Microfluidic device with stabilized liquid-fluid interface

Technical Field of the Invention

The invention relates to a microfluidic device comprising at least one microchannel designed to contain at least one liquid and at least a fluid immiscible with the liquid and the interface stabilizing means between the liquid and the fluid, said micro- channel being defined by bottom walls, side and top.

State of the art

The microlabs or microfluidic devices, better known as the Anglo-Saxon name "μ-TAS" (micro Total Analysis System) or "Lab-on-a-chip", are used to perform chemical or biological operations on samples of very small volumes. These volumes are, for example, an order of magnitude between the nanoliter and microliter. It is well known to use microfluidic devices to perform mixtures, separations, temperature controls, reactions or solvent extractions.

At this scale, a key challenge generated by the contacting of two immiscible phases with each other and, more particularly, during the mass transfer between the two phases, in the case of solvent extraction for example, is the stabilization of the interface between the two phases.

There are various methods for stabilizing liquid interfaces / liquid or liquid / gas. Thus, in a larger scale devices, it is known to stabilize the interface between two immiscible phases, through a porous membrane. For example, WO-A-9612540 discloses a device and method for the transfer of solute between two immiscible fluid phases, through a porous flat membrane to stabilize the interface between the two fluid phases.

This technique has been adapted to the scale of microlabs, as mentioned in the document "Fabrication of components and systems for chemical and biological microreactors" W. Ehrfeld and al. (Microreaction technology, IMRET1 1997, pages 72-90). This document describes the use of very thin membranes and selective in microlabs to perform extractions and filtrations.

It is also known to modify the surface properties of a microchannel wherein two immiscible phases are introduced. Thus the document "surface-directed liquid flow inside microchannels" Bin Zhao et al. (Science, Vol 291, 2001, pages 1023-1026) describes an interface stabilization method in a microchannel. Predetermined regions of the microchannel of the bottom are chemically treated in order to modify the wettability properties of the areas, which requires individual paths to the two phases. Each phase remains in fact shown on the area which corresponds the best to a wettability point of view. This technique is in particular used for applications where a large contact surface between the two phases is necessary, but it is impractical to implement.

It is also commonly applied, in a timely manner, a potential difference between two electrodes in order to move a fluid from one point to another. Thus, US-A-2002/0043463 describes a device for passing an electrolyte droplet placed in an immiscible liquid, a lower chamber to a superior room, with openings arranged in a wall separating the room top of the lower chamber. The time application of a potential difference between a first pair of electrodes makes it possible, in a first step, the displacement of the droplet along the lower chamber to bring it in front of a predetermined orifice of the wall. Then, a point of potential difference is applied between a second pair of electrodes respectively disposed at the lower chamber and the upper chamber so as to allow the passage of the drop of a chamber to the other through the orifice of Wall.

The US4818052 and WO-A-02,069,016 describe optical switches operating by moving in a microchannel, a first fluid with respect to a second fluid immiscible with the first fluid between first and second positions. Moving the first fluid can be accomplished by applying, in a timely manner, a potential difference between electrodes disposed on opposite walls of the microchannel. Each electrode covers part of the length of the microchannel, so as to cause a longitudinal displacement of the drop inside the microchannel, by application of a control signal sequence.

Applying a voltage in this type of device only possible to move a fluid in another immiscible fluid and a given point to another given point.

The invention

The invention is to provide a microfluidic device wherein the contact area between a liquid and a fluid immiscible with each other, is stabilized and is easy to implement, while maintaining a high contact surface between the liquid and the fluid.

According to the invention, this object is achieved in that the stabilizing means comprise at least one electrode disposed on at least a portion of a first wall of the microchannel, over the entire length thereof and at least one against electrode disposed over the entire length of the microchannel, on at least a portion of a second wall, arranged facing the electrode.

According to a development of the invention, the against-electrode is disposed on the entire second wall.

According to a preferred embodiment, the electrode and against electrode are respectively arranged on the bottom and top walls.

According to another characteristic of the invention, the fluid or liquid being electrically conducting, the microfluidic device comprises insulating means arranged between the electrode or the against-electrode and said fluid or said liquid.

According to another characteristic, the micro-channel has, at at least one end, two end microchannels designed to be driven respectively by the fluid and the liquid.

BRIEF DESCRIPTION OF DRAWINGS

Other advantages and features will become more apparent from the following description of specific embodiments of the invention given as non-limiting examples and represented in the accompanying drawings, wherein:<ul><li>Figure 1 is a schematic representation, in cross section, of a microfluidic device according to the invention.</li><li>Figures 2 and 3 illustrate respectively different embodiments of a microchannel of a microfluidic device according to the invention.</li><li>Figures 4 to 7 show schematically, in plan view, various steps of introducing a liquid and a fluid in a microfluidic device according to the invention.</li><li>Figures 8 to 11 are diagrammatic representations of various stages of completion of a microfluidic device according to the invention.</li></ul>

Description of particular embodiments.

In Figure 1, a microfluidic device 1, in particular used to produce solvent extractions comprises at least one micro-channel defined by a bottom wall 2 formed by a substrate 3, side walls 4 formed on the substrate and a top wall 5 parallel to the substrate. The microchannel is for contacting a liquid and a fluid forming two phases 6 and 7 not mixed together. By fluid is meant a liquid or a gas.

The microchannel is a hollow three-dimensional structure having a very high ratio of length to height. In the case where the length is very large relative to the width, one speaks of a micro-channel linear three dimensional structure. For example, the length of a microchannel is preferably of the order of a few millimeters to a few centimeters, while the width and height respectively of the order of tens to hundreds of micrometers. The microchannel may also have a very large width compared to its height, in particular when it contains many phases. We then speak of a surface-dimensional structure of micro-channel or micro chamber.

To stabilize the interface between two phases, the microfluidic device comprises at least one electrode disposed on at least a portion of a first wall of the microchannel, over the entire length thereof. Against at least one electrode is disposed over the entire length of the microchannel, on at least a portion of a second wall. The portion of the second wall having the against-electrode is arranged opposite the electrode. Against the electrode may also be disposed on the entire second wall. The width of the electrode and against the electrode is preferably of the order of several tens to several hundreds of micrometers.

The microfluidic device also comprises means for creating a potential difference between the electrode and the electrode against. The potential difference created of said electrostatic forces which alter certain properties of one of the two phases or two phases, depending on the sensitivity of the vis-a-vis phases of these forces. Thus, the forces can be of different natures, according to the characteristics of the liquid and the fluid brought into contact. They can, for example, modify the wetting characteristics of one phase or two phases relative to their support. In this case, the forces are called electrowetting forces or electrocapillarity. It may also be volume or dielectric forces acting on dielectric liquids.

The potential difference created keeps the most sensitive to the force created phase within an area enclosed by the electrode and the part of the electrode disposed against opposite the electrode, which stabilizes the interface between the two phases, it may be vertical or horizontal according to the arrangement of the electrodes. Thus, if the electrode and the against-electrode are respectively arranged on the bottom wall and the top wall, the interface is substantially vertical, whereas if the electrodes are disposed on the sidewalls, the interface is substantially horizontal.

In Figure 1, the electrode 9 is disposed on a portion of the bottom wall 2 and against the electrode 10 is disposed on the entire upper wall 5. The electrode 9 and the electrode 10 are against, respectively in contact with the stage 7 and the two layers 6 and 7. the electrode 9 and the part against the electrode 10 facing the electrode 9 then form a first predetermined area in which there is phase 7 , the stage 8 being disposed in a second micro-channel region disposed adjacent to the first zone.

The device also comprises an electrical contact pickup 11 which connects the electrode 9 with a voltage generator 12, also connected to the against-electrode 10. The voltage applied by the generator is either alternative, is continuous and it is the order of tens to hundreds of volts. In the case of an AC voltage, the electrical frequency may range from about a few tens of hertz to several tens of megahertz. Thus, the tension created between the two electrodes is constant, that is to say, it is not applied in a timely manner, but on the contrary for the duration of use of the microfluidic device, so that during this time, the interface between the two phases is stabilized. The voltage may for example be sinusoidal.

Phases introduced into the microchannel can be stationary or moving. If the phases are intended to be moving, the microchannel may comprise at least one end, two end microchannels designed to be driven respectively by the fluid and the liquid. Thus, in Figure 2, the liquid and the fluid is intended to flow in a micro-channel 13, respectively in first and second longitudinal and adjacent areas. The first zone is delimited, in Figure 2, by the electrode 9 while the second area corresponds to the free portion of the microchannel, that is to say, the portion having no electrode. The micro-channel 13 also includes turns to occupy less space than a linear micro-channel.

The ends of the microchannel 13 comprise, respectively, an inlet micro channel 14 and an outlet micro-channel 16, respectively for the introduction and the outlet of a first phase. Similarly, for the introduction and the outlet of a second phase, the two ends of the microchannel 13 comprise an inlet microchannel 15 and an outlet microchannel 17. The two phases circulate in the microphone -channel 13, along paths defined by the electrode and against the electrode. The path of the most sensitive stage to the potential difference created between the electrode and the electrode against the electrode is represented by 9 in Figure 2. It is disposed on a portion of the width of the bottom wall of micro-channel 13, over the entire length thereof, as well as over the entire length and width of the inlet micro-channels and output 15 and 17. the two phases can circulate in the same direction or in opposite directions .

According to alternative embodiments, the microfluidic device may comprise a plurality of micro-channels arranged in series or in parallel. Thus, in Figure 3, the micro-channel 13 of Figure 2 is connected to a second micro-channel 18 of the same geometry. The second microchannel 18 has an inlet 19 microchannel for introducing a third phase and an inlet micro channel 20 for the introduction of the first phase. The input micro-channel 20 is connected to the output of the microchannel 16 so as to allow passage of the first phase, the first microchannel 13 to the second micro-channel 18. This enables a second transfer mass between the first and third phases, the second phase of the first microchannel 13 being discharged through the outlet microchannel 17. the series connection of several micro-channels thus allows to carry out several successive extractions, while the parallel connection of several microchannels can simultaneously perform multiple extractions.

The two phases can be injected into the microfluidic device by any appropriate means. Thus, the liquid and the fluid can be introduced through a pump, a water column or a syringe pump or by capillarity or electroosmosis. Thus, as shown in Figures 4 to 7, the microchannel 13 comprises a reservoir 21 for receiving the second phase 7. A capillary 22 is also connected, by adhesion, to a micro-channel of the input 13 so introducing the first phase.

In Figure 5, a volume of the second phase 7 is deposited in the tank 21. Under the action of the potential difference applied between the against-electrode (not shown) and the electrode 9, the second phase 7, which is the most sensitive to the potential difference, is displayed within the area bounded by electrode 9 and the portion of the against-electrode facing the electrode 9 (Figure 6). The forces created by the potential difference also act as microfluidic pump, by causing the second phase 7 in the area of ​​the microchannel 13 represented by the electrode 9 on Figure 5. Once the second phase 7 injected and stabilized the first phase 6 is injected through the capillary 22 (Figure 7) and flows into the microchannel 13 in the free space of the micro-channel 13. the interface 8 between the first and second stages 6 and 7 remains stable during this flow.

The microfluidic device according to the invention thus enables to effectively stabilize the interface between two immiscible phases with each other without requiring a physical barrier between the two phases. This has the advantage of not restricting the contact surface between the two phases and therefore do not limit the mass transfer between the two phases in a small area.

According to a first embodiment, shown in Figures 8 to 11, the microfluidic device according to Figure 1 is made from a substrate 3, glass or silicon 500 microns thick, on which is formed, by photolithography, a gold electrode 9 (Figure 8). If the liquid or fluid is electrically conducting, the microfluidic device comprises insulating means for protecting the electrode and / or against the electrode of the liquid and / or fluid conductors made. The insulating means are arranged between the electrode or the electrode and against the liquid or fluid. The substrate 3 having the electrode can be electrically isolated, for example, with a layer 23 of silicon oxide or SiO₂ (Figure 9), said layer being deposited on the substrate in a deposition process vapor in plasma, better known under the name of process "PECVD" (Plasma enhanced chemical vapor deposition).

Sidewalls 4, a thick resin, are then performed on the substrate 3, by photolithography (Figure 10). The top wall 5, made of glass or plastic material such as polycarbonate for example, is adhesive by screen printing assembly 24 of the assembly (Figure 11). Before this step, a part of the width of the upper wall 5 was coated with a layer of indium tin oxide compound and, better known as the Anglo-Saxon name of ITO (Indium Tin Oxide). Form said layer against the electrode 10 and is optionally electrically insulated. The realization of such a microfluidic device has the advantage of being easy to implement.

The insulating layer 23 of a few micrometers can be made of an insulating polymer such as a dimer like Di Para xylylene better known under the trade name Parylene ®, vapor deposited after the completion of the sidewalls. The layer may also be in liquid fluorinated polymer such as Teflon® liquid, spin-coated prior to assembly by adhesive screen printing. The insulation against the electrode 10 is, for example, made on the upper wall, before assembly. It can be performed by depositing an insulating layer of a few micrometers in Parylene® or Teflon® deposited by the techniques already described for insulating the electrode 9. The electrode insulation and against -électrode may also be performed after the assembly of the lower and upper walls, depositing an insulating layer of a few micrometers in Parylene® (vapor deposition) or liquid Teflon® (deposit by circulation in the microchannel).

According to a second embodiment, the micro-channel is formed in the upper wall 5, by hot embossing. The thus structured top wall is then coated with an ITO layer to realize the electrode against. The assembly of the top wall on the substrate having the electrode is then performed by screen printing of glue. If the fluid and / or the liquid are electrically conductive, insulation of the electrode and against the electrode is performed by one of the techniques described in the first embodiment.

The invention is not limited to the embodiments described above. Thus, the electrode and against electrode may be respectively disposed on the sidewalls of the microchannel.

The electrode and against electrode may also be disposed facing one another, on the whole of a first and second walls. The fluid and the liquid which does not react in the same manner to the potential difference applied between the electrode and the electrode against the interface between the fluid-and the liquid is then stabilized by applying the potential difference .

In addition, the microfluidic device may contain a number of phases greater than two, each phase being immiscible with the adjacent phases. It is also possible to couple this technique with known techniques such as the use of a porous membrane or chemical treatment of the microchannel walls.