EMULSION PRODUCTION MICROFLUIDIC DEVICE

Abstract

Disclosed is an emulsion production microfluidic device which includes: a first channel, including an entry port configured to inject a phase to be dispersed, a second channel, including an entry port configured to inject a continuous phase and an emulsion exit port, and at least one array of microchannels, a height of each of the microchannels being smaller than a height of the first channel; the second channel includes a first part connected to the outlet of each microchannel and at least a second part along the first part, the first part being between the array of microchannels and the second part, the first part having a height greater that the height of each microchannel, and the second part having a height greater than the height of the first part.

Claims

1. An emulsion production microfluidic device which comprises: A first channel, comprising an entry port configured to inject a phase to be dispersed into the first channel, A second channel, comprising an entry port configured to inject a continuous phase into this second channel, and an emulsion exit port configured to extract an emulsion from the device, and At least one array of microchannels, arranged side by side, each microchannel comprising an inlet from the first channel, and an outlet to the second channel, a height h0 of each of the microchannels being smaller than a height h1 of the first channel, wherein the second channel comprises a first part connected to the outlet of each microchannel and at least a second part along the first part, the first part being between the array of microchannels and the second part, the first part having a height h2a greater that the height h0 of each microchannel, and the second part having a height h2b greater than the height h2a of the first part.

2. Device according to claim 1, wherein at least one microchannel comprises at least a part with a constant width W.

3. Device according to claim 2, wherein the width W of at least a part of a microchannel is comprised between 0.01 to 10,000 times the height h0.

4. Device according to claim 1, wherein at least one microchannel comprises a flared part.

5. Device according to claim 1, wherein the array of microchannels comprises a part which is common to at least two microchannels at the outlet location.

6. Device according to claim 1, wherein the array of microchannels comprises at least 10 microchannels.

7. Device according to claim 1, wherein the height h2a of the first part of the second channel is from 2 to 100 times greater than the height h0 of a microchannel.

8. Device according to claim 1, wherein the height h2b of the second part of the second channel is from 2 to 100 times greater than the height h2a of the first part of the second channel.

9. Device according to claim 1, wherein the height h1 of the first channel is from 2 to 1000 times greater than the height h0 of a microchannel.

10. Device according to claim 1, wherein the first channel has a width comprised between 1 to 100 times the height h1.

11. Device according to claim 1, wherein the second channel has a width comprised between 1 to 100 times the height h2b of the second part.

12. Device according to claim 1, wherein a hydrophilic molecule is adsorbed or grafted in at least part of the surfaces of the first channel, and/or the second channel, and/or the microchannel, to make the surface hydrophilic, or a hydrophobic molecule is adsorbed or grafted in at least part of the surfaces of the first channel, and/or the second channel, and/or the microchannel, to make the surface hydrophobic.

13. Device according to claim 2, wherein at least one microchannel comprises a flared part.

14. Device according to claim 3, wherein at least one microchannel comprises a flared part.

15. Device according to claim 2, wherein the array of microchannels comprises a part which is common to at least two microchannels at the outlet location.

16. Device according to claim 3, wherein the array of microchannels comprises a part which is common to at least two microchannels at the outlet location.

17. Device according to claim 4, wherein the array of microchannels comprises a part which is common to at least two microchannels at the outlet location.

18. Device according to claim 2, wherein the array of microchannels comprises at least 10 microchannels.

19. Device according to claim 3, wherein the array of microchannels comprises at least 10 microchannels.

20. Device according to claim 4, wherein the array of microchannels comprises at least 10 microchannels.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0116] Additional features and advantages of the present invention are described in, and will be apparent from, the description of the presently preferred embodiments which are set out below with reference to the drawings in which:

[0117] FIG. 1 diagrammatically shows a cross section of a microfluidic device 1 according to prior art.

[0118] FIG. 2A diagrammatically shows a cross section of a microfluidic device 100 according to the present invention.

[0119] FIG. 2B illustrates an experimental manufacture and use of a device according to FIG. 2A.

[0120] FIG. 3A shows a diagram of a microfluidic device 100′ for producing an emulsion according to a first embodiment compliant with the one of FIG. 2A (FIG. 3A), and FIG. 3B shows a corresponding cross-section along the dotted line A-A.

[0121] FIG. 4, comprising FIGS. 4A to 4I, illustrates various methods to manufacture channels or microchannels in a device according to the invention.

[0122] FIG. 5 shows three embodiments of microchannels according to the invention.

[0123] FIG. 6 shows snapshots of a microfluidic device according to the embodiment of FIG. 3A that produces emulsion for two different pressures (Pc) of the continuous phase while the pressure of the phase to be dispersed is set to 500 mbar. The heights of the different channels are indicated.

[0124] FIG. 7 represents frequency of drops formation as a function of the microchannel's number along the array of microchannels of a glass device according to the embodiment of FIG. 3A and the experiment of FIG. 6.

[0125] FIG. 8 illustrates a drop size distribution of an emulsion produced with a device according to FIG. 3A with decane as a phase to be dispersed.

[0126] FIG. 9 diagrammatically shows a microfluidic device according to a second embodiment of the invention.

[0127] FIG. 10 shows snapshots of a microfluidic device according to the embodiment of FIG. 9 that produces emulsion for two different pressures (Pc) of the continuous phase. The pressure of the phase to be dispersed is set to 350 mbar. The heights of the different areas are also indicated.

[0128] FIG. 11 shows frequency of drops formation as a function of the microchannel's number along the array of microchannels of a PDMS (polydimethylsiloxane) device according to the embodiment of FIG. 9. The first microchannel on the abscissa corresponds to a microchannel which is located close to the entrance of the continuous phase. Two pressures of the continuous phase (Pc) are used as in FIG. 10. The pressure of the phase to be dispersed is set to 350 mbar.

DETAILED DESCRIPTION OF THE INVENTION

[0129] FIG. 1 diagrammatically shows a cross section of a microfluidic device 1 according to prior art.

[0130] This device 1 comprises a first channel 1a, a second channel 1b, and microchannel 1c, linking the first channel to the second channel.

[0131] In use, a phase to be dispersed 2a, for example including at least an organic phase, is injected into the first channel 1a. The phase to be dispersed 2a passes through the microchannels 1c and forms a drop 2b at an end of the microchannel meeting the second channel 1b. In the second channel 1b, a continuous phase 2c, for example an aqueous phase, is injected and moves the drops 2b to an emulsion exit port of the device.

[0132] The drops 2b in the continuous phase 2c form an emulsion.

[0133] According to such embodiment, the microchannel 1c has a height h0 which is smaller than a height h1 of the first channel 1a and a height h2 of the second channel 1b.

[0134] As illustrated on FIG. 1, the second channel 1b has a uniform height.

[0135] A drawback of such embodiment is that the device, in particular at least the second channel 1b, can be easily clogged, and monitoring a continuous flow of the emulsion is difficult.

[0136] FIG. 2A diagrammatically shows a cross section of a microfluidic device 100 according to the invention.

[0137] This device 100 comprises a first channel 10, a second channel 20, and a microchannel 30, linking the first channel 10 to the second channel 20.

[0138] In use, a phase to be dispersed 2a, for example including at least an organic phase, is injected into the first channel 10. The phase to be dispersed 2a passes through the microchannel 30 and forms a drop 2b at an outlet 34 of the microchannel meeting the second channel 20. In the second channel 20, a continuous phase 2c, for example an aqueous phase, is injected and moves the drops 2b to an emulsion exit port of the device. More particularly, the continuous phase preferably flows transversely to a flow of the drops getting out the microchannels.

[0139] The drops 2b in the continuous phase 2c form an emulsion.

[0140] In this embodiment, the second channel 20 comprises a first part 21 which the outlet 34 of the microchannel 30 meets, and a second part 22, the first part 21 being between the microchannel 30 and the second part 22.

[0141] According to such embodiment, the microchannel 30 has a height h0 which is smaller than a height h1 of the first channel 10. Besides, the first part 21 of the second channel has a height h2a greater than the height h0 of the microchannel, and the second part 22 of the second channel has a height h2b greater than the height h2a of the first part 21 of the second channel.

[0142] According to a particular embodiment, h0=2 μm, h2a=20 μm, and h2b=200 μm.

[0143] According to a particular embodiment, the width of the first channel is 500 μm, the width of the first part of the second channel 21 is 200 μm, and the width of the second part of the second channel 22 is 1600 μm.

[0144] FIG. 2B illustrates an experimental manufacture of a device according to FIG. 2A.

[0145] According to an example of utilization of the device, a phase to be dispersed 2a is introduced in the first channel and flows through the microchannels 30.

[0146] In parallel, a continuous phase 2c, potentially comprising an aqueous phase, is introduced in the second channel 20, as illustrated by the arrow.

[0147] Thus this shows that the continuous phase 2c flows transversely to the arrival of the drops coming from the microchannels 30.

[0148] FIG. 2B also shows that the emulsion is compact in the first part 21 of the second channel 20, and is then diluted in the second part 22 of the second channel 20, which ensures a better continuous flow, and therefore a more continuous production of the emulsion.

[0149] A—First Device

[0150] A diagram of a microfluidic device 100′ for producing an emulsion is shown in FIGS. 3A and 3B (cross-section along the dotted line A-A) according to a first embodiment, compliant with the principle of FIG. 2A.

[0151] In one embodiment, the dimensions of the microfluidic parts of such microfluidic device 100′ can be about 10 cm (length L0)×1 cm (width WO). For example, the height of the device would be the biggest height amongst h1, h2b.

[0152] Microfluidic device 100′ comprises a first channel 10′, a second channel 20′, and two facing arrays 31′,32′ of microchannels 30′ linking the first channel 10′ to the second channel 20′.

[0153] In one embodiment, each array 31′,32′ comprises 1 000 microchannels 30′.

[0154] Each microchannel 30′ has an inlet 33′ from the first channel 10′ and an outlet 34′ to the second channel 20′ (see FIG. 3B).

[0155] The second channel 20′ is, in the present invention, centrally positioned in the device between the two arrays of microchannels 30′.

[0156] Besides, it is straight here.

[0157] The second channel 20′ comprises an entry port 23′ for the continuous phase, and an exit port 24′ for the emulsion formed by using the device. In use, the continuous phase flows form the entry port 23′ towards the exit port 24′ where the emulsion is collected.

[0158] As shown in FIG. 3B, the second channel 20′ is characterized by two different heights (h2a and h2b): a first part 21′ with the smallest of the two heights (h2a) located along the arrays of microchannels 30′, and a second part 22′ with the biggest of the two heights (h2b), here located in the center of the second channel 20′. Thus, the second channel 20′ here comprises two first parts 21′ and the second part 22′ is located between the two first parts 21′.

[0159] Here, a lengthwise direction L0 of the device is considered to be the direction of a flow along the second channel 20′.

[0160] The first channel 10′ here comprises an entry port 13′ for the phase to be dispersed, and an exit port 14′ for the phase to be dispersed which is configured to be open or closed.

[0161] When the exit port 14′ for the phase to be dispersed is closed, the phase to be dispersed is forced through the arrays of microchannels 30′ that lead to the second channel 20′ where the continuous phase flows from the entry port 23′ towards the emulsion exit port 24′ where the emulsion is collected.

[0162] Thus, the continuous phase in the second channel 20′ flows transversely to the flow of drops coming from the microchannels 30.

[0163] In the embodiment of FIG. 3A, the first channel 10′ is split in two parts 11′,12′, the first array 31′ of microchannels 30′ being situated between a first part 11′ of the two parts of the first channel 10′ and the second channel 20′, and the second array 32′ of microchannels 30′ being situated between a second part 12′ of the two parts of the first channel 10′ and the second channel 20′.

[0164] Therefore, here, the two parts 11′,12′ of the first channel 10′ surround the two arrays 31′,32′ of microchannels 30′ and the second channel 20′.

[0165] Here, height h1 of the first channel 10′ (in particular here of both parts 11′,12′) and height h2a of the first parts 21′ of the second channel 20′ are equal to 20 μm, height h0 of the microchannel 30′ is equal to 2 μm, and height h2b of the second part 22′ of the second channel 20′ is equal to 200 μm.

[0166] Here, the width of the first channel 10′ is 500 μm, the width of the first part of the second channel 21′ is 200 μm, and the width of the second part of the second channel 22′ is 1600 μm.

[0167] Besides, each microchannel 30′ has a length L, and at least a part with a width W (considered along the lengthwise direction of the device).

[0168] For example, the width W is equal to about 10 μm, and the length (considered between its inlet and its outlet) is equal to about 140 μm.

[0169] A distance e between two successive microchannels 30′ is for example equal to 40 μm.

[0170] A microfluidic device with a design as shown in FIGS. 3A and 3B is advantageously made of glass.

[0171] According to an example, the channels can be made by a wet etching method leading to bottom corners of channels having a rounded shape characterized by a radius of curvature equal to the channel's height.

[0172] Various example methods to manufacture a device according to the invention are illustrated in FIG. 4.

[0173] For example, a device according to the invention can be made by assembling a bottom plate with a top plate.

[0174] At least part of the first channel, the second channel, and/or the microchannels can be formed in at least the bottom plate.

[0175] For illustration, FIG. 4 shows a microchannel cross-section.

[0176] To this end, the following techniques can be used: [0177] Anisotropic etching or soft lithography, which usually lead to a rectangular cross section with right angle corners as shown in FIG. 4A), [0178] Isotropic etching, which usually leads to: [0179] rounded corners when applied on a glass substrate as illustrated in FIG. 4B), [0180] beveled corners when applied on a silicon substrate as illustrated in FIG. 4C).

[0181] The top plate with which it is then assembled can be flat, as illustrated in FIGS. 4D), 4E) and 4F), or etched too, as illustrated in FIGS. 4G), 4H) and 4I).

[0182] The bottom plate and the top plate assembled one to the other can be etched with different techniques if desired.

[0183] According to another embodiment, 3D printing, for example stereolithography, could also be used to manufacture at least part of the device.

[0184] As illustrated in FIG. 5, microchannels can have different shapes along their length.

[0185] According to one embodiment, FIG. 5A shows microchannels having a constant width W along their length L.

[0186] According to a second embodiment, FIG. 5B shows microchannels having a first part with a constant width W along their length L1 and a second part which is flared along their length L2.

[0187] According to a third embodiment, FIG. 5C shows microchannels having a first part with a constant width W along their length L1′ and a second part which is common to several microchannels along their length L2′, corresponding to coalescence of several microchannels.

[0188] The second parts of the microchannels have a same height h0.

1. First Emulsion Production Example

[0189] The phase to be dispersed 2a is decane (which is an alkane composed of a linear chain of ten atoms of carbon (C)), the continuous phase 2c is water with sodium dodecyl sulphate.

[0190] The flows of both phases are controlled by imposing a pressure on each reservoir containing the liquids and which are connected to the corresponding entry ports of the microfluidic device.

[0191] As shown in FIG. 6, oil-in-water drops 2b are formed at the end of the microchannels 30′, forming a compact emulsion having homogeneous size as revealed by the arrangement of the drops in a crystal like fashion.

[0192] The compact emulsion then flows to the central part 22′ of the collecting second channel 20′ having a greater height and where most of the continuous phase 2c flows.

[0193] This makes it possible to dilute the emulsion and thus to obtain a continuous production and collection of the emulsion at a high throughput.

[0194] The snapshots provided in FIG. 6 are taken at the end of the microchannel array for two different pressures (Pc) of the continuous phase 2c, namely Pc=100 mbar for the left hand picture, and Pc=200 mbar for the right hand picture. The pressure (Pd) of the phase to be dispersed 2a is set to 500 mbar.

[0195] FIG. 6 clearly shows that the collected emulsion is more diluted for a higher value of Pc.

[0196] The production rate depends mainly on the pressure (Pd) of the phase to be dispersed and weakly on the pressure (Pc) of the continuous phase thanks to the design of the microfluidic device according to the invention.

[0197] The production rates of about twenty microchannels at five locations along the array of microchannels of a glass device as shown in FIGS. 3A and 3B are shown in FIG. 7.

[0198] The first microchannel is located close to the entry port of the continuous phase. Two pressures of the continuous phase (Pc) are used as in FIG. 6. The pressure of the phase to be dispersed is set to 500 mbar.

[0199] As reported in FIG. 7, the frequency of drop formation along the array of microchannels is not affected by a modification of Pc.

[0200] The average frequency of drop formation per microchannel is about 130 Hz. This results in an overall production rate of the device of 2.6×10.sup.5 drops per second.

[0201] The average drop size is 8.5 μm and the corresponding coefficient of variation (CV), defined as the standard deviation of the size distribution divided by the mean size, is 7.5% (as illustrated by FIG. 8).

[0202] The corresponding throughput is 0.3 mL of phase to be dispersed per hour.

[0203] The microfluidic device can continuously produce emulsion drops over several days or weeks.

2. Second Emulsion Production Example

[0204] The phase to be dispersed 2a is a certified refractive index liquid (Series AA-xx with n=1.41, #1806Y, from Cargille Laboratories) and the continuous phase 2c is an aqueous solution of sodium dodecyl sulphate (SDS).

[0205] For a set of pressures, the average frequency of drop formation per microchannel is 90 Hz and the resulting drop size is 8.4 μm and the size distribution is characterized by a coefficient of variation of 4.8%.

3. Third Emulsion Production Example

[0206] Still using device of FIG. 3, the phase to be dispersed 2a comprises styrene, divinylbenzene, and nanoparticles of iron oxide covered by oleic acid; and the continuous phase 2c is water with of sodium dodecyl sulphate.

[0207] For a set of pressures, the average frequency of drop formation per microchannel is 30 Hz and the resulting mean drop size is 8.2 μm and the size distribution is characterized by a coefficient of variation of 7.2%.

[0208] B—Second Device

[0209] A microfluidic device 100″ according to a second embodiment of the invention is shown in FIG. 9.

[0210] Similar parts bear same numeral reference with an additional “′”.

[0211] The device 100″ differs from the previous one illustrated on FIG. 3 by the design of the first channel 10″, which is here made tortuous and split into several sub-channels, and in that there is no exit port for the phase to be dispersed in the first channel.

[0212] For example, the device 100″ is fabricated by soft lithography techniques.

[0213] It is made in polydimethylsiloxane (PDMS) and bonded on a glass plate.

[0214] In one embodiment, the height of the microchannels (h0) is 2.3 μm, the width W is 10 μm and the length L is 140 μm, the height of the first channel (h1) and of each first part of the second channel (h2a) is 20 μm and the height (h2b) of the second part of the second channel (collecting channel) is 240 μm.

[0215] Here, the width of the first part of the second channel 21″ is 490 μm, and the width of the second part of the second channel 22″ is 1600 μm.

[0216] Each array contains 500 microchannels, or a total of 1000 microchannel for the device.

[0217] An emulsion composed of fluorocarbon oil (FC40, 3M Fluorinert) as the phase to be dispersed 2a and an aqueous solution of sodium dodecyl sulphate as the continuous phase 2c is produced with the microfluidic device reported in FIG. 9.

[0218] FIG. 10 shows snapshots taken at the end of the microchannel array for two different pressures (Pc) of the continuous phase 2c, namely Pc=200 mbar for the left hand picture, and Pc=600 mbar for the right hand picture. The pressure (Pd) of the phase to be dispersed is set to 350 mbar.

[0219] As shown in this figure, the oil-in-water drops 2b are formed at the end of the microchannels 30″, forming a compact emulsion having homogeneous size as revealed by the arrangement of the drops 2b in a crystal like fashion.

[0220] The compact emulsion then flows to the central part 22″ of the collecting second channel 20″ having a higher height and where most of the continuous phase 2c is flowing. This makes it possible to dilute the emulsion and thus to obtain a continuous production and collection of the emulsion at a high throughput.

[0221] It is clearly visible that the collected emulsion is more diluted for a higher value of Pc.

[0222] FIG. 11 shows the production rate of about twenty microchannels at three locations along the array of microchannels 30″ of the PDMS device 100″ shown in FIG. 9.

[0223] The first microchannel 30″ is located close to the entry port 23″ of the continuous phase 2c.

[0224] As illustrated by this figure, the frequency of drop formation along the array of microchannels 30″ is not affected by a modification of Pc.