EP1773497A1 - Dispositif de deplacement et de traitement de volumes de liquide - Google Patents
Dispositif de deplacement et de traitement de volumes de liquideInfo
- Publication number
- EP1773497A1 EP1773497A1 EP05782022A EP05782022A EP1773497A1 EP 1773497 A1 EP1773497 A1 EP 1773497A1 EP 05782022 A EP05782022 A EP 05782022A EP 05782022 A EP05782022 A EP 05782022A EP 1773497 A1 EP1773497 A1 EP 1773497A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- conductive means
- drop
- substrate
- catenary
- hydrophobic surface
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502769—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
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- 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
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5025—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, implementing 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 opposite 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 IA).
- the electrode 4-1 located near the drop 2 is activated, the dielectric layer 6 and the hydrophobic layer 8, between this activated electrode and the droplet polarized by an electrode 10, act as a capacitor.
- the effects of electrostatic charge induce the displacement of the drop on this electrode.
- the electrode 10 may be a catenary, it then maintains electrical contact with the drop during its movement as described in document FR-2 841 063 (FIG. 2A).
- the drop can thus be displaced step by step (FIG. 1C) on the hydrophobic surface 8 by successive activation of the electrodes 4-1, 4-2, etc. and by guiding along the catenary 10. It is therefore possible to move liquids, but also to mix them (by bringing drops of different liquids near), and to perform complex protocols.
- 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 displacement phase 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 droplet 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 invention also relates to a method for treating a drop of liquid, for example by reaction or electrochemical detection or by electrophoresis or Joule effect, or treatment of a cell by cell lysis or by electroporation, comprising:
- 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.
- FIGS. 1A-1C illustrate the principle of moving a droplet on an electrode matrix by electrowetting
- FIGS. 2A to 2C illustrate an embodiment of the invention
- FIGS. 3A - 9B illustrate other variants and other embodiments of the invention.
- FIGS. 10A and 10B illustrate two-dimensional variants of the invention
- FIG. 11 illustrates the detection between two catenaries of the Fe II / II ⁇ pair .
- FIG. 12 illustrates the electrochemical detection of a species generated by an enzyme.
- FIGS. 13a and 13b are diagrammatic representations of an exemplary implementation of a device according to the present invention for calibrating a drop of liquid during different calibration steps;
- FIGS. 2A and 2B A first exemplary embodiment of the invention is illustrated in FIGS. 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 vis-à-vis the electrodes 24, or the portion of the hydrophobic surface 29 located above the electrodes 24.
- the supply means 34 connect these various electrodes together.
- these supply means can be switched in two ways, using switching means 33.
- 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 direction different from 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.
- FIGS. 3A and 3B A variant of the device described above is shown in FIGS. 3A and 3B, in which numerical references identical to those of FIGS. 2A-2C denote identical or similar elements.
- 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.
- displacement and reaction or heating can be simultaneous, using adequate switching means or second voltage generating means.
- FIGS. 4A and 4B Yet another variant of this device is shown in FIGS. 4A and 4B, on which numerical references identical to those of FIGS. 2A-2C denote identical or similar elements.
- FIG. 4A represents a longitudinal view of the device, on which only one of the two buried catenaries is visible, hiding the second, while Figure 4B shows a sectional view AA 'of the device, on which the two buried catenaries 50, 52 are visible, above a 24-1 electrode which hides the Other electrodes of the network 24.
- Figure 4B shows the means 34 voltage generators and the switching means 33.
- one or more of the electrodes 24 is / are under tension, as well as, for example, the catenary 52; this configuration is illustrated in FIGS. 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 for 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 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 shown in 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.
- it When it has the shape of a linear conductor, it may be oriented in a direction not necessarily parallel to the direction of the catenary 30, as shown in Figure 6, in 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.
- the two electrodes 30, 60 may be parallel to each other (for example as illustrated in FIGS. 3A and 3B), which makes it possible to carry out 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 above, the activation of one of the electrodes 24 will induce a displacement of the drop 22.
- one of the two conductors making it possible to induce a reaction in the drop can be buried in the upper substrate 120.
- one of the catenaries is still located above the substrate (here the catenary 30, but it could be the catenary 32).
- 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.
- 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 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. 7, on which the two catenaries are substantially perpendicular), or both The conductors may be parallel to each other (for example as illustrated in FIGS. 3A and 3B), which makes it possible to carry out the desired reaction at any point 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 FIG. 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.
- one or more of the electrodes 24 is / are under tension, as well as the electrode 50; this configuration is illustrated in FIG. 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 substrate. upper 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.
- a voltage is applied to each of the electrodes 130 and 50, generating a potential difference between these two electrodes, which can induce: an electrochemical reaction in the droplet 22 when in direct contact with the electrode 130 through the opening 127,
- 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.
- FIGS. 9A-9B The case of two electrodes buried in the upper substrate is illustrated in FIGS. 9A-9B, on which numerical references identical to those of FIGS. 2A-2C denote identical or similar elements.
- FIG. 9A shows a longitudinal view of the device, on which only one of the two buried catenaries is visible, hiding the second.
- Figure 9B shows a sectional view
- one or more of the electrodes 24 is / are energized, 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 drop 22.
- a voltage is applied to each of the catenaries 130 and 132, generating a potential difference between these two catenaries, which can induce a heating of this drop, and / or an electroporation reaction and / or a cell lysis-type reaction in this drop (this configuration is illustrated in FIGS. 9A and 9B).
- the invention can be implemented with a row of electrodes 24, thus a linear arrangement of these electrodes.
- These electrodes may however, in the context of the invention, be arranged according to any scheme, and in particular in 2 dimensions.
- FIGS. 10A and 10B Another aspect of the invention is therefore represented by FIGS. 10A and 10B on which numerical references identical to those of FIGS. FIGS. 2A-2C denote identical or similar elements.
- 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 may also be used in conjunction with the other embodiments to maintain a catenary at a predetermined distance from the hydrophobic layer 29.
- Another aspect of the invention is shown in 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.
- 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 FIGS. 2A-9B: activation of two neighboring electrodes 30,32 or 130,132 induce a potential difference between these two electrodes and a reaction or heating in the liquid of the drop.
- a second confinement substrate provided with a hydrophobic surface, with, where appropriate, again one or two buried electrodes for one or more rows and / or columns of electrodes.
- the hydrophobic surface of this second substrate may be provided with contact openings such as the opening 127 of Figure 8B.
- 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 (FIGS. 2A-3B, 5 -7) on the one hand and the hydrophobic surface 29 is, for example, between 1 ⁇ m and 100 ⁇ m or 500 ⁇ m.
- 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, aluminum or tungsten wires 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, ... 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 (FIGS. 5 - 9B), they are separated by a distance of, for example, between 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 ni 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 methods of micro ⁇ technologies, for example by photolithography.
- the electrodes 24 are made by depositing a metal layer (Au, Al, ITO, Pt, Cr, Cu, ...) by photolithography.
- a deposit of a hydrophobic layer is performed, such as a teflon deposit made by spinning.
- 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 FIGS. 2A - 2B.
- a drop of 1 ⁇ l of a solution of ferri / potassium ferrocyanide (10 -2 M) is deposited on the hydrophobic surface 29.
- An electrochemical measurement is then carried out in potential cyclic voltammetry between -40OmV and + 30OmV relative to the reference electrode.
- 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 is used to reference the potential of the working electrode.
- the electrolyte is conducting
- the non-zero current flows in the electrochemical cell.
- This circulation involves three different mechanisms: - in the electrodes, the current flows by displacement of the electrons (charge carriers), at the electrode / liquid interfaces, the current flows through redox reactions that take place there (electron transfer) between electrode and solution or redox species), in the solution, the current circulates by displacement of the ions (charge carriers).
- one of the electrodes of the device acts as a working electrode
- the other, the second electrode acts as both a counter-electrode and a reference electrode.
- Electrophoresis is a known method for separating charged species. Indeed, charged molecules present in an electric field will begin to migrate towards electrodes of opposite charge. 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 may serve to induce such an electrophoresis reaction in a drop of liquid.
- the electrodes of a device according to the invention may also serve as a heating resistor:
- the electrodes heating and transferring the heat to the liquid of the droplet 22
- 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. It also makes it possible to carry out electrophoresis reactions or to heat the liquid of the droplet 22.
- 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 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 FIG. 11.
- a second example relates to 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: MiIIiQ 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. During this movement only the catenary 30 intervenes.
- the product of the enzymatic reaction is detected by differential pulsed voltammetry using the catenaries 30 and 32 as the pair of electrodes, the catenary 30 serving as the and the catenary 32 serving both against electrode and reference electrode.
- a redox peak is obtained at -48OmV corresponding to the reduction of the generated enzyme product (see FIG. 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, the cresol red with ImM, is deposited on the chip then moved on it by applying a tension of 50V.
- Potential -1,4V for 10 sec is then applied between the two catenary, 30 and 32, thus causing hydrolysis of the water and the generation of OH "ions.
- These ions OH" make the solution basic, hence the appearance of a red indicator color with a pH greater than 8.8.
- FIGs 13a and 13b we can see a device according to the present invention, using the two catenaries 30, 32, and allowing a control of the size of the drops. These two catenaries are arranged at different heights relative to the substrate.
- 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. In addition, the flow of current can also denature the substances in solution, which could distort any subsequent analysis.
- the flow of current 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 the the
- 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, the drop can be moved on an evaporation path in one direction and the other until no current is 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 the
- third, fourth ... catenaries arranged at increasingly smaller distances from the substrate.
- This plurality of catenaries may allow the use of the microfluidic device for drops of different sizes, a control of the size of the drop over an entire evaporation path by detecting a continuous decrease in the volume of the drop, or a very fine determination of the size of the drops.
- catenaries can also be arranged in parallel, at the same height as the travel catenary but on the side and at different distances.
- second catenary arranged transversely to the first catenary (as in 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 evaporation of the drop to reduce the volume of the drop.
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- 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)
- Automatic Analysis And Handling Materials Therefor (AREA)
- Sampling And Sample Adjustment (AREA)
- Electrostatic Separation (AREA)
- Electrical Discharge Machining, Electrochemical Machining, And Combined Machining (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
Description
Claims
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 |
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EP1773497A1 true EP1773497A1 (fr) | 2007-04-18 |
EP1773497B1 EP1773497B1 (fr) | 2011-11-02 |
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ID=34946391
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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EP20050782022 Not-in-force EP1773497B1 (fr) | 2004-07-01 | 2005-06-30 | Dispositif de deplacement et de traitement de volumes de liquide |
Country Status (6)
Country | Link |
---|---|
US (1) | US8864967B2 (fr) |
EP (1) | EP1773497B1 (fr) |
JP (1) | JP5437575B2 (fr) |
AT (1) | ATE531452T1 (fr) |
FR (1) | FR2872438B1 (fr) |
WO (1) | WO2006013303A1 (fr) |
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WO2013016413A2 (fr) | 2011-07-25 | 2013-01-31 | Advanced Liquid Logic Inc | Dispositif et système d'actionneur à gouttelettes |
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2004
- 2004-07-01 FR FR0451400A patent/FR2872438B1/fr not_active Expired - Fee Related
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2005
- 2005-06-30 JP JP2007518668A patent/JP5437575B2/ja not_active Expired - Fee Related
- 2005-06-30 WO PCT/FR2005/050527 patent/WO2006013303A1/fr not_active Application Discontinuation
- 2005-06-30 US US11/631,389 patent/US8864967B2/en not_active Expired - Fee Related
- 2005-06-30 EP EP20050782022 patent/EP1773497B1/fr not_active Not-in-force
- 2005-06-30 AT AT05782022T patent/ATE531452T1/de active
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Also Published As
Publication number | Publication date |
---|---|
US20080302431A1 (en) | 2008-12-11 |
ATE531452T1 (de) | 2011-11-15 |
EP1773497B1 (fr) | 2011-11-02 |
JP5437575B2 (ja) | 2014-03-12 |
FR2872438B1 (fr) | 2006-09-15 |
US8864967B2 (en) | 2014-10-21 |
JP2008504124A (ja) | 2008-02-14 |
WO2006013303A1 (fr) | 2006-02-09 |
FR2872438A1 (fr) | 2006-01-06 |
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