 Ohm- cm.
  • the droplet 130 is generally electrically conductive and therefore droplet 130 generally sits at a voltage close to ground.
  • the droplet 130 may be considered to be conductive, having a resistivity less than 10 7 ohm-cm.
  • the applied voltage differential occurs entirely (or substantially entirely) across material within the second plate 115 which exhibits dielectric properties, such as the dielectric layer 260.
  • the dielectric layer 260 may comprise a dielectric material having a thickness of at least about 10 micrometers (e.g. 9.7, 9.8, 9.9, 10.1 , 10.2, 10.3).
  • the dielectric layer 134 may comprise a dielectric material having a thickness of at least about 20 micrometers (e.g. 19.7, 19.8, 19.9, 20.1 , 20.2, 20.3).
  • the dielectric layer 134 may comprise a dielectric material having a thickness of at least about 50 micrometers (e.g. 49.7, 49.8, 49.9, 50.1 , 50.2, 50.3).
  • the relative permittivity of the conductive-resistant medium 135 of the anisotropic layer 120 may be greater than about 20 (e.g. 19.5, 19.6, 19.7, 19.8, 19.9, 20, 20.1 , 20.2, 20.3, 20.4, 20.5). In some examples, the relative permittivity may be greater than about 25, 30, 35, 40, 45 50, 55, 60, 65, 70, or 75. In some instances, the relative permittivity may sometimes be referred to as a dielectric constant. Among other attributes, providing such relative permittivity may result in a lower voltage drop across the second plate 115. In some examples, the relative permittivity of the second plate 115 in the direction of the plane P2 may comprise lower than about 10. In some examples, it may comprise about 3.
  • the anisotropic layer 120 may comprise a low lateral conductivity (i.e. a conductivity along the plane P2, such as represented via directional arrow C) with a resistivity of at least 10 11 Ohm-cm (similar to the bulk conductivity). In some examples, this resistivity along the plane P2 (i.e. lateral conductivity) may comprise about 10 14 Ohm-cm.
  • the anisotropic conductivity layer 120 may comprise a high conductivity perpendicular (direction B) to the plane P, such as a resistivity which is on the order of, or less than, 10 9 Ohm-cm. In some examples, this resistivity may comprise 10 6 Ohm-cm. In at least some examples, the resistivity perpendicular to the plane P2 is at least about two orders of magnitude different from (e.g. lower) than the resistively along or parallel to the plane P2. In some such examples, this relatively high conductivity perpendicular to the plane P2 may sometimes be referred to as vertical conductivity with respect to the plane P2.
  • the abovenoted relatively low lateral conductivity (direction C) of the conductive resistant medium 135 may effectively force travel of the charges (applied by the electrode control element 160) to travel primarily in a direction (B) perpendicular to the plane P, such that the electric field E acting within the passageway 1 19 (i.e. conduit) may comprise an area (e.g. x-y dimensions) which are similar to the area (e.g. x-y dimensions) of each application of charges from the respective electrodes 372A, 372B of the electrode control element 160 directed to a specific target position (e.g. T1 , T2, etc.).
  • a specific target position e.g. T1 , T2, etc.
  • each respective conductive element 134 may comprise an array 347 of smaller conductive particles 348 which are aligned in an elongate pattern to approximate a linear element of the type shown as element 134 in FIGS. 2, 3A.
  • the array 347 of elements 348 (e.g. particles) may sometimes be referred to as a conductive path.
  • the conductive particles 348 may comprise metal beads with each bead ranging from 0.5 micrometers to about 5 micrometers in diameter (or a greatest cross-sectional dimension).
  • these smaller conductive particles 348 may be aligned during formation of the anisotropic layer 340 via application of a magnetic field until the materials (e.g.
  • the conductive particles, conductive-resistant medium solidify into their final form approximating the configuration shown in FIGS. 3B-3C.
  • the elongate pattern formed by array 347 of conductive particles 348 may comprise a resistivity of less than 10 9 Ohm-cm in some examples.
  • the conductive particles 348 may comprise conductive materials, such as but not limited to iron or nickel. In some examples in which the conductive particles 348 are not in contact with each other, such particles 348 may be spaced apart by a distance F1 as shown in FIG.
  • the material (e.g. polymer) forming the conductive-resistant medium 145 of the anisotropic layer 120 of the second plate 115 is interposed between the respective conductive particles 348 of the array 347 (e.g. forming the elongate pattern) defining elements 334.
  • the conductive-resistance medium 145 interposed between the conductive particles 348 may comprise a conductive bridge (between adjacent particles 348) having a length less than about a micrometer and as such, may exhibit a much smaller resistivity which is several (e.g. 2, 3, or 4) orders of magnitude less than the resistivity otherwise exhibited by the conductive-resistant medium 135. Accordingly, even when some conductive resistant medium 135 is interspersed between some of the aligned conductive particles 348, the elongate pattern (e.g.
  • the second plate 115 because of the anisotropic conductivity portion 120 arrangement of second plate 115, the second plate 115 exhibits a response time which is substantially faster than if the anisotropic conductivity portion 120 were omitted in favor of a primarily dielectric material or made of a partially conductive material without the conductive elements 134.
  • the anisotropic conductivity configuration of second plate 115 either may enable faster electrowetting movement of droplets 130 through passageway 119 due to higher electrical field on the droplet resulting in higher pulling forces and/or may permit use of thicker second plates 115, as desired (i.e. increasing the thickness of second plate 160, 360).
  • providing a relative thick/thicker second portion of the second plate 115 enables better structural strength, integrity, and/or better mechanical control of the gap between interior surface 111 of the first plate 110 and the interior surface 121 of the second plate 115.
  • the second plate 115 may comprise a thickness (D4) of about 30 micrometers to about 1000 micrometers. In some examples, the thickness (D4) may comprise about 30 micrometers to about 500 micrometers.
  • at least the anisotropic conductivity portion 120 of the second plate 115 may sometimes be referred to as a chargereceiving layer.
  • the anisotropic conductivity configuration (e.g. layer 120) forming at least a portion of second plate 115 in FIG. 3A stands in sharp contrast to at least some anisotropic conductive films (ACF) which may resemble a tape structure and involve the application of high heat and high pressure, which in turn may negatively affect the overall structure of the consumable microfluidic receptacle, such as but not limited to, any sensitive sensor elements or circuitry within the first plate 110.
  • at least some anisotropic conductive films (ACF) may be relatively thin and/or flexible such that they are unsuitable to stand alone as a bottom plate of a microfluidic device because they may lack sufficient structural strength and durability.
  • both of the electrode control element 160 and the microfluidic receptacle 102 are stationary during microfluidic operations, with the electrode control element 160 being arranged in a two-dimensional array (e.g. FIG. 1 B) to deposit charges in any desired target area of the microfluidic receptacle 102 in order to perform a particular microfluidic operation or sequence of microfluidic operations.
  • a two-dimensional array may comprise at least some of the substantially the same features and attributes as described in association with at least FIGS. 4B.
  • FIG. 4A is a diagram including a top plan view schematically representing an example consumable microfluidic device 400.
  • the microfluidic device 400 comprises at least some of substantially the same features and attributes as, and/or an example implementation including, the consumable microfluidic receptacle 102, 302 in FIGS. 1A-3C.
  • the microfluidic receptacle 102, 302 in FIGS. 1A-3C may comprise at least a portion of the example microfluidic device 400 in FIGS. 4A- 4B.
  • the microfluidic device 400 comprises a housing or frame 405 within which is formed an array 414 of interconnected passageways 419A, 419B, 419C, 419D, 419E, with each respective passageway being defined by a series of target positions 417.
  • the respective passageways 419A-419E are defined between a first plate (like first plate 110 in FIGS. 1A-3C) and a second plate (like second plate 115 in FIGS. 1A-3C), with each target position 417 corresponding to a target position (e.g. T1 or T2) shown in FIGS. 1A-3C at which a droplet (e.g. 130 in FIGS. 1A-3A) may be positioned.
  • a target position e.g. T1 or T2
  • a droplet e.g. 130 in FIGS. 1A-3A
  • each target position 417 may comprise a length of about 50 micrometers to about 5000 micrometers (i.e. 5 millimeters), while in some examples the length may be about 100 micrometers to about 2500 micrometers. In some examples, the length may be about 250 micrometers to about 1500 micrometers. In some examples, the length may be about 1000 micrometers. Meanwhile, in some examples, each target position 417 (and hence each electrode) may have a width commensurate with the length, such as the above-noted examples.
  • the respective target positions 417 and the passageways 419A-419E do not include control electrodes for moving droplets 130. Rather, droplets 130 are moved through the various passageways 419A, 419B, 419C, 419D, 419E via electrowetting pulling forces caused by applying charges from the individually controllable electrodes 172A-172D (or 372A, 372B, 372C, 372D in FIG. 3A) of releasable contact, electrode control element 160, as previously described in association with FIGS. 1A-3C.
  • the droplet(s) 130 move through the passageways via pulling forces (e.g. electrowetting forces) without any on-board control electrodes lining the paths defined by the various passageways 419A-419E.
  • pulling forces e.g. electrowetting forces
  • At least some of the respective target positions 417 may comprise an inlet portion which can receive a droplet 130 to begin entry into the passageways 419A-419E to be subject to microfluidic operations such as moving, merging, splitting, etc.
  • some of the example positions 421 A, 421 B, 423A, 423B may comprise an outlet portion, from which fluid may be retrieved after certain microfluidic operations.
  • the consumable microfluidic receptacle 400 of FIG. 4A may comprises features and attributes in addition to those described in association with FIGS. 1A-1 C.
  • the consumable microfluidic device 400 may comprise at least one fluid reservoir R at which various fluids (e.g. reagents, binders, etc.) may be stored and which may be released into at least one of the passageways 419A-419E.
  • release of such reagents or other materials may be caused by the same externally-caused pulling forces as previously described to movement droplet 130.
  • the passageways 419A-419E may form or define a lateral assay flow device in which some reagents, etc. may already be present at various target positions 417 within a particular passageway (e.g. 419A-419E) such that upon movement of various droplets 130 relative to such target positions 417 may result in desired reactions to effect a lateral flow assay.
  • the consumable microfluidic receptacle 400 does not store any liquids on board, and any liquids on which microfluidic operations are to be performed are added, such as in the example inlet locations 421 A, 421 B, 423A, 423B, as previously described.
  • a portion of the consumable microfluidic receptacle 400 may comprise at least one sensor (represented by indicator S in FIG. 4A) to facilitate tracking the status and/or position of droplets within a consumable microfluidic receptacle, as well as for determining a chemical or biochemical result ensuing from the various microfluidic operations, such as merging, splitting, etc.
  • sensors may be incorporated into the first plate 110 (FIGS.
  • the senor(s) may include external sensors, like optical sensors. In some such examples, such external sensors may be used to sense attributes of a fluid retrieved from an above-described outlet portion.
  • microfluidic operations to be performed via the consumable microfluidic receptacle 400 and an addressable electrode control element may be implemented in association with a control portion, such as but not limited to control portion 1300 in FIG. 10B and/or in association with an operations engine 1200 in FIG. 10A.
  • each target position (e.g. T1 , T2, etc.) may comprise a length (X2) which may comprise a length expected to be approximately the same size (e.g. length D2) as the droplet 130 to be moved.
  • the length (X2) of each target position (e.g. T1 , T2, etc.) may comprise between about 50 micrometers to about 5 millimeters, and may comprise a width similar to its length in some examples.
  • the target position also may sometimes be referred to as a droplet position.
  • each of the respective droplet positions also may sometimes be referred to as corresponding to the position, size, and/or shape of the below- described virtual electrodes (i.e. location where charges 144B are deposited to induce electrowetting movement) of the second plate or actual electrodes of the second plate 115.
  • the length (D1 ) of the droplet in passageway 119 may sometimes be referred as a length scale of the droplet (or target position of a droplet).
  • the target positions e.g. T1 , T2
  • the target positions may be immediately adjacent each other with virtually no spacing therebetween. Accordingly, at least some examples of the present disclosure do not face at least some of the challenges in moving droplets that may otherwise be posed by a distance between adjacent electrodes in such devices employing active control electrodes.
  • the example arrangements of the present disclosure to cause electrowetting movement of droplets stand in sharp contrast to some microfluidic devices which rely on dielectrophoresis to produce movement of particles.
  • At least some such dielectrophoretic devices comprise a distance between control electrodes (of a printed circuit board which form one of the microfluidic plates) which is substantially greater (e.g. 10 times, 100 times, etc. ) than a length scale (e.g. size) of a particle within a liquid to be moved.
  • the distance between control electrodes (in some dielectrophoretic devices) may be on the order of hundreds (i.e. 100’s) of micrometers, whereas the length scale of such particles may comprise on the order of hundreds (i.e. 100’s) nanometers.
  • the distance between electrodes in a dielectrophoretic device may sometimes be referred to as a length scale of such electrodes or as a length scale of the gradient (i.e. gradient length scale).
  • a droplet of liquid to be moved via electrowetting forces in at least some examples of the present disclosure may comprise a thickness between a first plate 110 and second plate 115 of about 200 micrometers, and a length (or width) extending across a target position (e.g. T1 , T2) (i.e. droplet position) of about 2 millimeters, in some examples.
  • a target position e.g. T1 , T2
  • dielectrophoresis may cause movement of a particle within a mass of fluid, where such particle may be about 100 nanometers diameter (or length, width, or the like) and many particles may reside within a droplet of liquid.
  • the dielectrophoretic device does not generally cause movement of an entire fluid mass.
  • FIG. 4B is a diagram including an isometric view schematically representing an example two-dimensional array of individually controllable electrodes, prior to releasable contact relative to, a portion of a consumable microfluidic receptacle.
  • an example arrangement 451 comprises a two-dimensional addressable electrode control element 460 in charging relation to a second plate 415 of a consumable microfluidic receptacle (e.g. 102 in FIGS. 1A, 1 C).
  • the addressable electrode control element 460 may comprise one example implementation of, and/or may comprise at least some of substantially the same features and attributes as, the addressable electrode control elements described in association with at least FIGS. 1A-3C and/or FIGS.
  • the second plate 415 (and associated consumable microfluidic receptacle) may comprise one example implementation of, and/or may comprise at least some of substantially the same features and attributes as, the second plate 115 (and associated consumable microfluidic receptacle 102) described in association with at least FIGS. 1A-3C and/or FIGS. 5A-9B.
  • the example addressable electrode control element 460 comprises a two dimensional array 471 of individually controllable (e.g. addressable) electrodes 472.
  • the array 471 comprises a size and a shape to cause controlled movement of droplets 130 to any one target position (e.g. 417 in FIG. 4A) of a corresponding array 458 of target droplet positions (e.g. 417 in FIG. 4A) implemented via the second plate 415 (of a consumable microfluidic receptacle).
  • at least some of the respective example addressable electrodes 472 of control element 460 may correspond to the example electrodes 172A-172D shown in FIGS. 1A-2 (also 372A-372D in FIGS.
  • any one of the addressable electrodes 472 in FIG. 4B also may be operated in a charge neutralizing mode in which charges are emitted having a polarity (e.g. negative) opposite the polarity of the charges (e.g. positive) used to initiate an electrowetting movement of the liquid droplet 130.
  • both the second plate 415 of the consumable microfluidic receptacle (e.g. 102) and the addressable electrode control element 460 remain stationary while the various respective electrodes 472 (of array 471 ) may be selectively operated (e.g. individually controlled) to control droplet movement for any or all of the target positions (e.g. 417 in FIG. 4A) of the second plate 415 (e.g. 115 in FIGS. 1A- 3C) of the consumable microfluidic receptacle.
  • FIG. 5A is a diagram 500 including a side sectional view schematically representing an example electrode control element 560 including electrodes 572A-572D.
  • the electrode control element 560 may comprise at least some of substantially the same features and attributes as the electrode control element 160, 360 of FIGS. 1A-4B, except with electrode control element 560 comprising apertures 580A extending through a central portion 574 of electrodes 572A-572D instead of extending through substrate 162 independent of electrodes 172A-172D as in FIGS. 1A-3C.
  • electrode control element 560 of FIG. 5A-5B would interact in least some of substantially the same ways with the consumable microfluidic receptacle 102, 302 as previously described in the examples of FIGS. 1A-4B.
  • an anisotropic conductivity portion 120 of consumable microfluidic receptacle e.g. 102 in FIGS. 1A-2; 302 in FIG. 3A
  • a negative pressure NP e.g. via port 190 of chamber 184 in FIG. 1 C
  • an anisotropic conductivity portion 120 of consumable microfluidic receptacle e.g. 102 in FIGS. 1A-2; 302 in FIG. 3A
  • FIG. 5B is a diagram including a top plan view schematically representing the example electrode control element 560 which was illustrated in the side sectional view of FIG. 5A.
  • the array 570 of electrodes 572A-572D (and other electrodes) is exposed on, and supported by, a first side 163 (e.g. top side) of the electrode control element 560 to be arranged in a grid (e.g. 2 x 4, 3 x4, 4 x 4, etc.) in which the respective electrodes are spaced apart (by gap 167) from each other by the distance X1 (e.g. FIGS. 1 A-1 B) and with the electrodes having a length X2.
  • a grid e.g. 2 x 4, 3 x4, 4 x 4, etc.
  • the example arrangement in FIGS. 5A-5B may simplify manufacture and/or assembly of the electrode control element 560, at least to the extent that it may be convenient to locate and form the apertures (e.g. 580A) as part of via defined by the central portion 574 of each electrode (e.g. 572A, 572B, etc.) which already extends between the first and second sides 163, 165 of the electrode control element 560.
  • the apertures e.g. 580A
  • each electrode e.g. 572A, 572B, etc.
  • the electrode control element 560 may comprise control circuitry portion 569, which may be electrically connected to at least electrodes 572A, 572B, etc. in order to implement the generation and application of charges via the respective electrodes 572A, 572B, etc. in accordance with the examples of the present disclosure.
  • the control circuitry 569 may comprise at least some of substantially the same features as, and/or be an example implementation of, the control portion 1300 described in association with at least FIGS. 10A-10C. While not shown explicitly in the other FIGS, it will be understood that the control circuitry portion 569 may be implemented with, and/or as part of, the electrode control elements in the other examples of the present disclosure.
  • FIG. 6A is a diagram 600 including a side sectional view schematically representing an example electrode control element 660.
  • the electrode control element 660 may comprise at least some of substantially the same features and attributes as the electrode control element 160, 360 of FIGS. 1A-4B, except with electrode control element 660 comprising apertures 680A-680D extending through a lateral end portions 671 B of electrodes 672A-672D (respectively) of at least first side 163 of substrate 162 of electrode control element 660, as shown in FIG. 6A.
  • This arrangement stands in contrast to the example implementation in FIGS.
  • FIG. 6A-6B in which apertures 180A extend through control circuity portion 162 (between sides 163, 165) in a manner which is independent of electrodes 172A-172D as in shown in FIGS. 1A-2.
  • the electrode control element 660 of FIG. 6A-6B would interact in at least some of substantially the same ways with the consumable microfluidic receptacle 102, 302 as previously described in the examples of FIGS. 1A-4B with regard to releasably securing the receptacle 102 and electrode control element 660 relative to each other via application of negative pressure (NP).
  • NP negative pressure
  • one end portion of an electrode (e.g. 672A) at first side 163 of control circuitry portion 660 may comprise a central end portion 671 A flanked by a pair of lateral end portions 671 B on opposite sides of the central end portion 671 A, with an aperture 680A extending through each respective lateral end portion 671 B.
  • another opposite end portion of an electrode e.g.
  • control circuitry portion 660 may comprise a central end portion 673A flanked by a pair of lateral end portions 673B on opposite sides of the central end portion 673A, with the same previously mentioned apertures 680A extending through each respective lateral end portion 673B.
  • the electrode control element 660 comprises a similar arrangement of a central end portion (e.g. 671 A, 673A) and lateral end portions (e.g. 671 B, 673B) for electrode 672B with respective apertures 680B, for electrode 672C with respective apertures 680C, and for electrode 672D with respective apertures 680D.
  • a central end portion e.g. 671 A, 673A
  • lateral end portions e.g. 671 B, 673B
  • electrode 672B with respective apertures 680B
  • electrode 672C with respective apertures 680C
  • electrode 672D with respective apertures 680D.
  • each respective electrode e.g. 672A, 672B, etc.
  • each respective electrode may comprise a solid or filled electronic via extending between the opposite first and second sides 163, 165 of the substrate 162 of the electrode control element 660.
  • such example arrangements may help provide an overall pattern of negative pressure which is generally more uniform across and along the anisotropic conductivity portion (e.g. 120) of the consumable microfluidic receptacle (e.g. 102 in FIG. 1A).
  • FIG. 6B is a diagram including a top plan view schematically representing the example electrode control element 660 of FIG. 6A, which was illustrated in the side sectional view of FIG. 6A.
  • the array 670 of electrodes 672A-672D (and other electrodes) is exposed on, and supported by, a first side 163 (e.g. top side) of the substrate 162 of electrode control element 660 to be arranged in a grid (e.g. 2 x 4, 3 x4, 4 x 4, etc.) in which the respective electrodes are spaced apart from each other by the distance X1 (e.g. FIGS. 1A-1 B) and with the electrodes having a length X2.
  • FIG. 1 e.g. FIGS. 1A-1 B
  • FIG. 6B also further illustrates a relationship of the central end portion 671 A and lateral end portions 671 B relative to apertures 680A and relative to each other.
  • a given electrode e.g. 672A
  • FIG. 7A is a diagram 700 including a side sectional view schematically representing an example electrode control element 760.
  • the electrode control element 760 may comprise at least some of substantially the same features and attributes as the electrode control element 560 of FIGS. 5A-5B (including example electrodes 572A-572D), except with electrode control element 760 comprising protrusions 777 located on the end portions 571 of the respective electrodes (e.g. 772A, 772B, etc.) .
  • the electrodes 772A-772D for electrode control element 760 in other respects the electrode control element 760 of FIG.
  • the protrusions 777 may be spaced apart from each other to form a recess 778 between adjacent protrusions 777 with a surface 579 of end portion 571 (of electrode 572A) defining a bottom of the recess 778, as shown for example electrode 572A. While not labeled in FIGS. 7A-7B for illustrative simplicity, it will be understood that the other electrodes 772B, 772C, 772D, etc. may comprise the same type of example arrangement including surface 579, recess 778, etc. In FIG. 7A, a particular number of protrusions 777 is depicted and as having a particular shape (e.g. rectangular) and/or spacing relative to each other. However, it will be understood that the protrusions 777 may comprise a wide variety of sizes and shapes, and may be implemented in a greater quantity or lesser quantity than shown in FIG.7A.
  • this example arrangement may provide for establishing more robust electrical connection between the electrode control element 760 and the anisotropic conductivity layer 120 of the consumable microfluidic receptacle 102, 302 (FIGS. 1A-4B).
  • dust or other debris may be encountered before or during intended contact between the consumable microfluidic receptacle 102, 302 and the electrode control element 760.
  • some sliding or other maneuvering may occur.
  • any dust or debris may fall into the recesses 778 between protrusions 777, which facilitates that the contact surface provided via the protrusions 777 may be free or relatively free from dust or debris and thereby able to form robust, direct electrical contact against the surface 122 of the anisotropic conductivity layer 120 of receptacle 102, 302.
  • FIG. 7B is a diagram including a top plan view schematically representing example electrode control element 760, which was illustrated in the side sectional view of FIG. 7A.
  • the array 770 of electrodes e.g. 772A, 772B, 772C, 772D, etc.
  • a first side 163 e.g. top side
  • the electrode control element 760 is arranged in a grid (e.g. 2 x 4, 3 x4, 4 x 4, etc.) in which the respective electrodes are spaced apart from each other by the distance X1 (e.g. FIGS. 1A-1 B) and with the electrodes having a length X2.
  • FIG. 7B also further illustrates a relationship of the protrusions 777, which at least partially define the recesses 778 for capturing dust, debris, etc..
  • a given electrode e.g. 772A
  • FIG. 8A is a diagram 800 including a side sectional view schematically representing an example electrode control element 860.
  • the electrode control element 860 may comprise at least some of substantially the same features and attributes as the electrode control element 760 of FIGS. 7A-7B, except with the electrode control element 860 comprising electrically conductive compliant members 812A, 812B, 812C, 812D, etc. (instead of protrusions 777 in FIGS. 7A-7B) for establishing robust electrical contact.
  • the electrically conductive compliant elements e.g.
  • the electrode control element 860 of FIG. 8A-8B would interact in at least some of substantially the same ways with the consumable microfluidic receptacle 102, 302 as previously described in the examples of FIGS. 1A-4B with regard to releasably securing the receptacle 102, 302 and electrode control element 860 relative to each other via application of negative pressure (NP).
  • NP negative pressure
  • the electrically conductive compliant elements (e.g. 812A, 812B, etc.) in FIG. 8A may enhance establishing robust electrical contact despite the presence of any dust, debris, particles, etc. in, around, near the electrode control element 860 and/or anisotropic conductivity layer 120 (FIG. 1A-4B).
  • the electrically conductive compliant elements (e.g. 812A, etc.) may comprise a compliant (e.g. resilient) foam material such as, but not limited to, a polyurethane foam sheet.
  • the electrically conductive compliant elements (e.g. 812A, etc.) may withstand multiple loadings while maintaining their resilience, which is suitable for a high number of iterations of releasably securing the electrode control element 860 to relative to different consumable microfluidic receptacles.
  • the electrically conductive compliant elements 812A, 812B, etc. are mounted on a consumable microfluidic receptacle 102, 302 as shown in FIG. 8B (such as by adhesive) instead of being mounted on the electrode control element 860 as in the example implementation of FIG. 8A.
  • the spacing between the respective compliant members 812A, etc. corresponds to a position and spacing of the end portions 571 of the respective electrodes 572A, 572B, etc. of the electrode control element 560 in FIG. 5A.
  • a spacing of X1 exists between some compliant members, such as between one of the compliant members 812A and 812B with spacing X1 corresponding to the spacing between the end portions 571 of adjacent electrodes (e.g. 812A, 812B).
  • an end portion 571 may comprise a length X2, as previously described in association with at least FIGS. 1A-2.
  • a spacing X4 exists between adjacent compliant members 812A, 812B, with spacing X4 corresponding to a diameter of the aperture (e.g. 580A) formed in the central portion of the respective electrode (e.g. 572). Via these spacings (X1 , X2, X4) for the respective compliant members (e.g.
  • the compliant members e.g. 812A, 812B
  • the compliant members are sized and spaced to become aligned with correspondingly sized, shaped, and positioned end portions 571 , apertures 580A, etc. of the respective electrodes 572A, 572B of an electrode control element (e.g. 160 in FIGS. 1A-2).
  • FIG. 9A is a diagram 900 including a side sectional view schematically representing an example device 901 and/or example method at a moment in time just prior to releasably securing, via application of negative pressure, a consumable microfluidic receptacle 902 and an electrode control element 960 relative to each other.
  • FIG. 9B is a diagram including a top plan view schematically representing the example negative pressure arrangement of the consumable microfluidic receptacle 902 in FIG. 9A.
  • FIG. 9C depicts a moment in time during which the respective consumable microfluidic receptacle 902 and electrode control element 960 have been releasably secured relative to each other via the application of negative pressure according to examples of the present disclosure.
  • the electrode control element 960 may comprise at least some of substantially the same features and attributes as the example electrode control element 160, 360 as previously described in association with at least FIGS 1 A-4B, except for omitting apertures 180A, 180B, 180C and further comprising springs 969A, 969B, which are further described below.
  • the consumable microfluidic receptacle 902 may comprise at least some of substantially the same features as the example consumable microfluidic receptacle 102, 302 as previously described in association with at least FIGS. 1A-4B, except further comprising a negative pressure arrangement 940 as further described below in association with FIGS. 9A-9B.
  • the negative pressure arrangement 940 of consumable microfluidic receptacle 902 comprises port 957, chamber 956, and a network 952 of channels 954, all of which are in fluid communication with each other for applying negative pressure.
  • the consumable microfluidic receptacle 902 comprises an anisotropic conductivity portion 920, which comprises at least some of substantially the same features and attributes as anisotropic conductivity portion 120 (FIGS. 1A- 4B), except further comprising the network 952 of channels 954 being formed (e.g. molded) in a first surface 922 of the anisotropic conductivity portion 920.
  • the port 957 and the chamber 956 are located lateral to the anisotropic conductivity portion 120 and therefore lateral to the network 952 of channels 954.
  • the respective channels 954 of network 952 are spaced apart and positioned relative to each other to generally correspond to a spacing between and relative position of the gaps 167 (between adjacent electrodes 172A, 172B, etc.) of the electrode control element 960.
  • each channel 954 of network 952 comprises a width (W1 in FIG. 9B) generally corresponding to the gap 167 (e.g. distance X1 ) between adjacent electrodes 172A, 172B, etc.
  • the width (W1) may be less than gap 167 or greater than the gap 167.
  • a distance (W2 in FIG. 9B) between adjacent channels 954 may correspond to a length (X2) of the respective electrodes 172A, etc.
  • the respective channels 954 may comprise any one of a wide variety of cross-sectional shapes and are not limited to the particular cross- sectional shape depicted in FIG. 9A.
  • the pattern of “negative pressure” channels 954 within the anisotropic conductivity layer 920 to generally correspond to the pattern of gaps 167 between adjacent electrodes 172A, 172B, etc.
  • the remaining portions 955 (FIG. 9B) of the anisotropic conductivity layer 920 remain unmodified to maximize their effectiveness in receiving and transferring charges from the surface of the end portions 171 of the electrodes 172A, 172B as each respective electrode 172A, 172B, etc. is selectively activated to cause electrowetting movement of the liquid droplet 130 within, and through, passageway 119 of the consumable microfluidic receptacle 902A.
  • the shell 104 includes a wall portion 958 which at least partially defines chamber 956 with the wall portion 958 extending between the port 957 and the main portion 955 of the shell 104.
  • the shell 104 defining the consumable microfluidic receptacle 902A comprises contact portions 987A, 987B on opposite sides of the receptacle 902, with each contact portion 987A, 987B comprising a sealing element 988, such as a gasket, O-ring, or the like.
  • springs 969A, 969B are mounted on a second side 165 (e.g. bottom side) of the substrate 162 of the electrode control element 960, such as, adjacent opposite ends 967A, 967B of the electrode control element 960.
  • each spring 969A, 969B is positioned in alignment with an expected application of downward force F on the contact portions 987A, 987B as shown in FIGS. 9A, 9C.
  • the consumable microfluidic receptacle 902 and the electrode control element 960 are aligned relative to each other, as previously described such that the channels 954 of the network 952 become aligned with the gaps 167 between adjacent electrodes 172A,, 172B, as shown in FIG. 9A.
  • a support e.g. 133 in FIG. 1A
  • the force F is applied to move the consumable microfluidic receptacle 902 toward the electrode control element 960 to establish releasable contact therebetween as shown in FIG. 9C.
  • the springs 969A, 969B associated with electrode control element 960 provide resistance or counter pressure against the force F (applied via contact portions 987A, 987B of receptacle 902) to enhance the sealing created at sealing elements 988 between the contact portions 987A, 987B (of the shell 104/105 of the consumable microfluidic receptacle 902) and the first side 163 (e.g. top surface) of the electrode contact element 960.
  • negative pressure may be applied at port 957, which draws negative pressure (e.g. suction) via and through chamber 956, which draws negative pressure through the network 952 of channels 954.
  • negative pressure draws the anisotropic conductivity layer 920 (of the consumable microfluidic receptacle 902) and the side 163 of the electrode control element 960 toward each other until releasable contact is achieved and maintained between the anisotropic conductivity layer 920 and the electrode control element 960.
  • the releasable securing of the receptacle 902 and the electrode control element 960 relative to each other is not achieved solely via the application of negative pressure NP. Rather, in some examples, the application of force F through (and at) contact portions 987A, 987B (of the consumable microfluidic receptacle 902A) and/or the springs 969A, 969B (associated with the electrode control element 960A) may cause, at least partially, some degree of releasable coupling between the consumable microfluidic receptacle 902A and the electrode control element 906A.
  • FIG. 10A is a block diagram schematically representing an example fluid operations engine 1200.
  • the operations engine 1200 may form part of a control portion 1300, as later described in association with at least FIG. 10B, such as but not limited to comprising at least part of the instructions 1311.
  • the operations engine 1200 may be used to implement at least some of the various example devices and/or example methods of the present disclosure as previously described in association with FIGS. 1 -9C and/or as later described in association with FIGS. 10B-11.
  • the operations engine 1200 (FIG. 10A) and/or control portion 1300 FIG.
  • an electrode control element e.g. 160, 360, etc.
  • a consumable microfluidic receptacle e.g. 102, 302, etc.
  • the operations engine 1200 may comprise a moving function 1202, a merging function 1204, and/or a splitting function 1206, which may track and/or control manipulation of droplets within a microfluidic device, such as moving, merging, and/or splitting, respectively.
  • the operations engine 1200 may comprise an electrode control engine 1220 to track and/or control parameters associated with operation of an addressable electrode array (including individually controllable electrodes) to build charges or neutralize charges on a consumable microfluidic receptacle (of a microfluidic device), as well as to track and/or control the polarity of such charges.
  • an alignment parameter (1232) is track and/or control alignment (e.g. via positioning) of an addressable electrode array to establish releasable contact against a consumable microfluidic receptacle to implement such building or neutralizing of charges.
  • the alignment parameter 1232 may be implemented with support 133 as previously described in association with at least FIGS. 1 A-1 C.
  • the operations engine 1200 may comprise a negative pressure parameter 1234 to control a timing, intensity, initiation, termination, etc. of applying negative pressure via the example arrangements to releasably secure a consumable microfluidic receptacle and an electrode control element relative to each other.
  • the intensity (e.g. amplitude) of applying negative pressure may comprise about 90 percent of ambient atmospheric pressure.
  • FIG. 10B is a block diagram schematically representing an example control portion 1300.
  • control portion 1300 provides one example implementation of a control portion forming a part of, implementing, and/or generally managing the example microfluidic arrangements, addressable electrode control elements, apertures, chambers, negative pressure sources, consumable microfluidic receptacles, microfluidic operations, control portion, instructions, engines, functions, parameters, and/or methods, as described throughout examples of the present disclosure in association with FIGS. 1A-10A and 10C-11.
  • control portion 1300 includes a controller 1302 and a memory 1310.
  • controller 1302 of control portion 1300 comprises at least one processor 1304 and associated memories.
  • the controller 1302 is electrically couplable to, and in communication with, memory 1310 to generate control signals to direct operation of at least some of the example microfluidic arrangements, addressable electrode control elements, apertures, chambers, negative pressure sources, consumable microfluidic receptacles, microfluidic operations, control portion, instructions, engines, functions, parameters, and/or methods, as described throughout examples of the present disclosure.
  • these generated control signals include, but are not limited to, employing instructions 1311 stored in memory 1310 to at least direct and manage microfluidic operations in the manner described in at least some examples of the present disclosure.
  • the controller 1302 or control portion 1300 may sometimes be referred to as being programmed to perform the above-identified actions, functions, etc.
  • controller 1302 In response to or based upon commands received via a user interface (e.g. user interface 1320 in FIG. 10C) and/or via machine readable instructions, controller 1302 generates control signals as described above in accordance with at least some of the examples of the present disclosure.
  • controller 1302 is embodied in a general purpose computing device while in some examples, controller 1302 is incorporated into or associated with at least some of the example microfluidic arrangements, addressable electrode control elements, consumable microfluidic receptacles, apertures, chambers, negative pressure sources, microfluidic operations, control portion, instructions, engines, functions, parameters, and/or methods, etc. as described throughout examples of the present disclosure.
  • processor shall mean a presently developed or future developed processor (or processing resources) that executes machine readable instructions contained in a memory or that includes circuitry to perform computations.
  • execution of the machine readable instructions such as those provided via memory 1310 of control portion 1300 cause the processor to perform the above-identified actions, such as operating controller 1302 to implement microfluidic operations, apply negative pressure for releasable securement, etc. via the various example implementations as generally described in (or consistent with) at least some examples of the present disclosure.
  • the machine readable instructions may be loaded in a random access memory (RAM) for execution by the processor from their stored location in a read only memory (ROM), a mass storage device, or some other persistent storage (e.g., non-transitory tangible medium or non-volatile tangible medium), as represented by memory 1310.
  • the machine readable instructions may include a sequence of instructions, a processor-executable machine learning model, or the like.
  • memory 1310 comprises a computer readable tangible medium providing non-volatile storage of the machine readable instructions executable by a process of controller 1302.
  • the computer readable tangible medium may sometimes be referred to as, and/or comprise at least a portion of, a computer program product.
  • controller 1302 may be embodied as part of at least one application-specific integrated circuit (ASIC), at least one field- programmable gate array (FPGA), and/or the like. In at least some examples, the controller 1302 is not limited to any specific combination of hardware circuitry and machine readable instructions, nor limited to any particular source for the machine readable instructions executed by the controller 1302.
  • ASIC application-specific integrated circuit
  • FPGA field- programmable gate array
  • control portion 1300 may be entirely implemented within or by a stand-alone device.
  • control portion 1300 may be partially implemented in one of the example microfluidic arrangements (e.g. addressable electrode control element and/or consumable microfluidic receptacle) and partially implemented in a computing resource separate from, and independent of, the example microfluidic arrangements (e.g. addressable electrode control element and/or consumable microfluidic receptacle) but in communication with the example microfluidic arrangements.
  • control portion 1300 may be implemented via a server accessible via the cloud and/or other network pathways.
  • the control portion 1300 may be distributed or apportioned among multiple devices or resources such as among a server, an example microfluidic arrangement, and/or a user interface.
  • control portion 1300 includes, and/or is in communication with, a user interface 1320 as shown in FIG. 10C.
  • user interface 1320 comprises a user interface or other display that provides for the simultaneous display, activation, and/or operation of at least some of the example microfluidic arrangements, addressable electrode control elements, apertures, chambers, negative pressure sources, consumable microfluidic receptacles, microfluidic operations, control portion, instructions, engines, functions, parameters, and/or methods, etc., as described in association with FIGS. 1A-10B and 11.
  • GUI graphical user interface
  • FIG. 11 is a flow diagram of an example method 1400.
  • method 1400 may be performed via at least some of the example microfluidic arrangements, addressable electrode control elements, apertures, chamber, negative pressure sources, consumable microfluidic receptacles, microfluidic operations, instructions, control portions, engines, functions, parameters, and/or methods, etc. as previously described in association with at least FIGS. 1A-7C.
  • method 1400 may be performed via at least some example microfluidic arrangements, addressable electrode control elements, apertures, chamber, negative pressure sources, consumable microfluidic receptacles, microfluidic operations, instructions, control portions, engines, functions, parameters, and/or methods, etc. other than those previously described in association with at least FIGS. 1 A-10C.
  • method 1400 comprises aligning an array of individually controllable electrodes of a substrate of an electrode control element to apply charges from the respective electrodes to an anisotropic conductivity portion of a consumable microfluidic receptacle to induce electrowetting movement of a liquid droplet within a conduit of the receptacle.
  • aligning an array of individually controllable electrodes of a substrate of an electrode control element to apply charges from the respective electrodes to an anisotropic conductivity portion of a consumable microfluidic receptacle to induce electrowetting movement of a liquid droplet within a conduit of the receptacle.
  • method 1400 comprises applying negative pressure through a plurality of apertures within at least one of the anisotropic conductivity portion and the substrate and through a chamber, in communication with the apertures, sealingly fixable to at least one of the receptacle and the substrate, to releasably secure the array of electrodes and the anisotropic conductivity portion relative to each other.

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Abstract

Un ensemble microfluidique numérique comprend un élément de commande d'électrode, l'élément comprenant un réseau d'électrodes pouvant être commandées individuellement et portées sur un premier côté d'un substrat, une chambre étanche par rapport à un second côté opposé du substrat et une pluralité d'ouvertures. Les ouvertures s'étendent à travers le substrat et entre les premier et second côtés respectifs dudit substrat, et en communication avec la chambre. Un support est destiné à aligner un réceptacle microfluidique consommable avec le réseau d'électrodes afin de recevoir des charges sur une partie à conductivité anisotrope du réceptacle, en vue de provoquer un mouvement d'électromouillage d'une gouttelette de liquide à l'intérieur du réceptacle microfluidique. Lors de l'application d'une pression négative à travers la chambre et les ouvertures, le réseau d'électrodes est fixé amovible contre le réceptacle microfluidique.
PCT/US2021/046557 2021-08-18 2021-08-18 Fixation amovible de réceptacle microfluidique consommable à l'aide de pression négative Ceased WO2023022714A1 (fr)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20130116128A1 (en) * 2011-11-07 2013-05-09 Illumina, Inc. Integrated sequencing apparatuses and methods of use
WO2015138648A1 (fr) * 2014-03-11 2015-09-17 Illumina, Inc. Cartouche microfluidique intégrée jetable, et procédés pour la fabriquer et l'utiliser
EP2102650B1 (fr) * 2006-11-24 2021-05-19 Agency for Science, Technology and Research Appareil pour traiter un échantillon dans une gouttelette de liquide

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2102650B1 (fr) * 2006-11-24 2021-05-19 Agency for Science, Technology and Research Appareil pour traiter un échantillon dans une gouttelette de liquide
US20130116128A1 (en) * 2011-11-07 2013-05-09 Illumina, Inc. Integrated sequencing apparatuses and methods of use
WO2015138648A1 (fr) * 2014-03-11 2015-09-17 Illumina, Inc. Cartouche microfluidique intégrée jetable, et procédés pour la fabriquer et l'utiliser

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