Device and method for generating droplets

Abstract

The invention relates to a device (1) for generating droplets (30) comprising a plurality of channels (20), wherein each channel (20) extends from an inlet (201) along a respective longitudinal axis (L) to an outlet (202), wherein said device (1) comprises a plurality of layers (10) of a substrate material arranged in a stack (100), wherein each layer (10) comprises a first side (101) and a second side (102) facing away from each other, and wherein said first side (101) of each layer (10) comprises a plurality of grooves (103), wherein said channels (20) are formed by said grooves (103) of said first side (101) of a respective layer (10) of said stack (100) and said second side (102) of a respective adjacent layer (10) of said stack (100). The invention further relates to a method for generating droplets (30) and a fabrication method of the device (1).

Claims

1. A device (1) for generating droplets (30) of a dispersed phase (D) in a continuous phase (C), comprising a plurality of channels (20), wherein each channel (20) comprises an inlet (201) and an outlet (202), and wherein each channel (20) extends from said inlet (201) along a respective longitudinal axis (L) to said outlet (202), so that droplets (30) of a dispersed phase (D) can be generated in a continuous phase (C) at said outlets (202) when a flow of said dispersed phase (D) from said inlets (201) to said outlets (202) is provided and said outlets (202) are in flow connection with a reservoir or conduit containing said continuous phase (C), characterized in that said device (1) comprises a plurality of layers (10) of a substrate material arranged in a stack (100), wherein each layer (10) comprises a first side (101) and a second side (102), wherein the first side (101) faces away from the second side (102), and wherein the first side (101) of each layer (10) comprises a plurality of grooves (103), wherein the grooves (103) of each first side (101) are covered by a second side (102) of an adjacent layer (10), such that said plurality of channels (20) is formed, wherein the inlets (201) are arranged on a front side (104) of the stack (100) and the outlets (202) are arranged on an opposing back side (105) of the stack (100), wherein each of the channels (20) comprises a nozzle (21) ending with the respective outlet (202), the outlet (202) comprising a first maximum cross sectional extension (e.sub.1) of the nozzle (21), and wherein the respective channel (20) comprises a second cross-sectional extension (e.sub.2) adjacent the respective nozzle (21), wherein said first maximum cross-sectional extension (e.sub.1) is larger than said second cross-sectional extension (e.sub.2).

2. The device (1) according to claim 1, characterized in that said front side (104) and said back side (105) extend perpendicular to the layers (10) of the stack (100).

3. The device (1) according to claim 1, characterized in that each channel (20) comprises a respective aspect ratio (a) between a length (I) of the respective channel (20) along said longitudinal axis (L) and a minimum cross-sectional extension (e.sub.min) perpendicular to said longitudinal axis (L), wherein said aspect ratio (a) is one of: at least 30, at least 75, or at least 120.

4. The device (1) according to claim 1, characterized in that said aspect ratio (a) is one of: 30 to 20000, 75 to 20000, or 120 to 20000.

5. The device (1) according to claim 1, characterized in that the device (1) comprises one of: at least 100 channels (20) or at least 1000 channels (20).

6. The device (1) according to claim 1, characterized in that said stack (100) comprises at least 10 layers (10).

7. The device (1) according to claim 1, characterized in that the channels (20) are parallel.

8. The device (1) according to claim 1, characterized in that the cross-sectional extension of the channels (20) is one of: 200 m or less, 50 m or less, 25 m or less, or 10 m or less.

9. The device (1) according to claim 1, characterized in that the device (1) further comprises a first reservoir or conduit (11) which is in flow connection with said inlets (201) of said channels (20) and a second reservoir or conduit (12) which is in flow connection with said outlets (202) of said channels (20).

10. The device (1) according to claim 9, characterized in that said device (1) comprises at least one additional reservoir or conduit (13), wherein said device (1) comprises a plurality of first channels (20a) connecting said first reservoir or conduit (11) to said at least one additional reservoir or conduit (13), and wherein said device (1) comprises a plurality of second channels (20b) connecting said at least one additional reservoir or conduit (13) to said second reservoir or conduit (12).

11. A method for generating droplets (30) of a dispersed phase (D) in a continuous phase (C) comprising providing a device (1) according to claim 1, wherein a flow of said dispersed phase (D) from said inlets (201) through said outlets (202) of said channels (20) into said continuous phase (C) is provided, and wherein a plurality of droplets (30) of said dispersed phase (D) is formed in said continuous phase (C).

12. The method according to claim 11, wherein a flow of a dispersed inner phase (D1) from inlets (201) through respective outlets (202) of a plurality of first channels (20a) of the device (1) into a dispersed middle phase (D2) is provided, wherein a plurality of first droplets (31) of the dispersed inner phase (D1) is formed in the dispersed middle phase (D2), and wherein a flow of the dispersed middle phase (D2) containing said first droplets (31) from inlets (201) through respective outlets (202) of a plurality of second channels (20b) of the device (1) into said continuous phase (C) is provided, wherein a plurality of second droplets (32) of said dispersed inner phase (D1) and said dispersed middle phase (D2) is formed in said continuous phase (C).

13. A method for fabricating a device (1) according to claim 1, wherein a plurality of layers (10) of a substrate material is provided, and wherein a plurality of grooves (103) is generated in a respective first side (101) of each layer (10), and wherein a stack (100) is formed from said layers (10), such that said first side (101) of each respective layer (10) contacts a respective second side (102) of an adjacent layer (10), such that said plurality of channels (20) is formed, wherein said layers (10) of said stack (100) are connected, particularly bonded to each other.

14. The method according to claim 13, wherein said grooves (20) in said first sides (101) of said layers (10) are generated by means of photolithography and subsequent etching.

Description

(1) The invention is further described by the following examples and figures, from which additional embodiments may be drawn.

(2) FIG. 1 shows a perspective view of a part of a device according to the invention comprising a stack of layers comprising channels;

(3) FIG. 2 shows a schematic representation of a device according to the invention;

(4) FIG. 3 shows a schematic of the formation of a droplet in a channel of the device according to the invention;

(5) FIG. 4 shows a perspective view of a channel of the device according to the invention;

(6) FIG. 5 shows different embodiments of channels of the device according to the invention comprising nozzles of different geometries;

(7) FIG. 6 shows a schematic representation of manufacturing processes of parts of devices according to the prior art (a) and the present invention (b);

(8) FIG. 7 shows an embodiment of the device according to the invention designed as an open reservoir system;

(9) FIG. 8 shows an embodiment of the device according to the invention designed as a closed flowing system;

(10) FIG. 9 shows an embodiment of the device according to the invention adapted for double emulsion generation.

(11) FIG. 1 shows a perspective view of a part of a device 1 according to the invention comprising a stack of layers 10 comprising channels 20. The layers 10 constitute individual arrays of parallelized distribution channels 20. As illustrated in FIG. 1, the layers 10 can be stacked-up and bonded (for example thermally) for the production of a three-dimensional device 1 resulting in a microfluidic brush emulsifier.

(12) Therein, the layers 10 each comprise a first side 101 comprising recesses 103, and a second side 102 opposing the first side 101. In the stack 100, the first side 101 of each layer 10 is covered by a second side 102 of an adjacent layer 10 stacked on top of the layer 10. As a result, the recesses 103 are covered by the second side 102, such that the channels 20 are formed.

(13) The final stack 100, obtained by stacking and connecting the layers 10, comprises a front side 104 and a back side 105, perpendicular to the layers 10 and in the depicted embodiment also perpendicular to the longitudinal axis L, that is perpendicular to the extension of the channels 20. Inlets 201 of the channels 20 are positioned on the back side 105, and outlets 202 of the channels 20 are positioned on the front side 104.

(14) FIG. 2 shows a cross-sectional view of a layer 10 (see FIG. 1) of a device 1 for generating droplets 30 of a dispersed phase D in a continuous phase C according to the present invention. The device 1 is connected to a first reservoir 11 (for example in case of an open reservoir system) or first conduit 11 (for example in case of a closed flowing system) which is in flow connection with a second reservoir 12 (for example in case of an open reservoir system) or second conduit 12 (for example in case of a closed flowing system) by means of a plurality of channels 20 of the device 1. For simplicity, only two channels 20 are depicted in FIG. 2, but the number of channels 20 may be much higher (see also FIG. 1), for example several thousand.

(15) The channels 20 extend from respective inlets 201 along a respective longitudinal axis L to respective outlets 202. According to the embodiment depicted in FIG. 2, the channels 20 are parallel to each other. However, other embodiments are possible within the scope of the present invention, in which the channels 20 are non-parallel and/or have different shapes (for example are bent or curved).

(16) Furthermore, the channels 20 have a respective length l along the longitudinal axis L and a minimum cross-sectional extension e.sub.min perpendicular to the longitudinal axis L, which is equal to the width w in the depicted example, wherein the width w extends in the plane of the respective layer 10, perpendicular to the longitudinal axis L.

(17) In other embodiments, the minimum cross-sectional extension e.sub.min may be equal to a height h of the respective channel 20, wherein the height h is measured along a direction which is perpendicular to the width w and the longitudinal axis L. The width w may also be equal to the height h in some embodiments. An aspect ratio a of the channels 20 is defined as the ratio of the length l and the minimum cross-sectional extension e.sub.min (in this case the width w).

(18) In the embodiment depicted in FIG. 2, the channels 20 comprise a section, in which the cross-sectional extension is constant (equal to the minimum cross-sectional extension e.sub.min), and a nozzle 21 positioned at or near the respective outlet 202, in which the cross-sectional extension increases. The nozzle 21 is in flow connection with the second reservoir or conduit 12 and comprises a first maximum cross-sectional extension e.sub.1 perpendicular to the longitudinal axis L, and a second cross-sectional extension e.sub.2 adjacent to the nozzle 21, that is at the connection between the nozzle 21 and the remaining channel 20, wherein the first maximum cross-sectional extension e.sub.1 is larger than the second cross-sectional extension e.sub.2. In the example shown in FIG. 2, the nozzle 21 is wedge-shaped (see also description of FIG. 5A). Other examples of shapes are depicted in FIGS. 5B to 5H.

(19) When a dispersed phase D, for example a hydrophobic substance such as an oil, is provided in the first reservoir or conduit 11, a continuous phase C, for example an aqueous phase, is provided in the second reservoir or conduit 12, and a pressure difference is provided between the first reservoir or conduit 11 and the second reservoir or conduit 12 (the dispersed phase D in the first reservoir or conduit 11 having a greater pressure than the continuous phase C in the second reservoir or conduit 12), a flow of the dispersed phase D through the channels 20 from the inlets 201 to the outlets 202 is generated, and droplets 30 of the dispersed phase D are formed at or near the respective outlets 202 upon mixing of the dispersed phase D and the continuous phase C at the connection or in the vicinity of the connection between the channels 20 and the second reservoir or conduit 12, that is at or in the vicinity of the respective outlets 202.

(20) When nozzles 21 are present at the outlets 202 of the channels 20, the rapid liquid transfer from the nozzle 21 to the second reservoir or conduit 12 causes a narrow liquid neck formation, and Rayleigh plateau instabilities occurring at the narrow neck lead to droplet 30 formation at the step of the nozzle 21. This mechanism advantageously uncouples droplet 30 size from flow rate of the dispersed phase D.

(21) Without wishing to be bound by theory, due to the high aspect ratio a (thus due to the great length of the channels 20 compared to their width w and/or height h), the flow resistance of the channels 20 is high enough to generate a flow of the dispersed phase D in almost all channels 20, such that droplets 30 are formed by almost all channels 20. This advantageously increases the amount of droplets 30 produced per unit of time. When using channels 20 of lower aspect ratio a, such as in devices of the prior art, only a small fraction of the channels 20 generate droplets 30 as a result of a heterogeneous pressure distribution of the dispersed phase D.

(22) FIG. 3 schematically illustrates the formation of a droplet 30 in the nozzle 21 of the channels 20. As shown, the dispersed phase D is flowed through the shallow distribution channel 20 over a wedge-shaped nozzle 21 to the second reservoir or conduit 12 containing the continuous phase C. The distribution channel 20 has a high aspect ratio a (ratio between length l and height h in this case).

(23) The working principle of the device 1 according to the invention is step emulsification, in which the dispersed phase D is flowing to the nozzle 21 (FIG. 3A), drawn out over a step 24 into the second reservoir or conduit 12 due to a Laplace pressure difference between the nozzle and the continuous phase reservoir (FIG. 3B), and finally emulsification (FIG. 3C).

(24) FIG. 4 shows a perspective view of an example of a channel 20 of the device 1 according to the invention. The channel 20 has a rectangular cross-section in respect of the longitudinal axis L, wherein the height h is the minimal cross-sectional extension e.sub.min. The channel 20 further comprises a wedge-shaped nozzle 21.

(25) FIG. 5 depicts schematic representations of different configurations of the nozzle 21 of the channels 20, wherein the respective first maximal cross-sectional extensions e.sub.1 and the respective second cross-sectional extensions e.sub.2 are indicated (see description of FIG. 2 for further details).

(26) FIG. 5A shows a wedge-shaped nozzle 21, which is limited by straight walls 22, which are arranged at an angle in respect of the longitudinal axis L, along which the channel 20 extends. For example, the angle may be 5 to 50. FIG. 5B shows a nozzle 21 limited by walls 22 comprising grooves 25. FIGS. 5C and 5D depict nozzles 21 limited by curved walls 22, wherein the inner walls form a convex shape in the nozzle 21 shown in FIG. 5C and a concave shape in the nozzle 21 illustrated in FIG. 5D. FIG. 5E shows a nozzle 21 with a rectangular cross-section. FIGS. 5F to 5H depict nozzles 21 comprising respective constrictions 23 having the second cross-sectional extension e.sub.2, wherein the cross-sectional extension at the constriction 23 is reduced compared to the section of the channel 20 adjacent to the nozzle 21.

(27) FIG. 6 shows a comparison of fabrication methods of the device 1 according to the invention by the method according to the invention over conventional methods of the prior art. As depicted in FIG. 6a, conventionally produced devices for generation of droplets are for example processed by drilling, lasering or etching a bulk material. This limits the device to straight holes with a low aspect ratio a.

(28) In contrast, the fabrication method according to the present invention (in particular using lithography) allows to implement high aspect ratio a channels 20 with a special channel 20 geometry, since multiple layers 10 are individually processed, stacked-up and connected, particularly bonded together.

(29) FIGS. 7 to 9 illustrate different possibilities to use the device 1 according to the invention.

(30) FIG. 7 shows a device 1 according to the invention, wherein the second reservoir or conduit 12 is an open second reservoir 12 containing the continuous phase C. When an external pressure p is applied to the first reservoir or conduit 11 of the device 1, for example by means of a pump, such as a syringe pump or a pressure pump, the dispersed phase D is forced through the channels 20 of the device 1, producing droplets 30 upon mixing with the continuous phase C. The produced droplets 30 are carried away from the channel 20 exits to the bottom of the second reservoir 12 by gravity.

(31) FIG. 8 shows a closed system with a flowing continuous phase C. Therein, an external pressure p is applied both to the first reservoir or conduit 11, and to the second reservoir or conduit 12, such that a respective flow of both the dispersed phase D and the continuous phase C is generated. Similar to the setup of FIG. 7, the dispersed phase D flows through the channels 20 of the device 1 (parts enclosed by the dashed line) and forms droplets 30 upon mixing with the continuous phase C, wherein the produced droplets 30 are flowing within the continuous phase 30 and are collected in an external reservoir 40.

(32) FIG. 9 shows a device 1 for the production of multiple emulsions comprising a first reservoir or conduit 11, an additional reservoir or conduit 13, and a second reservoir or conduit 12, wherein the first reservoir or conduit 11 is connected to the additional reservoir or conduit 13 by means of first channels 20a, and wherein the additional reservoir or conduit 13 is connected to the second reservoir or conduit 12 by means of second channels 20b. Such a system can be realized by combining multiple brush emulsifiers in series.

(33) As an example, the idea of double emulsion production is shown, where the first produced single emulsions are reinjected into the second brush emulsifier and the double emulsions are formed.

(34) Therein, a dispersed inner phase D1 is provided in the first reservoir or conduit 11, flowed through the first channels 20a and mixed with a dispersed middle phase D2 in the additional reservoir or conduit 13, forming first droplets 31. The dispersed middle phase D2 comprising the first droplets 31 is therefore a single emulsion of the dispersed inner phase D1 in the dispersed middle phase D2. This single emulsion is flowed through the second channels 20b and mixed with the continuous phase C in the second reservoir or conduit 12. Thereby, second droplets 32 of the dispersed inner phase D1 surrounded by the dispersed middle phase D2 are formed in the continuous phase C, constituting a double emulsion.

(35) A device 1 for the production of multiple emulsions may also be realized as a closed system with a flowing continuous phase C and/or a flowing dispersed middle phase D2, for example by applying an external pressure to the first reservoir or conduit 11 and/or the additional reservoir or conduit 13, such that a respective flow of the continuous phase C or the dispersed middle phase D2 is generated.

LIST OF REFERENCE SIGNS

(36) TABLE-US-00001 Device for generating droplets 1 Layer 10 First reservoir or conduit 11 Second reservoir or conduit 12 Additional reservoir or conduit 13 Channel 20 First channel 20a Second channel 20b Nozzle 21 Wall 22 Constriction 23 Step 24 Groove 25 Funnel 26 Droplet 30 Single emulsion droplet 31 Double emulsion droplet 32 External reservoir 40 Stack 100 First side 101 Second side 102 Groove 103 Front side 104 Back side 105 Inlet 201 Outlet 202 Longitudinal axis L Length l Width w Height h Minimum cross-sectional extension e.sub.min First maximum cross-sectional extension e.sub.1 Second cross-sectional extension e.sub.2 Aspect ratio a Dispersed phase D Continuous phase C Dispersed inner phase D1 Dispersed middle phase D2 Pressure p Angle