DROP FORMATION DEVICE IN A MICROFLUID CIRCUIT.

Abstract

The invention relates to a device (1) for forming drops in a microfluidic circuit, comprising a chamber (3) containing a first fluid and delimited by two opposing walls (10, 11) which diverge from each other in at least one given direction, and a microchannel (8) which contains a second fluid and which opens into an upstream area of ​​said chamber (3) with respect to the given direction, the opening of the microchannel (8) into the chamber (3) constituting an enlargement of the passage section of the second fluid and this enlargement causing the formation of drops (14) of the second fluid within the first fluid.

Description

A first technical area concerns lab-on-a-chip applications or other biotechnologies. In this area, a basic approach involves using a device with at least one microchannel for the flow of a first fluid, also called the carrier fluid, into which at least one second microchannel for the flow of a second fluid, immiscible with the first, opens perpendicularly. The first fluid (usually oil) shears the second fluid (usually water for biological applications) to form droplets of the second fluid, which are then transported by the first fluid. The flow rates of the two fluids and the geometry of the microchannels are adjusted to obtain a desired droplet size and frequency, which also depend on the viscosities of the two fluids. Such a device necessarily includes forcing mechanisms, such as a pump, to circulate the two fluids. Since droplet size depends on the flow rate of each fluid, precise adjustment of the fluid flow rates is necessary, which can complicate the implementation of this device. A second approach is that of so-called "digital" microfluidics, in which drops are typically formed by electrowetting, by applying different electrical voltages to different parts of the drops. The size of the droplets formed using this technique is much larger than that of nanodroplets or microdroplets. This technique also raises the issue of droplet contamination and evaporation. Finally, several approaches exist for producing droplets on demand by rapidly ejecting liquid through a needle or hole, using devices often similar to inkjet printer systems. These devices produce droplets that impact a surface with high energy, generating splashes. However, they also require expensive technical resources, such as a high-voltage power source or precision motors. A second technical field concerns materials science, in which several approaches have been developed to produce foams or emulsions, and therefore populations of bubbles or droplets. The applications are diverse and include the food and cosmetics industries. Other approaches involve encapsulating droplets within other droplets. For example, a water droplet can be encapsulated within an oil droplet, which is itself contained within water. All of these approaches require the use of expensive and difficult-to-implement forcing methods. In addition, generally speaking, the aim is to increase the flow rates of droplets produced, while ensuring that the drops or bubbles are monodisperse, i.e., of a constant and controlled size. The invention aims in particular to provide a simple, effective and economical solution to these problems. To this end, it proposes a device for forming droplets in a microfluidic circuit, characterized in that it comprises a chamber containing a first fluid and delimited by two opposing walls that diverge from each other in at least one direction. given, and a microchannel which contains a second fluid and which opens into an upstream area of ​​said chamber with respect to the given direction, the opening of the microchannel into the chamber comprising an increase in the cross-sectional area of ​​passage of the second fluid and this increase causing the formation of drops of the second fluid and their detachment from the second fluid contained in the microchannel. In this device, the second fluid is subjected, at the microchannel outlet in the chamber, to two opposing forces due to surface tension. The first force is a surface energy gradient due to the change in the surface area of ​​the droplet as it forms, which tends to extract the second fluid from the microchannel, forming a "finger" of the second fluid protruding into the chamber and attached to the second fluid contained in the microchannel, and then forming a droplet by separating the finger from the second fluid contained in the microchannel. A second force, acting in the opposite direction to the first and corresponding to the capillary force, tends to keep the second fluid finger attached to the second fluid contained in the microchannel. The aforementioned finger detaches from the second fluid contained in the microchannel when the first force becomes greater than the second force. However, the first force is, for a given microchannel and chamber geometry, a function of the volume of the second fluid finger. Thus, during operation, the volume of the finger will gradually increase until the first force becomes greater than the second, at which point the finger detaches to form a droplet. The droplet is then transported by the increased cross-section of the chamber, from upstream to downstream. It is noted that it is not necessary for the first and second fluids to be circulating; the only important thing is that the second fluid reaches the opening of the microchannel in the chamber. Therefore, it is not necessary to provide means of forcing the different fluids. The transport of the droplets of the second fluid in the The chamber results from the increase in the cross-sectional area. Indeed, a drop located in an area of ​​small cross-section, in which it has a flattened shape, will naturally be attracted to an area of ​​larger cross-section, in which it can take on a more spherical shape. Furthermore, the droplet size is essentially independent of the flow rate of the second fluid. It is essentially a function of the cross-section of the second fluid's inlet to the chamber and of the divergence of the opposing walls of the chamber, that is to say, a function of fixed and time-invariant geometric parameters, the droplet size thus being precisely calibrated. Droplet size is also independent of surface tension, since the same surface tension acts both to detach and retain the drops. Therefore, droplet size is independent of the exact nature of the fluids or their potential contamination, and depends only very slightly on the fluid's viscosity. Finally, the droplet size is also not influenced by the geometry of the walls located away from the microchannel outlet, so different chamber shapes can be used. The room used, for example, has a roughly rectangular cross-section whose height is contained between the two diverging opposite walls and whose length is large compared to the height. The length is thus, for example, greater than 10 times the height. Of course, the chamber can take other forms. In particular, the chamber walls can diverge in more than one direction. For example, the chamber can be spherical or ovoid. Preferably, the height of the chamber at the opening of the microchannel is less than the diameter of the drops to be formed. In a first embodiment, the flow rate of the first fluid in the chamber is substantially zero. In one embodiment, the flow rate of the first fluid in the chamber is set to a predetermined value. The divergence of the two opposite walls of the chamber corresponds, for example, to a slope of approximately 1 to 4% of one wall relative to the other. Of course, these values ​​are given only as an example, and the slope can have an infinitesimal value or a value of 100%, corresponding to a vertical wall in relation to a horizontal wall. According to another feature of the invention, the device includes means for locally modifying the surface tension of the second fluid. This allows, in particular, for adjusting the size of the drops produced relative to the size they would have without modification of the surface tension. In one embodiment of the invention, the means for modifying the surface tension of the second fluid include means for heating the second fluid, for example by a locally applied laser beam or by electrodes integrated into the microfluidic circuit or by using another means of temperature control. If the area directly upstream of the microchannel's outlet is heated, the surface tension tending to retain the second fluid within the microchannel decreases, and the effort required to draw a droplet of the second fluid out of the microchannel is reduced. Heating directly upstream of the outlet therefore tends to decrease droplet size. Conversely, if the area directly downstream of the microchannel outlet is heated, the surface tension that tends to draw the second fluid out of the microchannel is reduced. Heating directly downstream of the outlet therefore tends to increase droplet size. In general, heating produces the same effects as increasing the cross-section at the outlet of the microchannel, with regard to the formation of drops and their detachment. According to another feature of the invention, the device comprises several microchannels opening into the chamber. The microchannels can contain independent fluids or form branches originating from a single channel located upstream of the microchannels. According to one variant, the microchannels are essentially parallel to each other and open onto the same side of the chamber. According to a second variant, the chamber is annular in shape, with the microchannels arranged in a star shape and opening onto the inner periphery of the chamber. The invention further relates to a method for forming droplets of a second fluid in a first fluid contained in a microfluidic circuit, characterized in that it consists of bringing the second fluid to the inlet of a chamber containing the first fluid, the inlet of the chamber having two opposite walls which diverge inside the chamber, and pushing the second fluid into the inlet of the chamber to form inside it a droplet of the second fluid, this droplet gradually widening between the two opposite diverging walls of the chamber until it detaches at its upstream end of the supply of the second fluid. Preferably, the process consists of adjusting the droplet size of the second fluid by adjusting the inlet cross-section of the second fluid at the chamber inlet and the divergence of said opposite walls of the chamber and / or by modifying the surface tension by heating with a laser beam or by electrodes integrated into the microfluidic circuit or by other means of temperature control. The invention will be better understood and other details, features and advantages of the invention will become apparent upon reading the The following description is provided as a non-limiting example with reference to the attached drawings in which: - Figure 1 is a longitudinal cross-sectional view of the device according to the invention; - Figure 2 is a cross-sectional view of this device in which the formed drops are not shown; - Figure 3 is a diagram representing the size of the drops produced as a function of the flow rate of the second fluid; - Figure 4 is a schematic view of an alternative embodiment in which several microchannels arranged in parallel open into the chamber; - Figure 5 is a schematic view of another embodiment variant in which the microchannels form branches opening into the chamber; - Figure 6 is a schematic view of another embodiment variant in which the chamber is annular, with the microchannels arranged in a star shape. Figures 1 and 2 depict a droplet formation device 1 in a microfluidic circuit, comprising a body 2 in which a chamber 3 is formed, delimited by two parallel and opposite lateral walls 4 and by two opposite longitudinal walls 10, 11. The width L of the chamber 3, i.e., the distance between the two lateral walls 4, is on the order of 2 mm, for example. The chamber 3 further comprises a bottom wall 5 in the shape of a point 6 directed towards an opposite end 7 of the chamber 3. The body 2 further includes a microchannel 8, one end of which is connected to a connecting orifice 9, in particular for the connection of a syringe or a pipette, and the other end of which opens into the chamber 3 at the level of the tip 6 of the bottom wall 5. The lower longitudinal wall 10 of the chamber is a flat wall and the upper longitudinal wall 11 has a part oblique 12 which gradually moves away from the lower longitudinal wall 10 towards the opposite end 7 of chamber 3. The divergence of the two opposite walls 10, 11 of chamber 3 corresponds for example to a slope of between 1 and 4% approximately of one wall with respect to the other. In this way, the cross-section of chamber 3 increases progressively from the area into which the microchannel 8 opens towards the opposite end 7. The minimum height h1 of chamber 3, that is to say the height of chamber 3 at the level of the opening 13 of the microchannel 8, is on the order of 10 to 100 pm, and the maximum height h2 of chamber 3, that is to say the height of chamber 3 at the level of its open end 7, is on the order of 20 to 1000 pm. This device 1 can be combined with means for locally modifying the surface tension of the second fluid, including means for heating the second fluid, for example by electrodes integrated into the microcircuit or by using external temperature control. The surface tension decreases linearly with temperature, so that for a fixed surface, the surface energy (equal to the product of the total area and the surface tension) can be changed by heating with electrodes, in order to produce the same effects as increasing the cross-section at the outlet of the microchannel 8, with a decreasing temperature gradient at this outlet. An alternative embodiment of the invention is shown in Figure 4. In this embodiment, chamber 3 has a rectangular shape and is connected to several substantially parallel microchannels 8 opening onto the same side of chamber 3. Another variant is illustrated in Figure 5, in which the device comprises a network of microchannels 8 with branches, each branch originating from the same upstream source channel. The various branches open onto the same side of chamber 3. A final variant is shown in Figure 6. In this variant, chamber 3 has an annular shape and the device has several microchannels 8 arranged in a star shape, extending radially from a single source 15 until opening onto the inner periphery of chamber 3. These embodiment variations allow for the simultaneous formation of multiple droplet trains within the same chamber. This is particularly useful when producing droplet populations containing, for example, different ingredients. Depending on the requirements, the droplets thus formed can be manipulated or extracted from the device in the form of foam or emulsion. The operation of this droplet formation device will now be detailed. Chamber 3 is filled with a first fluid, for example oil. A syringe containing a second fluid, for example water, is then connected to the connection port 9 and water is injected into the microchannel 8 until it reaches the outlet 13 of the microchannel 8. As previously mentioned, the water at the outlet 13 of the microchannel 8 is subjected to two opposing forces due to surface tension. The first force is due to a surface energy gradient which tends to extract the water out of the microchannel 8, forming a finger 14a which protrudes into chamber 3 and is attached to the water contained in the microchannel 8. A second force, opposite to the first and corresponding to the capillary force, tends to keep the finger 14a attached to the water contained in the microchannel 8. Finger 14a detaches when the first force becomes greater than the second force. This first force is a function, for a given geometry of the microchannel 8 and chamber 3, of the volume of finger 14a. Thus, during operation, the volume of finger 14a increases gradually, until the first force becomes greater than the second force and the finger detaches to form a drop 14b. The dimensions of the microchannel 8 and the enlargement of the chamber 3 cross-section are calculated to obtain a droplet 14 of a specific size. In particular, the height h1 of the chamber 3 at the opening of the microchannel must be less than the diameter of the droplets 14 to be formed. The water drops 14b are thus successively formed in the chamber, provided that water is brought to the outlet 13 of the microchannel 8. Depending on the requirements, an oil flow rate can be imposed in chamber 3. The droplets 14b formed at the opening 13 of the microchannel 8 are naturally transported towards the opposite end 7 of the chamber 3, due to the widening of their cross-sectional area within the chamber. Indeed, as seen above, a droplet 14b located in an area of ​​small cross-section, where it takes on a flattened shape, will naturally be attracted to an area of ​​larger cross-section, where it can assume a more spherical shape and is therefore less constrained. As can be seen in Figure 1, the droplets 14b near the tip 6 have a larger apparent diameter d1 than the droplets 14b near the other end 7, due to their being compressed between the walls 10 and 12. Figure 3 is a graph showing the variation in the diameter of the droplets 14b, measured at a given position, as a function of the water flow rate entering through the microchannel 8. It can be seen that this variation is virtually zero even for a large variation in the applied flow rate, which shows that the invention makes it possible to obtain droplets 14 of calibrated size, regardless of the operating conditions, thus simplifying the implementation of such a droplet formation device. In the example shown in Figure 3, the size of the droplets 14b is on the order of a few hundreds of micrometers but a reduction in the dimensions of this device 1 would also make it possible to obtain drops 14 with a size of a few hundred nanometers, without significant modification of its operation. 5. The operation of the device is notably independent of the nature of the fluids (gas or liquid) and the value of the surface tension.

Claims

DEMANDS 1. Device (1) for forming droplets (14) in a microfluidic circuit, characterized in that it comprises a chamber (3) containing a first fluid and delimited by two opposing walls (10, 11) which diverge from each other in at least one given direction, and a microchannel (8) which contains a second fluid and which opens into an upstream area of ​​said chamber (3) with respect to the given direction, the opening (13) of the microchannel (8) into the chamber (3) comprising an increase in the cross-section of the passage of the second fluid and this increase causing the formation of droplets (14) of the second fluid and their detachment from the second fluid contained in the microchannel, independently of the flow of the first fluid and / or the second fluid.

2. Device according to claim 1, characterized in that the chamber (3) has a substantially rectangular section whose height is contained between the two diverging opposite walls (10, 11) and whose length is large in relation to the height.

3. Device according to claim 1 or 2, characterized in that the height (h1 ) of the chamber (3) at the outlet (13) of the microchannel (8) is less than the diameter of the drops (14) to be formed.

4. Device according to any one of claims 1 to 3, characterized in that the flow rate of the first fluid in the chamber is substantially zero.

5. Device according to any one of claims 1 to 3, characterized in that the flow rate of the first fluid in the chamber (3) is set to a determined value.

6. Device according to any one of claims 1 to 5, characterized in that the divergence of the two opposite walls (10, 11) of the chamber (3) corresponds to a slope of between 1 and 4% approximately of one wall with respect to the other.

7. Device according to any one of claims 1 to 6, characterized in that it comprises means for locally modifying the surface tension of the second fluid.

8. Device according to claim 7, characterized in that the means for modifying the surface tension of the second fluid comprise means for heating the second fluid, for example by a laser beam applied locally or by electrodes integrated into the microfluidic circuit.

9. Device according to any one of claims 1 to 8, characterized in that it comprises several microchannels (8) opening into the chamber.

10. Device according to claim 9, characterized in that the microchannels (8) are substantially parallel to each other and open onto the same side of the chamber (3).

11. Device according to claim 9, characterized in that the chamber (3) is annular in shape, the microchannels (8) being arranged in a star shape and opening onto the inner periphery of the chamber (3).

12. A method for forming droplets (14) of a second fluid in a first fluid contained in a microfluidic circuit, characterized in that it consists of bringing the second fluid to the inlet of a chamber (3) containing the first fluid, the inlet of the chamber (3) having two opposite walls (10, 11) which diverge inside the chamber (3), and pushing the second fluid into the inlet of the chamber (3) to form inside it a droplet (14) of the second fluid, this droplet gradually widening between the two opposite diverging walls (10, 11) of the chamber (3) until it detaches at its upstream end of the supply of the second fluid, independently of the flow of the first fluid and / or the second fluid.

13. A method according to claim 12, characterized in that it consists of adjusting the size of the droplets (14) of the second fluid by adjusting the cross-section of the supply of the second fluid to the inlet of the chamber (3) and the divergence of said opposite walls (10, 11) of chamber (3) and / or by modification of surface tension by heating by a laser beam or by electrodes integrated into the microfluidic circuit.