Method for counter-current liquid-liquid extraction in sub-millimetre conduit

Abstract

To provide a method for counter-current liquid-liquid extraction in a sub-millimeter conduit.SOLUTION: The method is implemented from an initial liquid drop stream in a conduit. The initial liquid drop stream is constituted of alternating drops of a first liquid (LB) and a second liquid (LNM) less wetting than the first liquid and immiscible with the first liquid, one of the two liquids comprising a component to be extracted toward the other of the two liquids. The method comprises the steps of: (a) applying a first pressure gradient along the conduit to generate a visco-inertial flow displacing a first volume of drop stream according to a first gradient and generating a film of first liquid displaced along an opposite orientation to the first gradient (the film being located between the drops of second liquid and the conduit); (b) stopping the application of the first pressure gradient; (c) applying a second pressure gradient along the conduit, in the opposite orientation to the first pressure gradient applied to generate a viscous-capillary flow displacing a second volume of drop stream; and (d) stopping the application of the second pressure gradient.SELECTED DRAWING: Figure 3

Description

[Technical Field]

[0001] This invention relates to the field of liquid-liquid extraction.

[0002] Liquid-liquid extraction is a method that involves bringing two immiscible or poorly immiscible liquid phases into contact with each other, thereby allowing for mass exchange of constituent components from one phase to the other. [Background technology]

[0003] Many liquid-liquid extraction methods exist. For example, one can refer to the paper in Non-Patent Document 1 (PA1), which references several techniques proposed to date.

[0004] Of these methods, liquid-liquid extraction using sub-millimeter conduits capable of extraction is particularly in demand.

[0005] A “submillimeter” conduit should be understood as a conduit having two dimensions not exceeding 1 millimeter. Most commonly, this conduit has a circular cross-section, but the present invention can be applied to other cross-sectional shapes, such as a square cross-section.

[0006] In fact, miniaturizing liquid-liquid extraction methods in sub-millimeter conduits offers several advantages.

[0007] The primary concern lies in the reduction of the volume of the liquid involved. This is especially true when the liquid is hazardous, scarce, or expensive. This is the case, for example, with liquids containing extracted radiochemical components, which may be encountered in medical or pharmaceutical applications. Furthermore, in the case of liquid loss to the environment, the volume involved significantly reduces the risk.

[0008] The second advantage is the permanent containment of liquids within the conduit. This containment is, of course, welcome for hazardous liquids, such as those containing radiochemical components. The risk of losing the liquid is also limited. In addition, containment means that the liquid elements can be easily handled, enabling simple automation.

[0009] Finally, the third concern is achieving extraction performance that is difficult to achieve on a larger scale. In fact, miniaturization generally allows for an increase in the flow density of material extracted from one liquid phase to the other, due to a high ratio of the exchange surface area between the two liquid phases to the volume occupied by each liquid phase.

[0010] Next, there are two main approaches to ensure the extraction of components between two immiscible liquid phases in a sub-millimeter conduit.

[0011] The first approach involves circulating two liquid phases in parallel (same orientation).

[0012] PA1 refers to several proposed parallel flow techniques, including techniques for implementing sub-millimeter conduits. In parallel flow, liquid-liquid exchange cannot exceed the extraction efficiency of the contact phase between the liquids, and therefore the extraction is generally not very quantitative. Nevertheless, effective parallel flow techniques are presented in more detail in Non-Patent Document 2 (PA2). This consists of using droplet flows of two immiscible liquid phases, all of which wet the sub-millimeter conduit. This means alternating droplets of one liquid phase with droplets of the other liquid phase along the conduit. The droplet flow can be generated by converging the two liquid phases at a T-junction upstream of the conduit.

[0013] The second approach involves circulating two liquid phases in a countercurrent (opposite direction). Countercurrent has the advantage of allowing for quantitative transfer from one liquid phase to the other by bringing the liquids into contact with each other at several extraction stages.

[0014] Various techniques for implementing this countercurrent approach have been proposed and have been adequately presented in the PA1 review. These include, in particular, (a) discontinuous multistage and (b) continuous methods of countercurrent liquid-liquid extraction.

[0015] The discontinuous multistage method (a) is particularly complex to implement, either because each stage involves the necessary attachments or because it includes delicate physicochemical methods to be carried out to separate the two liquid phases at the end of their contact. Extraction is typically discontinuous between the two stages.

[0016] The continuous method (b) requires that separation between the two phases be maintained at all times. The most common method of operation is to implement a (solid) separation membrane between two liquid phases circulating in a countercurrent. In addition to the simplicity of the associated installation, the accommodation of each of the two liquid phases is therefore much simpler than the discontinuous multistage method. In the membrane method, one of the control parameters is the size of the pores in the membrane that allow for the extraction (mass transfer) of components from one liquid phase to the other.

[0017] However, these membrane methods have several drawbacks, namely: - Limiting the pressure difference on both sides of the membrane, at the risk of compromising the mechanical integrity of the membrane; - Restricting mass transfer through the membrane (resistance provided by the diffusive boundary layers on each side of each surface of the membrane, as well as the pore size, thickness, and meandering of the membrane).

[0018] Therefore, designing a sufficiently thick membrane (that can withstand the pressure difference) while ensuring optimal mass transfer from one liquid phase to the other is difficult. Consequently, miniaturizing the apparatus for performing membrane-directed liquid-liquid extraction has inherent physical limitations that result in performance losses in the extraction method.

[0019] Other techniques are based on the continuous countercurrent liquid-liquid extraction method. These include the countercurrent chromatography method. Here, the separation of the liquid phases is maintained throughout the extraction process by a radial acceleration field (centrifugal force) applied to millimeter conduits wound around a helix. Since the centrifugal forces received by each of the two liquid phases are not the same, the difference in mass density between the two liquid phases is used to ensure separation. For example, Non-Patent Document 3 (PA3) can be referred to. However, this approach is not very useful for miniaturization because it is becoming increasingly difficult to achieve the separation effect by miniaturization. In a similar approach, a gravitational field is implemented instead of centrifugal force to separate the liquid phases. However, here too, below a certain size, the separation of the liquid phases is no longer effective. Thus, the performance loss of the liquid-liquid extraction method becomes significant.

Prior Art Documents

Patent Documents

[0020]

Patent Document 1

Non-Patent Documents

[0021]

Non-Patent Document 1

Non-Patent Document 2

Non-Patent Document 3

Summary of the Invention

[0022] One object of the present invention is to propose a method for counter-current liquid-liquid extraction in a submillimeter conduit with improved performance.

[0023] For this purpose, the present invention proposes a method for counter-current liquid-liquid extraction in a submillimeter conduit. This method includes the following steps implemented from an initial flow of droplets in the conduit, where the initial flow is composed of alternating droplets of a first liquid and droplets of a second liquid that is less wettable and immiscible with the first liquid, and one of the two liquids contains a component to be extracted towards the other of the two liquids. (The method is,) (a) Applying a first pressure gradient along the conduit so as to generate a visco-inertial flowing that displaces a first volume of droplet flow according to the first (pressure) gradient, and generating a film of the first liquid displaced along an orientation opposite to the first (pressure) gradient, where the film is located between the droplets of the second liquid and the conduit; (b) Stopping the application of the first pressure gradient; (c) Applying the second pressure gradient along the conduit in an orientation opposite to the first pressure gradient applied in step (a) so as to generate a visco-capillary flowing that displaces a second volume of droplet flow according to the second (pressure) gradient; (d) Stopping the application of the second pressure gradient; and comprising.

[0024] Methods according to the present invention may also include other features, either alone or in combination, which include the following features: - Step (d) is initiated when the second volume of droplet flow displaced during step (c) is equal to the first volume of droplet flow displaced during step (a); - Steps (a) through (d) are repeated N1 times, where N1 is a natural number greater than or equal to 1; - The droplet flow is regular; - At the end of step (d), steps (a) to (d) are advantageously repeated N1 times, a certain amount of the first liquid is located at one of the ends of the conduit, and the method then comprises the following steps; (A) A step of drawing a first liquid of that volume out of a conduit through the end of the conduit where that volume is located; (B) A step of generating a flow of liquid droplets in a conduit through the conduit end, wherein a first liquid of the volume is drawn out through the conduit end in step (A), and the flow consists of alternating droplets of the first liquid and droplets of the second liquid; - Process (B) includes, at the end of process (C), which consists of performing processes (a) to (d); - Process (C) is repeated N2 times, where N2 is a natural number greater than or equal to 1; - Processes (A) and (B) are repeated N3 times, where N3 is a natural number greater than or equal to 1; - The droplet flow generated in process (B) is regular; - The ratio of the average velocity of viscoinertial flow in process (a) to the average velocity of visco-capillary flow in process (c) is between 2.5 and 4; It may also include the following characteristics.

[0025] Further features and advantages of the present invention will become apparent from the following detailed description and refer to the accompanying drawings for their understanding. [Brief explanation of the drawing]

[0026] [Figure 1]This diagram shows a simplified representation of an apparatus capable of carrying out the liquid-liquid extraction method according to the present invention. [Figure 2] The present invention represents a sub-millimeter conduit containing a flow of liquid droplets, formed by alternating between a first liquid and a second liquid that is less humicially humicidal and immiscible with the first liquid, in which the method of the present invention is carried out. [Figure 3] The diagram includes four figures representing the oscillation period, i.e., the displacements of the first liquid droplet and the second liquid droplet in the counterflow, during the implementation of the method according to the present invention. [Figure 4] This includes three diagrams, illustrating the development of the initial droplet flow shown in Figure 2 during the repeated execution of several oscillation periods, as shown in the consecutive diagrams in Figure 3. [Figure 5] The diagram includes three figures (diagrams) illustrating other steps in the method according to the present invention, which are aimed at generating a new flow of droplets formed by alternating droplets of a first liquid and droplets of a second liquid. [Figure 6] This is a simplified diagram of an apparatus actually manufactured to carry out the method according to the present invention. [Modes for carrying out the invention]

[0027] [Detailed description of the invention] This invention proposes a method for counterflow liquid extraction in sub-millimeter conduits.

[0028] The starting point is a situation in which a flow of droplets is provided in a conduit, the flow consisting of alternating droplets of a first liquid LM and a second liquid LNM which is less wetting than the first liquid and immiscible with the first liquid, and one of the two liquids further contains components that are extracted toward the other of the two liquids.

[0029] The method according to the present invention is intended to carry out the following steps, namely: (a) A step of applying a first pressure gradient along a conduit to generate a viscoinertial flow that displaces a droplet flow of a first volume according to the first gradient, and generating a film of a first liquid displaced in an orientation opposite to the first gradient, wherein the film is located between a droplet of a second liquid and the conduit; (b) The step of stopping the application of the first pressure gradient; (c) the step of applying a second pressure gradient along the conduit in the opposite orientation to the first pressure gradient applied in step (b) to generate a viscous capillary flow that displaces a second volume of droplet flow according to the second gradient; and (d) The process of stopping the application of the second pressure gradient.

[0030] The execution of processes (a) to (d) defines the vibration period.

[0031] This point can be better understood by referring to Figures 1 to 3.

[0032] Figure 1 shows an apparatus capable of carrying out the above method. Figure 2 shows the initial state involving droplet flow of two liquid phases. Finally, Figure 3 shows the implementation of the steps of the method according to the present invention, along with the physical phenomena involved in explaining the counterflow displacement of the two liquid phases present in the sub-millimeter conduit.

[0033] Figure 1 shows a first open vial F1 containing a first liquid LM and a second closed vial F2 containing a second liquid LNM. The two vials F1 and F2 are connected by a sub-millimeter conduit CS, whose ends E1 and E2 are immersed in the first liquid LM of the first vial F1 and the second liquid LNM of the second vial F2, respectively. The fact that the second vial F2 is closed allows the pressure inside to be controlled by any suitable means (not shown), while the first vial F1 is open and remains at ambient (atmospheric) pressure. Thus, a pressure gradient can be applied along the sub-millimeter conduit.

[0034] In the initial situation, that is, before implementing the method according to the present invention as described above, the situation shown in Figure 2 is the starting point.

[0035] This droplet flow can be achieved using two tanks (not shown in Figure 1), one for the first liquid LM and the other for the second liquid LNM. Each tank is connected by capillaries to a T-shaped inlet, and the T-shaped outlet opens into a sub-millimeter conduit. In the initial state, droplets of the first liquid and droplets of the second liquid alternate along the sub-millimeter conduit CS.

[0036] As shown in Figure 2, the initial droplet flow is not necessarily regular, and the droplet volumes are not equal. In fact, to perform the liquid-liquid exchange operation, it is possible to inject a desired ratio (denoted α) between the average flow rate QLM of the first liquid and the average flow rate QLNM of the second liquid into the sub-millimeter conduit CS. Thus, this ratio is written as α = QLM / QLNM. In particular, depending on this ratio α, we will have a more or less regular droplet flow. However, a regular flow is advantageous in that it does not excessively degrade performance.

[0037] Figure 3, Table 1, is an enlarged view of Figure 2 at the level of a droplet of the second liquid. A single droplet of the second liquid LNM is observed, with droplets of the first liquid LM located on either side of it. When at rest, each liquid droplet is in contact with the inner wall of the sub-millimeter conduit CS, and due to surface tension, an interface exists between each droplet of the second liquid LNM and each droplet of the first liquid LM (the liquids are immiscible).

[0038] Given this situation, process (a) is carried out.

[0039] This is achieved by ensuring that the pressure in the second vial F2 is lower than the pressure in the first vial F1. The pressure gradient thus generated then pushes the entire droplet flow toward the second vial F2. Thus, the droplet flow of the first volume is displaced in the direction of the pressure gradient applied during this process (i.e., from left to right, as indicated by the double arrows in Figure 3, Table 2). The pressure difference must be large enough to generate advancement into a viscoinertial flow regime. In this flow regime, viscous and inertial forces (acceleration) are important due to the velocity generated by the pressure gradient. Surface tension (capillary force), particularly the surface tension due to the inner wall of the sub-millimeter conduit CS (which, in turn, does not change with the flow velocity), is negligible compared to the viscous and inertial forces. In this fluid regime, droplets of the second liquid LNM tend to stretch and move away from the inner wall of the sub-millimeter conduit, and a film of the first liquid is inserted between the droplets of the second liquid and the inner wall of the sub-millimeter conduit CS. The first liquid LM that forms the film originates from a droplet of the first liquid located to the right of the droplet of the second liquid LNM. Thus, the first liquid supplying the film is displaced in the opposite direction to the pressure gradient applied during this process (a). However, in the orientation of the pressure gradient applied during this process (a), there is an overall displacement of the droplets of the first and second liquids.

[0040] In step (b), the application of this pressure gradient is stopped.

[0041] Next, relaxation is observed in Figure 3, where the droplet of the second liquid LNM recombines with the inner wall of the sub-millimeter conduit CS. This recombination phenomenon also means that the film disappears as the first liquid in the film is pushed to the left. This situation is equivalent to the initial situation for the droplet flow as a whole, except that the second droplet is displaced in the orientation of the gradient applied in step (a), and the first liquid is displaced from the first droplet LM located to the right of the second droplet LNM to the first droplet located to the left of the first droplet.

[0042] Therefore, it can be said that there was a relative exchange between the first liquid and the second liquid.

[0043] However, at this point, the total volume of the liquid in the sub-millimeter conduit (i.e., the entire droplet flow) is displaced to the right in the direction of vial F2.

[0044] Next, in step (c), a pressure gradient opposite to the one applied in step (a) is applied between the two vials F1 and F2. This can be done by increasing the pressure at the level of the second vial F2. Furthermore, since the pressure gradient applied during step (c) is lower (in absolute value) than the pressure gradient applied during step (a), the flow regime is a viscous capillary regime (flow velocity at a lower absolute value than in step a). In this flow regime, the main forces are viscous forces and surface tension (capillary forces). Inertial forces are negligible. This flow regime has the effect of displacing the droplets of the first and second liquids in the direction imposed by the pressure gradient, i.e., from right to left in the direction of the first vial F1. At this time, the segment of the first liquid that is easily retained on the capillary wall is very small (in fact negligible). This can be seen in Figure 3, Table 4.

[0045] Step (c) effectively facilitates the general countercurrent motion between the two liquid phases. This countercurrent motion may be more or less important.

[0046] Next, in step (d), the application of this gradient is stopped.

[0047] At the end of step (d), the situation is the same as the initial situation (Figure 3, Table 1), except that the droplet of the second liquid has been displaced to the right and the droplet of the first liquid has been displaced to the left.

[0048] Advantageously, process (d) is carried out when the second volume of droplet flow displaced during process (c) is equal to the first volume of droplet flow displaced during process (a). This means that the volume of droplet flow ultimately displaced is zero-sum. Then there is a total directional displacement between the two liquid phases, i.e., there was no arbitrary overall motion in the initial droplet flow (initial = Figure 3, Table 1).

[0049] The performance of this liquid-liquid extraction method is very interesting.

[0050] This is due, on the one hand, to the large exchange surface available between the two liquid phases, which the method implements from the outset in a droplet flow, and on the other hand, to the fact that a stable interface between the two liquid phases (the less wetting first liquid and the second liquid) is maintained during the implementation of steps (a) to (d). This stability is substantially the same at the level of a given portion of the sub-millimeter conduit, and therefore depends on the control of the pressure at the first liquid / second liquid interface (essentially a longitudinal pressure gradient) at the level of that portion. The applied pressure gradient also allows for ensuring that the two liquid phases are displaced in a counterflow to achieve the desired extraction.

[0051] The method according to the present invention is particularly useful in miniaturizing the apparatus for carrying it out. In fact, the miniaturization of sub-millimeter conduits (which may mean higher viscous and capillary forces) can be compensated for by the pressure gradient applied in the method to obtain the aforementioned operations (viscoinertia regime, then viscous capillary regime), rather than causing problems with the efficiency of the extraction method. In fact, all other equal, the miniaturization makes it possible to increase the exchange surface ratio between droplets of the two liquid phases for each volume.

[0052] This device is also relatively simple (it has no moving mechanical parts, is not multi-stage, and does not have a membrane at the interface level between the two liquid phases that could experience a high pressure difference, etc.).

[0053] Advantageously, steps (a) to (d) can be repeated N1 times, where N1 is a natural number greater than or equal to 1. This is understood to allow the entire droplet of the second liquid to advance toward the second vial F2, and the entire droplet of the first liquid to advance toward the first vial F1.

[0054] However, by repeating steps (a) to (d) of the method according to the present invention many times, it can be seen that the droplet flow tends to produce liquid with large droplets (for both the first liquid and the second liquid) because small droplets tend to aggregate into larger droplets.

[0055] This point can be seen in Figure 4.

[0056] This gradually leads to a situation where the droplets become increasingly larger (from Figure 1 to Figure 3 in Figure 4). Figure 3 in Figure 4 is a particularly advanced example of this phenomenon.

[0057] Therefore, by continuing these vibrations (or oscillations), it is possible that all of the second liquid will be at the right end and the first liquid at the left end, and no alternating state will be observed. Thus, the droplet flow is gradually broken down by the displacement of each of the two liquids. From the above, it can be understood that what enables the liquids to be displaced in a countercurrent is the alternation of droplets of the first and second liquids in the droplet flow.

[0058] To avoid this situation, the droplet flow should be regenerated, especially after an oscillation period of a given number N1.

[0059] Otherwise, this could affect the extraction performance of the method because the contact surface area between the droplets of the first liquid and the second liquid tends to decrease (for example, assuming that in the situation shown in Figure 3 of Figure 4, it is not possible to perform the extraction of components from one liquid phase to the other liquid phase almost completely). Most importantly, this can affect the processing volumetric flow rate of the method, i.e., the amount of components extracted per unit time by the method. In fact, it can be seen that this flow rate is higher the more droplet streams consist of a large number of small droplets, i.e., droplets of short length.

[0060] Therefore, before repeating steps (a) to (d) of the liquid-liquid extraction method according to the present invention, it may be useful to ensure that the situation remains similar to that shown in Figure 4, Table 1.

[0061] Therefore, at the end of process (d), which is advantageously repeated N1 times, a certain amount of the first liquid is placed at one of the ends of the conduit.

[0062] Next, this method involves the following additional steps: (A) A step of drawing a first volume of liquid out of a conduit through the end of the conduit where the volume is located, (B) A step of generating a flow of droplets in a conduit through the conduit end, wherein a volume of a first liquid is drawn out through the conduit end in step (A), and the flow consists of alternating droplets of the first liquid LM and droplets of the second liquid LNM, This could be considered advantageous.

[0063] Here again, the droplet flow is advantageously regular for the reasons already mentioned.

[0064] This is explained in Figure 5.

[0065] In this diagram, we found that starting from the situation in Figure 2, after N1 repetitions of steps (a) to (d), we reached the situation in Figure 5, Table 1, and therefore the situation in Figure 4, Table 3.

[0066] In this case, as shown in Figure 5, Table 2, the volume of the first liquid is drawn from the side of the first vial F1.

[0067] Next, as shown in Figure 5, Table 3, a new droplet stream is generated according to step (B). Then, the new droplet stream with small droplets is injected into the sub-millimeter conduit. This ensures optimal processing volumetric flow rate and maintains optimal conditions, reducing the risk of performance loss in the extraction method.

[0068] The relative exchange ("stagnation") of the two liquid phases can be controlled by adjusting the volume drawn in process (A) and the respective volumes of the two liquids reinjected into the submillimeter conduit in process (B). In other words, the ratio of the scale of each counterflow rate to the respective volume of each liquid phase can be controlled in the submillimeter conduit.

[0069] α=Q LM / Q LNM It can be recalled that is the ratio of the average flow rate of the first liquid to the average flow rate of the second liquid. Note that β is the ratio of the volume of the first liquid to the volume of the second liquid. V is the volume of the first liquid drawn out in process (A), and V LM This is the volume of the first liquid injected in process (B), and V LNM Note that this is the volume of the second liquid injected in step (B) where the droplet flow is generated. Then, it is possible to perform operations at a given ratio α while guaranteeing a given ratio β. More precisely, VV LM =α*V LNM Furthermore, β=V LM / V LNM A penalty will be imposed.

[0070] Therefore, this method enables counterflow extraction according to a given ratio of the flow rate of the liquid phase and a given ratio of the volume of the liquid phase.

[0071] Next, a step (C) consisting of carrying out steps (a) to (d) can be added.

[0072] Conveniently, process (C) can be repeated N2 times, where N2 is a natural number greater than or equal to 1.

[0073] Similarly, if useful, processes (A) and (B) can be repeated N3 times, where N3 is a natural number greater than or equal to 1.

[0074] Here, we present a concrete example of the implementation using Figure 6. Figure 6 shows the in-process display, meaning it is neither the initial state nor the final state.

[0075] The entire implementation can be automated and managed remotely.

[0076] A specific mounting structure is provided having two syringes S1 and S2, one of which contains a first liquid and the other contains a second liquid. The first liquid is a mixture of ISANE 185 and 30% tributyl phosphate (TBP). The second liquid is a mixture of water and nitric acid, with a molar concentration of 4M. The second liquid is less wettable than the first liquid, and the two liquids are immiscible. In this example, the component extracted from one liquid phase to the other by liquid-liquid extraction is nitric acid, which is therefore initially in the second liquid and extracted toward the first liquid. The mixture thus formed is immiscible. Each syringe is equipped with capillaries C1 and C2 at its outlet, which merge at the level of a distribution T-joint (Te) opening into a sub-millimeter conduit CS. The sub-millimeter conduit CS is made of polytetrafluoroethylene (PTFE) with a circular cross-section having an inner diameter of 750 μm and a length of 1.8 m. The sub-millimeter conduit CS is placed flat on a table. At the other end of the sub-millimeter conduit is a vial F for collecting liquid. In an alternative embodiment, it may be possible to wrap the sub-millimeter conduit around a cylinder having a diameter greater than 2 cm, which also functions equally well.

[0077] The initial state is as follows:

[0078] The submillimeter conduit CS is filled with the first liquid. Syringe S1 is empty. Syringe S2 is filled with 1 mL of the second liquid. Capillaries C1 and C2 are filled with their respective liquids. Vial F is filled with the first liquid. The end of the submillimeter conduit CS is immersed in the first liquid at the interface between the air and the free surface of the first liquid.

[0079] Next, by pulling the piston P1 of syringe S1, 46 μL of the first liquid is drawn into syringe S1.

[0080] Subsequently, droplets of the first and second liquids are injected.

[0081] Once the flow of the first liquid droplet and the second liquid droplet is generated, steps (a) to (d) of this method are carried out.

[0082] Step (a) is performed to generate viscoinertial flow with an average flow velocity of 0.4 m / s in the sub-millimeter conduit. This is done by pushing the piston P1 of syringe S1 containing the first liquid, which applies overpressure at the T-junction level relative to the pressure at the vial F level. Step (c) is performed to generate viscocapillary flow with an average flow velocity of 0.04 m / s in the sub-millimeter conduit. This is done by pulling the piston P1 of syringe S1, which means a vacuum at the T-junction level relative to the pressure at the vial F level. Since the duration of step (c) is 10 times longer than the duration of step (a), at the end of one oscillation period, the total volume injected into the sub-millimeter conduit (first liquid + second liquid) is zero-sum.

[0083] Processes (a) to (d) are performed consecutively N1 = 10 times.

[0084] At the end of these 10 repetitions (or 10 oscillation periods), the second liquid droplet advances approximately 15 cm downward through a sub-millimeter conduit toward vial F (corresponding to a displacement volume of 66 μL).

[0085] Next, steps (A) and (B) of the above method (cycle) are carried out.

[0086] Subsequently, 64 μL of wetting liquid is drawn from the T-junction to syringe S1 via the sub-millimeter conduit CS (Step A). ​​This is done at a flow rate (velocity) of 15 μL / second.

[0087] Next (step B), 32 μL of the second liquid and 32 μL of the first liquid are simultaneously injected through a T-tube at the same flow rate of 5 μL / S for each liquid, thereby obtaining a flow of droplets formed by regularly alternating droplets of the first and second liquids. This is done by pushing pistons P1 and P2. Therefore, the ratio α defined above is α = 1 in this example.

[0088] Next, the above process was repeated for 313 oscillation periods (=N1+N2) and N3=31 cycles to empty the first liquid from vial F and completely fill it with the second liquid.

[0089] The above procedure has the following characteristics: - Extraction performance equivalent to that of the 3.2 theoretical stage multi-stage counterflow liquid-liquid extraction method in a 1.8m sub-millimeter conduit, and - Average flow rate 0.5μL / sec.

[0090] Here are some other specific examples of what has been done.

[0091] In the previous example, process (a) was performed in a sub-millimeter conduit at an average flow velocity of 0.4 m / s, and process (c) was performed at an average flow velocity of 0.04 m / s, i.e., a ratio of 10 to the nearest measurement error.

[0092] However, while keeping all other conditions equal and maintaining the average velocity between the different average flow velocity ratios between step (a) and step (c), and of course while maintaining the values that guarantee the visco-inertial type flowing during step (a) and the values that guarantee the capillary-viscous type flowing during step (c), other tests were conducted. Subsequently, it was found that a ratio of approximately 3.3 (which can be described as optimal), more broadly 2.5 - 4 (especially considering the margin of error related to the determination of velocity), between the average velocity of the visco-inertial flow in step (a) and the average velocity of the capillary-viscous flow in step (c) enables the acquisition of a maximized average flow rate.

[0093] This optimal ratio was found for many values of the average flow velocity in step (a).

[0094] Sub-millimeter conduits with a diameter of 300 microns were also tested. All other characteristics and operating conditions were maintained. Again, it was found that an optimal ratio of approximately 3.3, more broadly 2.5 - 4, between the average visco-inertial flow velocity in step (a) and the average capillary-viscous flow velocity in step (c) results in a maximized average flow rate.

[0095] Again, this optimal ratio was found for many values of the average visco-inertial flow velocity in step (a).

[0096] For example, when the average flow velocity in step (a) is 0.56 m / s, a maximum average flow rate of 0.8 μL / s was obtained when the average velocity in step (c) was 0.17 m / s. This average flow rate of 0.8 μL / s is estimated in the same way as the average flow rate of 0.5 μL / s obtained in an example where step (a) flows through the sub-millimeter conduit at an average flow velocity of 0.4 m / s and step (c) flows at an average flow velocity of 0.04 m / s, i.e., in a ratio of 10. That is, the ratio α = Q LM / Q LNM is 1. In fact, it was selected to determine the average flow rate Q LM of the wetting phase, which is determined for a sub-millimeter conduit through which a first liquid with higher wettability than the second liquid flows.

[0097] The same findings were obtained using sub-millimeter conduits with a diameter of 500 microns, and all else was equal, which allows the findings to be generalized to sub-millimeter pipes of much different diameters (300, 500, and 750 microns).

[0098] This is particularly important for industrial applications because, regardless of the diameter of the sub-millimeter conduit, it appears crucial that the ratio of the average flow rates in process (a) is 2.5 to 4 times higher than the average flow rate in process (c).

[0099] Furthermore, the value of the maximum average flow rate increases in proportion to the value of the average viscoinertia flow velocity in process (a). [Explanation of symbols]

[0100] CS sub-millimeter conduit LM First liquid LNM Second Liquid

Claims

1. 1. A method for countercurrent liquid-liquid extraction in a sub-millimeter conduit, the method comprising the following steps carried out from an initial flow of droplets in the conduit, the initial flow consisting of alternating droplets of a first liquid (LM) with droplets of a second liquid (LNM) that is less wettable than and immiscible with the first liquid, one of the two liquids containing a component to be extracted towards the other of the two liquids; (a) applying a first pressure gradient along the conduit to generate visco-inertial flowing that displaces a first volume of droplet stream according to a first pressure gradient, and generating a film of a first liquid displaced along an orientation opposite to the first pressure gradient, the film being located between the droplets of a second liquid and the conduit; (b) ceasing the application of the first pressure gradient; (c) applying a second pressure gradient along the conduit in an opposite direction to the first pressure gradient applied in step (a) to generate visco-capillary flowing that displaces a second volume of droplet stream according to the second pressure gradient; (d) ceasing the application of the second pressure gradient; The method comprising:

2. 2. The method of claim 1, wherein step (d) is initiated when the second volume of droplet flow displaced during step (c) is equal to the first volume of droplet flow displaced during step (a).

3. The steps (a) to (d) are １ Repeated N times １ The method of claim 1 , wherein is a natural number greater than or equal to 1.

4. The method of claim 1 , wherein the droplet stream is regular.

5. The steps (a) to (d) are preferably N １ At the end of step (d), a volume of the first liquid is placed at one of the ends of the conduit, and then the following steps are carried out: (A) withdrawing a volume of a first liquid from a conduit through an end of the conduit at which the volume of the first liquid is located; (B) generating a stream of droplets in the conduit through the end of the conduit from which a volume of the first liquid was withdrawn in step (A), the stream of droplets consisting of alternating droplets of the first liquid (LM) and droplets of the second liquid (LNM); 2. The method of claim 1, comprising:

6. The method according to claim 5, further comprising, after step (B), step (C) of carrying out steps (a) to (d).

7. The step (C) is N ２ Repeated N times ２ The method of claim 6, wherein is a natural number greater than or equal to 1.

8. The steps (A) and (B) are ３ Repeated N times ３ The method of claim 5, wherein is a natural number greater than or equal to 1.

9. 7. The method of claim 6, wherein the stream of droplets generated in step (B) is regular.

10. 10. The method according to any one of claims 1 to 9, characterized in that the ratio between the average velocity of the viscoinertial flow in step (a) and the average velocity of the viscocapillary flow in step (c) is between 2.5 and 4.

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