EP2591857A1 - Device and method for handling drops - Google Patents

Abstract

The device (1) has two micro-fluidic surfaces (3a, 3b) spaced from each other by a separation distance (H). Two electrical displacement tracks (5a, 5b) are placed at levels of the two micro-fluidic surfaces, respectively. The displacement tracks form fluidic fingers (9a, 9b) under an electric activation effect and are rupturable by under an electric deactivation effect by generating fluid drops. The two tracks are arranged such that the separation distance between the surfaces is greater than fluid thickness formed by the fingers and fluid thickness formed by the drops. An independent claim is also included for a method for handling fluid drops.

Description

TECHNICAL AREA

The present invention relates to the general field of drop formation and manipulation in a microfluidic device.

STATE OF THE PRIOR ART

In many fields, it is desired to form and manipulate drops to analyze small volume liquid samples in the simplest and least intrusive manner possible.

This may be the case, for example, for establishing biological and / or chemical interactions between two solutions for a chemical analysis, a biological or medical diagnosis, or in the field of genetic engineering or agro-food.

By way of illustration, mention may be made of the biochips which constitute, in the field of molecular biology, microsystems for the analysis of nucleic acid hybridization (DNA and / or RNA), or of the antigen-type interaction. antibody, protein / ligand, protein / protein, enzyme / substrate, etc. One can then look for kinetic parameters or equilibrium constants associated with these chemical or biological interactions.

In general, the manipulation of the drops or fluid flow can be carried out using hydrodynamic, electrical or magnetic means. Several handling techniques can be used, such as, for example, electrowool manipulation and dielectrophoresis effect manipulation.

EWOD electrowetting (Electrowetting on Dielectric) makes it possible to perform multiple elementary fluidic operations. This technique generally uses a pad of electrodes that is sequentially switched according to a suitable control to advance step by step a drop on a surface. Moving a EWOD drop can be achieved by using a potential difference between an electrode on a hood and another electrode on a substrate. The drop is thus directly in contact with the two planes. It is also possible to move a drop from one electrode to another by applying a potential difference between the incoming electrode and the surrounding fluid. However, a drop has its own volume as soon as it is formed and either it never comes into contact with the plane facing it, or it is always in contact with the plane facing it. This characteristic is not controllable. Likewise, this technique does not make it possible to form drops vis-à-vis from the different liquid flows.

The LDEP dielectrophoresis method is used for the formation of drops on a surface. However, to date this technique has been applied in an open configuration ( ie without a cover) or in a closed configuration with configurations identical to the displacement of drops by EWOD ( ie with a potential difference between an electrode array on a surface and a electrode representing the mass on the hood). In this configuration the liquid is in contact with the substrate and the hood.

There are several works mentioning liquid handling mechanisms on a surface by liquid dielectrophoresis.

The patent application WO2006025982 as well as the article of Ahmed and Jones entitled "Optimized liquid DEP droplet dispensing", J. Micromech. Microeng., 17 (2007), 1052-1058 describe a drop forming device by LDEP in an open configuration without hood. This device consists of a microfluidic platform composed of a substrate and two coplanar electrodes covered with a dielectric material. An AC signal is applied between the two electrodes which results in the displacement of a liquid on the platform.

Another patent application US20110056834 discloses a closed microfluidic device having two similar LDEP platforms facing each other and spaced from each other. The first platform (or substrate) comprises electrodes decoupled from each other and activated independently by an AC signal and the second platform (or cover) comprises an electrode acting as a mass. This configuration allows the flow of liquid to be displaced in several directions by LDEP effect. However, the liquid needs to touch both the hood and substrate electrodes to be able to be moved. Thus, this device does not allow the transfer of a liquid from one surface to another or the formation and the precise and reproducible manipulation of drops.

The object of the present invention is to overcome the aforementioned drawbacks by providing a more efficient and accurate device and method for forming and handling drops.

STATEMENT OF THE INVENTION

• des première et seconde surfaces microfluidiques parallèles et espacées l'une de l'autre d'une distance de séparation,
• au moins une première piste électrique de déplacement disposée au niveau de ladite première surface,
• au moins une seconde piste électrique de déplacement disposée au niveau de ladite seconde surface, lesdites première et seconde pistes définissant entre elles au moins une zone de croisement,
• l'une au moins desdites première et seconde pistes étant configurée(s) pour former par diélectrophorèse liquide, sous l'effet d'une activation électrique, un doigt fluidique respectif le long de ladite piste à partir d'un réservoir correspondant de liquide d'intérêt disposé de manière à pouvoir mettre en contact ledit liquide avec la surface associée, ledit doigt fluidique se rompant par capillarité sous l'effet d'une désactivation électrique, en générant au moins une goutte respective à partir dudit doigt fluidique dans ladite au moins une zone de croisement,
• les première et seconde pistes étant configurées pour que ladite distance de séparation entre lesdites première et seconde surfaces soit d'une part, supérieure à l'épaisseur fluidique formée par chaque doigt fluidique et, d'autre part, inférieure à l'épaisseur fluidique formée par chaque goutte.

The subject of the invention is a microfluidic device for handling a drop, comprising:

• first and second microfluidic surfaces parallel and spaced from one another by a separation distance,
• at least a first electrical displacement track disposed at said first surface,
• at least one second electrical displacement track disposed at said second surface, said first and second tracks defining between them at least one crossing zone,
• at least one of said first and second tracks being configured to form by liquid dielectrophoresis, under the effect of electrical activation, a respective fluidic finger along said track from a corresponding liquid reservoir; interest arranged so as to be able to bring said liquid into contact with the associated surface, said fluidic finger breaking by capillarity under the effect of an electrical deactivation, by generating at least one respective drop from said fluidic finger in said at least one a crossing zone,
• the first and second tracks being configured so that said separation distance between said first and second surfaces is on the one hand greater than the fluidic thickness formed by each fluidic finger and, on the other hand, less than the fluidic thickness formed by each drop.

Thus, a fluid finger formed on one of the first and second tracks will not be impacted by the other of said first and second tracks while permitting the interaction of each of the first and second tracks with the drop formed on one or the other of the first and second tracks. This makes it possible to form and manipulate drops on one or more locations and on one or two surfaces for many applications requiring drop transfers from one plane to another or mixing drops for biological and / or chemical interactions between different solutions simultaneously.

When the two fluids are miscible, a mixture is obtained during the bringing into contact of the two drops formed vis-a-vis. But by mixing is also meant a combination of immiscible liquids, the mixture then being two-phase, that is to say comprising two immiscible liquid phases, a liquid phase being for example encapsulated in a second liquid phase.

According to a first embodiment of the present invention, said first electrical path of displacement comprising a pair of substantially parallel and coplanar first electrodes disposed at said first surface for the formation under the effect of the electrical activation, of a first fluidic finger from a first reservoir of a first liquid of interest, said second electrical path of displacement comprising a pair of substantially parallel and coplanar second electrodes disposed at said second surface for formation under the effect of electrical activation of a second fluidic finger from a second reservoir of a second liquid of interest, said first and second fluidic fingers disrupting by capillarity under the effect of deactivation, generating at least one first drop and at least one second drop respectively that are mixed in said at least one crossing zone to form at least one overall drop.

This allows to cross first and second fluidic fingers, without they come into contact, and to form drops from the two different surfaces that will come into contact. Thus, this device is ideally suited for handling drops to achieve different applications requiring for example interactions or reactions between two volumes of liquids.

Advantageously, said pair of first electrodes comprising a plurality of first drop formation zones, so that at the deactivation of said pair of first electrodes, the first fluidic finger breaks into a plurality of first drops each located on one of said first drop formation areas.

This makes it possible to form drops reproducibly at strategic locations of the first surface.

Advantageously, said pair of second electrodes comprising a plurality of second drop formation zones each disposed opposite a first distinct drop formation zone thus forming a plurality of crossing zones, so that at the disabling said pair of second electrodes, the second fluid finger breaks into a plurality of second drops each located on one of said second drop forming zones, each second drop contacting the corresponding first drop to form an overall drop in the corresponding crossing zone.

This makes it possible to form blends between the drops of the first surface and those of the second surface in an entirely reproducible manner and at well-defined locations.

According to a particular configuration of the first embodiment, said first surface comprises a first network of m pairs of first electrodes each comprising a sequence of n first drop formation zones thus forming a first set of nm first drop formation zones, said second surface comprising a second network of n pairs of second electrodes each comprising a sequence of m seconds forming drop zones thus forming a second set of nm second drop formation zones, said first nm forming drop zones crossing said nm seconds drop formation zones to form a set of nm crossing zones.

This makes it possible to interact a very large number of different drops simultaneously and automatically from at least two solutions.

Advantageously, said pair of second electrodes is configured to move at least a second drop and / or at least one global drop located along said pair of second electrodes.

This makes it possible, for example, to use second electrodes having no drop-forming zones and to move a second drop to come into contact with a corresponding first drop located in a first drop-forming zone of said pair of first electrodes. to form a corresponding global drop. This also makes it possible to move the second drops and / or the overall drops for various chemical and / or biological protocols.

According to a second embodiment, said first electrical displacement track comprises a pair of substantially parallel and coplanar first electrodes disposed at said first surface for forming by liquid dielectrophoresis under the effect of electrical activation, of a finger fluidic from a reservoir of liquid of interest, said fluidic finger breaking by capillarity under the effect of deactivation, generating at least one drop, said second electrical path of displacement comprising second electrodes for the displacement of said at least one drop under the effect of an electrical activation of said second electrodes.

This makes it possible to form drops on a first surface, to transfer them to another surface and then to move them on this second surface in order to carry out various protocols for different biological and / or chemical applications.

Advantageously, the device comprises means for detecting a component of a drop formed at said at least one crossing zone.

This makes it possible to analyze the chemical and / or biological properties of the liquids.

According to a first variant, said detection means are optical means comprising a light source for emitting light onto said at least one drop and receiving means for receiving the light diffused by said at least one drop.

This makes it possible to manipulate and analyze samples in a short time simultaneously and accurately.

According to another variant, said detection means are electromechanical means comprising at least one plane oscillator, one side of which forms a detection surface belonging to one or the other of said first and second surfaces.

This allows for a simple, compact, and self-contained device for both handling and analyzing samples efficiently.

Advantageously, said detection surface has a hydrophilic zone intended to be covered by said at least one drop.

This allows the liquid to be placed on the most sensitive areas of the detection surface for optimal detection.

Advantageously, each of said first and second electrodes is covered with a dielectric layer.

This avoids direct contact between the liquid and the electrodes to prevent the electrolysis of the liquid.

• mise en contact d'au moins un premier réservoir comprenant un premier liquide d'intérêt avec au moins une première piste électrique de déplacement correspondante disposée au niveau d'une première surface microfluidique,
• mise en contact d'au moins un second réservoir comprenant un second liquide d'intérêt avec au moins une seconde piste électrique de déplacement correspondante disposée au niveau d'une seconde surface microfluidique, lesdites première et seconde surfaces étant parallèles et espacées l'une de l'autre d'une distance de séparation, lesdites au moins une première et au moins une seconde pistes de déplacement définissant entre elles au moins une zone de croisement,
• activation de ladite au moins une première piste de déplacement, de façon à former le long de ladite première piste un premier doigt fluidique correspondant,
• activation de ladite au moins une seconde piste de déplacement, de façon à former le long de ladite seconde piste un second doigt fluidique correspondant,
• désactivation de ladite au moins une première piste de déplacement, de sorte que le premier doigt fluidique correspondant se rompt par capillarité en générant au moins une première goutte située dans ladite au moins une zone de croisement,
• désactivation de ladite au moins une seconde piste de déplacement, de sorte que le second doigt fluidique se rompt par capillarité en générant au moins une seconde goutte située dans ladite au moins une zone de croisement, ladite distance de séparation entre lesdites première et seconde surfaces étant d'une part, supérieure à la somme des épaisseurs desdits premier et second doigts fluidiques, et, d'autre part, inférieure à la somme des épaisseurs desdites première et seconde gouttes, de sorte que lesdites première et seconde gouttes se mélangent dans ladite au moins une zone de croisement pour former au moins une goutte globale.

The invention also relates to a method for handling a drop, comprising the following steps:

• contacting at least a first reservoir comprising a first liquid of interest with at least a first corresponding electrical displacement track disposed at a first microfluidic surface,
• contacting at least one second reservoir comprising a second liquid of interest with at least a second corresponding electrical displacement track disposed at a second microfluidic surface, said first and second surfaces being parallel and spaced apart; the other of a separation distance, said at least one first and at least one second displacement tracks defining between them at least one crossing zone,
• activating said at least one first displacement track, so as to form along said first track a corresponding first fluidic finger,
• activating said at least one second displacement track, so as to form along said second track a corresponding second fluidic finger,
• deactivating said at least one first displacement track, so that the corresponding first fluidic finger breaks by capillarity by generating at least a first drop located in said at least one crossing zone,
• deactivating said at least one second displacement track, so that the second fluidic finger breaks by capillarity by generating at least a second drop located in said at least one crossing zone, said separation distance between said first and second surfaces being on the one hand, greater than the sum of the thicknesses of said first and second fluidic fingers, and, on the other hand, less than the sum of the thicknesses of said first and second drops, so that said first and second drops are mixed in said least one crossing zone to form at least one overall drop.

• mise en contact d'un ensemble de m premiers réservoirs comprenant m premiers liquides d'intérêt avec un réseau de m premières pistes correspondantes comprenant chacune une suite de n premières zones de formation de goutte formant ainsi un premier ensemble de nm premières zones de formation de goutte,
• mise en contact d'un ensemble de n seconds réservoirs comprenant n seconds liquides d'intérêt avec un réseau de n secondes pistes correspondantes comprenant chacune une suite de m secondes zones de formation de goutte formant ainsi un second ensemble de nm secondes zones de formation de goutte, lesdites nm premières zones de formation de goutte croisant respectivement lesdites nm secondes zones de formation de goutte pour former un ensemble de nm zones de croisement correspondantes,
• activation dudit réseau de m premières pistes, de façon à former un réseau de m premiers doigts fluidiques correspondants,
• activation dudit réseau de n secondes pistes, de façon à former un réseau de n seconds doigts fluidiques correspondants,
• désactivation dudit réseau de m premières pistes, de sorte que les m premiers doigts fluidiques correspondants se rompent par capillarité en générant un ensemble de nm premières gouttes dans ledit premier ensemble de nm premières zones de formation de goutte,
• désactivation dudit réseau de n secondes pistes, de sorte que les n seconds doigts fluidiques correspondants se rompent par capillarité en générant un ensemble de nm secondes gouttes dans ledit second ensemble de nm secondes zones de formation de goutte, les nm premières gouttes se mélangeant avec les nm secondes gouttes correspondantes pour former un ensemble de nm gouttes globales dans les nm zones de croisement correspondantes.

Advantageously, the method comprises the following steps:

• contacting a set of first m reservoirs comprising m first liquids of interest with a network of m first corresponding tracks each comprising a sequence of n first drop formation zones thus forming a first set of nm first formation zones of drop,
• contacting a set of n second reservoirs comprising n second liquids of interest with an array of n second corresponding tracks each comprising a sequence of m seconds forming drop zones thus forming a second set of nm second formation zones of drop, said first nm drop forming regions respectively crossing said nm second drop formation zones to form a set of nm corresponding crossover zones,
• activating said network of m first tracks, so as to form a network of m first corresponding fluidic fingers,
• activating said network of n second tracks, so as to form an array of n corresponding second fluidic fingers,
• disabling said network of m first tracks, so that the first m corresponding fluidic fingers break by capillarity by generating a set of nm first drops in said first set of nm first drop forming zones,
• disabling said network of n second tracks, so that the corresponding second n corresponding fluidic fingers break by capillarity by generating a set of nm seconds drops in said second set of nm second drop forming zones, the first nd drops mixing with the nm seconds corresponding drops to form a set of nm global drops in the corresponding nm crossing areas.

Advantageously, said first m reservoirs respectively comprise m first samples of different properties of a first solution and said n second reservoirs respectively comprise n second samples of different properties of a second solution thus forming nm different overall drops.

Advantageously, the method may comprise detection by optical, electromechanical, or electrophysiological means of the different interactions between said first and second solutions.

• mise en contact d'au moins un réservoir comprenant un liquide d'intérêt avec au moins une première piste électrique de déplacement correspondante disposée au niveau d'une première surface microfluidique, ladite première surface étant parallèle à une seconde surface microfluidique et espacée de celle-ci d'une distance de séparation, ladite seconde surface comprenant au moins une seconde piste électrique de déplacement définissant au moins une zone de croisement avec ladite au moins une première piste,
• activation de ladite au moins une première piste de déplacement, de façon à former le long de ladite première piste un doigt fluidique correspondant,
• désactivation de ladite au moins une première piste de déplacement, de sorte que le doigt fluidique correspondant se rompt par capillarité en générant au moins une goutte située dans ladite au moins une zone de croisement, ladite distance de séparation entre lesdites première et seconde surfaces étant d'une part, supérieure à l'épaisseur dudit doigt fluidique et, d'autre part, inférieure à l'épaisseur de ladite au moins une goutte, et
• activation de ladite au moins une seconde piste électrique de déplacement, de façon à déplacer ladite au moins une goutte.

The invention also relates to a method for handling a drop, comprising the following steps:

• contacting at least one reservoir comprising a liquid of interest with at least a first electrical path of corresponding displacement disposed at a first microfluidic surface, said first surface being parallel to a second microfluidic surface and spaced from it a distance of separation, said second surface comprising at least a second electrical path of displacement defining at least one crossing zone with said at least one first track,
• activating said at least one first displacement track, so as to form along said first track a corresponding fluidic finger,
• deactivating said at least one first displacement track, so that the corresponding fluidic finger breaks by capillarity by generating at least one drop located in said at least one crossing zone, said separation distance between said first and second surfaces being on the one hand, greater than the thickness of said fluidic finger and, on the other hand, less than the thickness of said at least one drop, and
• activating said at least one second electrical path of displacement, so as to move said at least one drop.

Other advantages and features of the invention will become apparent in the detailed non-limiting description below.

BRIEF DESCRIPTION OF THE DRAWINGS

• La Fig. 1 illustre de manière schématique un dispositif microfluidique de manipulation d'une goutte, selon l'invention ;
• La Fig. 2 est une vue schématique en coupe longitudinale d'un dispositif de manipulation selon un premier mode de réalisation préféré de l'invention ;
• Les Figs. 3A et 3B sont des vues schématiques de dessous du substrat supérieur du dispositif représenté sur la Fig. 2 ;
• Les Figs. 3C et 3D sont des vues schématiques de dessus du substrat inférieur du dispositif représenté sur la Fig. 2 ;
• La Fig. 3E est une vue détaillée d'une partie des électrodes de déplacement du dispositif représenté sur la Fig. 2 ;
• Les Fig. 4A à 4C sont des vues schématiques en coupe longitudinale du dispositif représenté sur la Fig. 2, illustrant la formation des gouttes de liquide ;
• Fig. 5 est une vue schématique en perspective de la zone de croisement du dispositif de la Fig. 2 ;
• Les Figs. 6A à 6E illustrent de manière schématique un dispositif de manipulation des gouttes, selon une configuration particulière du premier mode de réalisation préféré de l'invention ;
• Les Figs. 7A et 7B illustrent de manière schématique un dispositif de manipulation selon la configuration de la Fig. 6A, comportant des moyens de détection optiques ;
• Les Figs. 8A et 8B illustrent de manière schématique un dispositif de manipulation selon la Fig. 6A, comportant des moyens de détection électromécaniques ; et
• La Fig. 9 est une vue schématique en coupe longitudinale d'un dispositif de manipulation selon un deuxième mode de réalisation préféré de l'invention.

Embodiments of the invention will now be described, by way of nonlimiting examples, with reference to the accompanying drawings, in which:

• The Fig. 1 schematically illustrates a microfluidic device for handling a drop, according to the invention;
• The Fig. 2 is a schematic view in longitudinal section of a handling device according to a first preferred embodiment of the invention;
• The Figs. 3A and 3B are schematic bottom views of the upper substrate of the device shown in the Fig. 2 ;
• The Figs. 3C and 3D are schematic top views of the lower substrate of the device shown in FIG. Fig. 2 ;
• The Fig. 3E is a detailed view of a portion of the displacement electrodes of the device shown in FIG. Fig. 2 ;
• The Fig. 4A to 4C are schematic views in longitudinal section of the device represented on the Fig. 2 , illustrating the formation of drops of liquid;
• Fig. 5 is a schematic perspective view of the crossing zone of the device of the Fig. 2 ;
• The Figs. 6A to 6E schematically illustrate a device for handling drops, according to a particular configuration of the first preferred embodiment of the invention;
• The Figs. 7A and 7B schematically illustrate a handling device according to the configuration of the Fig. 6A , comprising optical detection means;
• The Figs. 8A and 8B schematically illustrate a handling device according to the Fig. 6A , comprising electromechanical detection means; and
• The Fig. 9 is a schematic view in longitudinal section of a handling device according to a second preferred embodiment of the invention.

DETAILED PRESENTATION OF THE PREFERRED EMBODIMENTS

The Fig. 1 schematically illustrates a microfluidic device 1 for handling a drop, according to the invention.

The microfluidic handling device 1 comprises a first microfluidic surface 3a and a second microfluidic surface 3b. The first and second surfaces 3a, 3b are parallel to each other and spaced from each other by a separation distance H.

Throughout the following description, by convention, a direct orthonormal coordinate system in Cartesian coordinates (X, Y, Z) presented on the Fig. 1 . The plane (X, Y) is parallel to said first and second surfaces 3a, 3b and the Z direction is oriented from the second surface 3b to the first surface 3a.

At least a first electrical displacement track 5a is disposed at the first surface 3a (here, only one first track is illustrated).

Similarly, at least a second electrical displacement track 5b is disposed at the second surface 3b (here, only one second track is shown).

By electrical track is meant either a continuous electrode, extending in a given direction, or a plurality of adjacent elementary electrodes. In the latter case, each electrode is separated from its neighbor by a small spacing, this spacing being typically 1 micron for a width of the electrode of 10 microns, the width being the dimension in a direction perpendicular to that of the spacing .

The first and second electrical tracks 5a, 5b of displacement define between them at least one crossing zone 7 vis-a-vis, without contact. In other words, they are not in contact with each other.

Indeed, the first and second tracks 5a, 5b are arranged in such a way that there is at least one straight line (in the Z direction) orthogonal to the first and second surfaces 3a, 3b intercepting the first track 5a at a first point 7a and the second track 5b at a second point 7b so that the space formed between these two points defines the crossing zone 7. The distance between the first and second points 7a, 7b is of course equal to the separation distance H .

It will be noted that the directions in the plane (X, Y) of the first and second tracks 5a, 5b may be intersecting at any angle forming a single crossing zone 7 ( Fig. 1 ) or, together, forming an infinity of crossing zones.

At least one of the first and second tracks 5a, 5b is configured to form by liquid dielectrophoresis, under the effect of an electrical activation, a respective fluid finger along the track.

By liquid dielectrophoresis ( LDEP, for Liquid Dielectrophoresis ) is meant the application of an electric force on an electrically insulating or conductive liquid, the force being generated by a non-uniform oscillating electric field. The formation of a fluid finger by liquid dielectrophoresis is described in particular in the article of Jones entitled "Liquid dielectrophoresis on the microscale", J. Electrostat, 51-52 (2001), 290-299 . When the liquid is located in an electric field, the molecules of the liquid acquire a non-zero dipole and become polarized. Insofar as the field is non-uniform, a Coulomb force appears and induces the displacement of the molecules of the liquid, and thus of all the liquid, towards a maximum of field.

The fluidic finger is formed along the respective track 5a, 5b from a reservoir 9a, 9b, corresponding liquid of interest disposed so as to be able to bring the liquid into contact with the associated surface 3a, 3b. The Fig. 1 shows a first reservoir 9a disposed at the first surface 5a and optionally a second reservoir (shown dashed) 9b disposed at the second surface 3b.

It should be noted that when the electrical control is stopped, the fluidic finger has an unstable shape. Capillary instability then develops rapidly and causes the finger to break in one or more drops, thereby lowering the surface energy of the liquid.

Thus, each fluidic finger formed on the first surface 3a and / or the second surface 3b breaks by capillarity under the effect of an electrical deactivation, by generating a respective drop (s) in the (the) ) crossing area (s) 7.

Moreover, the first and second tracks 5a, 5b are configured so that the separation distance H between the first and second surfaces 3a, 3b is on the one hand greater than the fluidic thickness formed by each fluidic finger and, d on the other hand, less than the fluidic thickness formed by each drop.

Thus, when only one of the tracks 5a, 5b is configured to form a fluid finger, the separation distance H is such that the fluidic finger does not touch the other track while at least one of the drops generated by this finger touches this other track.

On the other hand, when the first and second tracks 5a, 5b are configured to form first and second fluid fingers respectively, the separation distance H is such that the fluidic fingers do not touch while at least one of the drops generated by the first finger touches another drop among the drops generated by the second finger.

On the Fig. 2 is shown a microfluidic device for handling a drop according to a first embodiment of the invention.

The handling device 101 comprises an upper substrate 11a forming a cover and a lower substrate 11b, arranged facing one another. The terms "lower" and "higher" are here to be understood in terms of orientation along the Z direction of the orthonormal frame (X, Y, Z).

The cover 11a has a lower face formed of a dielectric layer 13a. The free surface of the dielectric layer 13a corresponds to the first surface 3a.

The lower substrate 11b has an upper face formed of a dielectric layer 13b. The free surface of the dielectric layer 13b corresponds to the second surface 3b.

The material of the lower substrate 11b or higher 11a may be chosen from among the following materials: glass, pyrex or an organic material such as polycarbonate or PEEK, monocrystalline silicon, polycrystalline silicon, diamond, silicon nitride, silicon dioxide, silicon oxide, nickel, tungsten or even platinum. The upper substrate 11a is advantageously made of a transparent material. The thickness of the upper substrate 11a or lower 11b may be between a few tens of microns and a few millimeters.

The device 101 has height separation walls 15 to provide a regular and precise separation distance H between the first and second surfaces 3a, 3b of the two substrates 11a and 11b. The material of the partition walls may be, for example, polymer, resin, dry films, or silicon.

The upper substrate 11a comprises a first reservoir 9a formed for example by a first orifice 9a passing through and opening at the first surface 3a. The first port 9a may be filled with a first liquid of interest 119a.

The lower substrate 11b has a second orifice 9b passing through and opening at the second surface 3b. The orifice 9b may be filled with a second liquid of interest 119b, thus forming a second reservoir 9b of liquid of interest 119b.

The liquid has any electrical conductivity. Advantageously, for the actuation of the liquid by LDEP and the setting up of the non-uniform electrical signal, this conductivity is less than 100 mSm ^-1 , or even less than 1 mSm ^-1 .

The handling device 101 comprises electrical means for forming the fluidic fingers by liquid dielectrophoresis. More particularly, the lower and upper substrates 11a, 11b respectively comprise first and second electrical tracks 5a, 5b of displacement to form liquid fingers by liquid dielectrophoresis on the first and second surfaces 3a, 3b, respectively. The direction of the first track 5a is represented, by way of example, parallel with that of the second track 5b thus forming a plurality of crossing zones 7.

It should be noted that the electrical means are similar to those presented in the article of Ahmed and Jones entitled "Optimized liquid DEP droplet dispensing", J. Micromech. Microeng., 17 (2007), 1052-1058 .

So, as shown in Fig. 3A the first electrical displacement track 5a comprises a pair of first displacement electrodes 51a, 52a disposed at the first surface 3a. The first electrodes 51a and 52a are parallel to each other, coplanar and substantially straight.

Similarly, as shown in figure 3C the second electrical displacement track 5b comprises a pair of second moving electrodes 51b, 52b disposed at the second surface 3b. The second electrodes 51b and 52b are parallel to each other, coplanar and substantially rectilinear.

The first and second displacement electrodes (51a, 52a, 51b, 52b) are indentations made of a metallic material, for example gold or aluminum.

The first dielectric layer 13a which forms the first surface 3a or the second dielectric layer 13b which forms the second surface 3b may be, for example, an oxide SiO ₂ , nitride (SiN, Si ₃ N ₄ ), resins, films SiOC, hydrophobic polymers such as Teflon (trademark - tetrafluoroethylene) or other fluoropolymers, a polymer of poly-p-xylylene (parylene) a high-k oxide deposited by the so-called ALD process (HfO ₂ , Al ₂ O ₃ , ZrO ₂ , SrTiO ₃ , BaTiO ₃ , Ba _(1-x) Sr _x TiO ₃ (BST) ...), and have a thickness of between a few nm (for example 10 nm or 25 nm) and a few microns ( for example 5 μm). It avoids the electrolysis of the liquid if it was in direct contact with the displacement electrodes (51a, 52a 51b, 52b).

With regard to the separation space H, the dimensions of the first and second electrodes 51b, 52b ( ie length and width of each electrode, and the distance between each pair of electrodes) are chosen so that, on the one hand, the sum a maximum thickness of a first finger to be formed on the first surface 3a and a maximum thickness of a second finger to be formed on the second surface 3b is less than the separation distance H and, secondly, the sum of a radius of a first drop to be formed on the first surface 3a and a radius of a second drop to be formed on the second surface is greater than the separation distance H.

Thus, a first fluidic finger 19a formed on the first surface 3a does not come into contact with a second fluidic finger 19b formed on the second surface 3b (see FIG. Figs. 6B and 6C ). On the other hand, when a first drop on the first surface 3a and a second drop on the second surface 3b are formed in the same crossing zone ( ie of the same coordinates (x, y)), they come into contact (see Figs. 5 , 6D and 6E ).

The first displacement electrodes 51a, 52a are connected to a first voltage generator 21a ( Fig. 3A ) for applying a first potential difference between these electrodes 51a, 52a. Similarly, the second displacement electrodes 51b, 52b are connected to a second voltage generator 21b ( Fig. 3C ) for applying a second potential difference between these electrodes 51b, 52b. The first generator and the second generator can be confused: there is then a single generator, which can apply different signals to each pair of electrode. In the latter case, the two pairs of electrodes (51a-51b and 52a-52b) can also be fed by the same signal.

The first or second applied voltage is an AC voltage whose frequency is between, for example, a few hertz (for the less conductive liquids) and a few megahertz, for example between 10 kHz and 10 MHz, and a preferential voltage from a few RMS volts to a few hundred RMS volts. When the liquid is very insulating, with for example a conductivity lower than 10 ^-9 Sm ^-1 , the frequency is of the order of the Hz.

Thus, under the effect of the electrical activation of the first electrodes 51a, 52a by the first generator 21a, a first fluidic finger 19a is formed on the pair of first electrodes 51a, 52a from the first reservoir 9a of first liquid. interest 119a ( Fig. 3A ).

Likewise, under the effect of the electrical activation of the second electrodes 51b, 52b by the second generator 21b, a second fluidic finger 19b is formed on the pair of second electrodes 51b, 52b from the second reservoir 9b of second liquid. interest 119b ( Fig. 3C ). Advantageously, the electrical activations are done simultaneously on both surfaces. And even more advantageously, the electrical deactivation is done simultaneously on both surfaces.

Moreover, as shown by Figs. 3B and 3D under the effect of the electrical deactivation (open circuits) of the first 51a, 52a and second 51b, 52b electrodes, the first and second fluidic fingers 19a, 19b break by capillary action, generating at at least a first drop 23a and at least a second drop 23b respectively which are mixed in at least one crossing zone 7 to form at least one overall drop ( Fig. 2 ).

Advantageously, as shown in Fig. 3E the pair of first displacement electrodes 51a, 52a (or respectively the pair of second displacement electrodes 51b, 52b) has a plurality of first drop forming zones (or respectively a plurality of second drop forming zones).

In particular, the Fig. 3E shows a pair of displacement electrodes 51, 52 (representing first or second displacement electrodes) having a plurality of drop forming zones 53, so that upon deactivation of the electrodes 51, 52, the fluidic finger breaks in a plurality of drops each located on one of these drop forming zones 53.

Indeed, each electrode 51, 52 has an inner edge 54, 55 and an outer edge 56, 57. The inner edges 54, 55 are arranged opposite one another.

Advantageously, the drop forming zones 53 are formed of planar protuberances, or planar bumps 531 and 532, which extend outwardly of each displacement electrode 51, 52. The bumps 531 and 532 are part of the electrodes 51 , 52 and are coplanar with these.

The bumps 531 and 532 are here arranged symmetrically with respect to each other and each belonging to a different displacement electrode 51, 52.

Thus, the displacement electrodes 51, 52 comprise rectilinear portions 58 and drop formation zones 53 interconnected by said rectilinear portions 58.

The inner edges 54, 55 of the displacement electrodes 51, 52 are spaced from each other by a distance g. The rectilinear portions 58 have a width denoted w and therefore the width ( ie the radius in the plane (Y, Z)) of the fluidic finger is given by R = w + g / 2. Each bump 531 and 532 is a half-disc of radius R _bump in the plane (X, Y) and whose center is located in the continuity of the border outer 56, 57 rectilinear portions 58. As detailed below, the radius R _hump of a bump is of the order of the radius R of the fluidic finger.

It is assumed that the section of the fluidic finger in the vertical plane (Y, Z) is semicircular, and that its surface is invariable along the electrodes. When the width w of the electrodes is of the same order of magnitude as their spacing g, the fluid finger at any point in the path covers an area inscribed between the two lateral ends of the electrodes. 2R is the distance separating these two straight ends ( ie the outer edges 56, 57 of the rectilinear portions 58 of the displacement electrodes 51, 52).

Preferably, the drop forming zones 53 are arranged equidistant from each other, preferably between 8R and 10R, and preferably at 9.016R.

As is detailed below, the spacing distance between the drop formation zones 53 is substantially equal to the most unstable wavelength λ _max of the fluid finger which extends along the displacement electrodes 51, 52 .

Advantageously, the pair of first electrodes 51a, 52a comprises a plurality of first drop forming zones 53 and the pair of second electrodes 51b, 52b comprises a plurality of second drop forming zones 53 (see FIG. Fig. 5 ).

At the deactivation of the first electrodes 51a, 52a, the first fluidic finger 19a breaks into a plurality of first drops 23a each located on one of these first drop-forming zones 53.

Likewise, upon the deactivation of the second electrodes 51b, 52b, the second fluidic finger 19b breaks into a plurality of second drops 23b each situated on one of these second drop-forming zones 53.

The second drop forming regions 53 are each disposed opposite a first distinct drop forming zone 53 thus forming a plurality of crossing zones 7 so that at the first 51a, 52a and 52a are deactivated. seconds 51b, 52b electrodes, each second drop 23b comes into contact with the corresponding first drop 23a to form a global drop 25 in the zone of corresponding crossing 7. This makes it possible to form fully reproducible mixtures between the drops of the first surface 3a and those of the second surface 3b. Reproducible means that the volume of the mixture and its location are controlled.

The operation of the handling device 101 according to, for example, the configuration of the Fig. 3E ( ie with displacement electrodes having a plurality of drop forming zones) is as follows, with reference to Figs. 4A to 4C .

In a first step ( Fig. 4A ), the first liquid of interest 119a is brought into contact with the first surface 3a from the first reservoir 9a.

Likewise, the second liquid of interest 119b is brought into contact with the second surface 3b from the second reservoir 9b.

We generate ( Fig. 4B ) a first oscillating and non-uniform electric field, under the effect of a first electrical control, by applying a voltage adapted to the first two displacement electrodes 51a, 52a.

The first fluidic finger 19a extends along the first two displacement electrodes 51a, 52a.

The first fluidic finger 19a substantially covers the first displacement electrodes 51a, 52a over their entire length, and has a contact width (in the plane (X, Y)) substantially equal to the distance 2R defined above and corresponding to the distance separating the outer edges of the first electrodes 51a, 52a, in their rectilinear part.

Similarly, we generate ( Fig. 4B ) a second oscillating and non-uniform electric field, under the effect of an electrical control, by applying a voltage adapted to the two second displacement electrodes 51b, 52b.

The second fluidic finger 19b extends along the two second displacement electrodes 51b, 52b substantially covering the second electrodes over their entire length.

Then, when the first electrical control is stopped ( figure 4C ), the first fluidic finger 19a breaks by capillarity into a plurality of first drops each located on a first drop formation zone.

Likewise, when the second electric control is stopped ( figure 4C ), the second fluidic finger 19b breaks by capillarity into a plurality of second drops each located on a second drop formation zone.

Indeed, the fluid finger 19a, 19b, in the absence of electrostatic force, is naturally unstable. The finger breaks under the effect of a hydrodynamic instability of the Rayleigh-Plateau type. This splitting of the finger into a plurality of drops makes it possible to reduce the surface energy of the liquid.

où k_max est le nombre d'onde. La longueur d'onde la plus instable s'écrit donc λ_max=9,016R, R étant le rayon du doigt fluidique.Instability is a capillarity / inertia competition and the most unstable wavelength is such that $k_{\max }\mathrm{.}R=1/\sqrt{2},$

where k _max is the wave number. The most unstable wavelength is therefore written λ _max = 9,016R, where R is the radius of the fluidic finger.

Also, the drop forming zones (53a, 53b) are spaced from each other by a distance substantially equal to λ _max . These drop formation zones make it possible to deform the interface of the fluidic finger 19a, 19b at the wavelength λ _max , and thus to "preselect" the desired wavelength.

Thus, the drops are formed simultaneously and are each located in a drop formation zone 53a, 53b.

Each drop has a calibrated volume. The volume depends on the width 2R of the fluidic finger 19a, 19b, the distance λ _max between the drop formation zones 53a, 53b and the _bump R radius of the protrusions, or bumps 531, 532, through the following equation: $$\frac{2\pi }{3}{\left(R_{\mathit{bump}}+R\right)}^3\approx \frac{\pi }{2}{R}^2{\lambda }_{\max }+\frac{2\pi }{3}{R_{\mathit{bump}}}^3$$

We substitute λ _max as a function of R in the equation above to arrive at a relation expressing R _bump as a function of R in the following way: $${\mathrm{R}}_{\mathrm{bump}}\mathrm{=}\mathrm{0.96}\mathrm{xR}\mathrm{~}\mathrm{R}$$

The spacing distance H between the first surface 3a and the second surface 3b, as well as the lateral dimensions g and w and optionally R _bump electrodes displacement 51, 52 are adapted so that the maximum thickness of the first and second fingers is less than the distance H and the sum of the radii of the first and second drops has a thickness greater than this distance H.

In other words, suppose that the rays (in the (Y, Z) plane) of the first and second fluidic fingers 19a, 19b are respectively R _A and R _B , then the rays of the first and second drops 23a, 23b are of the order of 2R _A and 2R _B respectively. In that case ( Fig. 5 ), the height H separating the first and second surfaces satisfies the following inequality: $${\mathrm{R}}_{\mathrm{AT}}\mathrm{+}{\mathrm{R}}_{\mathrm{B}}\mathrm{<}\mathrm{H}\mathrm{<}\mathrm{2}{\mathrm{R}}_{\mathrm{AT}}\mathrm{+}\mathrm{2}{\mathrm{R}}_{\mathrm{B}}\mathrm{.}$$

Indeed, the Fig. 5 is a schematic perspective view of the crossing zone of the device of the Fig. 2 .

The numerical examples given in the table associated with the Fig. 5 shows that for a separation distance H of the order of 50 .mu.m, the first electrodes 51a, 52a may have a width w _A of the order of 8 .mu.m to 16 .mu.m and be spaced from each other by a distance g _A of the order of 4 .mu.m to 8 .mu.m, and second electrodes 51b, 52b may have a width w _B of the order of 16 .mu.m to 20 .mu.m and be spaced from each other by a distance g _B of the order of 8μm to 10μm.

Then, the radius R _A of the first fluidic finger is of the order of 10 μm to 20 μm (R _A = w _A + g _A / 2), the distance λ _{A, max} between the first zones of formation of drop is from order 90μm to 180μm, the radius R _{A, bump} of the half-disc is of the order of 9.6μm to 19.2μm, the radius R _{A, drop} ( ie, R _{A, total} ) of the first drop 23a is of the order of 19.6μm to 39.2μm, and the VA volume of the first drop is of the order of 16 pL to 126 pL.

In addition, the radius R _B of the second fluidic finger is of the order of 20 μm to 30 μm, the distance λ _{B max} between the second drop formation zones is of the order of 180 μm to 270 μm, the radius R _{B, bump} of the half-disc is of the order of 19.2μm to 28.8μm, the radius R _{B, drop} ( ie R _{B, total} ) of the second drop is of the order of 39.2μm to 58.8μm the volume V _B of the second drop 23b is of the order of 126 μL to 426 μL, and the volume V _C of the overall drop is of the order of 252 μL to 442 μL.

Thus, the first and second drops 23a, 23b have a thickness sufficient for the first drops 23a of the first surface 3a to come to contact of the corresponding second drops 23b of the second surface 3b thus forming corresponding overall drops.

The method according to the invention makes it possible to form drops rapidly and to manipulate them accurately to achieve interactions between different solutions of interest.

est soit moins que 0,01ms pour une densité de liquide ρ=1000kg/m³, une demi-largeur R de doigt de l'ordre de quelques dizaines de micromètre et une tension de surface liquide/air σ=0,072Nm.It should be noted that the formation of a fluid finger 19a, 19b is indeed very fast, with a liquid displacement speed of the order of 1 to 10cm / s; it only takes 50 to 500 ms to form a 5mm fluidic finger. Moreover, the drops are formed even more rapidly, insofar as the characteristic time of instability capillarity / inertia $\sqrt{\rho R^3/\mathrm{\sigma }},$

is less than 0.01ms for a liquid density ρ = 1000kg / m ³ , a half-finger width R of the order of a few tens of microns and a liquid / air surface tension σ = 0.072Nm.

It should be noted that the drop forming zones 53 can be made on only one of the first and second surfaces 3a, 3b. Thus, drops are formed at the desired locations (that is to say at the level of the electrodes with growths) and the liquid can be moved again thanks to the electrodes vis-à-vis do not have an outgrowth .

By way of example (not shown), the pair of first displacement electrodes 51a, 52a may have a plurality of first drop forming regions 53a, while the pair of second electrodes 51b, 52b do not have one.

Thus, after the deactivation of the first electrodes 51a, 52a, the first fluidic finger 19a breaks into a plurality of first drops 23a each located on one of these first drop forming zones 53a. Then, the pair of second electrodes 51b, 52b can be activated to move at least a second drop 23b along these second electrodes, to come into contact with a corresponding first drop 23a located in a first drop forming zone 53 so that to form a global drop 25. In addition, the pair of second electrodes 51b, 52b can be activated to then move the overall drop 25 thus formed along the second electrodes.

This makes it possible, for example, to use solvents acting as an extractor on the first surface of the upper substrate while ionic liquids are moved on the second surface of the lower substrate to carry out a liquid-liquid extraction.

The Figs. 6A-6E schematically illustrate a microfluidic device for handling drops, according to a particular configuration of the first preferred embodiment of the invention.

The first surface 3a includes a first array of m pairs of first electrodes 51a, 52a each comprising a sequence of n first drop forming regions 53a thereby forming a first set of nm first drop forming regions 53a. The device 102 also comprises a set of m first reservoirs 9a of m first liquids of interest 119a arranged so as to be able to respectively contact the first m liquids of interest 119a with the m pairs of first electrodes 51a, 52a.

The second surface 3b includes a second array of n pairs of second electrodes 51b, 52b each comprising a sequence of m second drop forming regions 53b thereby forming a second set of nm second drop forming regions 53b. In addition, the device comprises an assembly of n second reservoirs 9b of n second liquids of interest 119b arranged so as to be able to respectively bring into contact the n second liquids of interest 119b with the n pairs of second electrodes 51b, 52b .

The first nm drop forming regions 53a are arranged to intersect the nm second drop forming zones 53b to form a set of nm crossing zones 7.

More particularly, the top view of the device 102 illustrated on the Fig. 6A shows three (m = 3) pairs of first electrodes 51a, 52a each comprising three (n = 3) first drop forming regions 53a and three (n = 3) pairs of second electrodes 51b, 52b each comprising three (m = 3) second drop forming zones 53b.

The first electrodes 51a, 52a of the first surface 3a can form, with respect to the electrodes 51b, 52b of the second surface 3b, any angle θ so long as the separation distance H is well dimensioned with respect to the widths w _A , w _B and gaps g _A , g _B pairs of electrodes so that the inequality (R _A + R _B ) <H <(2R _A + 2R _B ) is satisfied.

In the initial state, the mother drops of the first m liquids of interest 119a are in the first m reservoirs 9a at the beginning of the tracks of m pairs of first electrodes 51a, 52a. Likewise, the mother drops of the n second liquids of interest 119b are in the n second reservoirs 17b at the beginning of the tracks of n pairs of second electrodes 51b, 52b.

The Fig. 6B (top view) and the Fig. 6C (seen in section) show that when an oscillating signal with a frequency and a suitable voltage is sent by an alternating voltage source 21a, 21b on the first 51a, 52a and second 51b, 52b electrodes, first and second fluidic fingers 19a , 19b move along the electrodes without coming into contact. After a very short time (of the order of a few tens of milliseconds), the fluidic fingers 19a, 19b reach the ends of the electrodes. The profile of the fingers is a semi-disk and has radius R _A for the first fingers and R _B for the second fingers.

The Fig. 6D (top view) and the Fig. 6E (seen in section) show that as soon as the electrical circuit is opened and the electrodes (51a, 52a, 51b, 52b) are no longer powered, the liquid acts in such a way as to recover a minimum energy state by retracting towards the growths (drop formation zones). Thus, n first drops 23a with a radius of about 2 _{R A} are formed on the first nm drop forming regions 53a and nm second drops 23b with a radius of about 2 R _B are formed on the nm second drop forming zones 53b.

Thus, each of the first nm 23a drops from the first surface 3a interact with the corresponding drop 23b nm second drops from the second surface 3b to form a set of nm overall drops in the nm crossing zones 7.

This makes it possible to produce mixtures of biological components (for example, DNA strands) or chemicals in large numbers, simultaneously, and in a very fast time.

It is also possible to use solvents acting as extractors on the first surface of the upper substrate while ionic liquids are displaced on the second surface of the lower substrate.

The device can also be used to form a network of solid pillars with reconfigurable geometry. In this case, the displaced liquids are, for example, waxes or paraffins which have interesting melting and solidification properties.

Advantageously, the handling device comprises means for detecting a component of a drop formed at at least one crossing zone. These detection means may be optical, electromechanical, chemical or other means.

The Figs. 7A and 7B schematically illustrate a handling device according to a configuration of Figs. 6A-6E , and comprising optical detection means.

This device 103 is a microfluidic chip comprising an upper substrate 11a made of a transparent material and coupled to optical detection means 61, 63. These means comprise a light source 61 illuminating the overall drop (s). 25 through the transparent substrate 11a and a sensor, or means 63 for receiving light to receive the light diffused by this (these) drop (s) 25. Thus, the light diffused by a drop makes it possible to analyze the interaction which occurs inside this drop.

This example illustrates the production of a fluorescence response map on n ² chemical / biological reactions (here n = 4) from 2 n automated and simultaneous.

Indeed, from two biological or chemical solutions A and B respectively comprising α chemical or biological elements and β is prepared n _α sample (C _A1, C _A2, C _A3, C _A4) of the solution A in the first reservoirs 9a, and n _β samples (C _B1 , C _B2 , C _B3 , C _B4 ) of the solution B in the second reservoirs 9b, with different properties for each sample (for example, in concentrations of the product).

With the handling device 103 is formed simultaneously and automated n .n _{β α} 25 comprehensive drops different from each other from the interaction between _α n first and n drops corresponding second _β drops.

With the transmission means 61, a light excitation is sent which will be diffused by the different global drops 25. The light diffused and picked up by the reception means 63 makes it possible to determine precisely the fluorescence responses of the interactions or reactions between the elements. α and β ( Fig. 7B ).

According to one variant, the detection means are electromechanical means. In this case, the handling device comprises at least one detector on at least one of the upper and lower substrates. The detector may be a planar electromechanical oscillator disposed at a crossing zone and a face of which forms a detection surface belonging to one or the other of the first and second surfaces.

Indeed, Figs. 8A and 8B schematically illustrate electromechanical detection means integrated in a handling device according to a variant of the first embodiment. In particular, the Fig. 8A is a schematic view in longitudinal section of the device and the Fig. 8B is a schematic perspective view of a portion of the lower substrate of the device of the Fig. 8A .

The upper substrate 11a of the device 104 is similar to that previously described. Advantageously, the upper substrate 11a comprises a hydrophobic layer 14a formed on the dielectric layer 13a. The hydrophobic layer 14a which then forms the first surface 3a may be SiOC, PTFE (polytetrafluoroethylene), even parylene, and have a thickness of a few nanometers to a few microns.

Advantageously, the dielectric layer 13a and the hydrophobic layer 14a may be a single layer of the same material, which may be, for example, Teflon, parylene, SiOC.

The lower substrate 111b comprises a plurality of electromechanical oscillators 71 held in the substrate 111b by support means 73 ( Fig. 8B ). The upper face (i.e., the second surface 113b) of the lower substrate 111b then has sensing surfaces 114b formed by the faces of the oscillators 71.

The oscillators 71 may be similar or identical to those described in the international application WO2009 / 141515 , filed in the name of the applicant, describing a device for gravimetric detection of particles in a fluid medium.

Each oscillator 71 is here a square plate disposed above a cavity 75 allowing it to vibrate in its plane and out of plane. However, it may have other shapes, for example a disk, a ring, or a polygon.

Each plate 71 is mounted on the lower substrate 111b by support means 73, contact peaks ( Fig. 8B ) or possibly beams (not shown), distributed at the four corners of the oscillator 71 and oriented along the diagonals thereof.

The square plate 71 has a width of between 5 and a few hundred microns. Its thickness is typically less than or equal to one tenth of its width. The square plate 71 can be made of a material chosen from monocrystalline silicon, polycrystalline silicon, diamond, silicon nitride, silicon oxide, nickel, tungsten or even platinum or any other material used in the process. microsystems or electromechanical nanosystems (MEMS, NEMS).

The pair of second displacement electrodes 51b, 52b extends on the second surface 113b from a second reservoir (not shown), extends on the square plate 71 of the detection surface oscillator 114b, by the intermediary Support means 73. The pair of second electrodes 51b, 52b form a second drop forming zone 153b at the detection surface 113b.

In addition, the square plate 71 is disposed in a crossing zone 7 directly facing a first drop forming zone 53a of the first displacement electrodes.

Each oscillator 71 is adapted to be vibrated, preferably at its resonance frequency, by capacitive coupling with actuation electrodes 81, 82 arranged opposite the edge of the oscillator 71.

It should be noted that the oscillator 71 can vibrate, preferably in its plane, according to a predetermined vibration mode chosen from the Lamé mode, the volumetric expansion mode or the so-called "wineglass" mode ( Wine Glass ) or any other contour mode.

The gravimetric detection is performed by capacitive coupling between the oscillator 71 and two measurement electrodes 84, 85 arranged opposite the edge of the oscillator 71.

From the measured electric current, the difference in frequency between the effective vibration frequency and the initial frequency imposed is deduced therefrom.

The mode of formation of the first and second fluidic fingers is identical to that described above. In particular, the second fluidic finger is formed by liquid dielectrophoresis and extends on the lower substrate 111b and the oscillators 71 via the corresponding support means 73.

The second drop forming areas 153b are disposed on each detection surface 114b. Thus, when the electrical control is stopped, the second fluidic finger breaks by capillarity in a plurality of second drops, each being disposed on a second drop-forming zone 153b, and thus on a detection surface 114b of the oscillator 71 corresponding.

Each of the second drops 23b formed on the detection surfaces 114b interacts with the corresponding drop of the first drops 23a issuing from the first surface to form a set of overall drops on the different detection surfaces 114b. Gravimetric detection then makes it possible to analyze the interactions occurring inside these drops.

It should be noted that the detection surface 114b of the oscillator 71 can advantageously have a hydrophilic zone intended to be covered by the droplet.

Alternatively, the manipulation device may comprise electrophysiological detection means (not shown).

Indeed, the oscillators 71 in the lower substrate 11b can be replaced by electrophysiological sensors. These sensors record ionic currents flowing through cell membranes forming detection surfaces.

The lower substrate has, at the level of the detection surface, an opening acting as a fluidic chamber, one of whose walls is the lower face of the membrane.

There are also means for measuring the potential difference between two measuring points arranged on either side of the membrane for measuring ionic currents of the species passing through the membrane between the drop formed on the membrane and the chamber. fluidics.

On the Fig. 9 is shown a microfluidic device 201 for handling a drop according to a second embodiment of the invention.

The handling device 201 comprises a lower substrate 211b and an upper substrate 11a forming a cover, arranged facing one another.

The upper substrate 11a is identical to what has been described above and thus comprises at least one reservoir 9a of liquid of interest and at least one first electrical displacement track 5a disposed at the first surface 3a. Advantageously, the upper substrate 11a further comprises a hydrophobic layer 14a formed on the dielectric layer 13a.

Each first electrical displacement track 5a comprises a pair of substantially parallel and coplanar first electrodes 51a, 52a disposed at the first surface 3a for the formation by liquid dielectrophoresis under the effect of the electrical activation of a fluid finger from the reservoir 9a of corresponding liquid of interest. The fluidic finger breaks by capillarity under the effect of the deactivation, generating at least one drop 23a.

The lower substrate 211b has at least one second electrical displacement track 5b disposed at the second surface. The first and second electric displacement tracks define between them at least one crossing zone 7.

Each second electrical displacement track 5b comprises second electrodes 251b, 252b for the displacement of at least one drop 23a formed by the upper substrate 11a in a crossing zone 7.

By way of example, the second electrodes 251b, 252b may be square electrodes configured to move the drop (s) by EWOD under the effect of a suitable electrical activation of the second electrodes 251b, 252b and a second electrode. grounding the pair of first electrodes 51a, 52a knowing that the (the) drops has (s) a sufficient thickness to be in contact with the first and second electrodes.

Indeed, the spacing distance H between the first surface 3a and the second surface 3b, as well as the dimensions of the first displacement electrodes are adapted so that the maximum thickness of the fluidic finger is less than the distance H and that the drop has a thickness greater than this distance H.

In other words, suppose that the radius of a fluidic finger is R, then the radius of a drop is of the order of 2R. In this case, the height H separating the first and second surfaces satisfies the following inequality: $$\mathrm{R}\mathrm{<}\mathrm{H}<\mathrm{2}\mathrm{R}\mathrm{.}$$

For example, for a separation distance of the order of 50 .mu.m, the first electrodes 51a, 52a may have a width w of the order of 20 .mu.m and be spaced from each other by a distance g of the order of 20 .mu.m. The radius R of the fluidic finger will thus be of the order of R = w + g / 2 = 30 μm and the radius of a droplet will be of the order of 60 μm.

Note that according to this second embodiment, the drops are formed by the upper substrate 11a and thus the lower substrate 111b does not have a liquid reservoir of interest.

The second embodiment according to the invention makes it possible to transfer drops of liquid from the first surface 3a to the second surface 113b and to manipulate or then move this liquid through the displacement electrodes arranged at the second surface.

Advantageously, the device comprises optical, electromechanical, electrophysiological, or other detection means, made as described with reference to the first embodiment.

In particular, for the electromechanical detection means, the second electrodes may be configured for example to bring the drops to the detection surfaces.

In addition, the second surface may be functionalized, and / or have a temperature different from the first surface, and / or comprise biological components for carrying out various biological or chemical protocols.

Of course, various modifications may be made by those skilled in the art to the invention which has just been described, solely by way of non-limiting examples.

Claims (17)

Microfluidic device for handling a drop, characterized in that it comprises: first and second microfluidic surfaces (3a, 3b) parallel and spaced from one another by a separation distance (H), at least one first electrical displacement track (5a) disposed at said first surface (3a), at least one second electrical displacement track (5b) disposed at said second surface (3b), said first and second tracks defining between them at least one crossing zone (7), at least one of said first and second tracks (5a, 5b) being configured to form, by liquid dielectrophoresis, under the effect of electrical activation, a respective fluidic finger (9a, 9b) along said track from a corresponding reservoir of liquid of interest (9a, 9b) arranged to be able to bring said liquid into contact with the associated surface (3a, 3b), said fluidic finger breaking by capillarity under the effect of a deactivation generating at least one drop (23a, 23b) respectively from said fluid finger in said at least one crossing zone (7), the first and second tracks (5a, 5b) being configured so that said separation distance (H) between said first and second surfaces (3a, 3b) is on the one hand greater than the fluidic thickness formed by each fluidic finger and, on the other hand, less than the fluidic thickness formed by each drop. Device according to claim 1, said first electrical displacement track (5a) comprising a pair of substantially parallel and coplanar first electrodes (51a, 52a) disposed at said first surface (3a) for formation under the effect of the electrical activation of a first fluidic finger (9a) from a first reservoir (9a) of a first liquid of interest, said second electrical displacement track (5b) comprising a pair of second electrodes (51b, 52b) ) substantially parallel and coplanar disposed at said second surface (3b) for forming under the effect of electrical activation, a second fluidic finger (19b) from a second reservoir (9b) of a second liquid of interest, said first and second fluidic fingers (19a, 19b) breaking by capillarity under the effect of deactivation, generating at least a first drop (23a) and at least a second drop (23b) respectively mix in said at least one crossing zone (7) to form at least one overall drop (25). An apparatus according to claim 2, said pair of first electrodes (51a, 52a) having a plurality of first drop forming regions (53), so that upon deactivation of said pair of first electrodes, the first fluid finger (19a ) breaks into a plurality of first drops (23a) each located on one of said first drop forming zones. An apparatus according to claim 3, said pair of second electrodes (51b, 52b) having a plurality of second drop forming zones (53) each disposed opposite a first distinct drop forming zone thereby forming a plurality of crossing zones (7), so that upon deactivation of said pair of second electrodes, the second fluidic finger (19b) breaks into a plurality of second drops (23b) each located on one of said second formation zones droplet, each second drop coming into contact with the corresponding first drop (23a) to form a global drop (25) in the corresponding crossing zone. Device according to claim 4, said first surface (3a) comprising a first network of m pairs of first electrodes (51a, 52a) each comprising a sequence of n first zones of drop formation thus forming a first set of nm first formation zones droplet, said second surface (3b) having a second network of n pairs of second electrodes (51b, 52b) each comprising a sequence of m second drop forming zones thus forming a second set of nm second drop formation zones, said first nm drop forming regions intersecting said second drop forming zones to form a set of nm crossing zones (7). Device according to any one of claims 2 to 5, characterized in that said pair of second electrodes (51b, 52b) is configured to move at least a second drop (23b) and / or at least one overall drop (25) located along said pair of second electrodes. Device according to claim 1, said first electrical displacement track (5a) comprising a pair of substantially parallel and coplanar first electrodes (51a, 52a) arranged at said first surface (3a) for liquid dielectrophoresis formation under the effect electrical activation, a fluidic finger from a liquid reservoir of interest, said fluidic finger breaking by capillarity under the effect of deactivation, generating at least one drop, said second track (5b ) electric displacement comprising second electrodes (251b, 252b) for the displacement of said at least one drop under the effect of an electrical activation of said second electrodes. Device according to any one of the preceding claims, characterized in that it comprises means for detecting a component of a drop formed at said at least one crossing zone. Device according to Claim 8, characterized in that the said detection means are optical means comprising a light source (61) for emitting light on the said at least one drop and receiving means (63) for receiving the light diffused by said at least one drop. Device according to Claim 8, characterized in that the said detection means are electromechanical means comprising at least one oscillator (71) plane of which one side forms a detection surface (114b) belonging to one or the other of said first and second surfaces. Device according to claim 10, characterized in that said detection surface (114b) has a hydrophilic zone intended to be covered by said at least one drop. Device according to any one of claims 2 to 11, characterized in that each of said pairs of first and second electrodes is covered with a dielectric layer (13a, 13b). A method of handling a drop, characterized in that it comprises the following steps: contacting at least a first reservoir (9a) comprising a first liquid of interest (119a) with at least a first corresponding electrical displacement track (5a) disposed at a first microfluidic surface (3a), contacting at least one second reservoir (9b) comprising a second liquid of interest (119b) with at least a second corresponding electric displacement track (5b) arranged at a second microfluidic surface (3b), said first and second surfaces being parallel and spaced from each other by a separation distance (H), said at least one first and at least one second displacement tracks defining between them at least one crossing zone (7). ) activating said at least one first displacement track, so as to form along said first track a corresponding first fluidic finger (19a), activating said at least one second displacement track, so as to form along said second track a corresponding second fluidic finger (19b), deactivating said at least one first displacement track, so that the first corresponding fluidic finger breaks by capillarity by generating at least a first drop located in said at least one crossing zone; deactivating said at least one second displacement track, so that the second fluidic finger breaks by capillarity by generating at least a second drop (23b) located in said at least one crossing zone, said separation distance between said first and second surfaces being on the one hand, greater than the sum of the thicknesses of said first and second fluidic fingers, and, on the other hand, less than the sum of the thicknesses of said first and second drops, so that said first and second drops are mix in said at least one crossing zone to form at least one overall drop (25). The method of claim 13 including the steps of: contacting a set of first m reservoirs (9a) comprising m first liquids of interest with a network of m first corresponding tracks each comprising a sequence of n first drop formation zones thus forming a first set of first nms; drop formation areas, contacting a set of n second reservoirs (9b) comprising n second liquids of interest with an array of n second corresponding tracks each comprising a sequence of m seconds forming drop zones thus forming a second set of nm seconds drop forming zones, said first nm forming drop zones respectively crossing said nm second drop formation zones to form a set of nm corresponding crossover zones (7), activation of said network of first m tracks, so as to form a network of m first corresponding fluidic fingers, activation of said network of n second tracks, so as to form an array of n corresponding second fluidic fingers, disabling said network of m first tracks, so that the first m corresponding fluidic fingers break by capillarity by generating a set of first nm drops in said first set of nm first drop formation zones, deactivating said network of n second tracks, so that the corresponding second n corresponding fluidic fingers break by capillarity by generating a set of nm second drops in said second set of nm second drop formation zones, the first nm drops mixing with the corresponding nm second drops to form a set of nm global drops in the corresponding nm crossing areas. The method of claim 14, said first m first tanks respectively comprising m first samples of different properties of a first solution and said n second reservoirs respectively comprising n second samples of different properties of a second solution thus forming nm different overall drops. A method according to claim 15, comprising detection by optical, electromechanical, or electrophysiological means of the different interactions between said first and second solutions. A method of handling a drop, characterized in that it comprises the following steps: contacting at least one reservoir (9a) comprising a liquid of interest with at least a first corresponding electrical displacement track (5a) disposed at a first microfluidic surface (3a), said first surface being parallel to a second microfluidic surface (3b) and spaced therefrom by a separation distance (H), said second surface comprising at least a second electrical displacement track (5b) defining at least one crossing zone (7) with said at least one first track, activating said at least one first displacement track, so as to form along said first track a corresponding fluidic finger (19a), deactivation of said at least one first displacement track, so that the corresponding fluidic finger breaks by capillarity by generating at least one drop (23a) located in said at least one crossing zone, said separation distance between said first and second surfaces being on the one hand greater than the thickness of said fluidic finger and, on the other hand, less than the thickness of said at least one drop, and activation of said at least one second electric displacement track, so as to move said at least one drop.

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