Method for draining reservoirs of a microfluidic mixer

Abstract

The invention relates to a method for draining a microfluidic mixer (10) that is intended to mix two liquids, comprising: - at least a first liquid reservoir (11) and a second liquid reservoir (12); - a first inlet channel (21); - a second inlet channel (22); - the first inlet channel (21) and the second inlet channel (22) converging towards a junction (23) to which an outlet channel (25) is connected; - the method comprising a step of applying a first pressure (P1) inside the first liquid reservoir (11) and a second pressure (P2) inside the second liquid reservoir (12), wherein a first time profile of the first pressure (P1) and a second time profile of the second pressure (P2) are such that the first pressure (P1) and the second pressure (P2) are alternately greater than one another.

Description

DESCRIPTION TITLE: METHOD FOR EMPTYING RESERVOIRS OF A MICROFLUIDIC MIXER

[0001] The present invention relates to a method for emptying reservoirs of a microfluidic mixer. The invention finds a particularly advantageous, but not exclusive, application for emptying reservoirs of a microfluidic mixer used to carry out nanoprecipitations by mixing lipids dissolved in different solvents and molecules of interest in aqueous solution.

[0002] In a manner known per se, a microfluidic mixer may comprise at least a first liquid reservoir and a second liquid reservoir. A first inlet channel having a first hydraulic resistance is in fluid communication with the first liquid reservoir. A second inlet channel having a second hydraulic resistance is in fluid communication with the second liquid reservoir. The first inlet channel and the second fluid channel converge towards a junction to which is connected an outlet channel within which liquid mixing occurs.

[0003] Applying the same pressure inside the first tank and the second tank does not guarantee the complete evacuation of the liquids present in the tanks in the case where there is still liquid in one of the tanks while the other is finished emptying. Indeed, as soon as one of the tanks is completely emptied, the tank still containing liquid "sees" the same pressure at its inlet and outlet. As a result, no more liquid flows between these two points and the tank still containing liquid no longer empties. The system only blows air through the empty tank.

[0004] The problem is all the more difficult to address because it is often not possible to know which reservoir is still full, for example when the microfluidic circuit is inside a housing or the reservoirs are not transparent.

[0005] The invention aims to effectively remedy the aforementioned drawbacks by proposing a method for emptying a microfluidic mixer intended to mix two liquids comprising: - at least a first liquid reservoir intended to contain a first liquid and a second liquid reservoir intended to contain a second liquid, - a first inlet channel being in fluid communication with the first liquid reservoir, - a second inlet channel being in fluid communication with the second liquid reservoir, - said first inlet channel and said second inlet channel converging towards a junction to which is connected an outlet channel inside which a liquid mixture is intended to occur, - said method comprises a step of applying a first pressure inside the first liquid reservoir and a second pressure inside the second liquid reservoir, a first time profile of the first pressure and a second time profile of the second pressure being such that the first pressure and the second pressure are alternately greater than each other.

[0006] The invention thus guarantees that both tanks will necessarily end up being emptied regardless of their initial filling level and the actual emptying rates.

[0007] Furthermore, the invention ensures that in the event of untimely blockage of the outlet channel, the liquids will flow from one tank to the other alternately in small quantities, which prevents overflow.

[0008] According to one implementation of the invention, the first time profile of the first pressure has a first minimum pressure value and a first maximum pressure value, and the second time profile of the second pressure has a second minimum value and a second maximum value.

[0009] According to one implementation of the invention, the first minimum pressure value and the second minimum pressure value are greater than a existing pressure at the outlet of the outlet channel, in particular atmospheric pressure.

[0010] According to one implementation of the invention, the first minimum pressure value and the second minimum pressure value are identical and are for example of the order of 4x10 5 Pa (4 bars).

[0011] According to one implementation of the invention, the first maximum pressure value and the second maximum pressure value are identical and are for example of the order of 8x10 5 Pa (8 bars).

[0012] According to one implementation of the invention, the first time profile of the first pressure and the second time profile of the second pressure are periodic.

[0013] According to one implementation of the invention, the first time profile of the first pressure and the second time profile of the second pressure are chosen from sinusoidal, triangular or square wave type profiles.

[0014] According to one implementation of the invention, the first time profile of the first pressure and the second time profile of the second pressure each have a frequency between 0.01 Hz and 5 Hz and preferably 1 Hz.

[0015] According to one implementation of the invention, the first time profile of the first pressure and the second time profile of the second pressure are in phase opposition to each other.

[0016] According to one implementation of the invention, the first time profile of the first pressure and the second time profile of the second pressure evolve over time with a high first minimum pressure and a high second minimum pressure and relatively low pressure variations at the start of a draining phase to efficiently evacuate the liquids contained in the first liquid reservoir and in the second liquid reservoir, then a lower first minimum pressure and a lower second minimum pressure and greater pressure variations at the end of the draining phase.

[0017] According to one implementation of the invention, the first time profile of the first pressure and the second time profile of the second pressure are chosen so that the sum of the two pressures is constant at each instant at least over part of a duration of an emptying phase.

[0018] The present invention will be better understood and other characteristics and advantages will become apparent upon reading the detailed description which follows, comprising embodiments given for illustrative purposes with reference to the appended figures, presented as non-limiting examples, which may serve to complete the understanding of the present invention and the description of its embodiment and, where appropriate, contribute to its definition, in which:

[0019] [Fig. 1] Figure 1 is a schematic representation of a microfluidic mixer with which the emptying method according to the present invention is implemented;

[0020] [Fig. 2] Figure 2 is a graphical representation of the time profiles of the pressures applied inside the first liquid reservoir and the second liquid reservoir of the mixer of Figure 1.

[0021] Figure 1 shows a microfluidic mixer 10 intended to mix two fluids comprising at least a first liquid reservoir 11 intended to contain a first liquid and a second liquid reservoir 12 intended to contain a second liquid. The first liquid reservoir 11 is associated with a first pressure regulator 13 capable of varying a first pressure P1 applied by a first pressure source 14 inside the first liquid reservoir 11. The second liquid reservoir 12 is associated with a second pressure regulator 15 capable of varying a second pressure P2 applied by a second pressure source 16 inside the first reservoir. The first pressure source 13 and the second pressure source 16 may be pneumatic pressure sources. The first pressure source 13 and the second pressure source 16 may be separate or common.The pressures P1 and P2 are to be considered as overpressures compared to a pressure level existing at the outlet of the mixing channel 25. described in more detail below. A computer 19 is capable of controlling the pressure of the first pressure regulator 13 and the second pressure regulator 15.

[0022] A first inlet channel 21 having a first hydraulic resistance R1 is in fluid communication with the first liquid reservoir 11. A second inlet channel 22 having a second hydraulic resistance R2 is in fluid communication with the second liquid reservoir 12.

[0023] The first inlet channel 21 and the second inlet channel 22 converge, without a valve intermediary, towards a junction 23 to which is connected an outlet channel 25 inside which a liquid mixing is intended to occur. Each inlet channel 21, 22 has, without a valve intermediary, a first end in fluid communication with a corresponding reservoir 11, 12 and a second end in fluid communication with the outlet channel 25 via the junction 23. The first inlet channel 21, the second inlet channel 22 and the outlet channel 25 thus constitute a Y-shaped microfluidic circuit.

[0024] The output channel 25 has a hydraulic resistance R3 lower than each of the hydraulic resistances R1, R2 of the first input channel 21 and the second input channel 22 taken individually. Alternatively, the hydraulic resistance R3 may be of the same order of magnitude as the hydraulic resistances R1 and R2 taken individually. In some embodiments, the resistance R3 is lower than each of the hydraulic resistances R1, R2 of the first input channel 21 and the second input channel 22 taken individually. The first input channel 21, the second input channel 22 and the output channel 25 may be integrated into a microfluidic chip 26.

[0025] The outlet channel 25 may have any known shape of mixing channel, in particular a serpentine shape that is square on one side and rounded on the other (a so-called deflector configuration ("baffle" according to English terminology)) or be provided internally with walls increasing the folding of the flow on itself, thus promoting the mixing of the liquid (a so-called chevron configuration ("herringbone" according to English terminology)), or any other shape adapted to the application.

[0026] The computer 19 controls the first pressure regulator 13 and the second pressure regulator 15 so as to apply a first pressure P1 inside the first liquid reservoir 11 and a second pressure P2 inside the second liquid reservoir 12.

[0027] Advantageously, a first time profile TP1 of the first pressure P1 and a second time profile TP2 of the second pressure P2 are such that the first pressure P1 and the second pressure P2 are alternately greater than one another. A pressure time profile TP1, TP2 corresponds to the curve representing the evolution of the corresponding pressure P1, P2 as a function of time. Thus, following the temporal evolution of the first pressure P1 and the second pressure P2, the first pressure P1 is greater than the second pressure P2 at a given instant, for example at instant t1, then the second pressure P2 becomes greater than the first pressure P1 at another instant, for example at instant t2 and so on.

[0028] The first time profile TP1 of the first pressure P1 presents a first minimum pressure value MinP1 and a first maximum pressure value MaxP1.

[0029] The second time profile TP2 of the second pressure P2 has a second minimum value MinP2 and a second maximum value MaxP2.

[0030] The first minimum pressure value MinP1 and the second minimum pressure value MinP2 are greater than an existing pressure at the outlet of the outlet channel 25, in particular atmospheric pressure. According to an exemplary implementation, the first minimum pressure value MinP1 and the second minimum pressure value MinP2 are identical and are for example of the order of 4x10 5 Pa (4 bars). The first maximum pressure value MaxP1 and the second maximum pressure value MaxP2 are identical and are for example of the order of 8x10 5Pa (8 bar). Alternatively, the first minimum pressure value MinP1 and the second minimum pressure value MinP2 may be different. The first maximum pressure value MaxP1 and the second maximum pressure value MaxP2 may be different.

[0031] The first time profile TP1 of the first pressure P1 and the second time profile TP2 of the second pressure P2 may be periodic. Preferably, the first time profile TP1 of the first pressure P1 and the second time profile TP2 of the second pressure P2 are chosen from sinusoidal type profiles as shown in Figure 2, triangular or square wave.

[0032] The first time profile TP1 of the first pressure P1 and the second time profile TP2 of the second pressure P2 each have a frequency between 0.01 Hz and 5 Hz and preferably 1 Hz. It should be noted that a frequency that is too low has the disadvantage of losing the anti-overflow safety if the outlet channel 25 is blocked.

[0033] Advantageously, the first time profile of the first pressure P1 and the second time profile TP2 of the second pressure P2 are in phase opposition to each other, as shown in Figure 2. In other words, the first time profile TP1 of the first pressure P1 and the second time profile TP2 of the second pressure P2 have a phase shift of 180 degrees relative to each other. Alternatively, the phase shift between the two pressure time profiles TP1, TP2 may be different from 180 degrees.

[0034] According to a particular example of implementation, the first time profile TP1 of the first pressure P1 and the second time profile TP2 of the second pressure P2 evolve over time with for example a first minimum pressure MinP1 and a second minimum pressure MinP2 that are high and relatively low pressure variations at the start of a draining phase to efficiently evacuate the liquids contained in the first liquid reservoir 11 and in the second liquid reservoir 12, then a first minimum pressure MinP1 and a second minimum pressure MinP2 that are lower and greater pressure variations at the end of the draining phase. The expressions "lower" and "greater" are to be understood with reference to the pressure values ​​MinP1, MinP2 and pressure variations applied at the start of the draining phase.

[0035] The first time profile TP1 of the first pressure P1 and the second time profile TP2 of the second pressure P2 can be chosen so that the sum of the two pressures P1, P2 is constant at each instant at least over part of a duration of an emptying phase.

[0036] Of course, the various features, variants and / or embodiments of the present invention may be combined with each other in various combinations to the extent that they are not incompatible or mutually exclusive.

[0037] Furthermore, the invention is not limited to the embodiments described above and provided solely by way of example. It encompasses various modifications, alternative forms and other variants that may be envisaged by those skilled in the art within the scope of the present invention and in particular all combinations of the different modes of operation described above, which may be taken separately or in combination.

Claims

CLAIMS 1. Method for emptying a microfluidic mixer (10) intended to mix two liquids comprising: - at least a first liquid reservoir (11) intended to contain a first liquid and a second liquid reservoir (12) intended to contain a second liquid, - a first inlet channel (21) being in fluid communication with the first liquid reservoir 11, - a second inlet channel (22) being in fluid communication with the second liquid reservoir (12), - said first inlet channel (21) and said second inlet channel (22) converging towards a junction (23) to which is connected an outlet channel (25) inside which a liquid mixture is intended to occur, characterized in that said method comprises a step of applying a first pressure (P1) inside the first liquid reservoir (11) and a second pressure (P2) inside the second liquid reservoir (12), a first time profile (TP1) of the first pressure (P1) and a second time profile (TP2) of the second pressure (P2) being such that the first pressure (P1) and the second pressure (P2) are alternately greater than each other.

2. Method according to claim 1, characterized in that the first time profile (TP1) of the first pressure (P1) has a first minimum pressure value (MinP1) and a first maximum pressure value (MaxP1), and the second time profile (TP2) of the second pressure P2 has a second minimum value (MinP2) and a second maximum value (MaxP2).

3. Method according to claim 2, characterized in that the first minimum pressure value (MinP1) and the second minimum pressure value (MinP2) are higher than an existing pressure at the outlet of the outlet channel (25), in particular atmospheric pressure.

4. Method according to claim 2 or 3, characterized in that the first minimum pressure value (MinP1) and the second minimum pressure value (MinP2) are identical and are for example of the order of 4x10 5 Pa.

5. Method according to any one of claims 2 to 4, characterized in that the first maximum pressure value (MaxP1) and the second maximum pressure value (MaxP2) are identical and are for example of the order of 8x10 5 Pa.

6. Method according to any one of claims 1 to 5, characterized in that the first time profile (TP1) of the first pressure (P1) and the second time profile (TP2) of the second pressure (P2) are periodic.

7. Method according to claim 6, characterized in that the first time profile (TP1) of the first pressure (P1) and the second time profile (TP2) of the second pressure (P2) are chosen from sinusoidal, triangular or square wave type profiles.

8. Method according to any one of claims 1 to 6, characterized in that the first time profile (TP1) of the first pressure (P1) and the second time profile (TP2) of the second pressure (P2) each have a frequency between 0.01 Hz and 5 Hz and preferably 1 Hz.

9. Method according to any one of claims 1 to 7, characterized in that the first time profile of the first pressure (P1) and the second time profile (TP2) of the second pressure (P2) are in phase opposition to each other.

10. Method according to claim 2, characterized in that the first time profile (TP1) of the first pressure (P1) and the second time profile (TP2) of the second pressure (P2) evolve over time with a high first minimum pressure (MinP1) and a high second minimum pressure (MinP2) and relatively low pressure variations at the start of a draining phase to efficiently evacuate the liquids contained in the first liquid reservoir (11) and in the second liquid reservoir (12), then a lower first minimum pressure (MinP1) and a lower second minimum pressure (MinP2) and greater pressure variations at the end of the draining phase.

11. Method according to any one of claims 1 to 10, characterized in that the first time profile (TP1) of the first pressure (P1) and the second time profile (TP2) of the second pressure (P2) are chosen so that the sum of the two pressures (P1, P2) is constant at each instant at least over part of a duration of an emptying phase.