EP3632566A1 - Microfluidic circuit - Google Patents

Microfluidic circuit Download PDF

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Publication number
EP3632566A1
EP3632566A1 EP19201464.5A EP19201464A EP3632566A1 EP 3632566 A1 EP3632566 A1 EP 3632566A1 EP 19201464 A EP19201464 A EP 19201464A EP 3632566 A1 EP3632566 A1 EP 3632566A1
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EP
European Patent Office
Prior art keywords
drops
microchannel
trapping
fluid
bubbles
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP19201464.5A
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German (de)
French (fr)
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EP3632566B1 (en
Inventor
Charles Baroud
Rémi DANGLA
François GALLAIRE
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Centre National de la Recherche Scientifique CNRS
Ecole Polytechnique
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Centre National de la Recherche Scientifique CNRS
Ecole Polytechnique
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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502769—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements
    • B01L3/502784—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements specially adapted for droplet or plug flow, e.g. digital microfluidics
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02—Adapting objects or devices to another
    • B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
    • B01L2200/027—Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0647—Handling flowable solids, e.g. microscopic beads, cells, particles
    • B01L2200/0652—Sorting or classification of particles or molecules
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0864—Configuration of multiple channels and/or chambers in a single devices comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/089—Virtual walls for guiding liquids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0406—Moving fluids with specific forces or mechanical means specific forces capillary forces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/08—Regulating or influencing the flow resistance
    • B01L2400/084—Passive control of flow resistance
    • B01L2400/086—Passive control of flow resistance using baffles or other fixed flow obstructions

Definitions

  • the present invention relates to a microfluidic circuit comprising at least one microchannel in which a first fluid flows serving for the displacement of drops or bubbles of at least one second fluid.
  • a microfluidic circuit is described in the document WO 2006/018490 on behalf of the applicants.
  • This is made of a suitable material such as for example PDMS (poly-dimethylsiloxane) comprising microchannels typically having a width of approximately 100 ⁇ m and a depth of approximately 50 ⁇ m, in which very low flow rates can be passed d '' a fluid such as air, water, oil, reagents, etc.
  • PDMS poly-dimethylsiloxane
  • a laser beam whose wavelength is not absorbed by the material constituting the circuit, is focused on the interface of a first fluid flowing in a microchannel and of a second fluid present at least locally in this microchannel, to force or stop the flow of the first fluid in the microchannel, to split it into drops, to mix it with the second fluid, etc., focusing the laser beam on the fluid interface creating a temperature gradient along of this interface and causing a movement of fluids by thermocapillary convection.
  • this technology has been used to treat drops in a microfluidic circuit comprising at least one microchannel traversed by the drops.
  • the method used consists in causing a laser beam to act on the interface of these drops in a carrier fluid or on the interface of the drops in contact, in order to sort the drops, to form nano-drops from a drop of larger size or to merge drops in contact and cause reactions between the fluids contained in these drops.
  • the subject of the invention is another process for treating drops in a microfluidic circuit, which can optionally be used in combination with the prior treatment techniques described above.
  • the invention provides a microfluidic circuit comprising at least one microchannel for the flow of a first fluid transporting drops or bubbles of at least one second fluid, characterized in that the height of the microchannel is dimensioned to crush the drops or bubbles during their movement, and in that the microchannel comprises at least one channel, extending at least partly in the direction of flow of the first fluid or a zone for trapping drops or bubbles, this zone or channel having a height greater than that of the microchannel, so that at least some of the drops or bubbles of the second fluid in the microchannel are attracted and guided in the channel or in the trapping zone.
  • the surface energy of the drop is lower the smaller its external surface.
  • the minimum energy is therefore obtained by a drop of spherical shape and increases continuously as the drop moves away from this shape.
  • the surface energy can be calculated for a drop of known volume, for any position in the microchannel. Thus, we can predict whether or not the drop will be guided by a given channel by comparing the forces at play.
  • a drop placed in the microchannel and crushed has a large external surface. This drop thus naturally seeks to reduce its external surface, which causes it to migrate to the greater height channel when it arrives at a branch between the microchannel and the channel.
  • the drops are thus attracted to the channel and are displaced along it by the first fluid.
  • the drop remains trapped in the channel as long as the viscous driving force, in the normal direction to the local direction of the channel and exerted by the first fluid on the drop, is less than that necessary to deform the drop and restore it to its crushed shape.
  • This phenomenon is thus influenced by several parameters, such as the viscosity of the carrier fluid and that of the fluid of the drops, the size of the drop, the speed of the carrier fluid, the interfacial tension, the geometry of the channel, the thickness of the microchannel, etc.
  • the microchannel is delimited by two parallel walls, and the channel is formed by a groove of at least one of the walls of the microchannel, or between two parallel ribs of one of the walls of the microchannel.
  • bubbles or drops of at least two different types are transported by the first fluid and the channel constitutes a means of separation or sorting of the bubbles or drops, only those of a first type being guided in the channel.
  • the drops which are attracted to the channel are those for which the viscous force exerted by the first fluid on each drop is less than that necessary to deform the drop and restore it to its crushed shape.
  • the drops which flow in the direction of the carrier fluid without following the channel are those for which the viscous force exerted by the first fluid on the drop is greater than that necessary to deform the drop and restore its shape crushed.
  • the bubbles or the drops of different types have different sizes, viscosities, or surface tensions, which makes it possible to separate them from each other.
  • the channel comprises at least two successive parts of different height and / or width, a part of greater width and / or height being followed by a part of smaller width and / or height, in the direction of flow of the first fluid.
  • This type of channel makes it easy to separate two types of bubbles or drops. For example, bubbles of high viscosity or of large size will flow only along the very high part of the channel before being driven out of the channel by the carrier fluid, while bubbles with lower viscosity or smaller will flow not only along the high-rise portion of the channel but also along its low-rise portion.
  • the circuit comprises channels of different width and / or of different inclination with respect to the flow of the first fluid, which also makes it possible to be able to discriminate different types of bubbles or drops.
  • the circuit comprises zones for trapping drops or bubbles, formed by an enlargement of the cross section of the drops or bubbles in the microchannel or in a said channel, or by a local modification of the surface energy. microchannel and / or channel.
  • the circuit can include trapping zones in the microchannel, even in the absence of the channel. The drops or bubbles transported by the carrier fluid are then trapped in the trapping zones placed on their trajectory.
  • these trapping zones can be smaller than the size of the drops or bubbles to be trapped.
  • trapping zones can be adapted to a single type of bubble and / or can only contain a defined number of bubbles, for example one or two bubbles.
  • the trapping zones make it possible to immobilize one or more drops, which makes it possible for example to examine them using a microscope and / or to follow the progress of a reaction within a zone during a period of important time.
  • At least some of the trapping zones can be independent of each other.
  • At least some of the trapping zones are connected in series or in parallel by the microchannel or by the aforementioned channels.
  • the trap can be manufactured in such a way that the presence of a drop in it forces the following drops to continue their journey, in order to fill the traps located downstream.
  • a trapped drop is stationary but its content continues to be set in motion by the flow of the carrier fluid. In this way, the contents of the drop can be mixed even when it is stationary.
  • Such a phenomenon can in particular play an important role in the field of biological incubation or for the establishment of a chemical reaction.
  • the jump of one or more drops from one trapping zone to another may cause, by cascade effect, the movement of the trapped drops in the zones located in downstream.
  • obstacles are formed downstream of certain trapping zones to retain in these zones the bubbles or the drops which have been attracted to them.
  • At least one channel comprises means for slowing down or accelerating the bubbles or drops present in the channel, these means for slowing down or accelerating being formed by variations in width or height of the channel, or by rails or ribs of the walls of the corresponding microchannel, formed along the desired zones of deceleration or acceleration.
  • the circuit comprises means for forming parallel trains of drops or bubbles of different nature in a microchannel comprising parallel means of introducing drops or bubbles of different nature into the microchannel, and channels formed in this microchannel from the introduction means to guide the drops or bubbles leaving each introduction means to a predetermined area of the microchannel.
  • Each type of drop is thus brought to a predefined location in the microchannel. It is then possible to have series of drops of known nature at different levels of the microchannel.
  • the figure 1 shows schematically a first embodiment of a microcircuit 1 according to the invention.
  • the microcircuit 1 is formed in a plate of a suitable material such as for example PDMS (poly-dimethylsiloxane) by use of a common technique of flexible lithography, as is known from the aforementioned prior art.
  • a suitable material such as for example PDMS (poly-dimethylsiloxane)
  • One or more microchannels 2 can be formed on the surface of the plate, on which a glass microscope slide is stuck, for example.
  • the microchannel 2 has a rectangular section, the width L of which is defined by its horizontal transverse dimension, that is to say in the plane of the microcircuit 1, and the height h of which is defined by its dimension in the vertical direction, that is to say in a direction perpendicular to the plane of the microcircuit 1.
  • a groove 3 of rectangular or square section is formed in one of the two horizontal walls 4 which delimit the microchannel 2.
  • a second groove could be formed in the opposite horizontal wall, opposite the first 4.
  • the groove 3 thus forms a channel of larger section than the rest of the microchannel 2.
  • a first fluid called the carrier fluid, circulates in the microchannel 2, in the direction indicated by the arrow F, carrying with it drops 5 of a second fluid, of a different nature from the first fluid.
  • the second fluid may be in the form of drops or bubbles, without modifying the operation of the invention.
  • the drops 5 flowing in the narrow area of the microchannel are crushed.
  • they meet a channel 3 they take a less flattened shape there, for example a spherical or quasi-spherical shape, requiring less surface energy than the crushed form. It should be noted that the drops can remain crushed while being guided by the channel.
  • the determining criterion is that the surface energy of the drop in the channel is smaller than that outside the channel, the sphere corresponding to the minimum of this energy.
  • the drops can be larger or smaller than channel 3.
  • the figure 2 illustrates an alternative embodiment of the invention in which the groove defining the channel 3 has a concave or rounded shape.
  • FIG. 3 Another alternative embodiment is shown in figure 3 , in which one of the horizontal walls 4 is provided with two parallel ribs 6, spaced from one another, directed towards the inside of the microchannel 2 and delimiting between them a channel 3.
  • the drops 5 crushed between the top of the ribs 6 and the opposite wall 8, are directed either towards the channel 3, or in the other zones of the microchannel 2 located on either side of the ribs 6. In these zones , the drops 5 can find a spherical or quasi-spherical shape and therefore a lower surface energy. In this way, the ribs form barriers allowing to separate certain drops from the others.
  • the figure 4 represents, in top view, the shape of a channel 3.
  • the channel 3 comprises at least one part 9 extending along the axis A of the microchannel and therefore along the axis F of fluid flow carrier, at least a portion 10 extending obliquely to the aforementioned axis A, and / or at least a portion 11 of sinusoidal shape.
  • the trajectory of the drops 5 circulating along the channel 3 has a component according to the direction of flow of the carrier fluid, so that the drops 5 are always entrained by the carrier fluid, from upstream to downstream of channel 3 and microchannel 2.
  • the travel time of the drops 5 in the microchannel 2 is greater. In this way, the contents of the drops 5 can be observed using a microscope for a longer period of time, without the need to change the observation area over time.
  • the figure 5 illustrates a network of channels comprising a central channel 12 extending in the direction of the microchannel 2, on either side of which extend several auxiliary channels 13.
  • Each auxiliary channel 13 extends from the central channel 12 and leads to new to the latter, like diversion channels.
  • the drops 5 contain for example water and the carrier fluid is paraffin oil, the width of the microchannel 2 is 3 mm, that of the channels 12, 13 is 70 ⁇ m, the heights of the microchannel and channels are 50 ⁇ m and 35 ⁇ m respectively, and the 5 drops flow from left to right in the direction of arrow F.
  • the carrier fluid is paraffin oil
  • the width of the microchannel 2 is 3 mm
  • that of the channels 12, 13 is 70 ⁇ m
  • the heights of the microchannel and channels are 50 ⁇ m and 35 ⁇ m respectively
  • the 5 drops flow from left to right in the direction of arrow F.
  • the figure 6 represents a microchannel 2 in which a first fluid circulates forming a carrier fluid for drops of a first and a second type.
  • the drops of the first type 14 have a larger size than the drops of the second type 15.
  • the microchannel 2 is equipped with a channel 3 extending obliquely from upstream to downstream relative to the direction of circulation of the carrier fluid, represented by the arrow F.
  • the height and / or the width of the channel 3 are adjusted so that the largest drops 14 are carried with the carrier fluid in the direction of arrow F and the smallest drops 15 are drawn into the channel 3, then progress along it, from the 'upstream downstream, being driven by the carrier fluid.
  • the downstream end 16 of the channel 3 is provided with a reduction in its height or its width so that the viscous force exerted by the carrier fluid is greater than that necessary to crush the drops 15, so that the carrier fluid drives them again into the microchannel 2.
  • the drops 14 and 15 thus circulate, downstream of the channel 3, respectively along two axes B and C parallel to the flow of the carrier fluid and spaced from each other.
  • Such a microchannel thus makes it possible to sort two types of drops of different nature.
  • the figure 7 illustrates a microchannel 2 similar to that of the figure 6 , in which the drops of the first type 14 are relatively very viscous and the drops of the second type 15 are relatively not very viscous.
  • the height and / or width of the channel 3 are adjusted so that the more viscous drops 14 are carried with the carrier fluid and that only the less viscous drops 15 are drawn into the channel, then progress along it , from upstream to downstream, being driven by the carrier fluid and leaving the channel 3 at the downstream end thereof.
  • Such a microchannel 2 can also be used to sort drops having different surface tensions.
  • the figure 8 represents a microchannel of the type of those of Figures 6 and 7 , in which the channel successively presents, from upstream to downstream, zones of decreasing height and / or width 17 to 20.
  • Each zone is dimensioned so as to be able to discriminate a particular type of drop.
  • the carrier fluid causes four types of drops of different sizes or viscosities opposite the first zone 17, that is to say the widest and / or deepest zone.
  • the drops of the first type 21, that is to say the largest or the most viscous are entrained through this zone 17 by the carrier fluid, the trajectory of these drops 21 being hardly influenced by the presence of the channel 3.
  • the drops of the second, third and fourth types 22, 23, 24, smaller or less viscous than the first 21, are attracted to the first zone 17 of the channel 3 and follow it from upstream to downstream while being carried away by the carrier fluid, until arriving at the second zone 18, of smaller width and / or height.
  • the second zone 18 is dimensioned so that the drops of the second type 22 cannot penetrate there. These drops 22 are therefore extracted from the channel 3 and then circulate in the microchannel 2, along an axis parallel to the flow of the carrier fluid and spaced from their original axis of circulation.
  • the other zones 19 and 20 of the channel 3 are dimensioned so that the drops of the third type 23 flow successively in the first, second and third zones 17, 18, 19 before escaping out of the channel 3, and that the drops of the fourth type 24 circulate in each of the zones 17 to 20 of the channel 3 before escaping at the downstream end 16 of the channel 3.
  • the drops of each type 21 to 24 circulate, downstream of the channel 3, respectively along parallel axes of circulation and spaced from each other.
  • Such a microchannel therefore makes it possible to sort four types of drops of different nature.
  • the microchannel 2 is formed with four successive channels 3, the inclinations with respect to the flow of the first fluid are becoming smaller,
  • the first channel 3a the most inclined, separates the smallest drops 24,
  • the second channel 3b separates the slightly larger drops 23,
  • the third channel 3c separates the still slightly larger drops 22, and
  • the fourth channel 3d separates the larger drops 21.
  • the microchannel 2 can also be equipped with a channel 3, extending for example along the axis of circulation of the carrier fluid, and provided with a reduction in its width and / or in its height. This reduction can take the form of a step or a discontinuous step, or a progressive form such as that visible in figure 10 .
  • the geometry of the channels can be used as a motor to transport the drops.
  • the invention makes it possible to move the drops in a two-dimensional field, even in the absence of a flow of a carrier fluid.
  • the invention can even be used in order to move drops against the current with respect to the flow of the carrier fluid.
  • the channel 3 can be equipped with a widening zone 26 in step or progressive, so that the drop 5 flowing in the channel 3 is accelerated during the passage of this zone.
  • the braking of the drops 5 can also be obtained ( figure 12 ) by having on either side of the channel 3 in which they circulate, secondary channels 27 having the function of locally increasing the section of the microchannel 2. This has the effect of locally reducing the speed of circulation of the carrier fluid, and, consequently, the speed of circulation of the drops 5.
  • the number, the shape and the position of the secondary channels 27 can be modified as required, the important thing being the local increase in the section of the microchannel.
  • the opposite effect can be obtained by replacing the channels 27 with ribs forming a local decrease in the section of the microchannel 2.
  • the figure 13 represents a microchannel 2 comprising a trapping zone 28 for the drops, formed by a pocket or a cavity 29 formed in the wall of the microchannel 2.
  • the microchannel is not equipped with a channel, the drops transported by the flow of carrier fluid F being trapped in the trapping zone or zones if the latter are in the path of the drops.
  • the trapping zones can be smaller or larger than the drops or bubbles to be trapped, depending on the applications and the nature of the drops or bubbles.
  • the figure 14 represents a channel 3 equipped with a trapping zone 28 for the drops, formed by a pocket or cavity formed on one side of the channel 3, in a wall 4 of the microchannel 2.
  • the pocket 29 is connected to the channel 3 by a mouth 30 and is capable of trapping a predefined number of drops. In the case of figure 13 , this area can only hold a single drop 5.
  • the section of the mouth 30 can be adapted according to the applications. In the case where the mouth 30 has a larger section than that of the channel 3, the drop or drops 5 can be automatically drawn into the trapping zones 28.
  • the mouth 30 has a smaller section or substantially equal to that of the channel 3, it may be necessary to force the drops 5 to enter the trapping zone 28.
  • This can be achieved by any suitable means, by particular using the method described in the documents WO 2006/018490 and WO 2007/138178 and which uses a beam laser directed at the interface between a drop and the carrier fluid or between two drops, in order to influence the displacement of the drops.
  • the drops 5 can be removed from the trapping zones 28 by increasing the flow rate of the carrier fluid, or by forcing the drops 5 to exit using the aforementioned method.
  • the figure 15 shows a channel 3 on either side of which are formed several trapping zones 28, 29, spaced from each other and arranged in staggered rows.
  • Each trapping zone 28, 29 can be dimensioned to trap a predefined number of drops 5, one drop for the case of zones 28 and two drops for the case of zone 31, and / or to trap drops of a particular nature .
  • the microchannel 2 can also be equipped with a network of channels formed by a main channel 3, through which the drops arrive, from which extend one or more derived channels 31 in which are placed obstacles 32 making it possible to retain, at least temporarily, the drops 5 in the corresponding derived channel 31, as seen in the figure 16 . These then form trapping zones.
  • the derived channels 31 may or may not extend downstream of the obstacle 32.
  • the additional channels 31 can be equipped with wetting zones 33.
  • a wetting zone is formed by a zone whose wetting properties of the wall 4 have been modified.
  • the modification of the wetting properties can also be obtained using chemical methods, such as silanization or plasma attack, or even using physical methods, for example by introducing hydrophilic pads to which the drop comes. hang on (fakir effect).
  • the trapping zones can also include elements intended to react with the content of the drops, so as to form microreactors or in order to detect the presence of chemical molecules and / or biochemical in the drop (s) concerned.
  • a DNA sequence can be detected if the complementary sequence is grafted locally on the wall of the corresponding trapping zone.
  • the microchannel comprises for example two parallel channels 34, 35, each intended for the circulation of a particular type of drops 36, 37, from which extend derived channels 31 whose downstream ends form trapping zones 28.
  • the trapping zones 28 are arranged near or adjacent to each other so that a drop of a first type 36 is near or in contact with a drop of a second type 37.
  • the figure 19 represents a microchannel 2 having a channel 3 equipped with several successive trapping zones 28, arranged in series.
  • the trapping zones 28 form a buffer zone T defined by an enlargement of the microchannel and in which the drops 5 pass a determined duration necessary for example to incubate a chemical or biochemical reaction and / or to allow their observation.
  • the trapping zones 28 can also be in matrix arrangement as shown in figure 20 , via a main channel 3 and parallel derived channels 31, each connected to a determined number of trapping zones 28.
  • the figure 21 shows a microchannel 2 comprising means 38 for feeding parallel trains of drops of different nature 21 to 24, parallel means 39 for introducing drops of different nature into the microchannel 2, and channels 3 formed in the microchannel 2 to starting from the introduction means 39 to guide the drops 21 to 24 leaving each introduction means to a predetermined area of the microchannel 2.
  • parallel trains of different drops are formed in the microchannel.
  • microchannels presented above for the treatment of drops in a carrier fluid can also be used for the treatment of bubbles.
  • the invention makes it possible in particular to integrate the preparation of the samples into a microfluidic chip and to bring the samples to the observation points in a simple and robust manner.
  • a microfluidic circuit according to the invention can be applied in the field of biotechnology or “chemi-tech”, but also in the field of fluid display and the observation of reactions in microdrops.
  • microfluidic circuit could be presented in a format which has now become standard, such as “Micro-Arrays” or biochips, for example DNA or protein chips, or even cell culture chips.
  • biochips consist of a matrix of zones where the surface is functionalized with biomolecules, the size and the distance between these zones being approximately the same size as the microfluidic drops and the channels.
  • the invention makes it possible to bring specific drops, the content of which is known, to the functionalized sites and to bring them into contact with the surface in order to produce the hybridization which will allow biological measurement. In this way, the invention makes it possible to interface the biochip technology with the advantages of handling fluids in microfluidics.
  • the trajectory of the drops can be actively modified, using a laser, in order to bring the drops into a trap or into a determined area of a microchannel.
  • such a method can also be used to direct a drop from one channel to another, for example to choose between different trajectories that the drop could follow.
  • the wavelength of the laser should be chosen so that it is absorbed by the carrier fluid.
  • the carrier fluid may, if necessary, contain a dye (black ink for example) absorbing the wavelength of the laser.
  • the local heating of the carrier fluid using the laser in a channel or close to it, attracts the drop in this channel. Heating can also be carried out at the interface between the drop and the carrier fluid in order to attract the drop in a given channel.
  • the laser can be positioned in order to block the advance of a drop and divert it into another channel.
  • Heating can also be applied locally or globally using electrical heating elements.
  • such absorption can be done either directly by the material constituting the microchannel, or by depositing in the microchannel or in the channel a layer or a particle of a material absorbing laser radiation.
  • the dielectrophoresis forces can also be used to influence the trajectory of the drops, or to trap drops.

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  • Chemical & Material Sciences (AREA)
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  • Health & Medical Sciences (AREA)
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  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

L'invention concerne un circuit microfluidique (1) comprenant au moins un microcanal (2) d'écoulement d'un premier fluide transportant des gouttes (5) ou de bulles d'au moins un deuxième fluide, le microcanal (2) étant délimité par deux parois (4, 8), le microcanal (2) ayant une section transversale perpendiculaire à la direction d'écoulement du premier fluide de hauteur (h) définie entre les deux parois du microcanal (2), la hauteur (h) du microcanal (2) étant dimensionnée pour écraser les gouttes (5) ou les bulles lors de leur déplacement, le circuit étant caractérisé en ce que le microcanal (2) comporte une zone de piégeage de gouttes ou de bulles, cette zone de piégeage (28) ayant une hauteur (hc) supérieure à celle (h) du microcanal (2), de façon à ce qu'au moins certaines des gouttes (5) ou des bulles du deuxième fluide dans le microcanal soient piégées dans la zone de piégeage placée sur leur trajectoire.

Figure imgaf001
The invention relates to a microfluidic circuit (1) comprising at least one microchannel (2) for the flow of a first fluid transporting drops (5) or bubbles of at least one second fluid, the microchannel (2) being delimited by two walls (4, 8), the microchannel (2) having a cross section perpendicular to the direction of flow of the first fluid of height (h) defined between the two walls of the microchannel (2), the height (h) of the microchannel (2) being dimensioned to crush the drops (5) or the bubbles during their displacement, the circuit being characterized in that the microchannel (2) comprises a zone for trapping drops or bubbles, this trapping zone (28 ) having a height (hc) greater than that (h) of the microchannel (2), so that at least some of the drops (5) or bubbles of the second fluid in the microchannel are trapped in the trapping zone placed on their trajectory.
Figure imgaf001

Description

La présente invention concerne un circuit microfluidique comprenant au moins un microcanal dans lequel s'écoule un premier fluide servant au déplacement de gouttes ou de bulles d'au moins un deuxième fluide.The present invention relates to a microfluidic circuit comprising at least one microchannel in which a first fluid flows serving for the displacement of drops or bubbles of at least one second fluid.

Un circuit microfluidique est décrit dans le document WO 2006/018490 au nom des demandeurs. Celui-ci est réalisé dans un matériau approprié tel par exemple que du PDMS (poly-dimethylsiloxane) comportant des microcanaux ayant typiquement une largeur d'environ 100µm et une profondeur d'environ 50µm, dans lesquels on peut faire passer des débits très faibles d'un fluide tel que de l'air, de l'eau, de l'huile, des réactifs, etc.A microfluidic circuit is described in the document WO 2006/018490 on behalf of the applicants. This is made of a suitable material such as for example PDMS (poly-dimethylsiloxane) comprising microchannels typically having a width of approximately 100 μm and a depth of approximately 50 μm, in which very low flow rates can be passed d '' a fluid such as air, water, oil, reagents, etc.

Un faisceau laser dont la longueur d'onde n'est pas absorbée par le matériau constitutif du circuit, est focalisé sur l'interface d'un premier fluide s'écoulant dans un microcanal et d'un second fluide présent au moins localement dans ce microcanal, pour forcer ou arrêter l'écoulement du premier fluide dans le microcanal, pour le fractionner en gouttes, pour le mélanger au second fluide, etc., la focalisation du faisceau laser sur l'interface des fluides créant un gradient de température le long de cette interface et provoquant un mouvement des fluides par convection thermocapillaire.A laser beam whose wavelength is not absorbed by the material constituting the circuit, is focused on the interface of a first fluid flowing in a microchannel and of a second fluid present at least locally in this microchannel, to force or stop the flow of the first fluid in the microchannel, to split it into drops, to mix it with the second fluid, etc., focusing the laser beam on the fluid interface creating a temperature gradient along of this interface and causing a movement of fluids by thermocapillary convection.

Comme cela est connu du document WO 2007/138178 , également au nom des demandeurs, cette technologie a été utilisée afin de traiter des gouttes dans un circuit microfluidique comprenant au moins un microcanal parcouru par les gouttes. Le procédé utilisé consiste à faire agir un faisceau laser sur l'interface de ces gouttes dans un fluide porteur ou sur l'interface des gouttes en contact, pour faire des tris de gouttes, former des nano-gouttes à partir d'une goutte de taille supérieure ou pour fusionner des gouttes en contact et provoquer des réactions entre les fluides contenus dans ces gouttes.As is known from the document WO 2007/138178 , also on behalf of the applicants, this technology has been used to treat drops in a microfluidic circuit comprising at least one microchannel traversed by the drops. The method used consists in causing a laser beam to act on the interface of these drops in a carrier fluid or on the interface of the drops in contact, in order to sort the drops, to form nano-drops from a drop of larger size or to merge drops in contact and cause reactions between the fluids contained in these drops.

L'invention a pour objet un autre procédé de traitement des gouttes dans un circuit microfluidique, pouvant éventuellement être utilisé en combinaison avec les techniques de traitement antérieures décrites ci-dessus.The subject of the invention is another process for treating drops in a microfluidic circuit, which can optionally be used in combination with the prior treatment techniques described above.

A cet effet, l'invention propose un circuit microfluidique comprenant au moins un microcanal d'écoulement d'un premier fluide transportant des gouttes ou de bulles d'au moins un deuxième fluide, caractérisé en ce que la hauteur du microcanal est dimensionnée pour écraser les gouttes ou les bulles lors de leur déplacement, et en ce que le microcanal comporte au moins un chenal, s'étendant au moins en partie dans la direction d'écoulement du premier fluide ou une zone de piégeage de gouttes ou de bulles, cette zone ou le chenal ayant une hauteur supérieure à celle du microcanal, de façon à ce qu'au moins certaines des gouttes ou des bulles du deuxième fluide dans le microcanal soient attirées et guidées dans le chenal ou dans la zone de piégeage.To this end, the invention provides a microfluidic circuit comprising at least one microchannel for the flow of a first fluid transporting drops or bubbles of at least one second fluid, characterized in that the height of the microchannel is dimensioned to crush the drops or bubbles during their movement, and in that the microchannel comprises at least one channel, extending at least partly in the direction of flow of the first fluid or a zone for trapping drops or bubbles, this zone or channel having a height greater than that of the microchannel, so that at least some of the drops or bubbles of the second fluid in the microchannel are attracted and guided in the channel or in the trapping zone.

Dans le cas d'une goutte plongée dans un fluide, l'énergie de surface de la goutte est d'autant plus faible que sa surface externe est petite. L'énergie minimale est donc obtenue par une goutte de forme sphérique et augmente de façon continue au fur et à mesure que la goutte s'éloigne de cette forme. L'énergie de surface peut être calculée pour une goutte d'un volume connu, pour n'importe quelle position dans le microcanal. Ainsi, on peut prédire si la goutte sera ou non guidée par un chenal donné en comparant les forces en jeu.In the case of a drop immersed in a fluid, the surface energy of the drop is lower the smaller its external surface. The minimum energy is therefore obtained by a drop of spherical shape and increases continuously as the drop moves away from this shape. The surface energy can be calculated for a drop of known volume, for any position in the microchannel. Thus, we can predict whether or not the drop will be guided by a given channel by comparing the forces at play.

Une goutte placée dans le microcanal et écrasée présente une surface externe importante. Cette goutte cherche ainsi naturellement à réduire sa surface externe, ce qui l'amène à migrer vers le chenal de plus grande hauteur lorsqu'elle arrive à un embranchement entre le microcanal et le chenal.A drop placed in the microchannel and crushed has a large external surface. This drop thus naturally seeks to reduce its external surface, which causes it to migrate to the greater height channel when it arrives at a branch between the microchannel and the channel.

Les gouttes sont ainsi attirées par le chenal et sont déplacées le long de celui-ci par le premier fluide.The drops are thus attracted to the channel and are displaced along it by the first fluid.

Dans le cas où la direction du chenal n'est pas parallèle à la direction de l'écoulement du premier fluide (fluide porteur) dans le microcanal, la goutte reste prisonnière du chenal tant que la force d'entraînement visqueuse, dans la direction normale à la direction locale du chenal et exercée par le premier fluide sur la goutte, est inférieure à celle nécessaire pour déformer la goutte et lui redonner sa forme écrasée.In the case where the direction of the channel is not parallel to the direction of flow of the first fluid (carrier fluid) in the microchannel, the drop remains trapped in the channel as long as the viscous driving force, in the normal direction to the local direction of the channel and exerted by the first fluid on the drop, is less than that necessary to deform the drop and restore it to its crushed shape.

Ce phénomène est ainsi influencé par plusieurs paramètres, tels que la viscosité du fluide porteur et celle du fluide des gouttes, la taille de la goutte, la vitesse du fluide porteur, la tension interfaciale, la géométrie du chenal, l'épaisseur du microcanal, etc.This phenomenon is thus influenced by several parameters, such as the viscosity of the carrier fluid and that of the fluid of the drops, the size of the drop, the speed of the carrier fluid, the interfacial tension, the geometry of the channel, the thickness of the microchannel, etc.

Bien entendu, il est possible d'utiliser indifféremment des gouttes ou des bulles, sans modification sur le fonctionnement de l'invention.Of course, it is possible to use either drops or bubbles, without modification on the functioning of the invention.

Selon une caractéristique de l'invention, le microcanal est délimité par deux parois parallèles, et le chenal est formé par une rainure d'au moins l'une des parois du microcanal, ou entre deux nervures parallèles d'une des parois du microcanal.According to a characteristic of the invention, the microchannel is delimited by two parallel walls, and the channel is formed by a groove of at least one of the walls of the microchannel, or between two parallel ribs of one of the walls of the microchannel.

Avantageusement, des bulles ou des gouttes d'au moins deux types différents sont transportées par le premier fluide et le chenal constitue un moyen de séparation ou de tri des bulles ou des gouttes, seules celles d'un premier type étant guidées dans le chenal.Advantageously, bubbles or drops of at least two different types are transported by the first fluid and the channel constitutes a means of separation or sorting of the bubbles or drops, only those of a first type being guided in the channel.

Comme décrit précédemment, les gouttes qui sont attirés par le chenal sont celles pour lesquelles la force visqueuse exercée par le premier fluide sur chaque goutte est inférieure à celle nécessaire pour déformer la goutte et lui redonner sa forme écrasée.As described above, the drops which are attracted to the channel are those for which the viscous force exerted by the first fluid on each drop is less than that necessary to deform the drop and restore it to its crushed shape.

A l'inverse, les gouttes qui s'écoulent dans la direction du fluide porteur sans suivre le chenal sont celles pour lesquelles la force visqueuse exercée par le premier fluide sur la goutte est supérieure à celle nécessaire pour déformer la goutte et lui redonner sa forme écrasée.Conversely, the drops which flow in the direction of the carrier fluid without following the channel are those for which the viscous force exerted by the first fluid on the drop is greater than that necessary to deform the drop and restore its shape crushed.

En conséquence, des gouttes de grande taille ou très visqueuses seront moins enclines à suivre la trajectoire du chenal que des gouttes de faible taille ou peu visqueuses.Consequently, large or very viscous drops will be less inclined to follow the path of the channel than small or low viscous drops.

Selon une possibilité de l'invention, les bulles ou les gouttes de types différents ont des tailles, des viscosités, ou des tensions de surface différentes, ce qui permet de les séparer les unes des autres.According to one possibility of the invention, the bubbles or the drops of different types have different sizes, viscosities, or surface tensions, which makes it possible to separate them from each other.

Dans un mode de réalisation, le chenal comporte au moins deux parties successives de hauteur et/ou de largeur différente, une partie de largeur et/ou de hauteur plus grande étant suivie d'une partie de largeur et/ou de hauteur plus faible, dans le sens de l'écoulement du premier fluide.In one embodiment, the channel comprises at least two successive parts of different height and / or width, a part of greater width and / or height being followed by a part of smaller width and / or height, in the direction of flow of the first fluid.

Ce type de chenal permet de séparer facilement deux types de bulles ou de gouttes. A titre d'exemple, des bulles à forte viscosité ou de grande taille vont s'écouler uniquement le long de la partie de forte hauteur du chenal avant d'être chassées hors du chenal par le fluide porteur, alors que des bulles à plus faible viscosité ou de plus faible taille s'écouleront non seulement le long de la partie de forte hauteur du chenal mais également le long de sa partie de faible hauteur.This type of channel makes it easy to separate two types of bubbles or drops. For example, bubbles of high viscosity or of large size will flow only along the very high part of the channel before being driven out of the channel by the carrier fluid, while bubbles with lower viscosity or smaller will flow not only along the high-rise portion of the channel but also along its low-rise portion.

Selon une autre caractéristique de l'invention, le circuit comprend des chenaux de largeur différente et/ou d'inclinaison différente par rapport à l'écoulement du premier fluide, ce qui permet également de pouvoir discriminer différents types de bulles ou de gouttes.According to another characteristic of the invention, the circuit comprises channels of different width and / or of different inclination with respect to the flow of the first fluid, which also makes it possible to be able to discriminate different types of bubbles or drops.

Avantageusement, le circuit comprend des zones de piégeage de gouttes ou de bulles, formées par un agrandissement de la section de passage des gouttes ou des bulles dans le microcanal ou dans un chenal précité, ou encore par une modification locale de l'énergie de surface du microcanal et/ou du chenal.Advantageously, the circuit comprises zones for trapping drops or bubbles, formed by an enlargement of the cross section of the drops or bubbles in the microchannel or in a said channel, or by a local modification of the surface energy. microchannel and / or channel.

Le circuit peut comprendre des zones de piégeage dans le microcanal, même en l'absence du chenal. Les gouttes ou les bulles transportées par le fluide porteur sont alors piégées dans les zones de piégeage placées sur leur trajectoire.The circuit can include trapping zones in the microchannel, even in the absence of the channel. The drops or bubbles transported by the carrier fluid are then trapped in the trapping zones placed on their trajectory.

Par ailleurs, ces zones de piégeage peuvent être plus petites que la taille des gouttes ou des bulles à piéger.Furthermore, these trapping zones can be smaller than the size of the drops or bubbles to be trapped.

Ces zones de piégeage peuvent être adaptées à un seul type de bulles et/ou ne peuvent contenir qu'un nombre défini de bulles, par exemple une ou deux bulles.These trapping zones can be adapted to a single type of bubble and / or can only contain a defined number of bubbles, for example one or two bubbles.

Les zones de piégeage permettent d'immobiliser une ou plusieurs gouttes, ce qui permet par exemple de les examiner à l'aide d'un microscope et/ou de suivre le déroulement d'une réaction au sein d'une zone pendant une période de temps importante.The trapping zones make it possible to immobilize one or more drops, which makes it possible for example to examine them using a microscope and / or to follow the progress of a reaction within a zone during a period of important time.

Au moins certaines des zones de piégeage peuvent être indépendantes les unes des autres.At least some of the trapping zones can be independent of each other.

Alternativement, au moins certaines des zones de piégeage sont reliées en série ou en parallèle par le microcanal ou par des chenaux précités.Alternatively, at least some of the trapping zones are connected in series or in parallel by the microchannel or by the aforementioned channels.

Le piège peut être fabriqué de façon à ce que la présence d'une goutte dans celui-ci force les gouttes suivantes à continuer leur cheminement, afin de remplir les pièges situés en aval.The trap can be manufactured in such a way that the presence of a drop in it forces the following drops to continue their journey, in order to fill the traps located downstream.

Une goutte piégée est stationnaire mais son contenu continue d'être mis en mouvement par l'écoulement du fluide porteur. De cette façon, le contenu de la goutte peut être mélangé même lorsque celle-ci est stationnaire. Un tel phénomène peut notamment jouer un rôle important dans le domaine de l'incubation biologique ou pour la mise en place d'une réaction chimique.A trapped drop is stationary but its content continues to be set in motion by the flow of the carrier fluid. In this way, the contents of the drop can be mixed even when it is stationary. Such a phenomenon can in particular play an important role in the field of biological incubation or for the establishment of a chemical reaction.

Il est ainsi possible d'apporter des gouttes à proximité l'une de l'autre ou en contact l'une avec l'autre, afin de les fusionner et initier une réaction chimique, ou de comparer leur contenu.It is thus possible to bring drops close to one another or in contact with one another, in order to merge them and initiate a chemical reaction, or to compare their content.

Dans le cas de zones de piégeage reliées en série les unes aux autres, le saut d'une ou plusieurs gouttes d'une zone de piégeage à une autre peut entraîner, par effet de cascade, le mouvement des gouttes piégées dans les zones situées en aval.In the case of trapping zones connected in series with one another, the jump of one or more drops from one trapping zone to another may cause, by cascade effect, the movement of the trapped drops in the zones located in downstream.

Selon une autre caractéristique de l'invention, des obstacles sont formés en aval de certaines zones de piégeage pour retenir dans ces zones les bulles ou les gouttes qui y ont été attirées.According to another characteristic of the invention, obstacles are formed downstream of certain trapping zones to retain in these zones the bubbles or the drops which have been attracted to them.

Avantageusement, au moins un chenal comprend des moyens de ralentissement ou d'accélération des bulles ou gouttes présentes dans le chenal, ces moyens de ralentissement ou d'accélération étant formés par des variations de largeur ou de hauteur du chenal, ou par des rails ou des nervures des parois du microcanal correspondant, formés le long des zones de ralentissement ou d'accélération souhaitées.Advantageously, at least one channel comprises means for slowing down or accelerating the bubbles or drops present in the channel, these means for slowing down or accelerating being formed by variations in width or height of the channel, or by rails or ribs of the walls of the corresponding microchannel, formed along the desired zones of deceleration or acceleration.

Selon une autre caractéristique de l'invention, le circuit comprend des moyens de formation de trains parallèles de gouttes ou de bulles de nature différente dans un microcanal comprenant des moyens parallèles d'introduction des gouttes ou des bulles de nature différente dans le microcanal, et des chenaux formés dans ce microcanal à partir des moyens d'introduction pour guider les gouttes ou les bulles sortant de chaque moyen d'introduction jusqu'à une zone prédéterminée du microcanal.According to another characteristic of the invention, the circuit comprises means for forming parallel trains of drops or bubbles of different nature in a microchannel comprising parallel means of introducing drops or bubbles of different nature into the microchannel, and channels formed in this microchannel from the introduction means to guide the drops or bubbles leaving each introduction means to a predetermined area of the microchannel.

Chaque type de goutte est ainsi amené à un endroit prédéfini du microcanal. Il est alors possible de disposer des séries de gouttes de nature connue à différents niveaux du microcanal.Each type of drop is thus brought to a predefined location in the microchannel. It is then possible to have series of drops of known nature at different levels of the microchannel.

L'invention sera mieux comprise et d'autres détails, caractéristiques et autres avantages de l'invention apparaîtront à la lecture de la description suivante faite à titre d'exemple non limitatif en référence aux dessins annexés dans lesquels :

  • la figure 1 est une vue schématique représentant la section du microcanal ;
  • les figures 2 et 3 sont des vues correspondant à la figure 1, représentant deux autres formes de réalisation de l'invention ;
  • la figure 4 représente, en vue de dessus, un microcanal équipé d'un chenal ;
  • la figure 5 représente, en vue de dessus, un microcanal équipé d'un réseau de chenaux ;
  • les figures 6 à 9 sont des vues de dessus d'un microcanal selon différentes formes de réalisation de l'invention visant à séparer des gouttes de natures différentes ;
  • la figure 10 est une vue de dessus d'un microcanal équipé d'un chenal comportant des moyens de ralentissement des gouttes ;
  • la figure 11 est une vue de dessus d'un microcanal équipé d'un chenal comportant des moyens d'accélération des gouttes ;
  • la figure 12 est une vue de dessus d'un microcanal équipé d'un chenal principal et de chenaux annexes visant à ralentir les gouttes du chenal principal ;
  • la figure 13 est vue de dessus d'un microcanal équipé d'une zone de piégeage de bulles, en l'absence de chenal ;
  • les figures 14 et 15 sont des vues de dessus d'un chenal équipé de zones de piégeage de bulles ;
  • la figure 16 est une vue de dessus d'un réseau de chenaux comportant des obstacles ;
  • la figure 17 est une vue de dessus d'un réseau de chenaux comportant des zones mouillantes ;
  • la figure 18 est une vue de dessus de chenaux formant des microréacteurs ;
  • la figure 19 est une vue de dessus d'un microcanal comportant un chenal équipé de zones de piégeage disposées en série ;
  • la figure 20 est une vue de dessus d'un réseau matriciel de zones de piégeage.
  • la figure 21 montre un microcanal comportant des moyens d'alimentation de trains parallèles de gouttes de nature différente.
The invention will be better understood and other details, characteristics and other advantages of the invention will appear on reading the following description given by way of nonlimiting example with reference to the appended drawings in which:
  • the figure 1 is a schematic view representing the section of the microchannel;
  • the figures 2 and 3 are views corresponding to the figure 1 , representing two other embodiments of the invention;
  • the figure 4 represents, in top view, a microchannel equipped with a channel;
  • the figure 5 represents, in top view, a microchannel equipped with a network of channels;
  • the figures 6 to 9 are top views of a microchannel according to different embodiments of the invention aimed at separating drops of different natures;
  • the figure 10 is a top view of a microchannel equipped with a channel comprising means for slowing down the drops;
  • the figure 11 is a top view of a microchannel equipped with a channel comprising means for accelerating the drops;
  • the figure 12 is a top view of a microchannel equipped with a main channel and additional channels intended to slow down the drops of the main channel;
  • the figure 13 is seen from above of a microchannel equipped with a bubble trapping zone, in the absence of a channel;
  • the Figures 14 and 15 are top views of a channel equipped with bubble trapping zones;
  • the figure 16 is a top view of a network of channels comprising obstacles;
  • the figure 17 is a top view of a network of channels comprising wetting zones;
  • the figure 18 is a top view of channels forming microreactors;
  • the figure 19 is a top view of a microchannel comprising a channel equipped with trapping zones arranged in series;
  • the figure 20 is a top view of a matrix network of trapping zones.
  • the figure 21 shows a microchannel comprising means for feeding parallel trains of drops of different nature.

La figure 1 représente schématiquement une première forme de réalisation d'un microcircuit 1 selon l'invention.The figure 1 shows schematically a first embodiment of a microcircuit 1 according to the invention.

Le microcircuit 1 est formé dans une plaque d'un matériau approprié tel par exemple que du PDMS (poly-dimethylsiloxane) par utilisation d'une technique courante de lithographie souple, comme cela est connu de l'art antérieur précité.The microcircuit 1 is formed in a plate of a suitable material such as for example PDMS (poly-dimethylsiloxane) by use of a common technique of flexible lithography, as is known from the aforementioned prior art.

Un ou plusieurs microcanaux 2 peuvent être formés à la surface de la plaque, sur laquelle est collée une lame de microscope en verre, par exemple.One or more microchannels 2 can be formed on the surface of the plate, on which a glass microscope slide is stuck, for example.

Comme cela est visible à la figure 1, le microcanal 2 présente une section rectangulaire, dont la largeur L est définie par sa dimension transversale horizontale, c'est-à-dire dans le plan du microcircuit 1, et dont la hauteur h est définie par sa dimension dans le sens vertical, c'est-à-dire suivant une direction perpendiculaire au plan du microcircuit 1.As can be seen from the figure 1 , the microchannel 2 has a rectangular section, the width L of which is defined by its horizontal transverse dimension, that is to say in the plane of the microcircuit 1, and the height h of which is defined by its dimension in the vertical direction, that is to say in a direction perpendicular to the plane of the microcircuit 1.

Bien entendu, les termes qui précèdent ne sont utilisés que par référence aux dessins, et restent valables quelle que soit l'orientation du microcircuit.Of course, the above terms are used only with reference to the drawings, and remain valid regardless of the orientation of the microcircuit.

Une rainure 3 à section rectangulaire ou carrée est ménagée dans l'une des deux parois horizontales 4 qui délimitent le microcanal 2. Selon une variante de réalisation de l'invention, une seconde rainure pourrait être ménagée dans la paroi horizontale opposée, en regard de la première 4.A groove 3 of rectangular or square section is formed in one of the two horizontal walls 4 which delimit the microchannel 2. According to an alternative embodiment of the invention, a second groove could be formed in the opposite horizontal wall, opposite the first 4.

La rainure 3 forme ainsi un chenal de plus grande section que le reste du microcanal 2.The groove 3 thus forms a channel of larger section than the rest of the microchannel 2.

Un premier fluide, dit fluide porteur, circule dans le microcanal 2, dans le sens indiqué par la flèche F, en entraînant avec lui des gouttes 5 d'un second fluide, de nature différente du premier fluide.A first fluid, called the carrier fluid, circulates in the microchannel 2, in the direction indicated by the arrow F, carrying with it drops 5 of a second fluid, of a different nature from the first fluid.

Dans ce qui suit, le second fluide peut être sous forme de gouttes ou de bulles, sans modification du fonctionnement de l'invention.In what follows, the second fluid may be in the form of drops or bubbles, without modifying the operation of the invention.

Les gouttes 5 s'écoulant dans la zone étroite du microcanal sont écrasées. Lorsqu'elles rencontrent un chenal 3, elles y prennent une forme moins écrasée, par exemple une forme sphérique ou quasi-sphérique, nécessitant moins d'énergie de surface que la forme écrasée. Il est à noter que les gouttes peuvent demeurer écrasées tout en étant guidées par le chenal. Le critère déterminant est que l'énergie de surface de la goutte dans le chenal soit plus petite que celle hors du chenal, la sphère correspondant au minimum de cette énergie.The drops 5 flowing in the narrow area of the microchannel are crushed. When they meet a channel 3, they take a less flattened shape there, for example a spherical or quasi-spherical shape, requiring less surface energy than the crushed form. It should be noted that the drops can remain crushed while being guided by the channel. The determining criterion is that the surface energy of the drop in the channel is smaller than that outside the channel, the sphere corresponding to the minimum of this energy.

Les gouttes 5 qui rencontrent le chenal 3 circulent alors le long de celui-ci, en étant emportées par le fluide porteur.The drops 5 which meet the channel 3 then circulate along the latter, being carried away by the carrier fluid.

Les gouttes peuvent être plus grandes ou plus petites que le chenal 3.The drops can be larger or smaller than channel 3.

La figure 2 illustre une variante de réalisation de l'invention dans laquelle la rainure définissant le chenal 3 présente une forme concave ou arrondie.The figure 2 illustrates an alternative embodiment of the invention in which the groove defining the channel 3 has a concave or rounded shape.

Une autre variante de réalisation est représentée à la figure 3, dans laquelle l'une des parois horizontales 4 est pourvue de deux nervures parallèles 6, espacées l'une de l'autre, dirigées vers l'intérieur du microcanal 2 et délimitant entre elles un chenal 3.Another alternative embodiment is shown in figure 3 , in which one of the horizontal walls 4 is provided with two parallel ribs 6, spaced from one another, directed towards the inside of the microchannel 2 and delimiting between them a channel 3.

De cette manière, les gouttes 5 écrasées entre le sommet des nervures 6 et la paroi opposée 8, sont dirigées soit vers le chenal 3, soit dans les autres zones du microcanal 2 situées de part et d'autre des nervures 6. Dans ces zones, les gouttes 5 peuvent retrouver une forme sphérique ou quasi-sphérique et donc une énergie de surface plus faible. De cette façon, les nervures forment des barrières permettant de séparer certaines gouttes des autres.In this way, the drops 5 crushed between the top of the ribs 6 and the opposite wall 8, are directed either towards the channel 3, or in the other zones of the microchannel 2 located on either side of the ribs 6. In these zones , the drops 5 can find a spherical or quasi-spherical shape and therefore a lower surface energy. In this way, the ribs form barriers allowing to separate certain drops from the others.

La figure 4 représente, en vue de dessus, la forme d'un chenal 3. Dans cet exemple, le chenal 3 comprend au moins une partie 9 s'étendant selon l'axe A du microcanal et donc suivant l'axe F d'écoulement du fluide porteur, au moins une partie 10 s'étendant obliquement par rapport à l'axe A précité, et/ou au moins une partie 11 de forme sinusoïdale.The figure 4 represents, in top view, the shape of a channel 3. In this example, the channel 3 comprises at least one part 9 extending along the axis A of the microchannel and therefore along the axis F of fluid flow carrier, at least a portion 10 extending obliquely to the aforementioned axis A, and / or at least a portion 11 of sinusoidal shape.

Dans chacune des parties précitées, la trajectoire des gouttes 5 circulant le long du chenal 3 présente une composante suivant le sens d'écoulement du fluide porteur, de sorte que les gouttes 5 sont toujours entraînées par le fluide porteur, de l'amont vers l'aval du chenal 3 et du microcanal 2.In each of the abovementioned parts, the trajectory of the drops 5 circulating along the channel 3 has a component according to the direction of flow of the carrier fluid, so that the drops 5 are always entrained by the carrier fluid, from upstream to downstream of channel 3 and microchannel 2.

Dans le cas d'une partie oblique 10 ou d'une partie sinusoïdale 11 notamment, le temps de parcours des gouttes 5 dans le microcanal 2 est plus important. De cette manière, on peut observer à l'aide d'un microscope le contenu des gouttes 5 pendant une plus longue période, sans avoir besoin de modifier la zone d'observation au cours du temps.In the case of an oblique part 10 or a sinusoidal part 11 in particular, the travel time of the drops 5 in the microchannel 2 is greater. In this way, the contents of the drops 5 can be observed using a microscope for a longer period of time, without the need to change the observation area over time.

La figure 5 illustre un réseau de chenaux comportant un chenal central 12 s'étendant dans la direction du microcanal 2, de part et d'autre duquel s'étendent plusieurs chenaux auxiliaires 13. Chaque chenal auxiliaire 13 s'étend depuis le chenal central 12 et débouche à nouveau dans ce dernier, à la manière de chenaux de dérivation.The figure 5 illustrates a network of channels comprising a central channel 12 extending in the direction of the microchannel 2, on either side of which extend several auxiliary channels 13. Each auxiliary channel 13 extends from the central channel 12 and leads to new to the latter, like diversion channels.

Dans le cas de la figure 5, les gouttes 5 contiennent par exemple de l'eau et le fluide porteur est de l'huile de paraffine, la largeur du microcanal 2 est de 3 mm, celle des chenaux 12, 13 est de 70 µm, les hauteurs du microcanal et des chenaux sont respectivement de 50 µm et 35 µm, et les gouttes 5 s'écoulent de la gauche vers la droite dans le sens de la flèche F.In the case of figure 5 , the drops 5 contain for example water and the carrier fluid is paraffin oil, the width of the microchannel 2 is 3 mm, that of the channels 12, 13 is 70 μm, the heights of the microchannel and channels are 50 µm and 35 µm respectively, and the 5 drops flow from left to right in the direction of arrow F.

La figure 6 représente un microcanal 2 dans lequel circule un premier fluide formant un fluide porteur pour des gouttes d'un premier et d'un second types. Les gouttes du premier type 14 présentent une taille plus importante que les gouttes du second type 15.The figure 6 represents a microchannel 2 in which a first fluid circulates forming a carrier fluid for drops of a first and a second type. The drops of the first type 14 have a larger size than the drops of the second type 15.

Le microcanal 2 est équipé d'un chenal 3 s'étendant obliquement de l'amont vers l'aval par rapport au sens de circulation du fluide porteur, représenté par la flèche F. La hauteur et/ou la largeur du chenal 3 sont ajustées de façon à ce que les gouttes les plus grandes 14 soient emportées avec le fluide porteur dans le sens de la flèche F et que les gouttes les plus petites 15 soient attirées dans le chenal 3, puis progressent le long de celui-ci, de l'amont vers l'aval, en étant entraînées par le fluide porteur.The microchannel 2 is equipped with a channel 3 extending obliquely from upstream to downstream relative to the direction of circulation of the carrier fluid, represented by the arrow F. The height and / or the width of the channel 3 are adjusted so that the largest drops 14 are carried with the carrier fluid in the direction of arrow F and the smallest drops 15 are drawn into the channel 3, then progress along it, from the 'upstream downstream, being driven by the carrier fluid.

L'extrémité aval 16 du chenal 3 est pourvue d'une diminution de sa hauteur ou de sa largeur de façon à ce que la force visqueuse exercée par le fluide porteur soit plus importante que celle nécessaire pour écraser les gouttes 15, afin que le fluide porteur les entraîne à nouveau dans le microcanal 2. Les gouttes 14 et 15 circulent ainsi, en aval du chenal 3, respectivement selon deux axes B et C parallèles à l'écoulement du fluide porteur et écartés l'un de l'autre.The downstream end 16 of the channel 3 is provided with a reduction in its height or its width so that the viscous force exerted by the carrier fluid is greater than that necessary to crush the drops 15, so that the carrier fluid drives them again into the microchannel 2. The drops 14 and 15 thus circulate, downstream of the channel 3, respectively along two axes B and C parallel to the flow of the carrier fluid and spaced from each other.

Un tel microcanal permet ainsi de trier deux types de gouttes de nature différente.Such a microchannel thus makes it possible to sort two types of drops of different nature.

La figure 7 illustre un microcanal 2 similaire à celui de la figure 6, dans lequel les gouttes du premier type 14 sont relativement très visqueuses et les gouttes du second type 15 sont relativement peu visqueuses.The figure 7 illustrates a microchannel 2 similar to that of the figure 6 , in which the drops of the first type 14 are relatively very viscous and the drops of the second type 15 are relatively not very viscous.

La hauteur et/ou la largeur du chenal 3 sont ajustées de façon à ce que les gouttes plus visqueuses 14 soient emportées avec le fluide porteur et que seules les gouttes moins visqueuses 15 soient attirées dans le chenal, puis progressent le long de celui-ci, de l'amont vers l'aval, en étant entraînées par le fluide porteur et sortent du chenal 3 à l'extrémité aval de celui-ci.The height and / or width of the channel 3 are adjusted so that the more viscous drops 14 are carried with the carrier fluid and that only the less viscous drops 15 are drawn into the channel, then progress along it , from upstream to downstream, being driven by the carrier fluid and leaving the channel 3 at the downstream end thereof.

On rappelle que plus la goutte est visqueuse, plus l'effort exercé par le fluide porteur sur la goutte est important, cet effort permettant l'extraction de la goutte hors du chenal.It will be recalled that the more viscous the drop, the greater the effort exerted by the carrier fluid on the drop, this effort allowing the extraction of the drop out of the channel.

Un tel microcanal 2 peut également servir à trier des gouttes présentant des tensions de surface différentes.Such a microchannel 2 can also be used to sort drops having different surface tensions.

La figure 8 représente un microcanal de type de ceux des figures 6 et 7, dans lequel le chenal présente successivement, de l'amont vers l'aval, des zones de hauteur et/ou de largeur décroissantes 17 à 20.The figure 8 represents a microchannel of the type of those of Figures 6 and 7 , in which the channel successively presents, from upstream to downstream, zones of decreasing height and / or width 17 to 20.

Chaque zone est dimensionnée de façon à pouvoir discriminer un type de goutte particulier.Each zone is dimensioned so as to be able to discriminate a particular type of drop.

Dans le cas représenté à la figure 8, le fluide porteur entraîne quatre types de gouttes de tailles ou de viscosités différentes en regard de la première zone 17, c'est-à-dire la zone la plus large et/ou la plus profonde.In the case shown in figure 8 , the carrier fluid causes four types of drops of different sizes or viscosities opposite the first zone 17, that is to say the widest and / or deepest zone.

Les gouttes du premier type 21, c'est-à-dire les plus grosses ou les plus visqueuses sont entraînées au travers cette zone 17 par le fluide porteur, la trajectoire de ces gouttes 21 n'étant quasiment pas influencée par la présence du chenal 3.The drops of the first type 21, that is to say the largest or the most viscous are entrained through this zone 17 by the carrier fluid, the trajectory of these drops 21 being hardly influenced by the presence of the channel 3.

Les gouttes du deuxième, du troisième et du quatrième types 22, 23, 24, plus petites ou moins visqueuses que les premières 21, sont attirées par la première zone 17 du chenal 3 et suivent celle-ci de l'amont vers l'aval en étant emportées par le fluide porteur, jusqu'à arriver à la deuxième zone 18, de largeur et/ou de hauteur plus faible.The drops of the second, third and fourth types 22, 23, 24, smaller or less viscous than the first 21, are attracted to the first zone 17 of the channel 3 and follow it from upstream to downstream while being carried away by the carrier fluid, until arriving at the second zone 18, of smaller width and / or height.

La deuxième zone 18 est dimensionnée de façon à ce que les gouttes du deuxième type 22 ne puissent pas y pénétrer. Ces gouttes 22 sont donc extraites du chenal 3 et circulent ensuite dans le microcanal 2, selon un axe parallèle à l'écoulement du fluide porteur et écarté de leur axe de circulation d'origine.The second zone 18 is dimensioned so that the drops of the second type 22 cannot penetrate there. These drops 22 are therefore extracted from the channel 3 and then circulate in the microchannel 2, along an axis parallel to the flow of the carrier fluid and spaced from their original axis of circulation.

De la même manière que précédemment, les autres zones 19 et 20 du chenal 3 sont dimensionnées de façon à ce que les gouttes du troisième type 23 circulent successivement dans les premières, deuxième et troisième zones 17, 18, 19 avant de s'échapper hors du chenal 3, et que les gouttes du quatrième type 24 circulent dans chacune des zones 17 à 20 du chenal 3 avant de s'échapper à l'extrémité aval 16 du chenal 3.In the same way as previously, the other zones 19 and 20 of the channel 3 are dimensioned so that the drops of the third type 23 flow successively in the first, second and third zones 17, 18, 19 before escaping out of the channel 3, and that the drops of the fourth type 24 circulate in each of the zones 17 to 20 of the channel 3 before escaping at the downstream end 16 of the channel 3.

De cette manière, les gouttes de chaque type 21 à 24 circulent, en aval du chenal 3, respectivement suivant des axes de circulation parallèles et écartés les uns des autres.In this way, the drops of each type 21 to 24 circulate, downstream of the channel 3, respectively along parallel axes of circulation and spaced from each other.

Un tel microcanal permet donc de trier quatre types de gouttes de nature différente.Such a microchannel therefore makes it possible to sort four types of drops of different nature.

Bien entendu, le nombre de zones différentes du chenal peut être ajusté en fonction des besoins.Of course, the number of different zones of the channel can be adjusted as required.

Il est également possible de séparer plusieurs types de gouttes en ménageant différents chenaux 3 de dimensions et/ou d'inclinaisons différentes dans le microcanal par rapport au sens d'écoulement F du fluide porteur, comme cela est représenté à la figure 9.It is also possible to separate several types of drops by providing different channels 3 of different dimensions and / or inclinations in the microchannel relative to the direction of flow F of the carrier fluid, as shown in FIG. figure 9 .

Dans cette figure, le microcanal 2 est formé avec quatre chenaux successifs 3, dont les inclinaisons par rapport à l'écoulement du premier fluide sont de plus en plus faible, Le premier chenal 3a, le plus incliné, sépare les plus petites gouttes 24, le deuxième canal 3b sépare les gouttes un peu plus grandes 23, le troisième canal 3c sépare les gouttes encore un peu plus grandes 22, et le quatrième canal 3d sépare les gouttes les plus grandes 21.In this figure, the microchannel 2 is formed with four successive channels 3, the inclinations with respect to the flow of the first fluid are becoming smaller, The first channel 3a, the most inclined, separates the smallest drops 24, the second channel 3b separates the slightly larger drops 23, the third channel 3c separates the still slightly larger drops 22, and the fourth channel 3d separates the larger drops 21.

Le microcanal 2 peut également être équipé d'un chenal 3, s'étendant par exemple suivant l'axe de circulation du fluide porteur, et pourvu d'une diminution de sa largeur 25 et/ou de sa hauteur. Cette diminution peut présenter la forme d'un gradin ou d'une marche discontinue, ou encore une forme progressive telle que celle visible en figure 10.The microchannel 2 can also be equipped with a channel 3, extending for example along the axis of circulation of the carrier fluid, and provided with a reduction in its width and / or in its height. This reduction can take the form of a step or a discontinuous step, or a progressive form such as that visible in figure 10 .

De cette façon, une goutte 5 s'écoulant dans le chenal en étant entraînée par le fluide porteur sera freinée lors du passage du rétrécissement 25.In this way, a drop 5 flowing in the channel being entrained by the carrier fluid will be braked during the passage of the constriction 25.

Dans le cas où la vitesse du fluide porteur est nulle, la géométrie des chenaux peut être utilisée comme moteur pour transporter les gouttes. De cette façon, l'invention permet de déplacer les gouttes dans un champ bidimensionnel, même en l'absence d'un écoulement d'un fluide porteur. L'invention peut même être utilisée afin de déplacer des gouttes à contre-courant par rapport à l'écoulement du fluide porteur.In the case where the speed of the carrier fluid is zero, the geometry of the channels can be used as a motor to transport the drops. In this way, the invention makes it possible to move the drops in a two-dimensional field, even in the absence of a flow of a carrier fluid. The invention can even be used in order to move drops against the current with respect to the flow of the carrier fluid.

A l'inverse, comme représenté en figure 11, le chenal 3 peut être équipé d'une zone d'élargissement 26 en gradin ou progressive, de façon à ce que la goutte 5 circulant dans le chenal 3 soit accélérée lors du passage de cette zone.Conversely, as shown in figure 11 , the channel 3 can be equipped with a widening zone 26 in step or progressive, so that the drop 5 flowing in the channel 3 is accelerated during the passage of this zone.

Le freinage des gouttes 5 peut également être obtenu (figure 12) en disposant de part et d'autre du chenal 3 dans lequel elles circulent, des chenaux secondaires 27 ayant pour fonction d'augmenter localement la section du microcanal 2. Ceci a pour effet de diminuer localement la vitesse de circulation du fluide porteur, et, par voie de conséquence, la vitesse de circulation des gouttes 5.The braking of the drops 5 can also be obtained ( figure 12 ) by having on either side of the channel 3 in which they circulate, secondary channels 27 having the function of locally increasing the section of the microchannel 2. This has the effect of locally reducing the speed of circulation of the carrier fluid, and, consequently, the speed of circulation of the drops 5.

Bien entendu, le nombre, la forme et la position des chenaux secondaires 27 peuvent être modifiés en fonction des besoins, l'important étant l'augmentation locale de la section du microcanal. On peut obtenir l'effet inverse en remplaçant les chenaux 27 par des nervures formant une diminution locale de la section du microcanal 2.Of course, the number, the shape and the position of the secondary channels 27 can be modified as required, the important thing being the local increase in the section of the microchannel. The opposite effect can be obtained by replacing the channels 27 with ribs forming a local decrease in the section of the microchannel 2.

La figure 13 représente un microcanal 2 comportant une zone de piégeage 28 des gouttes, formée par une poche ou une cavité 29 réalisée dans la paroi du microcanal 2. Dans cette forme de réalisation, le microcanal n'est pas équipé d'un chenal, les gouttes transportées par le flux de fluide porteur F étant piégées dans la ou les zones de piégeage si ces dernières se trouvent sur la trajectoire des gouttes. Les zones de piégeage peuvent être plus petites ou plus grandes que les gouttes ou les bulles à piéger, en fonction des applications et de la nature des gouttes ou des bulles.The figure 13 represents a microchannel 2 comprising a trapping zone 28 for the drops, formed by a pocket or a cavity 29 formed in the wall of the microchannel 2. In this embodiment, the microchannel is not equipped with a channel, the drops transported by the flow of carrier fluid F being trapped in the trapping zone or zones if the latter are in the path of the drops. The trapping zones can be smaller or larger than the drops or bubbles to be trapped, depending on the applications and the nature of the drops or bubbles.

La figure 14 représente un chenal 3 équipé d'une zone de piégeage 28 des gouttes, formée par une poche ou cavité formée sur un côté du chenal 3, dans une paroi 4 du microcanal 2.The figure 14 represents a channel 3 equipped with a trapping zone 28 for the drops, formed by a pocket or cavity formed on one side of the channel 3, in a wall 4 of the microchannel 2.

La poche 29 est raccordée au chenal 3 par une embouchure 30 et est apte à piéger un nombre prédéfini de gouttes. Dans le cas de la figure 13, cette zone ne permet de contenir qu'une seule goutte 5.The pocket 29 is connected to the channel 3 by a mouth 30 and is capable of trapping a predefined number of drops. In the case of figure 13 , this area can only hold a single drop 5.

La section de l'embouchure 30 peut être adaptée en fonction des applications. Dans le cas où l'embouchure 30 présente une section plus importante que celle du chenal 3, la ou les gouttes 5 peuvent être automatiquement attirées dans les zones de piégeage 28.The section of the mouth 30 can be adapted according to the applications. In the case where the mouth 30 has a larger section than that of the channel 3, the drop or drops 5 can be automatically drawn into the trapping zones 28.

Dans le cas où l'embouchure 30 présente une section plus faible ou sensiblement égale à celle du chenal 3, il peut être nécessaire de forcer les gouttes 5 à entrer dans la zone de piégeage 28. Ceci peut être réalisé par tout moyen approprié, en particulier à l'aide de la méthode décrite dans les documents WO 2006/018490 et WO 2007/138178 et qui utilise un faisceau laser dirigé sur l'interface entre une goutte et le fluide porteur ou entre deux gouttes, afin d'influer sur le déplacement des gouttes.In the case where the mouth 30 has a smaller section or substantially equal to that of the channel 3, it may be necessary to force the drops 5 to enter the trapping zone 28. This can be achieved by any suitable means, by particular using the method described in the documents WO 2006/018490 and WO 2007/138178 and which uses a beam laser directed at the interface between a drop and the carrier fluid or between two drops, in order to influence the displacement of the drops.

Les gouttes 5 peuvent être retirées des zones de piégeage 28 en augmentant le débit du fluide porteur, ou en forçant les gouttes 5 à sortir à l'aide de la méthode précitée.The drops 5 can be removed from the trapping zones 28 by increasing the flow rate of the carrier fluid, or by forcing the drops 5 to exit using the aforementioned method.

La figure 15 représente un chenal 3 de part et d'autre duquel sont formées plusieurs zones de piégeage 28, 29, écartées les unes des autres et agencées en quinconce. Chaque zone de piégeage 28, 29 peut être dimensionnée pour piéger un nombre prédéfini de gouttes 5, une goutte pour le cas des zones 28 et deux gouttes pour le cas de la zone 31, et/ou pour piéger des gouttes d'une nature particulière.The figure 15 shows a channel 3 on either side of which are formed several trapping zones 28, 29, spaced from each other and arranged in staggered rows. Each trapping zone 28, 29 can be dimensioned to trap a predefined number of drops 5, one drop for the case of zones 28 and two drops for the case of zone 31, and / or to trap drops of a particular nature .

Le microcanal 2 peut également être équipé d'un réseau de chenaux formés d'un chenal principal 3, par lequel arrivent les gouttes, à partir duquel s'étendent un ou plusieurs chenaux dérivés 31 dans lesquels sont disposés des obstacles 32 permettant de retenir, au moins temporairement, les gouttes 5 dans le chenal dérivé correspondant 31, comme on le voit à la figure 16. Ceux-ci forment alors des zones de piégeage. Les chenaux dérivés 31 peuvent ou non s'étendrent en aval de l'obstacle 32.The microchannel 2 can also be equipped with a network of channels formed by a main channel 3, through which the drops arrive, from which extend one or more derived channels 31 in which are placed obstacles 32 making it possible to retain, at least temporarily, the drops 5 in the corresponding derived channel 31, as seen in the figure 16 . These then form trapping zones. The derived channels 31 may or may not extend downstream of the obstacle 32.

Selon une autre variante de réalisation de l'invention, visible en figure 17, les chenaux annexes 31 peuvent être équipés de zones mouillantes 33. Une zone mouillante est formée par une zone dont les propriétés de mouillage de la paroi 4 ont été modifiées.According to another alternative embodiment of the invention, visible in figure 17 , the additional channels 31 can be equipped with wetting zones 33. A wetting zone is formed by a zone whose wetting properties of the wall 4 have been modified.

Ceci peut être réalisé par exemple à l'aide d'une goutte d'eau qui est arrêtée ou ralentie dans une zone rendue hydrophile. La modification des propriétés de mouillage peut également être obtenue à l'aide de méthodes chimiques, telles que la silanisation ou l'attaque par plasma, ou encore à l'aide de méthodes physiques, par exemple en introduisant des plots hydrophiles auxquelles la goutte vient s'accrocher (effet fakir).This can be done for example using a drop of water which is stopped or slowed down in an area made hydrophilic. The modification of the wetting properties can also be obtained using chemical methods, such as silanization or plasma attack, or even using physical methods, for example by introducing hydrophilic pads to which the drop comes. hang on (fakir effect).

Les zones de piégeage peuvent également comporter des éléments destinés à réagir avec le contenu des gouttes, de façon à former des microréacteurs ou en vue de détecter la présence de molécules chimiques et/ou biochimiques dans la ou les gouttes concernées. A titre d'exemple, une séquence d'ADN peut être détectée si la séquence complémentaire est greffée localement sur la paroi de la zone de piégeage correspondante.The trapping zones can also include elements intended to react with the content of the drops, so as to form microreactors or in order to detect the presence of chemical molecules and / or biochemical in the drop (s) concerned. For example, a DNA sequence can be detected if the complementary sequence is grafted locally on the wall of the corresponding trapping zone.

Plusieurs gouttes peuvent également être amenées à proximité ou au contact l'une de l'autre comme cela est représenté à la figure 18. Pour cela, le microcanal comporte par exemple deux chenaux parallèles 34, 35, destinés chacun à la circulation d'un type particulier de gouttes 36, 37, à partir desquels s'étendent des chenaux dérivés 31 dont les extrémités aval forment des zones de piégeage 28.Several drops can also be brought close to or in contact with each other as shown in the figure 18 . For this, the microchannel comprises for example two parallel channels 34, 35, each intended for the circulation of a particular type of drops 36, 37, from which extend derived channels 31 whose downstream ends form trapping zones 28.

Les zones de piégeage 28 sont disposées à proximité ou de manière adjacente l'une par rapport à l'autre de façon à ce qu'une goutte d'un premier type 36 soit à proximité ou au contact d'une goutte d'un second type 37.The trapping zones 28 are arranged near or adjacent to each other so that a drop of a first type 36 is near or in contact with a drop of a second type 37.

Il est alors possible de fusionner les deux gouttes 36, 37 et faire réagir leur contenu, ou de comparer leur contenu.It is then possible to merge the two drops 36, 37 and react to their content, or to compare their content.

La figure 19 représente un microcanal 2 présentant un chenal 3 équipé de plusieurs zones de piégeage successives 28, agencées en série.The figure 19 represents a microchannel 2 having a channel 3 equipped with several successive trapping zones 28, arranged in series.

Lorsqu'une goutte 5 est piégée dans chacune des zones de piégeage 28 et qu'une goutte supplémentaire arrive par le chenal 3, celle-ci déloge la goutte du piège amont qui, elle-même, vient déloger la goutte du piège située directement en aval du précédent. Ceci entraîne, par effet de cascade, le mouvement de toutes les gouttes 5, d'une zone de piégeage 28 à une autre.When a drop 5 is trapped in each of the trapping zones 28 and an additional drop arrives via the channel 3, it dislodges the drop from the upstream trap which, itself, dislodges the drop from the trap located directly at downstream from the previous one. This causes, by cascade effect, the movement of all the drops 5, from one trapping zone 28 to another.

Les zones de piégeage 28 forment une zone tampon T définie par un élargissement du microcanal et dans laquelle les gouttes 5 passent une durée déterminée nécessaire par exemple pour incuber une réaction chimique ou biochimique et/ou pour permettre leur observation.The trapping zones 28 form a buffer zone T defined by an enlargement of the microchannel and in which the drops 5 pass a determined duration necessary for example to incubate a chemical or biochemical reaction and / or to allow their observation.

Les zones de piégeage 28 peuvent également être à disposition matricielle comme représenté en figure 20, par l'intermédiaire d'un chenal principal 3 et de chenaux dérivés 31 parallèles, reliés chacun à un nombre déterminé de zones de piégeage 28.The trapping zones 28 can also be in matrix arrangement as shown in figure 20 , via a main channel 3 and parallel derived channels 31, each connected to a determined number of trapping zones 28.

La figure 21 montre un microcanal 2 comportant des moyens d'alimentation 38 de trains parallèles de gouttes de nature différente 21 à 24, des moyens parallèles d'introduction 39 des gouttes de nature différente dans le microcanal 2, et des chenaux 3 formés dans le microcanal 2 à partir des moyens d'introduction 39 pour guider les gouttes 21 à 24 sortant de chaque moyen d'introduction jusqu'à une zone prédéterminée du microcanal 2. On forme ainsi des trains parallèles de gouttes différentes dans le microcanal.The figure 21 shows a microchannel 2 comprising means 38 for feeding parallel trains of drops of different nature 21 to 24, parallel means 39 for introducing drops of different nature into the microchannel 2, and channels 3 formed in the microchannel 2 to starting from the introduction means 39 to guide the drops 21 to 24 leaving each introduction means to a predetermined area of the microchannel 2. Thus, parallel trains of different drops are formed in the microchannel.

Les microcanaux présentés ci-dessus pour le traitement de gouttes dans un fluide porteur sont également utilisables pour le traitement de bulles.The microchannels presented above for the treatment of drops in a carrier fluid can also be used for the treatment of bubbles.

L'invention permet notamment d'intégrer la préparation des échantillons dans une puce microfluidique et d'apporter les échantillons vers les points d'observation de façon simple et robuste.The invention makes it possible in particular to integrate the preparation of the samples into a microfluidic chip and to bring the samples to the observation points in a simple and robust manner.

Un circuit microfluidique selon l'invention peut être appliqué dans le domaine de la biotechnologie ou de la « chimietech », mais également dans le domaine de l'affichage fluide et de l'observation de réactions dans des microgouttes.A microfluidic circuit according to the invention can be applied in the field of biotechnology or “chemi-tech”, but also in the field of fluid display and the observation of reactions in microdrops.

Un tel circuit microfluidique pourrait se présenter sous un format aujourd'hui devenu standard, tel que les « Micro-Arrays » ou biopuces, par exemple les puces à ADN ou à protéines, ou encore les puces de culture cellulaire.Such a microfluidic circuit could be presented in a format which has now become standard, such as “Micro-Arrays” or biochips, for example DNA or protein chips, or even cell culture chips.

Ces biopuces sont constituées d'une matrice de zones où la surface est fonctionnalisée avec des biomolécules, la taille et la distance entre ces zones étant d'environ la même taille que les gouttes microfluidiques et les chenaux. L'invention permet d'amener des gouttes particulières, dont le contenu est connu, vers les sites fonctionnalisés et de les amener en contact avec la surface afin de produire l'hybridation qui permettra la mesure biologique. De cette manière, l'invention permet d'interfacer la technologie des biopuces avec les avantages de la manipulation des fluides en microfluidique.These biochips consist of a matrix of zones where the surface is functionalized with biomolecules, the size and the distance between these zones being approximately the same size as the microfluidic drops and the channels. The invention makes it possible to bring specific drops, the content of which is known, to the functionalized sites and to bring them into contact with the surface in order to produce the hybridization which will allow biological measurement. In this way, the invention makes it possible to interface the biochip technology with the advantages of handling fluids in microfluidics.

Comme indiqué précédemment, la trajectoire des gouttes peut être modifiée de façon active, à l'aide d'un laser, afin d'amener les gouttes dans un piège ou dans une zone déterminée d'un microcanal.As previously indicated, the trajectory of the drops can be actively modified, using a laser, in order to bring the drops into a trap or into a determined area of a microchannel.

Dans le cas d'un microcanal comportant plusieurs chenaux, une telle méthode peut également être utilisée pour diriger une goutte d'un chenal à un autre, par exemple pour choisir entre différentes trajectoires que pourrait suivre la goutte.In the case of a microchannel comprising several channels, such a method can also be used to direct a drop from one channel to another, for example to choose between different trajectories that the drop could follow.

Pour cela, lorsque les fluides présentent un écoulement thermocapillaire normal, il convient de choisir la longueur d'onde du laser afin qu'elle soit absorbée par le fluide porteur. Le fluide porteur peut, si nécessaire, contenir un colorant (encre noire par exemple) absorbant la longueur d'onde du laser. Dans ce cas, le chauffage local du fluide porteur à l'aide du laser, dans un chenal ou à proximité de celui-ci, attire la goutte dans ce chenal. Le chauffage peut aussi être effectué à l'interface entre la goutte et le fluide porteur afin d'attirer la goutte dans un chenal déterminé.For this, when the fluids have a normal thermocapillary flow, the wavelength of the laser should be chosen so that it is absorbed by the carrier fluid. The carrier fluid may, if necessary, contain a dye (black ink for example) absorbing the wavelength of the laser. In this case, the local heating of the carrier fluid using the laser, in a channel or close to it, attracts the drop in this channel. Heating can also be carried out at the interface between the drop and the carrier fluid in order to attract the drop in a given channel.

Lorsque les fluides présentent un écoulement thermocapillaire anormal, le laser peut être positionné afin de bloquer l'avancée d'une goutte et la dévier dans un autre chenal.When the fluids have an abnormal thermocapillary flow, the laser can be positioned in order to block the advance of a drop and divert it into another channel.

Le chauffage peut également être appliqué localement ou globalement à l'aide d'éléments de chauffage électriques.Heating can also be applied locally or globally using electrical heating elements.

En outre, dans le cas où les fluides utilisés n'absorbent pas le laser, une telle absorption peut être faite soit directement par le matériau constitutif du microcanal, soit en déposant dans le microcanal ou dans le chenal une couche ou une particule d'un matériau absorbant la radiation laser.In addition, in the case where the fluids used do not absorb the laser, such absorption can be done either directly by the material constituting the microchannel, or by depositing in the microchannel or in the channel a layer or a particle of a material absorbing laser radiation.

Les forces de diélectrophorèse peuvent également être utilisées afin d'influencer la trajectoire des gouttes, ou encore pour piéger des gouttes.The dielectrophoresis forces can also be used to influence the trajectory of the drops, or to trap drops.

Claims (14)

Circuit micro fluidique (1) comprenant au moins un microcanal (2) d'écoulement d'un premier fluide transportant des gouttes (5) ou de bulles d'au moins un deuxième fluide, le microcanal (2) étant délimité par deux parois (4, 8), le microcanal (2) ayant une section transversale perpendiculaire à la direction d'écoulement du premier fluide de hauteur (h) définie entre les deux parois du microcanal (2), la hauteur (h) du microcanal (2) étant dimensionnée pour écraser les gouttes (5) ou les bulles lors de leur déplacement, le circuit étant caractérisé en ce que le microcanal (2) comporte une zone de piégeage de gouttes ou de bulles, cette zone de piégeage (28) ayant une hauteur (hc) supérieure à celle (h) du microcanal (2), de façon à ce qu'au moins certaines des gouttes (5) ou des bulles du deuxième fluide dans le microcanal soient piégées dans la zone de piégeage placée sur leur trajectoire.Microfluidic circuit (1) comprising at least one microchannel (2) for the flow of a first fluid transporting drops (5) or bubbles of at least one second fluid, the microchannel (2) being delimited by two walls ( 4, 8), the microchannel (2) having a cross section perpendicular to the direction of flow of the first fluid of height (h) defined between the two walls of the microchannel (2), the height (h) of the microchannel (2) being sized to crush the drops (5) or the bubbles during their displacement, the circuit being characterized in that the microchannel (2) comprises a zone for trapping drops or bubbles, this trapping zone (28) having a height (hc) greater than that (h) of the microchannel (2), so that at least some of the drops (5) or bubbles of the second fluid in the microchannel are trapped in the trapping zone placed on their trajectory. Circuit selon la revendication 1, caractérisé en ce que la zone de piégeage est formée par une cavité (29) réalisée dans une des parois du microcanal de hauteur (hc) plus grande que celle de la section transversale du microcanal (2).Circuit according to claim 1, characterized in that the trapping zone is formed by a cavity (29) formed in one of the walls of the microchannel of height (hc) greater than that of the cross section of the microchannel (2). Circuit selon la revendication 1 ou 2, comportant des zones de piégeage (28) de gouttes (5) ou de bulles, formées par une modification locale de l'énergie de surface du microcanal (2), notamment une modification locale des propriétés de mouillage d'une des parois (4, 5) du microcanal (2).Circuit according to claim 1 or 2, comprising trapping zones (28) of drops (5) or bubbles, formed by a local modification of the surface energy of the microchannel (2), in particular a local modification of the wetting properties one of the walls (4, 5) of the microchannel (2). Circuit selon la revendication 2 ou 3, caractérisé en ce qu'au moins certaines des zones de piégeage (28) sont indépendantes les unes des autres.Circuit according to claim 2 or 3, characterized in that at least some of the trapping zones (28) are independent of each other. Circuit selon l'une des revendication 2 ou 3, caractérisé en ce qu'au moins certaines des zones de piégeage (28) sont reliées en série ou en parallèle par le microcanal (2) ou par des chenaux (3).Circuit according to one of claims 2 or 3, characterized in that at least some of the trapping zones (28) are connected in series or in parallel by the microchannel (2) or by channels (3). Circuit selon l'une des revendications 2 à 5, caractérisé en ce que les zones de piégeage comportent des éléments destinés à réagir avec le contenu des gouttes ou des bulles (5).Circuit according to one of Claims 2 to 5, characterized in that the trapping zones comprise elements intended to react with the content of the drops or bubbles (5). Circuit selon l'une des revendications 2 à 6, caractérisé en ce que les zones de piégeage sont configurées pour piéger un nombre défini de gouttes, notamment une seule goutte ou deux gouttes.Circuit according to one of claims 2 to 6, characterized in that the trapping zones are configured to trap a defined number of drops, in particular a single drop or two drops. Procédé de traitement de gouttes ou de bulles dans un circuit microfluidique selon l'une des revendications précédentes comportant les étapes suivantes : - faire circuler le premier fluide transportant les gouttes (5) ou les bulles dans le microcanal, - piéger au moins une goutte (5) ou une bulle dans au moins une zone de piégeage (25) placées sur sa trajectoire. Method for treating drops or bubbles in a microfluidic circuit according to one of the preceding claims, comprising the following steps: - circulate the first fluid transporting the drops (5) or the bubbles in the microchannel, - trap at least one drop (5) or a bubble in at least one trapping zone (25) placed on its trajectory. Procédé selon la revendication 8, caractérisé en ce que la au moins une zone de piégeage est plus petite que la taille de la au moins une goutte (5) ou une bulle.Method according to claim 8, characterized in that the at least one trapping zone is smaller than the size of the at least one drop (5) or a bubble. Procédé selon la revendication 8, caractérisé en ce que la au moins une zone de piégeage est plus grande que la taille de la au moins une goutte (5) ou une bulle.Method according to claim 8, characterized in that the at least one trapping zone is larger than the size of the at least one drop (5) or a bubble. Procédé selon l'une quelconque des revendications 8 à 10, caractérisé en ce qu'au moins deux gouttes (5) ou bulles sont piégées dans la ou au moins une zone de piégeage (25).Method according to any one of Claims 8 to 10, characterized in that at least two drops (5) or bubbles are trapped in the or at least one trapping zone (25). Procédé selon l'une des revendications 8 à 11, dans lequel la circulation du premier fluide est maintenue dans le microcanal, la ou les gouttes ou la ou les bulles piégées dans la ou les zones de piégeage étant stationnaires et le deuxième fluide dans la ou les gouttes ou la ou les bulles piégées dans la ou les zones de piégeage étant mis en mouvement par la circulation du premier fluide.Method according to one of Claims 8 to 11, in which the circulation of the first fluid is maintained in the microchannel, the drop (s) or the bubble (s) trapped in the trapping zone (s) being stationary and the second fluid in the or the drops or the bubble (s) trapped in the trapping zone (s) being set in motion by the circulation of the first fluid. Procédé selon l'une des revendications 8 à 12, comportant une étape d'augmentation du débit du premier fluide dans le microcanal de sorte à retirer de la au moins une goutte (5) ou une bulle de la zone de piégeage dans laquelle elle est piégée.Method according to one of claims 8 to 12, comprising a step of increasing the flow rate of the first fluid in the microchannel so as to remove from the at least one drop (5) or a bubble from the trapping zone in which it is trapped. Procédé selon l'une des revendications 8 à 13, comportant l'examen des gouttes ou bulles (5) à l'aide d'un microscope et/ou le suivi du déroulement d'une réaction au sein d'une zone pendant une période de temps importante.Method according to one of claims 8 to 13, comprising examining the drops or bubbles (5) using a microscope and / or monitoring the progress of a reaction within a zone for a period significant time.
EP19201464.5A 2009-09-29 2010-09-29 Method of treatment of droplets or bubbles in a microfluidic circuit Active EP3632566B1 (en)

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