The invention relates to the microfluidics field.
In this field, the known devices generally use technologies of the MEMS type. The channels are produced by assembling together two plates, one of the plates having been etched in order to form grooves.
According to another family of devices, a network of microchannels is formed by replication techniques such as the moulding of polymeric materials (for example polycarbonate). Other materials such as PDMS can be cast in micromachined moulds, etc.
In all these known devices, the geometry of the microfluidic network is defined at the time of conception.
The manufacture thereof requires equipment of the clean room type, which involves considerable means and long manufacturing times.
For a new component geometry, it is therefore necessary to carry out a new cycle of conception, production, packaging, etc. This cycle is long (from one week to several months) and expensive, which has a detrimental effect on the progress of a project. The component is generally discarded after a single use.
Techniques are known for manipulating liquid in the form of droplets, which forms what is known as discrete or discontinuous microfluidics. This makes it possible to manipulate droplets actuated by electrical forces. This technique is different from the so-called microchannel microfluidics to which this patent relates.
In all the known techniques, the surfaces may be contaminated by chemical or biological reactions and the microfluidic component cannot be reused.
For applications in the medical diagnostics field, the components usually used are often designed for one single use. This involves a constraint with regard to a low cost of manufacture, which is unfortunately incompatible with MEMS technologies.
The invention aims to propose a device which can be produced very easily and which can be rapidly configured as a function of the requirements of a user, without involving cumbersome and laborious manufacturing processes.
The invention relates firstly to a method for producing a microfluidic network, including at least a first microfluidic channel, which method comprises:
a) introducing a first fluid and a second fluid between two plates provided with electrodes, these two fluids being immiscible, the first fluid being a liquid that can be hardened or solidified,
b) the interface between the two fluids being shaped by means of the electrodes so as to form at least said first fluidic flow channel,
c) solidifying or hardening the material of said first fluid.
The second fluid can be eliminated.
According to the invention, a component or a microfluidic network is formed in the gap between two plates arranged parallel to one another and comprising electrodes.
The invention makes it possible to manufacture a component comprising reconfigurable or reusable channels. The shaping of the channels and of the network of channels is controlled by electrical forces.
A first fluid material is arranged between the two plates. By virtue of the electrical forces and the second fluid, the shape of this fusible material (still in the fluid state) is imposed with the aim of defining a network of microchannels. This shaping can then be fixed, by polymerisation, hardening or crystallisation of the fusible material. The component thus comprises a microfluidic network formed of solid walls.
The first and second fluids may be both insulating, or else both conductive. In the latter case, the conductivity of the first fluid is different or very different from that of the second fluid. As a variant, one is insulating and the other is conductive.
In the solid state, the material of the first fluid may be fusible. A method according to the invention may then additionally comprise a step of fluidising the solidified material of said first fluid.
It is then possible to eliminate the first fluid and to replace it with a third fluid, which is for example also liquid and can also be hardened or solidified.
It is possible to repeat steps b) and c) using the first fluid or the third fluid and a second fluid which is immiscible with the first fluid or the third fluid. It is also possible to shape the first fluid or the third fluid, by means of the electrodes and the second fluid, so as to form at least a second fluidic flow channel, different from the first.
Since the change between the liquid state and the solid state is optionally reversible, it is then possible to reconstruct an identical microfluidic network, obtained according to the invention, by renewing the fusible material or else to construct another microfluidic network which is different from the previous one.
One and the same component produced according to the invention can therefore be reused a large number of times with a large variety of geometries of microfluidic networks. The formation of each microfluidic network is quick and does not require any micromanufacturing equipment.
The microfluidic network which can be produced using such a method may comprise various elements such as for example one or more pillars in a channel and/or one or more closed chambers and/or a convergent then divergent section and/or a narrowing or a constriction in at least one channel, and/or at least one serpentine-shaped channel.
The invention also relates to a microfluidic device, including a microfluidic network, comprising:
a) two plates or substrates, each being equipped with one or more electrodes,
b) at least one channel, the walls of which are made from a material obtained by the solidification or hardening of the material of a first fluid.
Means may be provided for varying a physical parameter of the material constituting the walls of the channel so as to cause this material to pass at least from the liquid state to the solid state.
These means are not necessarily integrated in the device. They may be means external to the device (UV lamp, or external heating means, etc.).
As a variant, the invention also relates to a microfluidic device, including a microfluidic network, comprising:
a) two plates or substrates, each being equipped with one or more electrodes,
b) at least one channel having solid walls,
c) means for varying a physical parameter of the material constituting the walls of the channel so as to cause this material to pass at least from the liquid state to the solid state, these means being integrated in the device or being external to the device (UV lamp, or external heating means, etc. . . . ).
In a method and a device according to the invention, the first fluid, or the material constituting the walls of the device, may be an adhesive, for example of the epoxy type, or silicone, or a resin, or a UV adhesive or an insulating adhesive or a gel, for example alginate or agarose, or a polymer, for example PDMS, or a liquid-solid phase change material, for example a material having a phase transition temperature between 50° C. and 150° C., for example paraffin, optionally loaded with conductive particles, or polycarbonate, or a metal or an alloy based on tin and/or lead.
The second fluid may be a gas, for example air, or an insulating fluid, such as oil, or a conductive fluid, such as water or an aqueous solution.
The invention makes it possible to form a microfluidic network of channels in a non-disposable component with the following advantages:
A first example of embodiment of the invention is shown schematically in
These figures show, in section, a device comprising two parallel substrates or plates 2, 4, between which a channel 9 is defined. A single channel is shown, but the invention applies to the production of any configuration of channels, for example of the type shown in plan view in any one of
Two immiscible fluid media 6, 8 are arranged in the space defined between the two parallel plates (or substrates) 2, 4, each of these plates comprising one or more electrodes 3, 13 (
The electrodes may be in direct contact with the medium separating the two plates. This is the case for the electrodes 3, 13 in
As a variant, the electrodes 3′, 13′ are buried in the substrates 2, 4 (situation in
The article by Jones et al., “Frequency-based relationship of electrowetting and dielectrophoretic liquid microactuation”, Langmuir, 19, 7646-51, 2003 provides explanations concerning the forces used in the case of a displacement of the DEP type and that used in the case of a displacement by electrowetting (EWOD). In both cases, use is made of the electrostatic stresses applied to the interface between the first and second fluids.
In both cases, the electrodes 3, 3′, 13, 13′ may be connected to means for selectively applying a voltage to each electrode, for example switching means 33 and voltage generating means 31 (see
Also in both cases, the distance E between the two plates or substrates 2, 4 may be between 1 μm and 500 μm; it is for example around 100 μm.
Typically, when the fluids are activated by DEP, the potential difference between the electrodes 3 associated with the substrate 2 and the electrode 13 associated with the substrate 4 is between 100 V or a few hundred V, for example 500 V, and 1000 V or a few thousand V, for example 5000 V, for a distance E of around 100 μm.
When the fluids are actuated by electrowetting, the potential differences between the electrodes 3′ and the electrode 13′ are around ten Volts, for example between 10 V and 50 V, typically 40 V for an insulator thickness of 1 μm.
In all the figures, the electrode associated with the substrate or plate 4 is shown as being a single electrode. As a variant, this substrate may also comprise a plurality of electrodes, opposite the electrodes 3.
The first fluid medium 6 may be a liquid material having the property of solidifying or hardening as a result of modification of one of its physical parameters, for example as a result of a decrease or increase in temperature, or as a result of insolation under a specific radiation range, for example photonic radiation, in particular UV. Means are provided in the device for bringing about such a modification, these being for example temperature control means. These means are arranged on or in at least one of the substrates 2, 4 or in the space between the substrates. They may also be external means, in particular in the case of UV insolation, using for example commercially available adhesives and lamps (see for example the products offered by the company Adler SA). It may be provided that one of the abovementioned physical parameters of the fluid is kept at a first level, so as to keep the material in fluid form, and then said parameter is varied in order to cause said material to pass into the solid form. Means may therefore be provided for keeping this physical parameter of the fluid at a first level, for example a temperature which enables it to be in liquid form, and then for varying said parameter, for example for causing the temperature to change so as to cause this material to pass into the solid form.
The second fluid medium 8 will make it possible, with the aid of the electrodes, to define in the first fluid medium 6 the geometry of the desired channel 9.
More specifically, the interface between the two fluids 6 and 8 is shaped by the electrostatic forces by virtue of the electrodes 3, 13, 3′, 13′ and the voltages applied thereto, in the context of fluid displacement of either the DEP type or the electrowetting type. The channel or channels to be produced can thus be given any desired shape.
The solidification of the first fluid medium 6 makes it possible to fix the shape of this channel or these channels. It is then possible to evacuate the second fluid 8 (
Examples of use or of application of the microfluidic component thus produced are given below. During use, and even simply after formation of the solid walls of the channels, the latter are well defined and it is no longer necessary to apply electrical forces in order to keep fixed the shape of the microfluidic network.
Once the device has been formed, and during use for transporting fluids or droplets, it will be possible to use the electrodes 3, 3′, 13, 13′ to control the diphasic flows or droplet flows in the microchannels produced.
After use of the component, for example to carry out medical or biological analyses, it is possible to dissolve the walls, for example by chemical attack on the first fluid medium 6. Then a new volume of fluid material 6 (and of the fluid 8) can be reinjected in order to once again form a new fluidic network according to the invention, according to what has been described above, in the same configuration of channels or in a different configuration of channels. The voltages applied to the electrodes 3, 3′, 13, 13′ are then adapted as a function of the desired new configuration.
A first configuration can be produced as explained above, by solidifying the material 6′, once again by means of a first modification of a physical parameter such as the temperature.
It is then possible to recreate the earlier microfluidic structure. As a variant, by changing the configuration of the electrical forces, it is possible to form a new microfluidic network, different from the earlier network.
The medium 6′ may be renewed after each operation of melting the material constituting the microfluidic network, which makes it possible to reconstruct channels 9 with walls made from a clean or non-polluted material. Since the fluidisable medium 6′ can be renewed at the time of each remelting, it is possible to reuse the same component a large number of times while minimising the risks of contamination or pollution of the component.
As shown in
The material of the medium 6, 6′ is for example an adhesive (in particular of the epoxy type, or silicone, or a resin, etc.). Before hardening, these adhesives are made sufficiently fluid (fluidity for example between 1 centipoise and a few tens of centipoises, for example 50 cp) to facilitate the shaping of the material. By way of example, this material may be a UV adhesive. The hardening then takes place by insolation of the component by a UV light source. Reference adhesives and UV sources are available from a number of manufacturers, for example Photobond, Adler, Vitralit. By way of example, mention may be made of the UV adhesive 6127N from Adler S. A. At least one of the plates 2, 4 is then transparent and the UV light source is placed facing the adhesive.
Another example of a material for the medium 6 is a gel (in particular alginate, or agarose, etc.). This may also be a polymer, such as PDMS for example.
The medium 6 may also be a liquid-solid phase change material. A material which has a phase transition temperature that is acceptable to the entire component and can easily be attained by the user will preferably be chosen. This transition temperature may therefore be around a few tens of ° C., for example between 50° C. and 150° C.
For example, the material of the medium 6 is paraffin, the transition temperature of which is substantially 60°. According to another example, this material is polycarbonate, or a metal or an alloy based on tin and/or lead, etc.: each of these materials has a transition temperature greater than 100° C.
The medium 8 may be a gas (air). This may be an insulating fluid, such as oil or water or an aqueous solution.
The material 8 is preferably selected as a function of the material 6 so as to be able to apply an electrical force to the interface of the two fluids.
The two fluids 6, 8 may be insulating, with different dielectric permittivities, the constant ∈ of the first fluid medium 6 being greater than the constant ∈ of the second fluid medium 8. In this case, the electrodes are arranged below the first fluid medium 6, as in
According to another example, just one of the two materials 6, 8 is conductive; the conductive material may be the material 6 or the material 8. Electrowetting is then used to control the geometry of the interface between these two materials. In this case, the electrodes 3′ will be arranged not below the interface 6-8 but rather below the one of the two fluid media 6, 8 that is conductive (or that is the most conductive).
A paraffin-(salt water) pair is possible. It is also possible to use a pair consisting of paraffin (loaded with conductive particles) and air. Other possible pairs are as follows:
One example of embodiment of a starting component for implementing the invention will be given in connection with
For this first example, two insulating fluids 6, 8 are used, and the interface is therefore manipulated by liquid DEP.
The fluidic component is formed by two parallel plates 2, 4 (
Electrodes 3 (
In the example of
Spacer means 5 are then formed on one of the two plates (
The two plates 2, 4 are then assembled (
Openings 7, 17 are provided for injecting fluids into this cavity. These openings may be obtained by piercing one of the plates 2, 4 or walls constituting the spacer means 5, as illustrated in the plan view of
Means (not shown) are provided for forming an electrical interface between the component and an electrical control system. Said interface comprises for example spot contacts or electrical wires.
Other means are provided for controlling the temperature of the component. For example, a Peltier-effect element (not shown in the figures) is pressed against the lower plate 2 of the component.
One example of use of this component will be described in connection with
In a first step, the component is filled with a fusible insulating material 6. The latter is injected in the liquid state into the space between the two substrates 2, 4 through one of the side openings 7, 17 (
The chip is then kept at a temperature above the melting point of the fusible liquid 6 by virtue of heating means provided for this purpose.
In a second step, the fusible liquid is electrically actuated. A voltage ΔV is applied between the electrodes 3 of the lower substrate and the electrode 13 of the upper substrate (
In a third step, the microchannel 9 will be formed by solidifying the fusible liquid 6. The temperature of the chip is lowered and the liquid 6 solidifies, thus forming a channel 9 with solid walls (
The fusible liquid 6 is for example paraffin, the liquid-solid transition temperature of which is from 40 to 70° C., depending on the composition or the additives. Paraffins also exist which have melting temperatures of around 90° C. (for example: Apieson®), and which can also be used in the context of the invention.
One variant of this example of use is shown in
The fluidic component is firstly formed in the manner explained above (
The cavity thereof is then completely filled with the fusible medium 6 (
A voltage is applied between the electrodes 3 of the lower plate 2 and the electrode 13 of the upper plate 4.
The fluid 8 is injected through one of the orifices 17 (
This process continues until the fluid 8 extends along the entire component (
By reducing the temperature, the medium 6 is solidified so as to fix the shape of the channel obtained.
To this end, the substrates 2, 4, the electrodes 3, 13 and a fusible material 6 are chosen in such a way that the latter—in the liquid state—is in the total wetting configuration on the surfaces of the substrates. Use may be made for example of paraffin, substrates made from glass and electrodes made from ITO. In this case, it has been found among the inventors that—from a microscopic point of view—a thin film 60 of paraffin always remains on the surface of the substrates 2, 4. This phenomenon may optionally be reinforced by applying a suitable surface treatment to the wetted surface. This configuration makes it possible to produce channels which are formed entirely by walls of fusible materials 6, since a thin film 60 resulting from the property of total wetting described above is present on the surfaces of the channel.
A second example of embodiment of a component for implementing the invention will be given in connection with
For this second example, use is made of two fluids 6, 8, of which one is insulating and the other is conductive; the interface is thus manipulated by electrowetting.
The fluidic component is formed by two parallel plates 2, 4 (
The lower plate 2 comprises at least one metal layer 3 for defining the electrodes. These electrodes 3 are obtained by depositing and then etching a thin layer of a metal which may be selected from Au, Al, ITO (Indium Tin Oxide), Pt, Cu, Cr, etc. The conventional microtechnologies of microelectronics are used, for example photolithography.
The thickness of the electrodes 3, 13 is from a few tens of nm to a few μm, for example from 10 nm to 10 μm. The width of the motifs is from a few μm to a few mm, for example from 5 μm to 10 mm.
The space 1 between two adjacent motifs is around a few microns, for example between 1 μm and 50 μm.
After structuring of the electrodes, the plate 2 may preferably be covered with an insulating layer 12 for example of Si3N4, or of SiO2, etc.
A thick layer of resin 5 is deposited for example by lamination of a film of photosensitive resin of the Ordyl type (sold by Elga). The thickness of this film is for example between 10 μm and 500 μm. This layer is then structured by photolithography. This layer makes it possible to define the space between the two plates 2, 4. The motifs of this layer are pillars or beads.
Finally, a hydrophobic layer 14 is preferably deposited, such as for example a deposit of Teflon or of SiOC, as described in the document WO 2007/003720.
The upper substrate 4 comprises a thin metal layer 13, for example selected from Au, Al, ITO (Indium Tin Oxide), Pt, Cu, Cr, etc. Here too, a hydrophobic layer 16 may be deposited, such as for example a deposit of Teflon or of SiOC.
The two plates are pressed together and optionally bonded to one another.
Holes in the upper plate 4 or side openings 7, 17 in the bead of resin 5 are provided for injecting the fluids, for example through capillary tubes 18 adhesively bonded to these orifices (
Means (not shown) are provided for forming an electrical interface between the component and an electrical control system. Other means are provided for controlling the temperature of the component. For example, a Peltier-effect element (not shown in the figures) is pressed against the lower plate 2 of the component.
One example of use of this type of component will be given in connection with
The component (
The shape of the aqueous solution then covers the electrodes 3.
The fusible material 6 can then be solidified: it will thus store the shape obtained, that is to say, in the case of the example in
However, as in the previous example, any type of channel geometry can be envisaged by varying the number and geometry of the electrodes 3 of the lower plate.
In all the examples and embodiments described above, the electrodes are in the form of strips. However, the shape of the electrodes can be more complex than these simple strips, so as to form a network of channels with complex geometries. For instance, it is possible to form one or more pillars in a channel and/or one or more closed chambers and/or a convergent then divergent section and/or a narrowing in at least one channel, and/or at least one serpentine-shaped channel, each of these elements being formed in the material 6, which is initially liquid and then solidified or hardened.
For instance,
As a variant, shown in
Regardless of the mode of implementation of the invention,
As in the first example of embodiment (
For reasons of simplification of the drawing, the networks of
The electrodes used to produce the channels may be used again to manipulate the droplets by electrowetting. For instance, at the branching 37, the droplets 42 can be oriented towards one of the two orifices 7, 7′ by activating the electrodes 33 or 35 when a droplet 22 is located in the vicinity thereof.
As an example of application, it is possible to test chemical or biological reactions in each droplet. Depending on the result of the reaction, the user can sort the droplets by electrowetting so as for example to discard the droplets which have not reacted and to keep only those which have reacted. This example makes it possible to show that, with the components described by the invention, it is possible to carry out microfluidics of the hydrodynamic type in a channel, or microfluidics based on droplet manipulation by electrowetting. In the example, the droplets are manipulated simultaneously by the hydrodynamic effects and by electrowetting in the same component. Various applications are envisaged for the invention.
For example, the invention makes it possible to obtain a rapid prototyping technique, since the user modifies easily and with a high degree of interactivity the shape of the channels. The optimisation of a design of a microfluidic component is much quicker than with the techniques of the prior art.
The invention moreover makes it possible to carry out successively biological or chemical reactions without having to change the chip, while limiting the risk of contamination between the successive uses. Ultimately, only the medium 6 is the consumable part. Furthermore, a cleaning of the substrate and of the electrodes can be envisaged between two uses.
Potential applications are thus lab-on-a-chip applications, for the analysis field, for example environmental analysis or diagnostics.
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WO2009/130274 | 10/29/2009 | WO | A |
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