EP1773497B1 - Vorrichtung zur bewegung und behandlung von flüssigkeitsvolumina - Google Patents

Vorrichtung zur bewegung und behandlung von flüssigkeitsvolumina Download PDF

Info

Publication number
EP1773497B1
EP1773497B1 EP20050782022 EP05782022A EP1773497B1 EP 1773497 B1 EP1773497 B1 EP 1773497B1 EP 20050782022 EP20050782022 EP 20050782022 EP 05782022 A EP05782022 A EP 05782022A EP 1773497 B1 EP1773497 B1 EP 1773497B1
Authority
EP
European Patent Office
Prior art keywords
drop
conducting means
substrate
catenary
buried
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.)
Not-in-force
Application number
EP20050782022
Other languages
English (en)
French (fr)
Other versions
EP1773497A1 (de
Inventor
Gilles Marchand
Yves Fouillet
Philippe Clementz
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.)
Commissariat a lEnergie Atomique et aux Energies Alternatives CEA
Original Assignee
Commissariat a lEnergie Atomique CEA
Commissariat a lEnergie Atomique et aux Energies Alternatives CEA
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 Commissariat a lEnergie Atomique CEA, Commissariat a lEnergie Atomique et aux Energies Alternatives CEA filed Critical Commissariat a lEnergie Atomique CEA
Publication of EP1773497A1 publication Critical patent/EP1773497A1/de
Application granted granted Critical
Publication of EP1773497B1 publication Critical patent/EP1773497B1/de
Not-in-force legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

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
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04B—POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B19/00—Machines or pumps having pertinent characteristics not provided for in, or of interest apart from, groups F04B1/00 - F04B17/00
    • F04B19/006—Micropumps
    • 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
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/089—Virtual walls for guiding liquids
    • 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
    • B01L2300/16—Surface properties and coatings
    • B01L2300/161—Control and use of surface tension forces, e.g. hydrophobic, hydrophilic
    • B01L2300/165—Specific details about hydrophobic, oleophobic surfaces
    • 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
    • B01L2300/18—Means for temperature control
    • B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
    • B01L2300/1816—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using induction heating
    • 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
    • B01L2300/18—Means for temperature control
    • B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
    • B01L2300/1827—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using resistive heater
    • 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
    • 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
    • B01L3/5025—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures for parallel transport of multiple samples
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T137/00—Fluid handling
    • Y10T137/206—Flow affected by fluid contact, energy field or coanda effect [e.g., pure fluid device or system]
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T137/00—Fluid handling
    • Y10T137/206—Flow affected by fluid contact, energy field or coanda effect [e.g., pure fluid device or system]
    • Y10T137/218—Means to regulate or vary operation of device
    • Y10T137/2185—To vary frequency of pulses or oscillations

Definitions

  • the invention relates to a device and a method for moving small volumes of liquid, using electrostatic forces to obtain this displacement.
  • the invention particularly relates to a discrete microfluidic handling device, or microfluidic drop, for chemical or biological applications.
  • the forces used for displacement are electrostatic forces.
  • the document FR 2 841 063 describes a device implementing a catenary facing electrodes activated for displacement.
  • a drop 2 rests on a network 4 of electrodes, from which it is isolated by a dielectric layer 6 and a hydrophobic layer 8 ( Figure 1A ).
  • the effects of electrostatic charge induce the displacement of the drop on this electrode.
  • the electrode 10 may be a catenary, it then maintains an electrical contact with the drop during its displacement as described in document FR - 2 841 063 ( Figure 2A ).
  • the drop can thus be moved step by step ( figure 1C ), on the hydrophobic surface 8, by successive activation of the electrodes 4-1, 4-2, etc. and by guiding along the catenary 10.
  • This type of displacement is increasingly used in devices for biochemical, chemical or biological analyzes, whether in the medical field, or in environmental monitoring, or in the field of quality control.
  • the invention relates to a device for moving a small volume of liquid under the effect of an electrical control, comprising a first hydrophobic surface substrate provided with first electrically conductive means, second electrically conductive means arranged vis-à- screw of the first conductive means, or in correspondence of these first means, or vis-à-vis the portion of the hydrophobic surface which covers the first electrically conductive means, characterized in that it comprises third conductive means forming with the second conducting means of the analysis means or for inducing a reaction or means for heating a volume of liquid.
  • One of the second and third electrically conductive means may be used in the phase of displacement of the drops of liquids of interest in order to bring the drop onto the desired zone of the first electrically conductive means, the second electrically conductive means being associated with the third means in a couple, for example a pair of electrodes in electrical contact with the drop or the liquid, so as to perform, for example, an electrochemical detection of a redox species present in the drop or drops (two-electrode detection) , or an electrophoretic system, or a heating system or other reactions.
  • one of the second and third electrically conductive means has two functions.
  • a displacement function is provided by energizing the drop for electrowetting.
  • a second function is provided, which is a detection function, for example electrochemical.
  • the second electrically conductive means will then be either a working electrode or a counter electrode.
  • the second conductive means comprise a catenary or a wire, substantially parallel to the hydrophobic surface.
  • the catenary or the wire may be buried in the first substrate, at a non-zero distance from the hydrophobic surface, for example between 1 ⁇ m and 100 ⁇ m or 500 ⁇ m.
  • the third conductive means may also comprise a catenary or a wire, which may be non-buried in the first substrate, at a non-zero distance from the hydrophobic surface, for example between 1 ⁇ m and 100 ⁇ m or 500 ⁇ m.
  • the two catenaries or wires may be parallel to each other and to the hydrophobic surface.
  • the two catenaries or wires may not be parallel to each other, but remain parallel to the hydrophobic surface.
  • One of the catenaries can be buried under the hydrophobic surface.
  • the catenaries can be directed substantially parallel to each other.
  • the third conductive means may comprise a plane conductor buried beneath the hydrophobic surface.
  • the second conductive means may comprise a catenary or a wire buried beneath the hydrophobic surface.
  • the third conductive means may then also include a catenary or a buried wire, the two buried catenaries being directed substantially parallel to each other.
  • the third conductive means may comprise a planar electrode buried beneath the hydrophobic surface.
  • the second conductive means may comprise a buried plane electrode.
  • the third conductive means may then comprise a buried conductor, of flat or wired form.
  • the third conductive means may comprise a catenary or a wire directed perpendicularly to the catenary or wire of the second electrically conductive means.
  • a device as described above may further comprise a second substrate with a hydrophobic surface, this second substrate conferring on the assembly a confined structure.
  • It may also further comprise a second substrate with a hydrophobic surface, this second substrate conferring on the assembly a confined structure, the third conductor being buried in the second substrate, under its hydrophobic surface.
  • the third conductor can then be in the form of catenary or buried wire, or in the form of a buried plane conductor.
  • the surface of the second substrate may be locally perforated to form a contact zone between a drop of liquid positioned between the two substrates and the third conductor.
  • the second substrate may also be disposed at a distance from the first substrate of between 10 ⁇ m and 100 ⁇ m or 500 ⁇ m.
  • a device as described above may further comprise a second substrate with a hydrophobic surface, this second substrate conferring on the assembly a confined structure, the second and third conductors being buried in the second substrate, under its hydrophobic surface.
  • the second and third conductors can then each be in the form of catenary or wire.
  • the second electrically conductive means, or both electrodes can thus for example provide electrophoretic separation and / or a heating function.
  • the tilting of a displacement configuration to a reaction or reading or heating configuration can be fast, allowing several drops to be processed one after the other, in a continuous flow assay protocol, for example, or for high flow rate analyzes.
  • a first embodiment of the invention is illustrated on the Figures 2A and 2B .
  • a device or microfluidic component according to the invention comprises a lower substrate 20 provided with a matrix 24 of independent electrodes.
  • Each of these electrodes 24 is electrically connected to a conductor 26.
  • the electrodes 24 are covered with an insulating layer 28 and a hydrophobic layer 29.
  • hydrophobic nature of this layer means that a drop 22 has a contact angle on this layer of greater than 90 °.
  • a single layer can combine these two functions, for example a teflon layer.
  • This device comprises a first catenary 30, allowing electrowetting, and a second catenary 32 forming an electrode pair with the first catenary 30.
  • the first catenary is located opposite the electrodes 24, or the portion of the hydrophobic surface 29 situated above the electrodes 24.
  • Supply means 34 connect these various electrodes together.
  • one or more of the electrodes 24 is / are under tension, as well as the catenary 30 this configuration is illustrated in FIG. Figure 2A ; as already explained above, the activation of one of the electrodes 24 will induce a displacement of the droplet 22.
  • a voltage is applied to each of the catenaries 30 and 32, generating a non-zero potential difference between these two catenaries, which can induce an electrochemical reaction in the droplet 22, and / or a heating of this droplet , and / or an electroporation detection or reaction and / or a cell lysis-type reaction in this drop if there is the presence of a cell in the drop.
  • a voltage can be applied to one or more of the electrodes 24, simultaneously with the voltage applied between the catenaries 30 and 32, which makes it possible to cause, at the same time as the above reaction, a displacement of the drop 22.
  • One of the two catenaries is therefore bifunctional and can be used for a displacement on the hydrophobic surface 29 or for any reaction electrochemical or any other reaction for which there is a need for two electrodes (for example: electrophoresis, electroporation, cell lysis).
  • the second conductor may be arranged in a different direction than the first conductor.
  • the catenary 30 is kept parallel to the alignment of the electrodes 24, while the second catenary is directed substantially perpendicular to the first catenary, but parallel to the plane of the layer 29 and the substrate 20, or ( Figure 2C ) is directed substantially perpendicular to the plane of the layer 29 and the substrate 20.
  • the displacement of the drop 22 of liquid takes place in the same manner as above, while a reaction or heating is induced by establishing a non-zero potential difference between the electrodes 30 and 32.
  • One of the catenaries is still located above the substrate (here the catenary 30, but it could be the catenary 32).
  • Another electrode 40 here a catenary, is buried in the substrate 20, for example under the hydrophobic layer 29. This buried electrode can be flat, instead of being a catenary.
  • one or more of the electrodes 24 is / are under tension, as well as, for example, the catenary 30. It could also be the electrode 40 that is energized in place of the catenary 30; this configuration is illustrated in figure 3A ; as already explained above, the activation of one of the electrodes 24 will induce a displacement of the droplet 22.
  • a voltage is applied between the catenaries 30 and 40, generating a potential difference between these two catenaries, which can induce an electrochemical reaction / detection in the drop 22, and / or a heating of this drop, and / or an electroporation reaction and / or a cell lysis type reaction of cells present in the drop.
  • displacement and reaction or heating can be simultaneous, using adequate switching means or second voltage generating means.
  • the Figure 4A represents a longitudinal view of the device, on which only one of the two buried catenaries is visible, hiding the second, while the Figure 4B represents a sectional view AA 'of the device, on which the two buried catenaries 50, 52 are visible, above an electrode 24-1 which hides the other electrodes of the network 24.
  • the voltage generating means 34 and the switching means 33 are also shown.
  • one or more of the electrodes 24 is / are under tension, as well as, for example, the catenary 52; this configuration is illustrated in Figures 4A and 4B ; as already explained above, the activation of one of the electrodes 24 will induce a displacement of the droplet 22.
  • a voltage is applied to each of the catenaries 50 and 52 using the means 34 and 33 (situation not shown in the figures), generating a non-zero potential difference between these two catenaries, which can inducing a heating of this drop, and / or an electroporation reaction and / or a cell lysis type reaction of this drop.
  • the invention also relates to other embodiments, particularly of the confined type, with an upper substrate.
  • An upper substrate 120 comprises a hydrophobic layer 129, for example Teflon. Like the layer 29, it is in contact with the droplet 22.
  • the two conductors 30, 32 are located in this example between the two substrates 20, 120 and are both in direct contact, mechanical and electrical, with the drop 22.
  • the device is shown in the displacement position of the drop, a reaction or heating being induced by switching means 33 switching.
  • displacement and reaction or heating can be induced simultaneously, by appropriate switching means or by means of a second voltage source.
  • one of the two conductors making it possible to induce a reaction in the drop can be buried in the lower substrate 20.
  • one of the catenaries is still located above the substrate (here the catenary 30, but this could be catenary 32).
  • Another electrode 60 for example a catenary, is buried in the substrate 20, for example under the hydrophobic layer 29, leaving only the conductor 30 in mechanical and electrical contact with the drop.
  • This embodiment allows a displacement of the drop using the conductors 24 and the conductor 30, and the induction of a reaction with the application of a difference in voltages between the conductors 60 and 30 (which is represented on the figure 6 ).
  • the buried electrode 60 may have the shape of either a linear conductor or a catenary, or the shape of a plane conductor.
  • the buried electrode 60 When it has the shape of a linear conductor, it can be oriented in a direction not necessarily parallel to the direction of the catenary 30, as illustrated in FIG. figure 6 on which the two catenaries are substantially perpendicular; and the advantage of this structure is that only one drop at a time is in electrical contact with the two electrodes. Or the two electrodes 30, 60 may be parallel to each other (for example as illustrated in FIGS. Figures 3A and 3B ), which makes it possible to achieve the desired reaction at any place above the electrodes 24. The same advantage is offered when the buried electrode 60 has the shape of a plane conductor.
  • one or more of the electrodes 24 is / are under tension, as well as the catenary 30; as already explained above, the activation of one of the electrodes 24 will induce a displacement of the droplet 22.
  • one of the two conductors for inducing a reaction in the drop can be buried in the upper substrate 120.
  • Another electrode 70 for example a catenary, is buried in the substrate 120, for example under the hydrophobic layer 129, leaving only the conductor 30 in mechanical and electrical contact with the drop.
  • This embodiment allows a displacement of the drop using the conductors 24 and the conductor 30, and the induction of a reaction with the application of a difference in voltages between the conductors 70 and 30.
  • the buried electrode 70 may have the shape of either a linear conductor or a catenary, or the shape of a plane conductor.
  • the buried electrode 70 When in the form of a linear conductor, it may be oriented in a direction not necessarily parallel to the direction of the catenary 30 (as shown in FIG. figure 7 , on which the two catenaries are substantially perpendicular), or the two conductors may be parallel to each other (for example, as illustrated in FIGS. Figures 3A and 3B ), which makes it possible to achieve the desired reaction at any place above the electrodes 24.
  • the same advantage is offered when the buried electrode 70 has the shape of a plane conductor.
  • one or more of the electrodes 24 is / are under tension, as well as the catenary 30; this configuration is illustrated in figure 7 ; as already explained above, the activation of one of the electrodes 24 will induce a displacement of the droplet 22.
  • a voltage is applied to each of the electrodes 30 and 70, generating a non-zero potential difference between them, which can induce an electrochemical reaction in the drop 22, and / or a heating of this drop, and or an electroporation reaction and / or a cell lysis-type reaction in this drop.
  • each of the two conductors for inducing a reaction in the drop is buried in one of the substrates.
  • the other electrode 130 for example a catenary, is buried in the substrate 120, for example over the hydrophobic layer 129.
  • This embodiment allows a displacement of the drop using the conductors 24 and the conductor 50 and the induction of a reaction with the application of a difference in voltages between the conductors 130 and 50.
  • Each of the buried electrodes 50, 130 may have the shape of either a linear conductor or a catenary, or the shape of a plane conductor.
  • both have the shape of a linear conductor
  • they can be oriented in directions that are not necessarily parallel to each other (as illustrated in FIG. figure 7 , on which the two catenaries are substantially perpendicular), or the two conductors may be parallel to each other (for example as illustrated in FIG. figure 8A ) which makes it possible to carry out the desired reaction or detection at any place above the electrodes 24.
  • the same advantage is offered when one of the two buried electrodes has the shape of a plane conductor (in particular that of the substrate 120) while the other has the shape of a linear conductor aligned above the electrodes 24, or when the two electrodes each have the shape of a plane conductor.
  • one or more of the electrodes 24 is / are under tension, as well as the electrode 50; this configuration is illustrated in figure 8A ; as already explained above, the activation of one of the electrodes 24 will induce a displacement of the droplet 22.
  • a voltage is applied to each of the electrodes 130 and 50, generating a non-zero potential difference between them, which can induce heating in the droplet 22, and / or an electroporation and / or a cell lysis-type reaction in this drop if there are cells in the drop.
  • one of the buried conductors for example the conductor 130 of the upper substrate 120, is locally in physical contact with the drop 22 due to an opening 127 made in the hydrophobic layer 129, for example by lithography and etching of this layer 129.
  • the two electrodes are both located either in the lower substrate or in the upper substrate. None of the electrodes are located in mechanical contact with the drop.
  • Two catenaries 130 and 132 are buried in the substrate 120, for example under the hydrophobic layer 129.
  • the Figure 9A represents a longitudinal view of the device, on which only one of the two buried catenaries is visible, hiding the second.
  • the Figure 9B represents a sectional view BB 'of the device, on which the two buried catenaries 130, 132 are visible, above an electrode 24-1 which hides the other electrodes of the network 24.
  • one or more of the electrodes 24 is / are under tension, as well as, for example, the catenary 130; as already explained above, the activation of one of the electrodes 24 will induce a displacement of the droplet 22.
  • the invention can be implemented with a row of electrodes 24, thus a linear arrangement of these electrodes.
  • Electrodes may however, in the context of the invention, be arranged according to any scheme, and in particular in 2 dimensions.
  • the substrate 20 supports an array of electrodes 24, distributed in rows and columns, covered with an insulating layer 28 and a hydrophobic layer 29.
  • micro-catenaries can be positioned at a given distance from the surface of the substrate by means of spacers 70.
  • the spacer technique can also be used in conjunction with the other embodiments to maintain a catenary at a predetermined distance from the hydrophobic layer 29.
  • FIG. 10B Another aspect of the invention is shown in the figure 10B .
  • the substrate 20 supports an array of electrodes 24, distributed in rows and columns, covered with a thin insulating layer 28 and a hydrophobic layer 29.
  • a first series of micro-catenaries 30, 32 is paralleled along the lines of electrodes.
  • micro-catenaries are positioned at a given distance from the surface of the substrate by means of spacers 70.
  • a second series of micro-catenaries 130, 132 is paralleled but placed perpendicularly to the series of micro-catenaries 30, 32, that is to say in the direction of the columns of electrodes 24.
  • micro-catenaries are positioned at a given distance from the surface of the substrate by means of spacers 72.
  • the spacers 70 and 72 may be of different heights. Thus, it is possible to move drops in two perpendicular directions.
  • these 2D embodiments function in the same manner as described above in connection with the Figures 2A-9B : Activation of two neighboring electrodes 30,32 or 130,132 induces a potential difference between these two electrodes and a heating reaction or in the liquid of the drop.
  • Electrodes of these 2D embodiments are connected to switching means, not shown on the Figures 10A and 10B but in a manner analogous to that described above in connection with the preceding figures.
  • the economy is made of a wired wiring step; in addition (the wetted surface is only located on the hydrophobic surfaces 29 and 129) are then best used the wetting properties of the corresponding layer 29, 129.
  • the distance between the conductors 30, 32 ( Figures 2A - 3B , 5 - 7 ) on the one hand and the hydrophobic surface 29 is for example between 1 micron and 100 microns or 500 microns.
  • the catenaries 30, 32 are for example in the form of son diameter between 10 microns and a few hundred microns, for example 200 microns. These wires may be gold or aluminum wires or tungsten or other conductive materials.
  • the buried electrode is obtained by depositing and then etching a thin layer of a metal selected from Au, Al, Ito, Pt, Cu, Cr, etc. using conventional microtechnology technologies.
  • the thickness is from a few tens of nm to a few microns.
  • the width of the pattern is from a few ⁇ m to a few nm (flat electrodes).
  • two substrates 20, 120 are used ( Figures 5 - 9B ), they are separated by a distance of, for example, 10 ⁇ m and 100 ⁇ m or 500 ⁇ m.
  • a drop of liquid 22 will have a volume of between, for example, 1 nanolitre and a few microliters, for example between 1 nl and 5 ⁇ l or 10 ⁇ l.
  • each of the electrodes 24 will for example have a surface of the order of a few tens of ⁇ m 2 (for example 10 ⁇ m 2 ) up to 1 mm 2 , depending on the size of the drops to be transported, the spacing between adjacent electrodes being for example between 1 .mu.m and 10 .mu.m.
  • the structuring of the electrodes 24 can be obtained by conventional microtechnology methods, for example by photolithography.
  • the electrodes 24 are made by depositing a metal layer (Au, Al, ITO, Pt, Cr, Cu, ...) by photolithography.
  • the substrate is then covered with a dielectric layer of Si 3 N 4 , SiO 2 , ... Finally, a deposit of a hydrophobic layer is performed, such as a teflon deposit made by spinning.
  • Methods for producing chips incorporating a device according to the invention may be directly derived from the methods described in the document FR - 2 841 063 : Instead of making a catenary row of electrodes, it is two, or is made a buried plane conductor and a catenary.
  • Conductors and in particular buried catenaries, may be made by depositing a conductive layer and etching this layer in the appropriate pattern of conductors, before deposition of the hydrophobic layer.
  • electrochemical detection of a redox species will be given. This detection is carried out using a device according to the invention, for example the device of the Figures 2A - 2B .
  • a drop of 1 ⁇ l of a solution of ferri / potassium ferrocyanide (10 -2 M) is deposited on the hydrophobic surface 29.
  • the catenary 30 used for displacement plays the role of working electrode while the second electrode 32 acts as counter-electrode and reference electrode.
  • An electrochemical measurement is then carried out in potential cyclic voltammetry between -400mV and + 300mV relative to the reference electrode;
  • electrochemistry makes it possible to describe the chemical phenomena coupled with reciprocal exchanges of electrical energy.
  • the electrochemical reaction that occurs at the surface of an electrode is the result of the transfer of electric charge across the interface between it and an electroactive species (in one direction or the other).
  • two electrodes (working electrode and counter-electrode) are immersed in an electrolytic solution containing an electroactive species.
  • a third electrode (reference electrode) is used to reference the potential of the working electrode.
  • Electrophoresis is a known method for separating charged species. Indeed charged molecules in an electric field will begin to migrate to the opposite charge electrode. The migration rate will depend on the charge / mass ratio of the molecule, which effectively separates molecular species of different charges / mass.
  • the electrodes of a device according to the invention can be used to induce such an electrophoresis reaction in a drop of liquid.
  • the invention makes it possible to implement detections or electrochemical reactions, when at least one of the two electrodes is in physical contact with the drop.
  • the invention can also be applied to electroporation methods, which make it possible to open or modify the membrane of a cell (which is then the droplet 22) and thus to bring into the cell other chemicals , transported by means of the electrodes as described above, or brought manually, for example by means of a pipette.
  • a first example of electrochemical detection of a redox species has been given in connection with the figure 11 .
  • a second example concerns the electrochemical detection of a species generated by an enzyme.
  • a first reaction mixture is prepared as follows: 50 mM phosphate-citrate buffer, pH 6.5 (10 ml), o-phenylene diamine (OPD, 20 mg) and hydrogen peroxide (4 ⁇ l).
  • a second mixture is prepared as follows: MilliQ water (9 ⁇ l) and "horse radish" peroxidase (1 ⁇ l at 20 ⁇ M).
  • a drop of 0.5 .mu.l of the first mixture is converged on the chip to a drop of 0.5 .mu.l of the second mixture by applying a voltage of 50V.
  • the product of the enzymatic reaction is detected by differential pulsed voltammetry using as the pair of electrodes the catenaries 30 and 32, the catenary 30 serving as electrode of and the catenary 32 serving both against electrode and reference electrode.
  • a redox peak is obtained at -480mV corresponding to the reduction of the enzymatic product generated (see figure 12 ).
  • a second example concerns the displacement of a drop followed by a localized variation of electro-controlled pH.
  • a drop of a reaction medium is moved and then the pH is varied to stop or start a reaction.
  • this pH is electrochemically varied using the invention.
  • a drop of buffered solution (PBS pH 7.4) containing a colored indicator, cresol red 1 mM, is deposited on the chip and then moved on it by applying a voltage of 50V.
  • a potential of -1.4V for 10 s is then applied between the two catenaries, 30 and 32, thus causing the hydrolysis of water and the generation of OH - ions.
  • These OH ions - make the solution basic, hence the appearance of a red indicator color with a pH greater than 8.8.
  • the buffer compensates for the pH and the red color disappears.
  • the second catenary 32 allows a heating of a drop of liquid or small volume of liquid 22 by Joule contact or effect. Heating by heat transfer is preferred because the current flow in the drop may be too dependent on its content, for example its salt concentration. Heating by transfer means heating by contact, the electrodes heat because of their internal resistance, transferring heat to the liquid of the drop.
  • the current flow between the catenaries 30, 32 can advantageously make it possible to determine an order of magnitude of the drop size, making it possible to further control the evaporation.
  • a small current flows between the two catenaries. The detection of this current informs the presence of a drop 22 of sufficient size to come into contact, in the example shown, with the second catenary 32. This detection makes it possible to determine an approximate size of the drop.
  • the second catenary is disposed substantially parallel to the substrate at a distance d.
  • the drop has a height h.
  • h is at least equal to d
  • a current flows between the catenaries 30 and 32, which makes it possible to deduce that the height h is at least greater than d.
  • h is less than d.
  • the drop 22 has a height h greater than d and puts the two catenaries 30, 32 in electrical contact.
  • This two-catenary system has the advantage of allowing both to heat to accelerate evaporation and to allow a calibration of the drops. Indeed, it is possible to connect the detection of the current to the displacement electrodes 4. Thus, one can move the drop on an evaporation path in one direction and the other until no current is no longer detected between the two catenaries. We will then know that the size of the drop is less than a given value. Displacement favors evaporation, thus speeding up the process. It is also possible to leave the drop in place, and let the liquid evaporate until there is no more contact between the drop 22 and the catenary 32.
  • third, fourth ... catenaries arranged at increasingly smaller distances from the substrate.
  • This plurality of catenaries may allow use of the microfluidic device for drops of different sizes; a control of the size of the drop over an evaporation path by detecting a continuous decrease in the volume of the drop, or a very fine determination of the drop size.
  • catenaries can also be arranged in parallel, at the same height as the travel catenary but on the side and at different distances.
  • catenary secondaries arranged transversely to the first catenary (as on the figure 10B for example) discretely and at increasingly smaller distances from the substrate.
  • the size control is then carried out in an ad hoc manner, when the drop meets a second catenary.
  • the detection of a current can then generate a command to prolong the evaporation of the drop to reduce the volume of the drop.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Analytical Chemistry (AREA)
  • Mechanical Engineering (AREA)
  • General Engineering & Computer Science (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
  • Electrical Discharge Machining, Electrochemical Machining, And Combined Machining (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Electrostatic Separation (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Sampling And Sample Adjustment (AREA)

Claims (36)

  1. Vorrichtung zur Verlagerung eines kleinen Flüssigkeitsvolumens unter der Einwirkung einer elektrischen Steuerung, umfassend ein erstes Substrat mit einer hydrophoben Oberfläche (29), das mit elektrisch leitenden Mitteln (24) ausgestattet ist, wobei zweite elektrisch leitende Mittel (30, 50, 130) den ersten leitenden Mitteln gegenüberliegend angeordnet sind, dadurch gekennzeichnet, dass sie dritte leitende Mittel (32, 40, 60, 70, 130, 132) umfasst, die zusammen mit den zweiten leitenden Mitteln Mittel zur Analyse oder zum Induzieren einer Reaktion oder Mitte zum Heizen eines Flüssigkeitsvolumens bilden, wobei die ersten elektrisch leitenden Mittel zusammen mit den zweiten elektrisch leitenden Mitteln die Verlagerung des Flüssigkeitsvolumens durch Elektrobenetzung ermöglichen.
  2. Vorrichtung nach Anspruch 1, wobei die zweiten leitenden Mittel eine Kettenleitung oder einen Draht (30, 50, 130) im Wesentlichen parallel zur hydrophoben Oberfläche umfassen.
  3. Vorrichtung nach Anspruch 2, wobei die Kettenleitung oder der Draht in einem Abstand ungleich 0 von der hydrophoben Oberfläche nicht im ersten Substrat vergraben ist.
  4. Vorrichtung nach Anspruch 3, wobei der Abstand zwischen 1 µm und 100 µm oder 500 µm enthalten ist.
  5. Vorrichtung nach Anspruch 2, 3 oder 4, wobei auch die dritten leitenden Mittel (32, 40, 60, 70, 130, 132) eine Kettenleitung oder einen leitenden Draht umfassen.
  6. Vorrichtung nach Anspruch 5, wobei die Kettenleitung oder der Draht in einem Abstand ungleich Null von der hydrophoben Oberfläche nicht im ersten Substrat vergraben ist.
  7. Vorrichtung nach Anspruch 6, wobei der Abstand zwischen 1 µm und 100 µm oder 500 µm enthalten ist.
  8. Vorrichtung nach Anspruch 5, 6 oder 7, wobei die zwei Kettenleitungen oder Drähte zueinander sowie zur hydrophoben Oberfläche (29) parallel sind.
  9. Vorrichtung nach einem der Ansprüche 5 bis 7, wobei die zwei Kettenleitungen oder Drähte zueinander nicht parallel sind, jedoch parallel zur hydrophoben Oberfläche (29) sind.
  10. Vorrichtung nach einem der Ansprüche 2 bis 5, wobei eine der Kettenleitungen (40, 50) unter der hydrophoben Oberfläche (29) vergraben ist.
  11. Vorrichtung nach Anspruch 10, wobei die Kettenleitungen in im Wesentlichen paralleler Weise zueinander geführt sind.
  12. Vorrichtung nach Anspruch 2, 3 oder 4, wobei die dritten leitenden Mittel einen ebenen Leiter umfassen, der unter der hydrophoben Oberfläche (29) vergraben ist.
  13. Vorrichtung nach Anspruch 1 oder 2, wobei die zweiten leitenden Mittel eine Kettenleitung oder einen Draht umfassen, die/der unter der hydrophoben Oberfläche (29) vergraben ist (50).
  14. Vorrichtung nach Anspruch 13, wobei auch die dritten leitenden Mittel (52) eine(n) vergrabene(n) Kettenleitung oder Draht umfassen, wobei die zwei vergrabenen Kettenleitungen in im Wesentlichen zueinander paralleler Weise geführt sind.
  15. Vorrichtung nach einem der Ansprüche 1 bis 4, wobei die dritten leitenden Mittel eine ebene Elektrode umfassen, die unter der hydrophoben Oberfläche (29) vergraben ist.
  16. Vorrichtung nach Anspruch 1, wobei die zweiten leitenden Mittel eine vergrabene ebene Elektrode umfassen.
  17. Vorrichtung nach Anspruch 16, wobei die dritten leitenden Mittel einen vergrabenen Leiter mit ebener oder drahtförmige Gestalt umfassen,
  18. Vorrichtung nach einem der Ansprüche 1 bis 4, wobei die dritten leitenden Mittel eine Kettenleitung oder einen Draht umfassen, die/der orthogonal zur Kettenleitung oder zum Draht der zweiten elektrisch leitenden Mittel geführt ist.
  19. Vorrichtung nach einem der Ansprüche 1 bis 18, ferner umfassend ein zweites Substrat (120) mit einer hydrophoben Oberfläche (129), wobei dieses zweite Substrat der Gesamtanordnung eine begrenzte Struktur verleiht.
  20. Vorrichtung nach einem der Ansprüche 1 bis 4 oder 13 oder 16, ferner umfassend ein zweites Substrat mit einer hydrophoben Oberfläche (129), wobei dieses zweite Substrat der Gesamtanordnung eine begrenzte Struktur verleiht, wobei der dritte Leiter (70, 130) in dem zweiten Substrat unter der hydrophoben Oberfläche (129) vergraben ist.
  21. Vorrichtung nach Anspruch 20, wobei der dritte Leiter die Form einer vergrabenen Kettenleitung oder eines vergrabenen Drahts aufweist, oder auch die Form eines vergrabenen ebenen Leiters.
  22. Vorrichtung nach Anspruch 20 oder 21, wobei die Oberfläche des zweiten Substrats lokal durchbrochen ist, um eine Kontaktzone (127) zwischen einem Flüssigkeitstropfen, der zwischen den zwei Substraten positioniert ist, und dem dritten Leiter zu bilden.
  23. Vorrichtung nach einem der Ansprüche 19 bis 22, wobei das zweite Substrat in einem Abstand vom ersten Substrat angeordnet ist, der zwischen 10 µm und 100 µm oder 500 µm enthalten ist.
  24. Vorrichtung nach Anspruch 1, ferner umfassend ein zweites Substrat mit einer hydrophoben Oberfläche (129), wobei dieses zweite Substrat der Gesamtanordnung eine begrenzte Struktur verleiht, wobei der zweite und der dritte Leiter (130, 132) in dem zweiten Substrat unter seiner hydrophoben Oberfläche (129) vergraben sind.
  25. Vorrichtung nach Anspruch 24, wobei der zweite und der dritte Leiter jeweils die Form einer Kettenleitung oder eines Drahts haben.
  26. Vorrichtung nach einem der Ansprüche 1 bis 25, wobei die hydrophobe Oberfläche des ersten Substrats und/oder jene des zweiten Substrats aus Teflon ist/sind.
  27. Verfahren zur Behandlung eines Flüssigkeitstropfens (22) durch elektrochemische Reaktion, umfassend:
    - Das In-Kontakt-Bringen eines Flüssigkeitstropfens (22) mit den Elektroden einer Vorrichtung nach einem der Ansprüche 1 bis 13 oder 16 bis 21,
    - das Anlegen einer Potentialdifferenz zwischen den zweiten und den dritten leitenden Mitteln.
  28. Verfahren zur Behandlung eines Flüssigkeitstropfens (22) durch Elektrophorese, umfassend:
    - Das In-Kontakt-Bringen eines Flüssigkeitstropfens (22) mit den Elektroden einer Vorrichtung nach einem der Ansprüche 1 bis 26,
    - das Anlegen einer Potentialdifferenz zwischen den zweiten und den dritten leitenden Mitteln.
  29. Verfahren zur Behandlung einer Zelle durch zelluläre Lyse, umfassend:
    - Das In-Kontakt-Bringen einer Zelle mit den Elektroden einer Vorrichtung nach einem der Ansprüche 1 bis 26,
    - das Anlegen einer Potentialdifferenz zwischen den zweiten und dritten leitenden Mitteln.
  30. Verfahren zum Heizen eines leitenden Flüssigkeitstropfens (22) mittels Joule-Effekt, umfassend:
    - Das In-Kontakt-Bringen eines Flüssigkeitstropfens mit den elektrisch leitenden Mitteln einer Vorrichtung nach einem der Ansprüche 1 bis 26,
    - das Anlegen einer Potentialdifferenz zwischen den zweiten und den dritten leitenden Mitteln.
  31. Verfahren zur Steuerung oder zur Kalibrierung der Größe eines Tropfens (22), umfassend:
    - Das In-Kontakt-Bringen eines Flüssigkeitstropfens mit den zweiten und den dritten elektrisch leitenden Mitteln (30, 32) einer Vorrichtung nach einem der Ansprüche 1 bis 26,
    - das Fließenlassen eines Stroms zwischen den zweiten und den dritten elektrisch leitenden Mitteln,
    - das Verdampfen des Tropfens, bis der Strom nicht mehr zwischen den zweiten und den dritten elektrisch leitenden Mitteln fließt.
  32. Verfahren nach Anspruch 31, ferner umfassend eine Verlagerung des Tropfens durch Elektrobenetzung während des Verdampfens.
  33. Verfahren zur Behandlung einer Zelle durch Elektroporation, umfassend:
    - Das In-Kontakt-Bringen einer Zelle mit den Elektroden einer Vorrichtung nach einem der Ansprüche 1 bis 26,
    - das Anlegen einer Potentialdifferenz zwischen den zweiten und den dritten leitenden Mitteln.
  34. Vorrichtung zur Kalibrierung eines Flüssigkeitstropfens, umfassend eine Vorrichtung nach einem der Ansprüche 1 bis 26 sowie Mittel zur Steuerung eines Stroms, der zwischen den zweiten und den dritten elektrisch leitenden Mitteln fließt.
  35. Vorrichtung nach Anspruch 34, wobei die zweiten und die dritten elektrisch leitenden Mittel jeweils eine Kettenleitung umfassen, wobei die zwei Kettenleitungen in Höhen angeordnet sind, die bezüglich der hydrophoben Oberfläche verschieden sind.
  36. Vorrichtung nach Anspruch 35, ferner umfassend weinigstens eine zusätzliche Kettenleitung, die in einem Abstand von der hydrophoben Oberfläche angeordnet ist, weiche verschieden ist vom Abstand zwischen dieser Oberfläche und den zwei vorgenannten Kettenleitungen.
EP20050782022 2004-07-01 2005-06-30 Vorrichtung zur bewegung und behandlung von flüssigkeitsvolumina Not-in-force EP1773497B1 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR0451400A FR2872438B1 (fr) 2004-07-01 2004-07-01 Dispositif de deplacement et de traitement de volumes de liquide
PCT/FR2005/050527 WO2006013303A1 (fr) 2004-07-01 2005-06-30 Dispositif de deplacement et de traitement de volumes de liquide

Publications (2)

Publication Number Publication Date
EP1773497A1 EP1773497A1 (de) 2007-04-18
EP1773497B1 true EP1773497B1 (de) 2011-11-02

Family

ID=34946391

Family Applications (1)

Application Number Title Priority Date Filing Date
EP20050782022 Not-in-force EP1773497B1 (de) 2004-07-01 2005-06-30 Vorrichtung zur bewegung und behandlung von flüssigkeitsvolumina

Country Status (6)

Country Link
US (1) US8864967B2 (de)
EP (1) EP1773497B1 (de)
JP (1) JP5437575B2 (de)
AT (1) ATE531452T1 (de)
FR (1) FR2872438B1 (de)
WO (1) WO2006013303A1 (de)

Families Citing this family (48)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101146595B (zh) 2005-01-28 2012-07-04 杜克大学 用于在印刷电路板上操作液滴的装置和方法
CA2606750C (en) 2005-05-11 2015-11-24 Nanolytics, Inc. Method and device for conducting biochemical or chemical reactions at multiple temperatures
US9476856B2 (en) 2006-04-13 2016-10-25 Advanced Liquid Logic, Inc. Droplet-based affinity assays
US20140193807A1 (en) 2006-04-18 2014-07-10 Advanced Liquid Logic, Inc. Bead manipulation techniques
US8389297B2 (en) 2006-04-18 2013-03-05 Duke University Droplet-based affinity assay device and system
US7901947B2 (en) 2006-04-18 2011-03-08 Advanced Liquid Logic, Inc. Droplet-based particle sorting
US7439014B2 (en) 2006-04-18 2008-10-21 Advanced Liquid Logic, Inc. Droplet-based surface modification and washing
US8637324B2 (en) 2006-04-18 2014-01-28 Advanced Liquid Logic, Inc. Bead incubation and washing on a droplet actuator
WO2007123908A2 (en) 2006-04-18 2007-11-01 Advanced Liquid Logic, Inc. Droplet-based multiwell operations
US8980198B2 (en) 2006-04-18 2015-03-17 Advanced Liquid Logic, Inc. Filler fluids for droplet operations
US10078078B2 (en) 2006-04-18 2018-09-18 Advanced Liquid Logic, Inc. Bead incubation and washing on a droplet actuator
US8658111B2 (en) 2006-04-18 2014-02-25 Advanced Liquid Logic, Inc. Droplet actuators, modified fluids and methods
US8716015B2 (en) 2006-04-18 2014-05-06 Advanced Liquid Logic, Inc. Manipulation of cells on a droplet actuator
US8809068B2 (en) 2006-04-18 2014-08-19 Advanced Liquid Logic, Inc. Manipulation of beads in droplets and methods for manipulating droplets
WO2009111769A2 (en) 2008-03-07 2009-09-11 Advanced Liquid Logic, Inc. Reagent and sample preparation and loading on a fluidic device
US8685344B2 (en) 2007-01-22 2014-04-01 Advanced Liquid Logic, Inc. Surface assisted fluid loading and droplet dispensing
KR101503510B1 (ko) 2007-02-09 2015-03-18 어드밴스드 리퀴드 로직, 아이엔씨. 자성 비즈를 이용하는 액적 작동기 장치 및 방법
US8872527B2 (en) 2007-02-15 2014-10-28 Advanced Liquid Logic, Inc. Capacitance detection in a droplet actuator
WO2011084703A2 (en) 2009-12-21 2011-07-14 Advanced Liquid Logic, Inc. Enzyme assays on a droplet actuator
WO2008116209A1 (en) 2007-03-22 2008-09-25 Advanced Liquid Logic, Inc. Enzymatic assays for a droplet actuator
US8951732B2 (en) 2007-06-22 2015-02-10 Advanced Liquid Logic, Inc. Droplet-based nucleic acid amplification in a temperature gradient
US8702938B2 (en) 2007-09-04 2014-04-22 Advanced Liquid Logic, Inc. Droplet actuator with improved top substrate
MX2010007034A (es) 2007-12-23 2010-09-14 Advanced Liquid Logic Inc Configuraciones para eyector de gotas y metodos para realizar operaciones de gota.
FR2930457B1 (fr) * 2008-04-24 2010-06-25 Commissariat Energie Atomique Procede de fabrication de microcanaux reconfigurables
US8852952B2 (en) 2008-05-03 2014-10-07 Advanced Liquid Logic, Inc. Method of loading a droplet actuator
EP2286228B1 (de) 2008-05-16 2019-04-03 Advanced Liquid Logic, Inc. Tröpfchenaktuatorvorrichtungen und verfahren zur manipulation von kügelchen
FR2933713B1 (fr) * 2008-07-11 2011-03-25 Commissariat Energie Atomique Procede et dispositif de manipulation et d'observation de gouttes de liquide
US8877512B2 (en) 2009-01-23 2014-11-04 Advanced Liquid Logic, Inc. Bubble formation techniques using physical or chemical features to retain a gas bubble within a droplet actuator
US8926065B2 (en) 2009-08-14 2015-01-06 Advanced Liquid Logic, Inc. Droplet actuator devices and methods
US8846414B2 (en) 2009-09-29 2014-09-30 Advanced Liquid Logic, Inc. Detection of cardiac markers on a droplet actuator
WO2011057197A2 (en) 2009-11-06 2011-05-12 Advanced Liquid Logic, Inc. Integrated droplet actuator for gel electrophoresis and molecular analysis
EP2553473A4 (de) 2010-03-30 2016-08-10 Advanced Liquid Logic Inc Tröpfchenoperationsplattform
US8632670B2 (en) * 2010-04-13 2014-01-21 Purdue Research Foundation Controlled flow of a thin liquid film by electrowetting
US9011662B2 (en) 2010-06-30 2015-04-21 Advanced Liquid Logic, Inc. Droplet actuator assemblies and methods of making same
US8982574B2 (en) * 2010-12-29 2015-03-17 Stmicroelectronics S.R.L. Contact and contactless differential I/O pads for chip-to-chip communication and wireless probing
WO2012154745A2 (en) 2011-05-09 2012-11-15 Advanced Liquid Logic, Inc. Microfluidic feedback using impedance detection
US9140635B2 (en) 2011-05-10 2015-09-22 Advanced Liquid Logic, Inc. Assay for measuring enzymatic modification of a substrate by a glycoprotein having enzymatic activity
US8901043B2 (en) 2011-07-06 2014-12-02 Advanced Liquid Logic, Inc. Systems for and methods of hybrid pyrosequencing
AU2012279420A1 (en) 2011-07-06 2014-01-30 Advanced Liquid Logic Inc Reagent storage on a droplet actuator
US9513253B2 (en) 2011-07-11 2016-12-06 Advanced Liquid Logic, Inc. Droplet actuators and techniques for droplet-based enzymatic assays
WO2013016413A2 (en) 2011-07-25 2013-01-31 Advanced Liquid Logic Inc Droplet actuator apparatus and system
WO2013070627A2 (en) 2011-11-07 2013-05-16 Illumina, Inc. Integrated sequencing apparatuses and methods of use
WO2013078216A1 (en) 2011-11-21 2013-05-30 Advanced Liquid Logic Inc Glucose-6-phosphate dehydrogenase assays
US9223317B2 (en) 2012-06-14 2015-12-29 Advanced Liquid Logic, Inc. Droplet actuators that include molecular barrier coatings
BR112014032727B1 (pt) 2012-06-27 2021-12-14 Illumina France Método e sistema para realizar operações de gotícula em uma gotícula em um atuador de gotículas para redução da formação de bolhas
US9863913B2 (en) 2012-10-15 2018-01-09 Advanced Liquid Logic, Inc. Digital microfluidics cartridge and system for operating a flow cell
KR101598847B1 (ko) * 2014-01-23 2016-03-02 부경대학교 산학협력단 액적의 직접 충전 및 전기영동에 기반한 전기천공 기기, 장치 및 방법
JP7333794B2 (ja) * 2018-05-24 2023-08-25 オックスフォード ナノポール テクノロジーズ ピーエルシー エレクトロウェッティングデバイスにおける液滴界面

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2543320B1 (fr) * 1983-03-23 1986-01-31 Thomson Csf Dispositif indicateur a commande electrique de deplacement d'un fluide
FI980874A (fi) * 1998-04-20 1999-10-21 Wallac Oy Menetelmä ja laite pienten nestemäärien kemiallisen analyysin suorittamiseksi
US6565727B1 (en) * 1999-01-25 2003-05-20 Nanolytics, Inc. Actuators for microfluidics without moving parts
US6777245B2 (en) * 2000-06-09 2004-08-17 Advalytix Ag Process for manipulation of small quantities of matter
US20040231987A1 (en) * 2001-11-26 2004-11-25 Keck Graduate Institute Method, apparatus and article for microfluidic control via electrowetting, for chemical, biochemical and biological assays and the like
FR2841063B1 (fr) * 2002-06-18 2004-09-17 Commissariat Energie Atomique Dispositif de deplacement de petits volumes de liquide le long d'un micro-catenaire par des forces electrostatiques
US6911132B2 (en) * 2002-09-24 2005-06-28 Duke University Apparatus for manipulating droplets by electrowetting-based techniques

Also Published As

Publication number Publication date
FR2872438B1 (fr) 2006-09-15
WO2006013303A1 (fr) 2006-02-09
EP1773497A1 (de) 2007-04-18
FR2872438A1 (fr) 2006-01-06
JP5437575B2 (ja) 2014-03-12
US20080302431A1 (en) 2008-12-11
JP2008504124A (ja) 2008-02-14
ATE531452T1 (de) 2011-11-15
US8864967B2 (en) 2014-10-21

Similar Documents

Publication Publication Date Title
EP1773497B1 (de) Vorrichtung zur bewegung und behandlung von flüssigkeitsvolumina
CA2294627C (fr) Procede d'identification et/ou de dosage de substances biologiques, presentes dans un liquide conducteur, dispositif et capteur d'affinite utiles pour la mise en oeuvre de ce procede
EP1714700A1 (de) Mikrofluidische Vorrichtung und Verfahren zum Stoffaustausch zwischen zwei nichtmischbaren Phasen
Trojanowicz Recent developments in electrochemical flow detections—a review: part I. Flow analysis and capillary electrophoresis
EP1778976B1 (de) Elektrodenadressierungsverfahren
EP0886773B1 (de) Detektion von molekülen und molekülkomplexen
EP2282827B1 (de) Vorrichtung zur Trennung von Biomolekülen aus einer Flüssigkeit
Aghdaei et al. Formation of artificial lipid bilayers using droplet dielectrophoresis
EP1796843B1 (de) Vorrichtung zur dielektrophoretischen trennung von partikeln in einer flüssigkeit
US20100133105A1 (en) Optoelectronic Separation of Biomolecules
WO2006134307A1 (fr) Dispositif de pompage par electromouillage et application aux mesures d'activite electrique
FR2866493A1 (fr) Dispositif de controle du deplacement d'une goutte entre deux ou plusieurs substrats solides
WO2009109727A1 (fr) Procede de fonctionnalisation de la paroi d'un pore.
JP2013529287A (ja) 駆動電極のアレイを有するマイクロ流体チャネルデバイス
EP1570091B1 (de) Methode zur elektronischen detektion wenigstens einer spezifischen interaktion zwischen einem proben- und einem zielmolekül
EP1889053A2 (de) Planare vorrichtung mit durch dynamische elektrobenetzung automatisierter well-adressierung
US20090166222A1 (en) Electrical nanotraps for spectroscopically characterizing biomolecules within
Wagner et al. Light-addressable potentiometric sensors (LAPS): recent trends and applications
WO2011064265A1 (fr) Dispositif électrochimique pour la détermination de propriétés antioxydantes de la peau
FR2889515A1 (fr) Dispositif de controle du deplacement d'un volume liquide entre deux ou plusieurs substrats solides et procede de deplacement
Rianasari et al. Inkjet-printed thiol self-assembled monolayer structures on gold: Quality control and microarray electrode fabrication
EP1869439A1 (de) Verfahren zur voltametrischen elektrochemischen analyse sowie vorrichtung zur durchführung davon
EP3538882B1 (de) Vorrichtung, system und verfahren im zusammenhang mit der vorkonzentrierung von analyten
EP0186577A2 (de) Vorrichtung für Kreuzelektrophorese
FR2921157A1 (fr) Electrode pour systeme microfluidique

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20061219

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU MC NL PL PT RO SE SI SK TR

DAX Request for extension of the european patent (deleted)
17Q First examination report despatched

Effective date: 20090323

RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: COMMISSARIAT A L'ENERGIE ATOMIQUE ET AUX ENERGIES

GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

GRAS Grant fee paid

Free format text: ORIGINAL CODE: EPIDOSNIGR3

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU MC NL PL PT RO SE SI SK TR

REG Reference to a national code

Ref country code: GB

Ref legal event code: FG4D

Free format text: NOT ENGLISH

REG Reference to a national code

Ref country code: CH

Ref legal event code: EP

REG Reference to a national code

Ref country code: IE

Ref legal event code: FG4D

REG Reference to a national code

Ref country code: DE

Ref legal event code: R096

Ref document number: 602005030998

Country of ref document: DE

Effective date: 20120112

REG Reference to a national code

Ref country code: NL

Ref legal event code: VDEP

Effective date: 20111102

LTIE Lt: invalidation of european patent or patent extension

Effective date: 20111102

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20111102

Ref country code: IS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20120302

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20111102

Ref country code: PT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20120302

Ref country code: SI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20111102

Ref country code: PL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20111102

Ref country code: NL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20111102

Ref country code: GR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20120203

REG Reference to a national code

Ref country code: IE

Ref legal event code: FD4D

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: CY

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20111102

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20111102

Ref country code: IE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20111102

Ref country code: EE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20111102

Ref country code: CZ

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20111102

Ref country code: BG

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20120202

Ref country code: DK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20111102

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: IT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20111102

Ref country code: RO

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20111102

PLBE No opposition filed within time limit

Free format text: ORIGINAL CODE: 0009261

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

Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT

REG Reference to a national code

Ref country code: AT

Ref legal event code: MK05

Ref document number: 531452

Country of ref document: AT

Kind code of ref document: T

Effective date: 20111102

26N No opposition filed

Effective date: 20120803

REG Reference to a national code

Ref country code: DE

Ref legal event code: R097

Ref document number: 602005030998

Country of ref document: DE

Effective date: 20120803

BERE Be: lapsed

Owner name: COMMISSARIAT A L'ENERGIE ATOMIQUE ET AUX ENERGIES

Effective date: 20120630

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: AT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20111102

Ref country code: MC

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20120630

REG Reference to a national code

Ref country code: CH

Ref legal event code: PL

REG Reference to a national code

Ref country code: CH

Ref legal event code: PL

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: ES

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20120213

Ref country code: CH

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20120630

Ref country code: LI

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20120630

Ref country code: BE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20120630

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: FI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20111102

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: TR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20111102

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LU

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20120630

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: HU

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20050630

REG Reference to a national code

Ref country code: FR

Ref legal event code: PLFP

Year of fee payment: 12

REG Reference to a national code

Ref country code: FR

Ref legal event code: PLFP

Year of fee payment: 13

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: GB

Payment date: 20170616

Year of fee payment: 13

Ref country code: FR

Payment date: 20170630

Year of fee payment: 13

Ref country code: DE

Payment date: 20170614

Year of fee payment: 13

REG Reference to a national code

Ref country code: DE

Ref legal event code: R119

Ref document number: 602005030998

Country of ref document: DE

GBPC Gb: european patent ceased through non-payment of renewal fee

Effective date: 20180630

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: DE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20190101

Ref country code: GB

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20180630

Ref country code: FR

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20180630