Microfluidic device for emulsion production

Abstract

The present invention relates to an emulsion production microfluidic device (100, 100', 100'') comprising a first channel (10, 10', 10'') comprising an inlet port configured to inject a dispersed phase (2a), a second channel (20, 20', 20'') comprising an inlet port configured to inject a continuous phase (2c) and an emulsion outlet port, and at least one row of microchannels (30, 30', 30''), wherein the height h0 of each of the microchannels is smaller than the height h1 of the first channel. and at least one row of microchannels (30, 30', 30''), wherein the second channel comprises a first portion (21, 21', 21'') connected to the outlet (34, 34') of each microchannel and at least a second portion (22, 22', 22'') along the first portion (21, 21', 21''), the first portion being between the row of microchannels and the second portion, a height h2a of the first portion being greater than a height h0 of each microchannel, and a height h2b of the second portion being greater than the height h2a of the first portion.

Description

[Technical field]

[0001] The present invention relates to a microfluidic device for producing an emulsion. [Background technology]

[0002] An emulsion is a mixture of at least two, usually immiscible, liquids. By definition, one liquid (called the dispersed phase) is dispersed in another liquid (called the continuous phase).

[0003] There are two main types of emulsions: true emulsions, where oil is the dispersed phase and water is the continuous phase, like an oil-in-water emulsion, and inverse emulsions, where water is the dispersed phase and oil is the continuous phase, like a water-in-oil emulsion.

[0004] The dispersed phase may be a mixture of several miscible fluids, a solution of amphiphilic or non-amphiphilic small molecules, macromolecules, or a dispersion of solid or liquid particles, the latter thus forming a double or multiple emulsion, or a combination of the various above mentioned options.

[0005] The continuous phase generally contains one or more surfactants (amphiphilic molecules) as well as solutes, polymers, or even particles.

[0006] Emulsification methods are known for obtaining droplets with a diameter of a few micrometers, for example the shear emulsification method, obtained using a device comprising two coaxial cylinders, one of which rotates, or the membrane emulsification method, which is based on the use of a porous material through which the dispersed phase is injected.

[0007] However, the emulsion droplets produced by these methods are characterized by a coefficient of variation in droplet size, defined as the ratio of the standard deviation of the droplet size to the mean droplet size, of at least 15%.

[0008] Therefore, microfluidics is considered as an efficient tool to obtain calibrated emulsion droplets.

[0009] For example, Patent Document 1 describes a microfluidic device.

[0010] In such devices, the dispersed phase travels from a first channel through microchannels arranged parallel to one another to a second channel, the height of the microchannels being smaller than the height of the channel.

[0011] Droplets are formed at one end of a microchannel, which opens laterally to the microchannel network into a second channel, into which the continuous phase is injected. The drop size is proportional to the height of the microchannel and is less dependent on the width of the microchannel. Below a critical flow rate, the drop size is weakly dependent on the flow rate of the dispersed phase in the microchannel, which depends on the pressure on either side of said microchannel. Above such critical flow rate, the drop size becomes significantly larger, resulting in a broad drop size distribution inside the microchannel network.

[0012] Additionally, the emulsion droplets present in the second channel are driven by the continuous phase towards the outlet of the device, which is connected to a reservoir.

[0013] Since the microchannel is arranged in series transversely to the second channel, the volume of droplets in the continuous phase increases along the flow direction of the continuous phase.

[0014] Overly concentrated emulsions can have a detrimental effect on their production: increasing the volume fraction of the dispersed phase (i.e. droplets) in the continuous phase increases the viscosity of the emulsion and thus the corresponding pressure loss. In addition, the adhesive forces that exist between the droplets also increase this effect.

[0015] To control flow rate by pressure regulation, the pressure of the continuous phase must be adjusted to avoid clogging of the device.

[0016] However, flow control can be difficult to use due to the relatively low production rates and small droplet sizes. It is often necessary to provide a high flow rate of the continuous phase to sufficiently dilute the emulsion.

[0017] Furthermore, the pressure conditions in the first microchannel can be unfavourable: the flow rate of the dispersed phase through the microchannel depends on the pressure on either side of the microchannel: increasing the pressure of the continuous phase to avoid clogging of the device would result in the need to modify or stop the drop-producing part of the upstream microchannel. [Prior art documents] [Patent documents]

[0018] [Patent Document 1] U.S. Patent Application No. 14 / 890,817 (U.S. Patent Application Publication No. 2016 / 0091145) Summary of the Invention [Problem to be solved by the invention]

[0019] The present invention relates to a microfluidic device for producing emulsions, which exhibit remarkable homogeneity, i.e. a droplet size distribution coefficient of less than or equal to 15%, or less than or equal to 10%, and an average size, e.g. mean size, which may vary between a few micrometers, e.g. a few micrometers and a few tens of micrometers.

[0020] The invention also relates to a microfluidic device that allows the production conditions of the emulsion to be improved, for example allowing the continuous production and mass production of said emulsion. [Means for solving the problem]

[0021] Accordingly, the present invention provides an emulsion production microfluidic device, the emulsion production microfluidic device comprising: - a first channel including an inlet port configured to inject a dispersed phase into the first channel; - a second channel including an inlet port configured to inject a continuous phase into said second channel and an emulsion outlet port configured to extract an emulsion from said device; - at least one row of microchannels arranged side-by-side, each microchannel including an inlet from the first channel and an outlet to the second channel, and a height h0 of each of the microchannels being smaller than a height h1 of the first channel; Equipped with The device comprises: The second channel includes a first portion connected to an outlet of each microchannel and at least a second portion along the first portion, the first portion being between the row of microchannels and the second portion, a height h2a of the first portion being greater than a height h0 of each microchannel, and a height h2b of the second portion being greater than the height h2a of the first portion. Effect of the Invention

[0022] Thus, the present invention separates the droplet formation step (i.e., emulsification step) to construct the emulsion by dense emulsion along the microchannel and the emulsion collection step by lateral flow to dilute the emulsion and thus facilitate its exit from the device.

[0023] In other words, the second channel is configured to drive a flow including at least a continuous phase between an inlet port and an outlet port, and the microchannel is configured to inject a droplet stream of the dispersed phase into the second channel transverse to the second channel flow.

[0024] The invention makes it possible to homogenize the flow at the outlet of the microchannel and to create a change in hydrodynamic resistance between the first and second portions of the second channel.

[0025] For this purpose, the present invention separates the second channel into two parts, a first part configured to perform a drop formation process from the microchannel and a second part configured to perform a drop collection process.

[0026] The second channel is characterized by at least two different heights, i.e. a first part near the microchannel, characterized by a height h2a several times greater than the height of the microchannel, and - the second portion adjacent to the first portion is characterized by at least one height h2b that is several times greater than the height of the first portion.

[0027] Such a device is also called a "closed device" since it contains an inlet port for the dispersed phase, an emulsion outlet port, and a stream running within the device, which allows for collection of the droplets formed within the device (i.e. the emulsion is formed within the device).

[0028] The height h2a of the first portion of the second channel is preferably constant or may vary slightly, e.g. increase, from the microchannel to the second portion, but in either case the height h2a of the first portion is significantly greater than the height h0 of the microchannel, and the height h2b of the second portion of the second channel is significantly greater than the height h2a of the first portion.

[0029] The length of the device is considered herein to be the direction of flow along the second channel between the inlet port and the emulsion outlet port, and the width of the device is considered to be orthogonal to the length of the device, and the height is orthogonal to the length and width.

[0030] Additionally, the length of a microchannel is considered to be the direction from the inlet to the outlet of the microchannel. The width of a microchannel is perpendicular to its length. When a microchannel is perpendicular to a second channel, the width of the microchannel runs parallel to the length of the device. The height of a microchannel is parallel to the height of the device.

[0031] The same applies to the first channel, which has a height direction parallel to the height direction of the device.

[0032] The height h0 of at least one microchannel of the array of microchannels is considered as constant.

[0033] For example, h0 is equal to about 2 μm.

[0034] A microchannel includes at least a portion (along its length) that has a constant width W.

[0035] According to one embodiment, the microchannel may include a portion having an increased width, e.g., a flared portion, preferably between the portion having a constant width and the second channel, i.e., the flared portion preferably comprises the outlet of the microchannel.

[0036] According to one embodiment, portions of at least two microchannels having a constant width W merge.

[0037] For example, a microchannel array includes a common portion of at least two microchannels having the same height h0 at the outlet location.

[0038] According to one embodiment, the width W of at least a part of a microchannel is 0.01 to 10000 times the height h0 of at least a part of said microchannel.

[0039] For example, the width W of at least a part of the microchannel is 2 to 10000 times its height h0, such as 2 to 1000 times its height h0, or 100 or 20 times, and preferably equal to 5 times the height h0.

[0040] For example, W is equal to about 10 μm.

[0041] For example, a microchannel having a constant width along its length, approximately 10 μm (width)×2 μm (height), is formed to produce droplets with a diameter d of approximately 8 μm.

[0042] For example, the width W of at least a part of the microchannel is 0.01 to 1 times the height h0 thereof, and preferably 0.01 to 0.5 times the height h0 thereof.

[0043] In such cases, depending on the particular microfabrication technique, the microchannels can be greater in height than they are in width.

[0044] According to another embodiment, the length of the microchannel is between 2 and 1000 times, preferably 100 times, its height h0.

[0045] The selection of the length in combination with the height allows for tuning of the hydrodynamic resistance of the microchannel.

[0046] For example, the distance e between two consecutive microchannels is equal to 2 to 100 times the width W of the microchannel, such as about 4 times the width W of the microchannel.

[0047] According to one embodiment, the cross section of the microchannel is square, or semicircular, or triangular.

[0048] For example, at least one corner of the rectangular cross section may be right-angled or curved, such as rounded or beveled.

[0049] According to another embodiment, at least one of the microchannels can include at least one groove along its length, which facilitates localization of drop formation, particularly when the width of the microchannel is very wide, i.e., more than 20 times its height h0.

[0050] For example, the microchannel array includes at least 10 microchannels, such as 100 to 100,000 microchannels, and preferably about 1,000 microchannels.

[0051] For example, the microfluidic portion of the device preferably has a length L0 between 2 cm and 20 cm, a width W0 between 0.5 cm and 10 cm, and a height between 0.1 cm and 2 cm.

[0052] The pressure of the continuous phase, and therefore the flow rate, can be adjusted to dilute the emulsion during production as desired without modifying the emulsification process, allowing optimal production of the emulsion without interruptions, i.e. continuous production.

[0053] As a result, the number of microchannels can be increased compared to devices with single height secondary channels, which further increases the manufacturing speed.

[0054] In such a device, the dispersed phase is introduced into the first channel through its inlet port.

[0055] The first channel may optionally include an exit port for the dispersed phase that is configured to be opened and closed.

[0056] When the exit port of the first channel is closed, the dispersed phase is forced through the array of microchannels, which open into the second channel, and when the exit port of the first channel is open, the first channel can be purged without having to flow through the array of microchannels.

[0057] As the dispersed phase passes from the first channel through the microchannel into the first portion of the second channel, droplets form at the end of the microchannel that opens into the first portion of the second channel.

[0058] At the same time, the continuous phase is injected into the second channel through its inlet port and drives the droplets towards the emulsion outlet port of the second channel.

[0059] More specifically, the continuous phase is, for example, injected into a second portion of the second channel and extends into a first portion of the second channel.

[0060] For example, the second channel may be straight, eg, at least between its inlet port and its emulsion outlet port.

[0061] However, the second channel may also be serpentine, which further allows for an increase in the number of microchannels and therefore the production speed.

[0062] For example, the emulsion outlet port of the second channel is configured to connect with a tank for collecting the emulsion.

[0063] For example, such a device can be used to produce droplets for the synthesis of functionalized solid particles that may be useful in the biotechnology field.

[0064] According to one embodiment, the device includes two rows of microchannels.

[0065] According to one embodiment, at least one of the first channel or the second channel is flanked by an array of microchannels.

[0066] For example, the device may include at least two first channels, a first of two microchannel rows located between a first of the two first channels and a second of the two microchannel rows located between a second of the two first channels and the second of the two microchannel rows, In other words, in such a case, there is a single second channel flanked by a microchannel row, and also flanked by a first channel.

[0067] Or for example, the device may include at least two second channels, a first of two microchannel rows located between a first of the two second channels and the first channel, and a second of the two microchannel rows located between a second of the two second channels and the first channel. In other words, in such cases, there is a single first channel flanked on either side by a microchannel row, and also flanked on either side by a second channel.

[0068] The height of the first portion of the second channel is h2a.

[0069] For example, the height h2a of the first portion of the second channel is 2 to 100 times, preferably 10 times, larger than the height h0 of the microchannel.

[0070] For example, h2a is equal to about 20 μm.

[0071] For example, the height h2b of the second portion of the second channel is 2 to 100 times, preferably 10 times, greater than the height h2a of the first portion of the second channel.

[0072] For example, h2b is equal to about 200 μm.

[0073] The first channel has a height h1.

[0074] For example, the height h1 of the first channel is 2 to 1000 times, preferably 10 times, larger than the height h0 of the microchannel.

[0075] According to one embodiment, the height h1 of the first channel is equal to the height h2a of the first portion of the second channel.

[0076] For example, h1 is equal to about 20 μm.

[0077] For example, the width of the first channel is 1 to 100 times the height h1.

[0078] For example, the width of the second channel is 1 to 100 times the height h2b of the second portion thereof.

[0079] For example, the width of the first portion of the second channel is 1 to 100 times, preferably 10 times, the height h2a, and the width of the first portion of the second channel specifies the dimension of the first portion of the second channel that extends from the microchannel to the second portion of the second channel.

[0080] The microfluidic device is advantageously made of glass, since it is compatible with most solvents, thus allowing a greater variety of emulsion formulations to be used.

[0081] Additionally, microfabrication techniques using glass substrates provide precise and reproducible microchannel features.

[0082] According to another advantageous embodiment, the device may be made from silicon.

[0083] For example, it is desirable for at least some of the surfaces of the first channel, second channel, and / or microchannel to be hydrophilic (or hydrophobic) and to remain hydrophilic (or hydrophobic) for as long as possible during emulsion production to limit or prevent wetting of the glass by the dispersed phase, particularly when the dispersed phase includes an organic phase, and to ensure an efficient emulsification process.

[0084] Furthermore, an interesting option is that the surface properties can be modified to make them hydrophilic or hydrophobic, depending on the type of emulsion to be produced.

[0085] For this purpose, according to one embodiment, hydrophilic molecules are adsorbed or associated with at least a portion of the surface of the first channel and / or the second channel and / or the microchannel, rendering the surface hydrophilic, or hydrophobic molecules are adsorbed or associated with at least a portion of the surface of the first channel and / or the second channel and / or the microchannel, rendering the surface hydrophobic.

[0086] Where possible, the entire surface of the first channel, the second channel and the microchannels are coated with hydrophilic or hydrophobic molecules.

[0087] Hydrophilic or hydrophobic molecules can be characterized by a high energy of attachment to a surface.

[0088] According to one embodiment, the hydrophilic or hydrophobic molecule may be a polymer.

[0089] An interesting hydrophilic molecule may be a silane coupled with poly(ethylene glycol) (PEG), in particular for devices made of glass or silicon.

[0090] Interesting hydrophobic molecules, in particular for devices made of glass or silicon, may be silanes, for example silanes coupled with organic compounds, for example organofunctional alkoxysilanes such as octadecyltrichlorosilane.

[0091] A related method may be as follows.

[0092] For example, the surface is activated with piranha solution, a solution containing sulfuric acid together with hydrogen peroxide (H2O2).

[0093] The surface is then rinsed and then functionalized with a hydrophilic or hydrophobic solution.

[0094] For example, hydrophilic or hydrophobic molecules that prevent wetting of the organic phase are adsorbed onto the surface.

[0095] For example, hydrophilic or hydrophobic molecules that prevent wetting of the organic phase may be covalently attached onto the surface.

[0096] According to one embodiment, several devices incorporating at least some of the features described above can be used in parallel.

[0097] This can further increase the speed at which the emulsion can be produced.

[0098] For example, a method for manufacturing such a device incorporating at least some of the features described above may include the following steps: - Prepare a plate called the bottom plate. - forming at least a portion of the first channel and / or the second channel and / or the microchannel in a bottom plate; The bottom plate is assembled with a plate, referred to herein as the top plate, to form the device. The process may include the steps of:

[0099] For example, at least a portion of the first channel, and / or the second channel, and / or the microchannel may be formed by wet or dry etching, or soft lithography, or by 3D printing techniques such as stereolithography.

[0100] According to one embodiment, the method may also include forming a complementary portion of the first channel, and / or the second channel, and / or the microchannel in the top plate.

[0101] For example, the first channel, and / or the second channel, and / or the complementary portion of the microchannel may be formed by wet or dry etching, or soft lithography, or by 3D printing techniques such as stereolithography.

[0102] This step is preferably performed prior to assembling the top plate with the bottom plate.

[0103] For example, etching the bottom plate and / or the top plate may include anisotropic etching.

[0104] For example, etching the bottom plate and / or the top plate may include an isotropic etch.

[0105] Of course, numerous other techniques may be used.

[0106] Additionally, different techniques may be used for the bottom and top plates that are formed to be assembled together, if desired.

[0107] According to another embodiment, the second portion of the second channel can be formed by etching the glass substrate (top plate and / or bottom plate) so as to obtain a semi-cylinder or, if the substrate (forming the top plate and / or bottom plate) is made of silicon, a triangle is obtained.

[0108] According to another embodiment, at least a portion of the device is formed by 3D printing, for example stereolithography, allowing a variety of different shapes to be provided.

[0109] Additional features and advantages of the present invention are described in, or will be apparent from, the following description of the presently preferred embodiments taken in conjunction with the drawings. [Brief description of the drawings]

[0110] [Figure 1] FIG. 1 is a cross-sectional view that shows a schematic diagram of a microfluidic device based on the prior art. [Figure 2A] FIG. 2A is a schematic cross-sectional view of a microfluidic device 100 according to the present invention. [Figure 2B] FIG. 2B illustrates the trial manufacture and use of a device based on FIG. 2A. [Diagram 3] FIG. 3A is a schematic diagram showing a microfluidic device 100' for producing an emulsion based on a first embodiment conforming to the microfluidic device of FIG. 2A (FIG. 3A), and FIG. 3B is a corresponding cross-sectional view taken along dashed line AA. [Figure 4] FIG. 4, including FIGS. 4A-4I, illustrates various methods of fabricating channels or microchannels in a device according to the present invention. [Diagram 5] FIG. 5 shows three embodiments of a microchannel according to the present invention. [Figure 6] Figure 6 shows snapshots of a microfluidic device based on the embodiment of Figure 3A producing emulsions for two different continuous phase pressures (Pc), with the dispersed phase pressure set at 500 mbar. Different channel heights are indicated. [Figure 7] FIG. 7 shows the frequency of droplet formation as a function of the number of microchannels along the microchannel array of a glass device based on the embodiment of FIG. 3A and the testing of FIG. [Figure 8] FIG. 8 shows the droplet size distribution of an emulsion produced by a device based on FIG. 3A using decane as the dispersed phase. [Figure 9] FIG. 9 is a schematic diagram showing a microfluidic device according to a second embodiment of the present invention. [Figure 10] Figure 10 is a snapshot showing a microfluidic device according to the embodiment of Figure 9 producing emulsions in response to two different pressures of the continuous phase (Pc). The pressure of the dispersed phase is set to 350 mbar. The heights of the different regions are also shown. [Figure 11] Figure 11 shows the droplet formation frequency as a function of the number of microchannels along the microchannel row of a PDMS (polydimethylsiloxane) device based on the embodiment of Figure 9. The first microchannel on the abscissa corresponds to the microchannel located close to the inlet of the continuous phase. The two pressures (Pc) of the continuous phase are taken from Figure 10. The pressure of the dispersed phase is set to 350 hPa (mbar). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0111] FIG. 1 is a schematic cross-sectional view of a microfluidic device 1 according to the prior art.

[0112] The device 1 includes a first channel 1a, a second channel 1b, and a microchannel 1c connecting the first channel to the second channel.

[0113] In use, a dispersed phase 2a, for example comprising at least one organic phase, is injected into the first channel 1a. The dispersed phase 2a passes through the microchannel 1c and forms droplets 2b at the end of the microchannel which opens into the second channel 1b. A continuous phase 2c, for example an aqueous phase, is injected into the second channel 1b, which drives the droplets 2b towards the emulsion exit port of the device.

[0114] The droplets 2b in the continuous phase 2c form an emulsion.

[0115] According to such an embodiment, the height h0 of the microchannel 1c is smaller than the height h1 of the first channel 1a and the height h2 of the second channel 1b.

[0116] As shown in FIG. 1, the second channel 1b has a uniform height.

[0117] A drawback of such an embodiment is that the device, particularly at least the second channel 1b, easily becomes clogged, making it difficult to monitor a continuous flow of emulsion.

[0118] FIG. 2A is a schematic cross-sectional view of a microfluidic device 100 according to the present invention.

[0119] The device 100 includes a first channel 10 , a second channel 20 , and a microchannel 30 connecting the first channel 10 to the second channel 20 .

[0120] In use, a dispersed phase 2a, for example comprising at least an organic phase, is injected into the first channel 10. The dispersed phase 2a passes through the microchannel 30 and forms droplets 2b at the microchannel outlet 34 which opens into the second channel 20. A continuous phase 2c, for example an aqueous phase, is injected into the second channel 20 and drives the droplets 2b towards the emulsion outlet port of the device. More specifically, the continuous phase preferably flows transversely to the droplet flow exiting the microchannel.

[0121] The droplets 2b in the continuous phase 2c form an emulsion.

[0122] In this embodiment, the second channel 20 includes a first portion 21 where the outlet 34 of the microchannel 30 opens, and a second portion 22, with the first portion 21 being located between the microchannel 30 and the second portion 22.

[0123] In such an embodiment, the height h0 of the microchannel 30 is less than the height h1 of the first channel 10. In addition, the height h2a of the first portion 21 of the second channel is greater than the height h0 of the microchannel, and the height h2b of the second portion 22 of the second channel is greater than the height h2a of the first portion 21 of the second channel.

[0124] According to a specific embodiment, h0=2 μm, h2a=20 μm, and h2b=200 μm.

[0125] According to a specific embodiment, the width of the first channel 10 is 500 μm, the width of the first portion 21 of the second channel is 200 μm, and the width of the second portion 22 of the second channel is 1600 μm.

[0126] FIG. 2B illustrates the trial manufacture and use of a device based on FIG. 2A.

[0127] According to an example application of the device, the dispersed phase 2 a is introduced into the first channel and flows through the microchannel 30 .

[0128] In parallel, a continuous phase 2c, possibly comprising an aqueous phase, is introduced into a second channel 20, as indicated by the arrow.

[0129] Thus, the figure shows that the continuous phase 2c flows transversely to the arrival of the drops from the microchannel 30.

[0130] 2B also shows that the emulsion is dense in a first portion 21 of the second channel 20 and then becomes diluted in a second portion 22 of the second channel 20. This ensures better continuous flow and therefore more continuous production of the emulsion.

[0131] A-First Device 3A and 3B (cross-section along dashed line AA) show a schematic diagram of a microfluidic device 100' for producing an emulsion, according to a first embodiment conforming to the principle of FIG. 2A.

[0132] In one embodiment, the dimensions of the microfluidic portion of such a microfluidic device 100' may be approximately 10 cm (length L0) x 1 cm (width W0), for example, the height of the device being the greatest height of h1, h2b.

[0133] The microfluidic device 100' comprises a first channel 10', a second channel 20' and two facing rows 31', 32' of microchannels 30' connecting the first channel 10' to the second channel 20'.

[0134] In one embodiment, each row 31', 32' contains 1000 microchannels 30'.

[0135] Each microchannel 30' has an inlet 33' from the first channel 10' and an outlet 34' to the second channel 20' (see FIG. 3B).

[0136] The second channel 20' is in accordance with the present invention centrally positioned within the device between two rows of microchannels 30'.

[0137] In addition to this, the second channel is now straight.

[0138] The second channel 20' includes an inlet port 23' for the continuous phase and an outlet port 24' for the emulsion formed by using the device. In use, the continuous phase flows from the inlet port 23' towards the outlet port 24' where the emulsion is collected.

[0139] As shown in Fig. 3B, the second channel 20' is characterized by two different heights (h2a and h2b). That is, the first portion 21' having the smallest height (h2a) of the two heights is disposed along the row of the microchannels 30', and the second portion 22' having the largest height (h2b) of the two heights is disposed here in the center of the second channel 20'. Thus, the second channel 20' includes here two first portions 21', and the second portion 22' is disposed between the two first portions 21'.

[0140] The length direction L0 of the device is considered here to be the flow direction along the second channel 20'.

[0141] The first channel 10' here comprises an inlet port 13' for the dispersed phase and an outlet port 14' for the dispersed phase, which is configured to be opened and closed.

[0142] When the outlet port 14' for the dispersed phase is closed, the dispersed phase is forced through the array of microchannels 30'. The microchannels lead into a second channel 20'. In the second channel 20', the continuous phase flows from an inlet port 23' towards an emulsion outlet port 24'. At the emulsion outlet port 24' the emulsion is collected.

[0143] In this way, the continuous phase in the second channel 20 ′ flows transversely to the droplet flow coming from the microchannel 30 .

[0144] In the embodiment of Figure 3A, the first channel 10' is divided into two portions 11', 12'. A first row 31' of microchannels 30' is located between the first of the two portions 11' of the first channel 10' and the second channel 20', and a second row 32' of microchannels 30' is located between the second of the two portions 12' of the first channel 10' and the second channel 20'.

[0145] Thus, here, the two portions 11', 12' of the first channel 10' surround two rows 31', 32' of microchannels 30' and the second channel 20'.

[0146] Here, the height h1 of the first channel 10' (specifically here of both parts 11', 12') and the height h2a of the first part 21' of the second channel 20' are equal to 20 μm, the height h0 of the microchannel 30' is equal to 2 μm, and the height h2b of the second part 22' of the second channel 20' is equal to 200 μm.

[0147] Here, the width of the first channel 10' is 500 μm, the width of the first part 21' of the second channel is 200 μm and the width of the second part 22' of the second channel is 1600 μm.

[0148] Additionally, each microchannel 30' has a length L and at least a portion having a width W (considered along the length of the device).

[0149] For example, the width W is equal to about 10 μm and the length (considered between the inlet and the outlet) is equal to about 140 μm.

[0150] The distance e between two successive microchannels 30' is for example equal to 40 μm.

[0151] A microfluidic device having the configuration shown in Figures 3A and 3B is advantageously made from glass.

[0152] According to one embodiment, the channel can be formed by a wet etching process that results in the bottom corners of the channel having a rounded shape characterized by a radius of curvature equal to the height of the channel.

[0153] Examples of various methods for fabricating a device according to the present invention are shown in FIG.

[0154] For example, a device according to the present invention can be formed by assembling a bottom plate with a top plate.

[0155] At least a portion of the first channel, the second channel, and / or the microchannel may be formed in at least the bottom plate.

[0156] For illustration purposes, FIG. 4 shows a microchannel cross section.

[0157] For this purpose, the following techniques can be used. - Anisotropic etching or soft lithography, which usually results in a square cross section with right angle corners as shown in FIG. 4A). - Isotropic etching, which is usually - when applied onto a glass substrate, it results in rounded corners, as shown in FIG. 4B) - When applied onto a silicon substrate, it results in bevelled corners as shown in FIG. 4C).

[0158] The top plate that is then assembled with the substrate may be flat, as shown in Figures 4D), 4E), and 4F), or may be etched, as shown in Figures 4G), 4H), and 4I).

[0159] The bottom and top plates which are assembled together can be etched by different techniques if desired.

[0160] According to another embodiment, at least a portion of the device can be manufactured using 3D printing, for example stereolithography.

[0161] As shown in FIG. 5, microchannels can have different shapes along their length.

[0162] According to one embodiment, the microchannel shown in FIG. 5A has a constant width W along the length L of the microchannel.

[0163] According to a second embodiment, the microchannel shown in FIG. 5B has a first portion having a constant width W along the microchannel length L1 and a second portion that flares out along the microchannel length L2.

[0164] According to a third embodiment, the microchannel shown in FIG. 5C has a first portion having a constant width W along the length L1' of the microchannel and a second portion common to several microchannels along the length L2' of the microchannel corresponding to the merging of several microchannels.

[0165] The second portion of the microchannel has the same height h0.

[0166] 1. Example of the Production of the First Emulsion The dispersed phase 2a is decane (a straight-chain alkane having 10 carbon (C) atoms), and the continuous phase 2c is water containing sodium dodecyl sulfate.

[0167] The flow rates of both phases are controlled by applying pressure to the respective reservoirs containing the liquids, which are connected to corresponding inlet ports of the microfluidic device.

[0168] As shown in FIG. 6, oil-in-water droplets 2b form at the end of the microchannel 30' forming a dense emulsion with uniform droplet size as evidenced by the crystal-like arrangement of the droplets.

[0169] The dense emulsion then flows to the central portion 22' of the second collecting channel 20' having a greater height, where most of the continuous phase 2c flows.

[0170] This dilutes the emulsion, thus allowing continuous production and collection of the emulsion to be achieved at high throughput.

[0171] The snapshots provided in Figure 6 were taken at the end of the microchannel array for two different pressures (Pc) of the continuous phase 2c: in the left-hand picture Pc = 100 mbar and in the right-hand picture Pc = 200 mbar. The pressure of the dispersed phase 2a (Pd) is set to 500 mbar.

[0172] FIG. 6 clearly shows that the higher the Pc value, the more highly diluted the collected emulsion.

[0173] Due to the configuration of the microfluidic device according to the present invention, the production rate depends mainly on the pressure of the dispersed phase (Pd) and only weakly on the pressure of the continuous phase (Pc).

[0174] The production rate of approximately 20 microchannels at five locations along the microchannel array of the glass device shown in FIGS. 3A and 3B is shown in FIG.

[0175] The first microchannel is located near the inlet port of the continuous phase. Two pressures of the continuous phase (Pc) are used as shown in Figure 6. The pressure of the dispersed phase is set at 500 hPa (mbar).

[0176] As reported in FIG. 7, the drop formation frequency along the microchannel array is not affected by the modification of Pc.

[0177] The average drop formation frequency per microchannel is about 130 Hz, which gives a total fabrication rate for the device of 2.6 × 10 per second. 5 It becomes drops.

[0178] The mean droplet size is 8.5 μm and the corresponding coefficient of variation (CV), defined as the standard deviation of the droplet size distribution divided by the mean size, is 7.5% (as shown in FIG. 8).

[0179] The corresponding throughput is 0.3 mL of dispersed phase per hour.

[0180] Microfluidic devices are capable of continuously producing emulsion droplets over a period of days or weeks.

[0181] 2. Example of Second Emulsion Production The dispersed phase 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 sulfate (SDS).

[0182] For a range of pressures, the average drop formation frequency per microchannel is 90 Hz, the resulting drop size is 8.4 μm, and the drop size distribution is characterized by a coefficient of variation of 4.8%.

[0183] 3. Example of the Third Emulsion Production Still using the device of FIG. 3, the dispersed phase 2a contains styrene, divinylbenzene, and iron oxide nanoparticles coated with oleic acid, and the continuous phase 2c is water containing sodium dodecyl sulfate.

[0184] For a range of pressures, the average drop formation frequency per microchannel is 30 Hz, the resulting average drop size is 8.2 μm, and the drop size distribution is characterized by a coefficient of variation of 7.2%.

[0185] B - Second Device A microfluidic device 100'' according to a second embodiment of the present invention is shown in FIG.

[0186] Similar parts have the same reference numbers with an additional "'".

[0187] The device 100'' differs from the previously described device shown in FIG. 3 by the configuration of the first channel 10'', which here is serpentine and divided into several sub-channels, and in that there is no exit port for the dispersed phase within the first channel.

[0188] For example, device 100'' is fabricated by soft lithography techniques.

[0189] It is fabricated in polydimethylsiloxane (PDMS) and bonded onto a glass plate.

[0190] In one embodiment, the height (h0) of the microchannel is 2.3 μm, the width W is 10 μm, and the length L is 140 μm, and the height (h1) of the first channel and the height (h2a) of the first portion of each of the second channels is 20 μm, and the height (h2b) of the second portion of the second channel (collection channel) is 240 μm.

[0191] In this case, the width of the first portion of the second channel 21'' is 490 μm and the width of the second portion 22'' of the second channel is 1600 μm.

[0192] Each row contains 500 microchannels, or a total of 1000 microchannels for the device.

[0193] An emulsion consisting of a fluorocarbon oil (FC40, 3M Fluorinert) as dispersed phase 2a and an aqueous solution of sodium dodecyl sulfate as continuous phase 2c is produced by the microfluidic device reported in FIG.

[0194] The snapshots shown in Figure 10 were taken at the end of the microchannel array for two different pressures (Pc) of the continuous phase 2c: in the left-hand picture Pc = 200 mbar and in the right-hand picture Pc = 600 mbar. The pressure of the dispersed phase (Pd) is set to 350 mbar.

[0195] As shown in this figure, oil-in-water droplets 2b form at the end of a microchannel 30'' and form a dense emulsion with uniform droplet size, as evidenced by the crystal-like arrangement of the droplets 2b.

[0196] The dense emulsion then flows to the central portion 22'' of the second collection channel 20'' having a greater height, where most of the continuous phase 2c flows. This dilutes the emulsion, thus allowing continuous production and collection of emulsions to be achieved at high throughput.

[0197] It can be clearly seen that the higher the Pc value, the more highly diluted the collected emulsion.

[0198] FIG. 11 shows the fabrication of approximately 20 microchannels at three locations along the row of microchannels 30'' of the PDMS device 100'' shown in FIG.

[0199] The first microchannel 30'' is located near the inlet port 23'' of the continuous phase 2c.

[0200] As shown by this figure, the drop formation frequency along the row of microchannels 30'' is not affected by the modification of Pc. The following are some embodiments of the present invention. [Aspect 1] An emulsion production microfluidic device (100, 100', 100''), comprising: - a first channel (10, 10', 10'') comprising an inlet port (13, 13', 13'') configured to inject a dispersed phase (2a) into said first channel; - a second channel (20, 20', 20'') comprising an inlet port (23', 23'') configured to inject a continuous phase (2c) into said second channel and an emulsion outlet port (24', 24'') configured to extract the emulsion from said device; - at least one row (30, 30', 30'') of microchannels (30, 30', 30'') arranged side-by-side, each microchannel comprising an inlet (33', 33'') from said first channel and an outlet (34', 34'') to said second channel, the height h0 of each of said microchannels being smaller than the height h1 of said first channel; Equipped with The device comprises: the second channel (20, 20', 20'') comprises a first portion (21, 21', 21'') connected to an outlet (34, 34') of each microchannel (30, 30', 30'') and at least a second portion (22, 22', 22'') along the first portion (21, 21', 21''), the first portion (21, 21', 21'') being between the row of microchannels (30, 30', 30'') and the second portion (22, 22', 22''), a height h2a of the first portion (21, 21', 21'') being greater than a height h0 of each microchannel (30, 30', 30''), and a height h2b of the second portion (22, 22', 22'') being greater than a height h2a of the first portion (21, 21', 21''). [Aspect 2] The device according to embodiment 1, characterized in that at least one microchannel (30, 30', 30'') comprises at least a portion having a constant width W. [Aspect 3] The device according to aspect 2, wherein the width W of at least a portion of the microchannel (30, 30', 30'') is 0.01 to 10,000 times the height h0 of the microchannel. [Aspect 4] The device according to any of the preceding embodiments, characterized in that at least one microchannel (30, 30', 30'') comprises a flared portion. [Aspect 5] The device according to any one of the preceding embodiments, characterized in that the array of microchannels (30, 30', 30'') comprises a portion common to at least two microchannels at the location of the outlet. [Aspect 6] The device according to any of the preceding embodiments, characterized in that the array of microchannels (30, 30', 30'') comprises at least 10 microchannels, such as 100 to 100000 microchannels, preferably about 1000 microchannels. [Aspect 7] The device according to any one of the preceding aspects, characterized in that the height h2a of the first portion (21, 21', 21'') of the second channel (20, 20', 20'') is 2 to 100 times, preferably 10 times, greater than the height h0 of the microchannel (30, 30', 30''). [Aspect 8] The device according to any one of the first to seventh aspects, characterized in that a height h2b of the second portion (22, 22', 22'') of the second channel (20, 20', 20'') is 2 to 100 times, preferably 10 times, greater than a height h2a of the first portion (21, 21', 21'') of the second channel (20, 20', 20''). [Aspect 9] The device according to any one of the preceding aspects, characterized in that the height h1 of the first channel (10, 10', 10'') is 2 to 1000 times, preferably 10 times, greater than the height h0 of the microchannel (30, 30', 30''). [Aspect 10] The device according to any one of the first to ninth aspects, wherein the width of the first channel (10, 10', 10'') is 1 to 100 times the height h1 of the first channel. [Aspect 11] The device according to any one of the first to tenth aspects, wherein the width of the second channel (20, 20', 20'') is 1 to 100 times the height h2b of the second channel. [Aspect 12] 12. The device according to any one of aspects 1 to 11, characterized in that hydrophilic molecules are adsorbed or combined with at least a portion of the surface of the first channel (10, 10', 10'') and / or the second channel (20, 20', 20'') and / or the microchannel (30, 30', 30'') to make the surface hydrophilic, or hydrophobic molecules are adsorbed or combined with at least a portion of the surface of the first channel (10, 10', 10'') and / or the second channel (20, 20', 20'') and / or the microchannel (30, 30', 30'') to make the surface hydrophobic.

Claims

1. An emulsion production microfluidic device (100, 100', 100''), comprising: a first channel (10, 10', 10'') comprising an inlet port (13', 13'') configured to inject the dispersed phase (2a) into said first channel, a second channel (20, 20', 20'') comprising an inlet port (23', 23'') adapted to inject a continuous phase (2c) into said second channel and an emulsion outlet port (24', 24'') adapted to extract the emulsion from said device; at least one row (30, 30', 30'') of microchannels (30, 30', 30'') arranged side-by-side, each microchannel comprising an inlet (33', 33'') from said first channel and an outlet (34', 34'') to said second channel, the height h0 of each of said microchannels being smaller than the height h1 of said first channel; Equipped with The device comprises: the second channel (20, 20', 20'') comprises a first portion (21, 21', 21'') connected to an outlet (34, 34') of each microchannel (30, 30', 30'') and at least a second portion (22, 22', 22'') along the first portion (21, 21', 21''), the first portion (21, 21', 21'') being between the row of microchannels (30, 30', 30'') and the second portion (22, 22', 22''), a height h2a of the first portion (21, 21', 21'') being greater than a height h0 of each microchannel (30, 30', 30''), and a height h2b of the second portion (22, 22', 22'') being greater than a height h2a of the first portion (21, 21', 21'').

2. The device of claim 1, wherein at least one microchannel (30, 30', 30'') comprises at least a portion having a constant width W.

3. 3. A device according to claim 2, characterized in that the width W of at least a part of the microchannel (30, 30', 30'') is between 0.01 and 10000 times the height h0 of said microchannel.

4. 4. The device according to claim 1, wherein at least one microchannel (30, 30', 30'') comprises a flared portion that widens towards the outlet (34', 34'').

5. 5. A device according to any one of claims 1 to 4, characterized in that the row of microchannels (30, 30', 30'') comprises a portion common to at least two microchannels at the location of an outlet.

6. A device according to any one of the preceding claims, characterized in that the array of microchannels (30, 30', 30'') comprises at least 10 microchannels.

7. 7. The device according to claim 1, characterized in that the height h2a of the first portion (21, 21', 21'') of the second channel (20, 20', 20'') is 2 to 100 times greater than the height h0 of the microchannel (30, 30', 30'').

8. 8. The device according to claim 1, characterized in that the height h2b of the second portion (22, 22', 22'') of the second channel (20, 20', 20'') is 2 to 100 times greater than the height h2a of the first portion (21, 21', 21'') of the second channel (20, 20', 20'').

9. The device according to any one of the preceding claims, characterized in that the height h1 of the first channel (10, 10', 10'') is 2 to 1000 times greater than the height h0 of the microchannel (30, 30', 30'').

10. A device according to any one of the preceding claims, characterized in that the width of said first channel (10, 10', 10'') is between 1 and 100 times the height h1 of said first channel.

11. A device according to any one of the preceding claims, characterized in that the width of said second channel (20, 20', 20'') is between 1 and 100 times the height h2b of said second channel.

12. 12. The device according to claim 1, characterized in that hydrophilic molecules are adsorbed or combined with at least a portion of the surface of the first channel (10, 10', 10'') and / or the second channel (20, 20', 20'') and / or the microchannel (30, 30', 30'') to make the surface hydrophilic, or hydrophobic molecules are adsorbed or combined with at least a portion of the surface of the first channel (10, 10', 10'') and / or the second channel (20, 20', 20'') and / or the microchannel (30, 30', 30'') to make the surface hydrophobic.

Images