Apparatus and method for generating droplets

Abstract

Disclosed herein is an apparatus for producing a dispersion of a first phase within a second phase, the apparatus comprising a first inlet (2) opening into a first chamber (4) for supplying the first phase, a second inlet opening into a second chamber for supplying the second phase, and a dispersion outlet (6) for collecting the dispersion. The apparatus further comprises a membrane (7) separating the first chamber (4) and the second chamber (5) and including a first surface (8) facing the first chamber (4) and a second surface (9) facing the second chamber (5). The membrane (7) comprises a plurality of channels (10) extending from the first surface (8) to the second surface (9) and providing fluid communication between the first chamber (4) and the second chamber (5). Each channel (10) has a channel inlet (11) located on the first face (8) and a channel outlet (12) located on the second face (9). The first chamber (4) is typically configured to provide substantially equal flow rates of the first phase through all of the individual channels (10).

Description

Technical Field

[0001] The present invention relates to an apparatus, a single-layer film, and a method for generating a dispersion in which a first phase is dispersed in a second phase. In particular, the apparatus is a microfluidic brush emulsifier that operates according to the principle of stepwise emulsification, also called microchannel emulsification.

Background Art

[0002] Monodisperse droplets in the size range from micrometers to millimeters are widely used in the fields of pharmaceutics, cosmetics, diagnostics, food, and materials science. In emulsions, monodispersity improves stability, enables accurate control of the amounts of multiple chemical or biological reactions, and enables the generation of periodic structures. Microfluidics provides a sophisticated platform for accurately forming monodisperse droplets. These monodisperse droplets can be further cured to produce so-called microcapsules for encapsulation of active ingredients such as drugs, fragrances, flavors, peptides, biological samples such as bacteria or phages, fertilizers, pesticides, and other health-promoting active substances.

[0003] Currently, most industrial processes for the production of microcapsules utilize spray drying, high-speed rotation with high shear force, ultrasonication, mixing, and / or shaking. Notably, such processes generally have the drawback of insufficient size control. However, accurate size control is an important factor, particularly in selective drug delivery.

[0004] Conventional microfluidic membranes according to the prior art are made from bulk materials as starting materials. As a processing step, holes are drilled by etching with a microdrill, laser, wet etching, or deep reactive ion etching. In these methods, since the channels are processed along the final flow direction, the possible size and shape of the final membrane are limited. Prior art devices have the drawback that only a very small part of the channels actively generate droplets, which significantly reduces the efficiency of emulsification. Therefore, it would be desirable to increase this efficiency, especially for large-scale industrial applications of droplet generating devices.

[0005] An emulsification device (International Publication No. WO 2014 / 186440) consisting of a two-dimensional array of parallelized droplet makers is known from the prior art. High-throughput production is limited in such two-dimensional microfluidic devices. In such devices, a maximum rate of 25 mL / h can be achieved to produce monodisperse emulsions. SUMMARY OF THE INVENTION

[0006] Previously known methods for generating monodisperse droplets have been plagued by significant limitations. Known methods allow for the generation of droplets with accurate size control, and thus reproducible quality, but are severely limited by the overall operating capacity or can be carried out with high operating capacity but have insufficient reproducibility and size control. Typically, the maximum rate of generation of a dispersion of a first phase in a second phase achieved in the prior art is 25 ml / h (Ofner et al. Macromol. Chem. Phys. 2016, 218, 1600472; Amstad et al. Rapid Production of Droplets 2013, 1 - 70.).

[0007] Accordingly, a general object of the present invention is to improve the state of the art regarding the generation of monodisperse droplets, thereby preferably at least partially avoiding the drawbacks of the prior art.

[0008] In a preferred embodiment, a process and an apparatus for carrying out the above process are provided, whereby high operating capabilities and high reproducibility can be achieved, particularly with regard to droplet size control.

[0009] In a further preferred embodiment, a process and an apparatus for carrying out the above process are provided, whereby a uniform pressure is applied to the first phase used.

[0010] In a further embodiment, a membrane is provided, whereby high operating capabilities are enabled while maintaining high reproducibility.

[0011] The overall object is achieved by the subject matter of the independent claims. Further preferred embodiments are obtained from the dependent claims, the description and the drawings.

[0012] According to a first aspect, the present invention relates to an apparatus for producing a dispersion in which a first phase is dispersed in a second phase, the apparatus comprising a first inlet for supplying the first phase, which opens into a first chamber, a second inlet for supplying the second phase, which opens into a second chamber, and a dispersion outlet for collecting the dispersion. Further, the apparatus comprises a membrane separating the first chamber and the second chamber and including a first face facing the first chamber and a second face facing the second chamber. The membrane comprises a plurality of channels extending from the first face to the second face and providing a fluid connection between the first chamber and the second chamber. Each channel comprises a channel inlet arranged on the first face and a channel outlet arranged on the second face. The first chamber may typically be configured such that the flow rate of the first phase through all of the individual channels is substantially equal. In the state of the art, particularly due to a non-uniform pressure distribution of the first phase, only a small portion of the channels are enabled to actively generate droplets. However, an equal pressure distribution across the first face enables a stable flow of the first phase into the second phase and enables the generation of droplets having a reproducible quality at a high throughput of up to 5 liters per hour.

[0013] The membrane can typically be a single-layer membrane. Thus, such a membrane is made from a uniform material and does not include a phase interface or transition region in addition to the plurality of channels of the membrane. In some embodiments, the membrane can be replaceable. In particular, the membrane can be a membrane as described in any of the aspects and embodiments disclosed herein.

[0014] In certain embodiments, the membrane can be disk-shaped. Thus, the membrane can include a circular contour. The plurality of channels of the membrane are typically microchannels. For example, the channels can have a diameter in the range of 0.25 μm to 2000 μm, preferably 2 μm to 800 μm. Typically, the channels are arranged substantially parallel to each other.

[0015] The generated dispersion is typically a stable dispersion and / or a fine particle dispersion. That is, the dispersion contains droplets of the first phase within the second phase. The first and second phases are typically fluids, particularly liquids. Further, the first and second phases can also be dispersions, particularly emulsions. The first and second phases are typically immiscible. Thus, when the first phase is a polar phase, particularly aqueous, the second phase is non-polar, particularly oily. Similarly, when the first phase is non-polar, the second phase is polar. The first phase typically contains not only the carrier liquid but also active ingredients such as drugs, peptides, antibodies, DNA, RNA, fragrances, flavors, odoriferous substances, pigments, dyes, bacteria, viruses, phages, pesticide components, non-drug classification substances, etc. In certain embodiments, the first phase can consist of the active ingredient. The term "first phase" typically refers to the phase that is dispersed within the second phase during the process according to the present invention. Thus, in some embodiments, the first phase can be referred to as the "dispersed phase". The second phase can usually be the continuous phase in which the droplets of the first phase are dispersed.

[0016] In certain embodiments, the second chamber can be made from glass, or a transparent polymer such as PTFE, polymethyl (meth)acrylate or polyoxymethylene, or from a metal such as steel, aluminum or titanium. Generally, the apparatus can comprise a container, such as a glass vessel, that partially forms the second chamber. Together with the membrane, the container can form the second chamber. In some embodiments, the first chamber can be made from a metal, such as aluminum or steel, or from a transparent polymer, such as PTFE, polymethyl (meth)acrylate or polyoxymethylene.

[0017] Typically, the dispersion outlet can be connected to a product container. The dispersion outlet can be in fluid communication with a three-way valve that is switchable between a product container and a waste container in some embodiments.

[0018] In some embodiments, the first chamber is configured such that, in the operating state, the pressure along the first side of the membrane is substantially isobaric. For example, the first inlet can comprise a nozzle for providing an isobaric distribution across the first side of the membrane. In particular, a spray nozzle can be used. Alternatively, the first chamber can be shaped such that an isobaric distribution across the first side of the membrane is provided.

[0019] In a further embodiment, the first chamber has a cross-section that is rounded with respect to the cross-section, which is perpendicular to the membrane and rotationally symmetric with respect to the central longitudinal axis. As used herein, the term "rounded cross-section" refers to a continuous curve without increase, in particular a curve having a radius of at least 1 mm, in particular at least 5 mm, in particular at least 10 mm, in a cross-section perpendicular to the membrane. It is understood that the curvature in cross-section can be described as part of a circle having the above radius. Thus, the side walls of the first chamber can converge continuously towards each other in the upstream direction. The central longitudinal axis is an axis that extends in the longitudinal direction of the device, is arranged at the center of the device, and / or is perpendicular to the membrane and intersects the center of the membrane. For example, the first chamber can have a U-shaped cross-section, or be rounded concavely, or be semi-circular. The rounded cross-section typically has no edges, and thus, excluding the edges, this causes the pressure distribution to be non-uniform when the first phase is passed through the membrane. Preferably, the first chamber can have the shape of a spherical dome. The shape of the first chamber can generally, preferably, be substantially rotationally symmetric with respect to the central longitudinal axis.

[0020] In a particular embodiment, the dispersion outlet can be arranged substantially on the central longitudinal axis, and / or the axis is perpendicular to the membrane and intersects the center of the membrane. Preferably, the second chamber tapers towards the dispersion outlet. For example, at least a part of the second chamber can be arched or conical towards the dispersion outlet. These embodiments ensure that the droplets are not trapped and all can be collected directly through the dispersion outlet.

[0021] In some embodiments, the first chamber has the shape of a hemisphere or a frustum of a cone. Typically, the hemisphere or frustum of a cone opens towards the membrane, i.e., the maximum radius is typically closest to the membrane. As used herein, the term "hemisphere" includes other spherical segments such as one-third of a sphere. Thus, in some embodiments, the shape of the first chamber is a spherical dome or a spherical cap. Preferably, when the first chamber is in the shape of a spherical dome and / or particularly hemispherical, the first inlet can be arranged adjacent to or in the region of the pole of the spherical dome of the first chamber, particularly in the region of the hemispherical first chamber. Such a shape has the advantage of helping to evenly distribute the flow of the substance of the first phase across the first surface of the membrane, thereby providing an even pressure distribution adjacent to the individual channels. The first inlet can be arranged, for example, substantially perpendicular to the central longitudinal axis, i.e., substantially parallel to the first surface of the membrane, or parallel to the central longitudinal axis, i.e., perpendicular to the first surface of the membrane.

[0022] In a further embodiment, the second surface of the membrane includes a total opening area that is larger than the total opening area of the first surface. Such a membrane has the advantage that high-quality droplets are produced even at a flow rate of up to 5 l / h. In some embodiments, the flow rate per channel can be between 1 μl / h and 50 ml / h, preferably between 10 μL / h and 5 ml / h.

[0023] In certain embodiments, each channel comprises a channel outlet having a cross-sectional area that is larger than the cross-sectional area of the remainder of each respective channel. In the longitudinal direction, i.e., the direction of flow, the channel outlet has a typical length of several micrometers, e.g., from 200 μm to 20 mm, preferably from 500 μm to 5 mm. The channel outlet can be, for example, funnel-shaped, V-shaped, or U-shaped. In some embodiments, the channel outlet can have an elliptical contour. In particular, since the channel outlet is not rotationally symmetric, it has a length / width ratio of 3 or more. Thus, the channel outlet may not have a circular or square cross-section. Such a channel outlet enables the separation of droplets without an external force. As a result, the formation of droplets of the first phase within the second phase is separated and thus substantially independent of the flow rate. According to the Young-Laplace equation, the pressure at the channel outlet is higher than that in the second reservoir for immiscible liquid interfaces. Thus, a pressure gradient is generated along the direction of flow, which causes the separation of individual droplets from the fluid thread. Thus, a pressure gradient is generated at the end of the channel, which promotes the separation of the fluid boundary layer and thus the formation of individual droplets. When reaching the channel outlet, the droplets separate without an external force due to the pressure gradient of the dispersed phase inside and outside the channel. Such nozzles have the advantage of decoupling the flow rate from the emulsification process.

[0024] In some embodiments, the first inlet is arranged at an angle of at most approximately 90° with respect to the channels of the membrane. Typically, all channels are arranged substantially parallel to each other. This has the beneficial effect that the first phase is not pressed directly onto the membrane, which further enables a uniform pressure distribution across each channel of the membrane. For example, the angle between the first inlet and the channels of the membrane can be between 60° and 90°, particularly between 75° and 90°. Preferably, the first inlet is arranged substantially laterally, preferably perpendicular to a plurality of channels of the membrane. Thus, in such embodiments, the first inlet can be parallel to the first surface of the membrane.

[0025] In a further embodiment, the device comprises a membrane holder for attaching the membrane.

[0026] In certain embodiments, the device comprises a container holder for holding the container, which partially forms the second chamber. The container holder can be fixedly and removably connected to the membrane holder. The container holder and / or the membrane holder and / or the base can be made of any suitable material, such as a plastic material like PTFE, polymethyl (meth)acrylate or polyoxymethylene, or a metal, preferably steel.

[0027] Preferably, when the container is a glass container, a damping pad can be arranged between the glass container and the container holder to avoid damage to the glass container and to seal the glass container.

[0028] In some embodiments, the membrane holder includes clamping means for attaching the membrane, and the membrane holder and / or the clamping means are configured to accommodate membranes of various thicknesses. Typically, the clamping means can be adjustable. Examples of clamping means include screws, clamps, bolts, locks, etc.

[0029] In some embodiments, the device comprises a base, and preferably, the first chamber is partially formed by the base.

[0030] In a further embodiment, the base and / or the membrane holder comprise at least one sealing portion for sealing the membrane against the base and / or the membrane holder. The sealing ring can be configured to completely surround the perimeter of the membrane in a circumferential direction. The sealing ring can also comprise a gas outlet that is in fluid communication with the first chamber and is configured to discharge any gas present in the first chamber from the first chamber.

[0031] In some embodiments, the base and / or the membrane holder comprises a spacing. Such spacing enables the use of membranes of different thicknesses.

[0032] In some embodiments, the first chamber comprises a gas outlet, in particular a fluid switch such as a valve. The gas outlet and the membrane are arranged such that gas within the first chamber is directed towards the gas outlet and removed from the first chamber via the gas outlet while the first phase is supplying the first chamber, in particular during the first / initial filling of the first chamber with the first phase. In some examples, the membrane is inclined with respect to the central longitudinal axis of the device. Thus, the angle in a cross-sectional view along the central longitudinal axis between the central longitudinal axis and the first and / or second surfaces of the membrane is different from 90°. For example, the acute angle between the second surface of the membrane and the central longitudinal axis can be between 45° and 89°, preferably between 70° and 88°, more preferably between 78° and 87°. In such embodiments, the gas outlet can be arranged at the upper end of the first chamber formed by the membrane and another chamber wall. Thereby, any residual gas, in particular air, present in the first chamber, for example before using the device, rises towards the membrane and, due to the inclined arrangement of the membrane, is ensured to be directed towards the upper end and thus towards the gas outlet. Usually, the channels of the membrane are too narrow for air to pass through, and thus all remaining gas can be removed by the gas outlet described in the above embodiments. Otherwise, it would negatively affect the uniform droplet size and distribution or prevent the first fluid from reaching all microchannels, thus reducing the throughput. Typically, the gas outlet can be in fluid communication with the environment of the device.

[0033] In some embodiments, the apparatus comprises at least one heater for heating the first phase and / or the second phase and / or at least one cooler for cooling the first phase and / or the second phase. Heating or cooling either phase can be beneficial since the curing of the generated dispersed droplets can be readily enabled by a temperature change, for example by allowing the dispersion to cool. Typically, the at least one heater can provide sufficient thermal energy to heat the first phase and / or the second phase up to a maximum of 100 °C, 125 °C, or 150 °C. The heater can comprise, for example, a heating bath such as a water bath or an oil bath. Alternatively, the heater can be an IR radiator, a heating coil, or any other suitable heater.

[0034] In a further embodiment, the apparatus comprises a first reservoir for the first phase and / or a second reservoir for the second phase, and the flow rate through the membrane is adjustable. Both the first and second reservoirs can be pressurized. For example, the reservoir can be fluidly connected to a pressure source such as a compressor. Alternatively, the reservoir can be a syringe and can be pressurized by a common syringe pump and / or a plunger or a peristaltic pump, a gear pump, or any other pump system.

[0035] The dispersion outlet can be fluidly connected, for example, to a product container and / or a waste container. Alternatively, or additionally, a post-treatment container can be disposed between the second reservoir and the product container or the waste container. In some embodiments, the second reservoir can further function as a post-treatment container.

[0036] In some embodiments, a flow restrictor is disposed between the second reservoir for the second phase and the second chamber. Such a restrictor is beneficial since the second chamber typically does not provide a large flow resistance to the second phase. Thus, by using the flow restrictor, the apparatus is more stable since an unintentional pressure difference, for example due to fluctuations in air pressure, can be avoided.

[0037] In a further embodiment, the second inlet comprises a supply channel that is at least partially circumferentially arranged about a central longitudinal axis, wherein the axis is perpendicular to the first and second faces of the membrane and intersects the center of the membrane. The supply channel comprises one or more openings to the second chamber. Being arranged at least partially circumferentially about the above-mentioned axis means that the supply channel can have a contour of a partial circle, such as a semi-circle or a third of a circle. Preferably, the supply channel is completely circumferentially arranged about the central longitudinal axis, wherein the axis is perpendicular to the membrane and intersects the center of the membrane. In such an embodiment, the supply channel forms a ring-shaped structure. Preferably, the supply channel comprises a plurality of openings to the second chamber, which are particularly distributed substantially uniformly along the circumference of the supply channel. Typically, one or more openings of the supply channel can be arranged in the direction of the dispersion outlet, i.e., such that the openings face the dispersion outlet. Embodiments comprising a supply channel have the advantage that the second phase can be introduced into the second chamber uniformly and smoothly without causing harmful turbulence that would adversely affect the uniform shape and size distribution of the generated micro-droplets. In some embodiments, one or more openings of the supply channel are arranged such that vortices are generated when the second phase is provided to the second chamber. In particular, one or more openings can be tubular, and the longitudinal axis of each tubular opening can be inclined with respect to the central longitudinal axis of the device. Typically, all tubular openings are inclined uniformly. The generation of vortices is beneficial, firstly, in that surface stabilizers that may generally be included in the first and / or second phase can be more uniformly distributed, and thus, thereby enhancing the stability of the formed dispersion, and secondly, in that the transport of the generated dispersion to the dispersion outlet is accelerated, which is particularly beneficial when the densities of the first and second phases are substantially equal.

[0038] Typically, the supply channel is arranged at the bottom of the second chamber, i.e., adjacent to the membrane. The supply channel can also be arranged, for example, circumferentially around the membrane. The supply channel can have a diameter of from 2 mm to 100 mm, preferably from 5 mm to 20 mm.

[0039] Alternatively, the second inlet can preferably constitute a single inlet that opens directly into the second chamber from the side of the second chamber.

[0040] In some embodiments, the device can include a control unit. Typically, the control unit can be a circuit, a microprocessor, or the like.

[0041] In some embodiments, the device can include a storage device configured to store data. The storage device is an interface to a microprocessor, a hard drive, or a cloud-based system. This storage device is not part of the membrane.

[0042] In some embodiments, the device can be provided with an input panel such as a keyboard, a touch screen, etc. for data input by the user. The device can also be provided with an information system such as a display, a screen, etc. for presenting data to the user.

[0043] In a further embodiment, the membrane comprises a tag, preferably a computer-readable tag. The tag can be a 2D or 1D tag, barcode, hologram, RFID tag, or chip. The device can further comprise a reading unit configured to obtain data from the tag and a control unit configured to process the data from the tag. The data can also be associated with desired quality values of the generated monodisperse droplets, such as particle size and size distribution, and threshold values of their lower and upper limits, which can be obtained via the reading unit. Further, the data can be associated with process parameters, such as the pressure applied to the first and / or second chamber, the flow rate or pressure of the first and / or second phase, the temperature of the first and / or second phase, the materials used, in particular the quality values measured by the analysis unit, the viscosity, interfacial tension, contact angle, duration of droplet generation, etc. of the first and / or second phase. The data can also be associated with parameters of the membrane itself, i.e., channel size such as channel outlet shape, diameter, aspect ratio, length, etc., and surface functionality such as membrane thickness and / or diameter, hydrophobic or hydrophilic treatment, membrane material, such as steel glass or polymer, date of use, etc.

[0044] The reading unit and the control unit are not part of the membrane. The reading unit can be, for example, an optical scanner, a camera, etc. The processing of data by the control unit may include, for example, acquiring specific data associated with process parameters such as the pressure applied to the first and / or second chamber, the flow rate of the first and / or second phase, the temperature of the first and / or second phase, etc., and adjusting these parameters, particularly automatically, when the device is operated. This makes it possible to store optimal parameters for each specific membrane or membrane type. Depending on specific membrane characteristics such as thickness, total opening area, channel outlet shape, etc., specific process parameters should ideally be optimized. Instead of optimizing each membrane individually, parameters optimized for each membrane type can be used. These optimized parameters can be stored as data directly on the specific membrane via a tag, or alternatively, they can be stored inside the device itself, i.e., in a storage device. In the latter case, the tag of the membrane is associated with a specific code associated with a specific dataset such as process data or desired quality values stored in the storage device. Then, when the user simply inserts the membrane into the device, the reading unit acquires data from the tag, transmits the data to the control unit, and the control unit can then adjust the corresponding process parameters based on the data obtained by acquiring a set of specific process parameters associated with the specific code stored in the storage device and associated with the membrane or a specific code on the membrane. The reading unit can be positioned so that it can read the tag when the membrane is inserted into the membrane holder, i.e., when it is positioned between the first chamber and the second chamber. Alternatively, the reading unit may be positioned at any suitable location in the device. The user can then scan the tag of the membrane before introducing it into the membrane holder. The reading unit can also be portable, such as a portable scanner.

[0045] In some embodiments, the device further comprises a transmitter unit configured to transmit data, in particular process data, such as the pressure applied to the first and / or second chamber, the flow rate of the first and / or second phase, the temperature of the first and / or second phase, etc., of the actually applied process parameters, to a receiver. Process data as described herein may also include logbook entries, i.e., information about the usage period, usage location, user ID, etc. The transmission can be performed by any method known to those skilled in the art, for example, via Bluetooth (registered trademark), WiFi, Ethernet, online transmission, etc. The transmission can be performed, for example, in real time, i.e., the process parameters are directly transmitted during the use of the device.

[0046] In some embodiments, the control unit may comprise a storage device, in particular an interface to a hard drive or a cloud-based system, for recording and storing actual process data in real time. The control unit may be configured to retrieve the process data stored in the storage device, for example, on demand or at regular time intervals. Optionally, the data may then be provided to the transmitter unit, which then transmits the data to the receiver. As an alternative to transmitting the data to the receiver in real time, the data may be stored in the storage device and retrieved and transmitted by the transmitter unit at regular time intervals or on demand.

[0047] In some embodiments, the receiver may be a membrane storage device included in the membrane. In such embodiments, the transmitter unit may transmit the actually utilized process parameters to the membrane storage device.

[0048] In some embodiments, the apparatus may comprise an analysis unit with a sensor, preferably an optical sensor, configured to determine and control quality values such as the size and size distribution of the generated monodisperse droplets. The optical sensor may be configured to measure and / or determine, for example, the diffraction of light, i.e., to determine the refractive index of the product being analyzed.

[0049] In a preferred embodiment, the analysis unit may comprise a detection chamber configured to enable determination of quality values of the generated dispersion. The detection chamber may preferably be configured to accommodate only a single layer of the generated monodisperse droplets or a single monodisperse droplet. For example, the detection chamber may comprise or consist of a transparent material. The detection chamber may be configured such that the generated monodisperse droplets contained therein are maintained in a steady or unsteady state during analysis. It is also possible for the detection chamber to be a microchannel having a diameter typically larger than the diameter of the generated monodisperse droplets. For example, the diameter may be less than 5000 μm, less than 2000 μm, less than 1000 μm, or less than 500 μm. In such embodiments, the generated monodisperse droplets can be analyzed by the sensor while they are within the microchannel. It is understood that the sensor is generally arranged and positioned such that it can analyze the droplets.

[0050] The analysis unit is arranged downstream of the membrane. For example, the analysis unit may be in fluid communication with a channel branching from a second chamber, or the analysis unit may be arranged downstream of the dispersion outlet. Downstream of the dispersion outlet, the apparatus may include a fluid junction, which can be controlled, in particular, by a switch in fluid communication with the analysis unit. For example, the control unit may be configured such that the switch is automatically or on-demand operated in a manner such that a limited number of the generated monodisperse droplets are directed towards and into the analysis unit, especially while the apparatus is operating. Thus, the analysis unit enables in-line quality control directly while the monodisperse droplets are being generated.

[0051] Typically, it is understood that the control unit, the transmission unit, the storage device, the reading unit, and the analysis unit are operably connected to each other.

[0052] In some embodiments, the analysis unit is operably connected to the control unit, the transmission unit, and / or the storage device. Thus, the obtained quality values, such as the particle size and size distribution of the generated monodisperse droplets, can be stored in the storage device and transmitted or directly acquired by the membrane as described above.

[0053] In some embodiments where the device comprises a transmitter unit as described above, the transmitter unit can be configured to transmit quality parameters to a receiver. The quality parameters can be transmitted in real time or on demand, each at regular time intervals.

[0054] In some embodiments, the control unit can be configured to monitor the quality parameters and detect whether the quality parameters fall below or exceed predefined upper and / or lower threshold values. The threshold values associated with the data can be obtained from the membrane, i.e., can be directly stored via tags on the membrane or the tags can include specific codes associated with specific upper and lower threshold values stored in the storage device, such as upper and lower droplet sizes. In such embodiments, an alarm can be triggered when the quality parameters fall below or exceed the predefined upper and / or lower threshold values. The alarm can be, for example, an acoustic signal, a visual signal, and / or a tactile signal. Additionally, or alternatively, the control unit can switch off the device, i.e., disable the provision of additional first and / or second phases, if the quality parameters fall below or exceed the predefined threshold values.

[0055] In a second aspect, the present invention comprises a membrane for generating a dispersion in which a first phase is dispersed in a second phase, the membrane comprising a first surface and a second surface opposite thereto, and a plurality of channels extending from the first surface to the second surface through the membrane. Each channel comprises a channel inlet disposed on the first surface, a channel outlet disposed on the second surface, and a main section disposed between the channel inlet and the channel outlet, the channel outlet including a shape deviating from the shape of the main section.

[0056] In some exemplary embodiments, the shape of the channel outlet is asymmetric. For example, with respect to a cross-section perpendicular to the direction of flow through the channel, the shape of the channel outlet may have a rectangular or elliptical cross-section.

[0057] Typically, the main section is defined as the entire section between the channel inlet and the channel outlet. The main section typically has a constant diameter over the entire length of the main section.

[0058] In some embodiments, the second surface of the membrane includes a total opening area that is larger than the total opening area of the first surface.

[0059] Preferably, the cross-sectional area of the channel outlet is larger than the cross-sectional area of the remainder of the channel.

[0060] A membrane as described in any of the embodiments of the second aspect of the present invention can generally be used in an apparatus as described herein.

[0061] The membrane can typically be a single-layer membrane. That is, the membrane is made from a single piece. Preferably, such a membrane is made from a bulk material and does not include a phase interface or transition region in addition to the plurality of channels of the membrane. Such a membrane has advantages with respect to the quality of the generated droplets because any phase interface and transition are detrimental to droplet formation and droplet stability.

[0062] In some embodiments, the membrane may be replaceable. The plurality of channels of the membrane are typically microchannels. For example, each channel may have a cross-sectional area of 0.04 μm 2 ~4000000 μm 2 , preferably 4 μm 2 ~640000 μm 2 at any position of the channel (main section and / or channel inlet) except at the cross-section at the channel outlet, while the cross-sectional area at the channel outlet may be larger.

[0063] In further embodiments, the channel outlet may be wedge-shaped. In particular, the channel outlet may include an elliptical cross-section with respect to a horizontal plane perpendicular to the extending channel, i.e., the channel outlet may be larger in a first direction than in a second direction.

[0064] Typically, each channel is defined by a channel wall. The channel wall may be curved, i.e., the channel wall may be shaped convexly or concavely towards the channel outlet. Further, each channel may include a constriction having a cross-section smaller than the cross-section of the remainder of the channel, and the constriction is disposed adjacent to the channel outlet. Thus, the constriction is disposed between the channel outlet and the remainder of the channel.

[0065] In certain embodiments, each channel outlet may have an elliptical profile. Thus, the channel outlet may have an elliptical cross-section with respect to a plane that is horizontal with respect to the extending channel and parallel to the first or second surface of the membrane. Since any edge within the channel may lead to unstable and inhomogeneous droplets, a channel outlet having an elliptical profile has a beneficial effect on the quality of the formed droplets.

[0066] In some embodiments, the membrane is disk-shaped. Such a membrane may have a circular profile. Alternatively, the membrane may have an angular, particularly triangular or rectangular profile.

[0067] In certain embodiments, the membrane comprises from 1 to 10,000,000, preferably from 20 to 500,000 channels.

[0068] In a further embodiment, the membrane has from 0.06 channels / cm 2 to 600,000 channels / cm 2 , preferably from 20 channels / cm 2 to 30,000 channels / cm 2 .

[0069] In some embodiments, the membrane is made of a polymeric material such as glass or polymethyl (meth)acrylate or PTFE, or a metallic material such as steel.

[0070] In a further embodiment, the membrane is produced by 3D printing, in particular additive manufacturing or subtractive manufacturing. The membrane can be produced by 3D laser machining of the channel structure followed by wet etching with an acid such as hydrofluoric acid or a base such as potassium hydroxide. When a steel or plastic membrane is used, the membrane can be produced by micromachining using methods such as drilling, milling, turning or laser melting, erosion.

[0071] In some embodiments, particularly in the main section, the cross-sectional area of the remainder of each channel is from 0.125 μm 2 to 4 mm 2 , preferably from 10 μm 2 to 0.5 mm 2 .

[0072] In a further embodiment, the cross-sectional area of each channel outlet is from 0.12 μm 2 to 36,000,000 μm 2 , preferably from 12 μm 2 to 5,760,000 μm 2 . In particular, the total opening area of the second face of the membrane can be from 300% to 1500%, preferably from 400% to 900%, and is greater than the total opening area of the channels at any other given location such as the main section and / or the channel inlet.

[0073] In a further embodiment, the aspect ratio of each channel, defined as channel length / minimum diameter, is from 5 to 1000, particularly from 10 to 500, more specifically from 10 to 50.

[0074] In certain embodiments, each channel of the membrane has a cross-section that is rounded with respect to the horizontal plane. That is, each channel has substantially no edges, at least within the channel and / or the channel outlet. Such channels are beneficial because edges can negatively affect the pressure distribution, flow characteristics, and reproducibility of the generated dispersed droplets. The horizontal plane is in the same plane as the membrane and the first and second surfaces of the membrane. Typically, both the channel outlet and the remainder of the channel can have a rounded cross-section.

[0075] In a further embodiment, the membrane has a thickness between 0.05 mm and 20 mm, particularly between 0.1 mm and 20 mm, particularly between 0.1 mm and 5 mm, particularly between 0.5 and 20 mm. Typically, the thickness of the membrane is equal to the total length of each channel. The total length of each channel is the sum of the length of each channel outlet and the length of the remainder of the channel.

[0076] In some embodiments, the membrane comprises at least one solid support structure without channels that divides the membrane into two or more channel-containing portions. The solid support structure enhances the stability of the membrane. Such a solid support structure can be integral with the membrane or can constitute an additional element disposed on the first and / or second surface of the membrane. If there are several solid support structures, they can extend parallel to the first and / or second face of the membrane, i.e., horizontally with respect to the extending channels. The solid support structure can be a straight beam. Typically, the support structure has no channels. Usually, only a very small fraction of the total surface area of the first and / or second face of the membrane is part of the support structure. The total surface area of at least one support structure (or all combined support structures) compared to the total surface area of the channel-containing portions can be less than 1:10, preferably less than 1:15, and particularly less than 1:20. The support structures can be arranged such that each part of the channel-containing portion has a triangular shape, preferably at least 6, particularly at least 10. Since the relatively large total opening area of the channels can cause the membrane to be relatively fragile, the solid support structure reinforces the membrane, facilitates handling of the membrane, and avoids breakage. In a further embodiment, the membrane comprises a tag, preferably a computer-readable tag. The tag can be a 2D or 1D tag, barcode, hologram, RFID tag, or chip. The tag can be computer-readable. Preferably, the tag contains data that can be associated with desired quality values of the generated monodisperse droplets, such as particle size and size distribution, and threshold values of their lower and upper limits, which can be obtained via a reading unit. Further, the data can be associated with process parameters, such as the pressure applied to the first and / or second chamber, the flow rate of the first and / or second phase, the temperature of the first and / or second phase, the materials used, etc. The data can also be associated with parameters of the membrane itself, i.e., channel size such as channel outlet shape, diameter, aspect ratio, length, etc., and the thickness of the membrane.Data can be stored directly within the tag, or the tag can be associated with specific codes for specific data stored in a device, particularly a device as described in combination with the use of a membrane in any of the aspects and embodiments of this specification.

[0077] In some embodiments, the membrane can comprise a membrane storage device configured to receive and store data transmitted by a transmitter device. The membrane storage device can be an electronic circuit, a microprocessor, etc. Thus, the membrane can store the actual process parameters utilized from the device, particularly the transmitter device. Thus, the membrane can be returned to the manufacturer, who can obtain and analyze the process parameters.

[0078] In certain embodiments, the membrane can comprise a membrane seal ring that completely circumferentially surrounds the perimeter of the membrane. Such a membrane seal ring can have a C-shaped cross-section that not only enables complete circumferential surrounding of the perimeter of the membrane but also enables complete surrounding of small portions of the first and second faces of the membrane. The membrane seal ring can preferably be made from a suitable polymeric material such as rubber, silicone, etc.

[0079] According to another aspect, the present invention includes a method for generating a dispersion in which a first phase is dispersed within a second phase using a device according to any of the embodiments described herein. The method includes providing a device as described in any of the embodiments disclosed herein, supplying the first phase through a first inlet to a first chamber, and supplying the second phase through a second inlet to a second chamber, where the first phase flows from the first chamber through a plurality of channels of the membrane into the second chamber to form a dispersion in which the first phase is dispersed within the second phase.

[0080] Typically, pressure can be applied to the first phase within the first chamber. For example, the pressure can be applied via a pressurized first reservoir of the device and / or via an external gas pressure supply line. Optionally, pressure may be applied to the second phase within the second chamber.

[0081] In some embodiments, the dispersion generated within the second chamber is collected via a dispersion outlet. Preferably, the dispersion is collected continuously during the generation of the dispersion within the second chamber.

[0082] In some embodiments, the first and / or second phase may include a surface stabilizer to stabilize a dispersion generated by the dispersion of the first phase within the second phase. Preferably, the surface stabilizer is included only in the second phase. For example, the surface stabilizer can be a surfactant such as an anionic, cationic, or amphoteric surfactant. The surface stabilizer can also be a soap or a suitable protein. Additionally, or alternatively, the surface stabilizer can be solid particles, preferably hydrophobic, hydrophilic, or Janus-type particles, configured to provide a Pickering emulsion, depending on the application. For example, the solid particles can be colloidal silica. In some embodiments, the amount of the surface stabilizer in the first and / or second phase exceeds the critical micelle concentration, particularly between 0.001 wt% and 5 wt%, particularly between 0.01 wt% and 5 wt%, particularly between 0.1 wt% and 5 wt%.

[0083] In some embodiments, the pressure along the first surface of the membrane is substantially isobaric. Thus, the pressure in each of the plurality of channels can be substantially uniform.

[0084] In a further embodiment, the mass flow rate of the first phase through the individual channels is substantially equal across the entire membrane. Thus, the throughput through each of the individual channels is substantially equal.

[0085] In some embodiments, an overpressure of up to 10 bar is applied to the first phase in the first chamber. Preferably, the absolute pressure applied to the first phase can be up to 11 bar.

[0086] In a further embodiment, the pressure of the second phase in the second chamber is from 0.01 bar to 10 bar, preferably from 0.01 bar to 1 bar.

[0087] In some embodiments, the pressure of the second phase is reduced by a flow restrictor before the second phase is supplied to the second chamber.

[0088] In some embodiments, the reading unit acquires data from the tags on the membrane, and the acquired data is provided to a control unit that processes the data. Typically, the reading can be performed before the first and / or second phases are provided. The data can be associated with desired quality values of the generated monodisperse droplets, such as particle size and size distribution, and threshold values of their lower and upper limits, and can be acquired via the reading unit. Further, the data can be associated with process parameters such as the pressure applied to the first and / or second chambers, the flow rates of the first and / or second phases, the temperature of the first and / or second phases, the materials used, etc. The data can also be associated with parameters of the membrane itself, i.e., channel size such as channel outlet shape, diameter, aspect ratio, length, etc., and the thickness of the membrane. The processing of the data by the control unit can include, for example, acquiring specific data associated with process parameters such as the pressure applied to the first and / or second chambers, the flow rates of the first and / or second phases, the temperature of the first and / or second phases, etc., and, when the device is operated, particularly automatically, adjusting these parameters. Depending on specific membrane characteristics such as thickness, total opening area, channel outlet shape, etc., specific process parameters should ideally be optimized. Instead of optimizing each membrane individually, parameters optimized for each membrane type can be used. These optimized parameters can be stored as data directly on the specific membrane via the tags, or alternatively, can be stored inside the device itself, i.e., in a storage device. In the latter case, the tags of the membrane are associated with a specific code associated with a specific data set stored in the storage device, such as process data or desired quality values. Then, when the user simply inserts the membrane into the device, the reading unit acquires data from the tags, transmits the data to the control unit, and the control unit can then adjust the corresponding process parameters based on the data acquired by obtaining a set of specific process parameters associated with the specific code on the membrane and stored in the storage device, either directly from the membrane or via the specific code on the membrane.

[0089] In some embodiments, data is transmitted by a transmitting unit to a receiver. The data can be actual process parameters being applied, such as the pressure applied to the first and / or second chamber, the flow rate of the first and / or second phase, the temperature of the first and / or second phase, etc., which are actual process data. Process data as described herein can also include logbook entries, i.e., information about the usage period, usage location, user ID, etc. The transmission can be performed by any method known to those skilled in the art, for example, via Bluetooth®, WiFi, Ethernet, online transmission, etc. The transmission can be performed, for example, in real time, i.e., the process parameters are transmitted directly during the use of the device, i.e., while the first and / or second phase is being supplied.

[0090] Alternatively, the actual process data can be recorded and stored in a storage device. The control unit can obtain the stored process data, for example, on demand or at regular time intervals. Optionally, the data can then be provided to a transmitter unit, which then transmits the data to a receiver. As an alternative to transmitting the data to the receiver in real time, the data can be stored in a storage device and retrieved and transmitted by a transmitter unit at regular time intervals or on demand.

[0091] In some embodiments, the receiver can be a membrane storage device provided in a membrane. In such embodiments, the transmitter unit can transmit the actually utilized process parameters to the membrane storage device.

[0092] In some embodiments, the generated dispersion contains monodisperse droplets, and at least one of the generated monodisperse droplets is analyzed in an analysis unit equipped with a sensor. The analysis can be performed in-line, i.e., during the supply of the first and / or second phase, as well as after the supply of the first and / or second phase has been stopped. Furthermore, the analysis can include determining and controlling quality values such as the size and size distribution of the generated monodisperse droplets. The optical sensor can be configured to measure and / or determine, for example, the diffraction of light, i.e., to determine the refractive index of the product being analyzed.

[0093] In a preferred embodiment, the analysis unit can comprise a detection chamber configured to enable determination of quality values of the generated dispersion. The detection chamber can preferably accommodate only a single layer of the generated monodisperse droplets, or a single monodisperse droplet. For example, the detection chamber can contain or consist of a transparent material. The detection chamber can accommodate the generated monodisperse droplets in a steady or unsteady state during analysis. It is also possible for the detection chamber to be a microchannel having a diameter typically larger than the diameter of the generated monodisperse droplets. For example, the diameter can be less than 5000 μm, less than 2000 μm, less than 1000 μm, or less than 500 μm. In such embodiments, the generated monodisperse droplets can be analyzed by the sensor while they are within the microchannel. It is understood that the sensor is generally arranged and positioned so as to be able to analyze the droplets.

[0094] In some embodiments, the analysis unit is operably connected to a control unit and / or a storage device. Thus, the obtained quality values such as the particle size and size distribution of the generated monodisperse droplets can be stored in the storage device or directly obtained by the film as described above.

[0095] In a further embodiment, the transmitter unit can transmit quality parameters to the receiver. The quality parameters can be transmitted in real-time or on-demand, respectively, at regular time intervals.

[0096] In some embodiments, the quality parameters are monitored by the control unit. If it is detected that the quality parameters fall below and / or exceed a predefined upper threshold value and / or lower threshold value, an alarm may be triggered and / or the supply of the first and / or second phases may be stopped immediately. The alarm may be, for example, an acoustic signal, a visual signal, and / or a tactile signal.

[0097] The generated dispersion of the first phase in the second phase can be further processed to produce capsules and particles such as microcapsules, microparticles, nanocapsules, nanoparticles, etc. Typical methods include thermosetting by heating or cooling, chemical, ultraviolet or thermally induced polymerization, solvent extraction, chemical reaction, interfacial reaction, gelation, crosslinking, irradiation, complex coacervation, and other methods known to those skilled in the art. The microcapsules or microparticles can have an average diameter of 1 μm to 1000 μm, and the nanoparticles or nanocapsules can have an average diameter of 1 nm to less than 1 μm. However, it is also possible to produce particles and capsules with an average diameter exceeding 1000 μm and up to a maximum of 5 mm, or a maximum of 3 mm.

[0098] According to a further aspect, the present invention relates to a system for generating a dispersion having a plurality of core droplets, comprising at least two devices connected in series, each according to any of the embodiments described herein. Thus, a first dispersion having a first set of dispersed droplets is formed in a first device, which is then provided to a first chamber of a second device located downstream of the first device. The first set of dispersed droplets flows through the channels of the membrane of the second device and thus forms a plurality of core droplets in the second phase. As will be understood by those skilled in the art, a multi-core droplet is a droplet comprising an internal core and an additional layer surrounding the internal core. Each of the internal core and the single layer can be made of a different material. However, it is also possible for them to be made of the same material if at least part of the layer and / or the internal core is separated by at least one different material. Additionally or alternatively, a plurality of emulsions can be formed by adding an emulsion to a device according to any of the embodiments described herein, particularly to the first and / or second phase, by methods known to those skilled in the art, such as shaking, sonication, high shear emulsification, spray drying, etc.

[0099] According to another aspect, the present invention relates to an apparatus for generating a dispersion in which a first phase is dispersed in a second phase, the apparatus comprising: a first inlet for supplying a first phase, opening into a first chamber; a second inlet for supplying a second phase, opening into a second chamber; a dispersion outlet for collecting a dispersion in which the first phase is dispersed in the second phase; and a membrane holder for holding a membrane capable of separating the first chamber and the second chamber, wherein the first chamber has a cross-section that is rounded with respect to the cross-section, and is rotationally symmetric with respect to a central longitudinal axis that intersects the center of the first chamber and the center of the second chamber. This aspect of the present invention can also be combined with one or more of the embodiments described herein, particularly one or more of the embodiments described with respect to the first aspect of the present invention. The apparatus also comprises, in some embodiments, a membrane as described in any of the aspects and embodiments described herein, arranged to separate the first chamber and the second chamber and including a first surface facing the first chamber and a second surface facing the second chamber. The membrane can further be held by the membrane holder.

Brief Description of the Drawings

[0100] The invention described herein will be more fully understood from the detailed description given hereinbelow and from the accompanying drawings, which should not be considered as limiting the invention described in the appended claims. The drawings are as follows.

[0101]

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

Figure 10

DETAILED DESCRIPTION OF THE INVENTION

[0102] FIG. 1 shows an apparatus 1 for generating a dispersion in which a first phase is dispersed in a second phase. The apparatus 1 includes a container 19 made of glass and a base 14 made of metal. The base 14 includes a first inlet (not shown, see FIG. 2) for supplying the first phase, which opens into a first chamber. The first chamber is partially formed by the base 14 and a membrane 7 (see FIG. 2). The container 19 includes a second inlet 3 for supplying the second phase, which opens into a second chamber, and a dispersion outlet 6 for collecting the dispersion generated in the second chamber. The second chamber is formed by the container 19 and the membrane 7 (see FIG. 2). The apparatus 1 further includes a membrane holding structure 20 fixedly connected to the base 14. Further, the apparatus includes a container holding structure 21 fixedly connected to the membrane holding structure 20 via clamping means 18. As a result, the container 19 is fixedly connected to the base 14.

[0103] Figure 2 shows a cross-sectional view of apparatus 1. Apparatus 1 comprises a base 14 having a first inlet 2 for supplying a first phase. Inlet 2 opens into a first chamber 4 that is partially formed by base 14. Apparatus 1 further includes a container 19 having a second inlet 3 for supplying a second phase and a dispersion outlet 6 for collecting a dispersion in which the first phase is dispersed in the second phase. Second inlet 3 opens into a second chamber 5 that is partially formed by container 19. The first chamber and the second chamber are separated by a membrane 7. As can be readily seen from FIG. 2, the first chamber has a cross-section that is rounded with respect to a corresponding cross-section along a central longitudinal axis 15 and perpendicular to membrane 7. In the particular embodiment shown, first chamber 4 has a semi-circular cross-section and thus may have the shape of a hemisphere. First inlet 2 is located in the region of the pole 13 of the hemisphere. Second chamber 5 extends along the longitudinal direction of the apparatus, intersects the centers of the first and second chambers, is perpendicular to membrane 7, and tapers towards dispersion outlet 6 that is located on longitudinal axis 15 which intersects the center of the membrane. As can be seen, longitudinal axis 15 constitutes the central axis of the longitudinal apparatus. In the embodiment shown, the second chamber is arched towards dispersion outlet 6. Thus, second chamber 6 has a U-shaped cross-section. First inlet 2 is arranged at an angle of approximately 90° with respect to central axis 15 and generally the membrane channels that are parallel to central axis 15. Apparatus 1 comprises a membrane holder 20 and a container holder 21, which are fixedly connected to each other via releasable clamping means 18. Membrane 7 is attached to membrane holder 20 by clamping the membrane between membrane holder 7 and base 14. Membrane holder 20 is fixedly connected to base 14 via clamping means 18. In certain cases, a pad 23, which is a foam pad, can be arranged between container 19 and container holder 21 to securely fix glass container 19 between membrane holder 20 and container holder 21. Membrane holder 20 comprises a groove 22 for receiving container 19.

[0104] Figure 3 shows an exploded view of the partially cut-away apparatus 1. As can be seen, the first chamber is partially formed by the base 14 and has a hemispherical shape. The first inlet 2, which is arranged at an angle of approximately 90° with respect to the central axis 15, is located at the pole of the hemisphere. The base 14 comprises a spacing 16 that allows the use of different membranes of different thicknesses, and the membrane holder 20 comprises a sealing ring 17. The membrane 7 is arranged between the ring 16 and the ring 17. The design of the apparatus 1 with adjustable clamping means 18 allows the use of membranes of different thicknesses. The membrane holder 20 further comprises a circumferential groove 22 for receiving the lower end portion of the container 19. The clamping means 18 fixedly and releasably connect the membrane holder 20 to the container holder 21.

[0105] Figure 4 shows a schematic diagram of the apparatus 1 according to a preferred embodiment of the present invention. A second chamber 5 is formed by a container 19 and a membrane 7 that separates the first chamber 4 from the second chamber 5. The container 19 is provided with a dispersion outlet 6 that is in fluid connection with a product container 29 and a waste container 30. Generally, the fluid flow can be controlled by a valve such as a three-way valve. The apparatus 1 further comprises a first reservoir 24 that is in fluid communication with the first chamber 4 for providing a first phase to the first chamber 4 via a first inlet 2. A flow meter for measuring the fluid flow of the first phase is arranged between the first reservoir 24 and the first inlet 2. The first reservoir 24 is in fluid connection with a pressure source 32. Further, a pressure regulator 27a is arranged between the first reservoir 24 and the pressure source 32. In addition to the first reservoir 24, the apparatus 1 comprises a rinsing reservoir 31 that is in fluid communication with both the first chamber 4 and the pressure source 32. The rinsing reservoir 31 is configured to provide a rinsing solution to the first chamber 4 for cleaning the apparatus 1 after its intended use. Generally, when the rinsing solution is provided to the first chamber 4, the three-way valve arranged between the product and waste containers 29 and 30 and the dispersion outlet 6 is configured such that the rinsing solution can flow into the waste container 30. The apparatus 1 further comprises a heater 33 that is configured to heat the first and second chambers during the generation of the dispersed phase. Further, the second chamber 5 is in fluid communication with a second reservoir 25 for supplying a second phase to the second chamber 5. A flow restrictor 26 and a flow meter 28 are arranged between the second chamber 5 and the second reservoir 25. In the embodiment shown, the flow restrictor 26 is arranged behind the flow meter 28 in the direction of the flow. The second reservoir 25 is further in fluid connection with the pressure source 32. In addition, a second pressure regulator 27b is arranged between the second reservoir 25 and the pressure regulator 27a. In a typical experiment, the first reservoir was pressurized with an overpressure of 0.08 bar and the second reservoir was pressurized with an overpressure of 0.4 bar. A 1 L product container can be filled with the generated dispersion of the first phase in the second phase in less than 12 minutes.The device 1 further comprises a reading unit 39 configured to acquire data from the tag of the membrane 7, and a control unit 40 configured to process the data from the tag. Generally, the reading unit can be arranged at any suitable position. For example, the user can scan the tag of the membrane before placing the membrane between the first chamber and the second chamber. Alternatively, the reading unit and the tag may generally be arranged such that the tag can be directly read when the membrane is positioned between the first chamber 4 and the second chamber 5. The device 1 further comprises a transmitter unit 41 configured to transmit data to a receiver. Generally, the transmitter unit 41, the control unit 40, and the reading unit 39 can be functionally connected. The device 1 also includes an analysis unit 42 equipped with sensors for determining and controlling quality values, in particular the size and size distribution of the generated monodisperse droplets. The analysis unit 42 is positioned downstream of the membrane 7, and in this case, downstream of the dispersion liquid outlet 6.

[0106] FIG. 5 shows a single-layer membrane 7 for generating a dispersion in which a first phase is dispersed in a second phase, which can be used in an apparatus as described in any of the embodiments disclosed herein. The membrane 7 has a first surface 8 (not shown) and, in the operating state, a second surface 9 facing the second chamber. A plurality of microchannels 10 extend through the membrane 7. Each channel 10 has an elliptical contour. The membrane 7 further has a computer-readable tag 43 attached to the second surface 9. In addition, the membrane 7 comprises a membrane seal ring 44 that completely circumferentially surrounds the periphery of the membrane. The membrane 7 can further comprise a membrane storage device 45 configured to receive and store data transmitted by a transmitter device in some cases.

[0107] Figure 6 shows a single-layer film 7 having a thickness T of Figure 5 in a cross-sectional view along A-A. The film includes a first surface 8 and a second surface 9. A plurality of channels 10 (drawn with exaggerated dimensions) each extend from the first surface 8 of the film to the second surface 9 of the film. Each channel includes a channel inlet 11 disposed on the first surface 8 and a channel outlet 12 disposed on the second surface 9. A main section M is disposed between each channel inlet and the channel outlet. As can be easily seen, the second surface 9 includes a total opening area that is larger than the total opening area of the first surface 8. Further, the shape of each channel outlet 12 is different from the shape of the remaining portion of the channel, i.e., the main section M and the channel inlet 11. The cross-sectional area of each channel outlet 12 is larger than the cross-sectional area of the remaining portion of the corresponding channel 10. In the illustrated embodiment, the channel outlet 12 is wedge-shaped.

[0108] Figure 7 shows a schematic partial cross-sectional view of the selection of channels with channel outlets of various shapes. For example, Figure 7a) shows a wedge-shaped channel outlet. Figure 7b) shows an angled channel outlet. Figures 7c) and 7d) show channel outlets in which the channel walls are curved convexly (Figure 7c) or concavely (Figure 7d). Figures 7e) to 7g) show channels with constrictions disposed adjacent to the channel outlets and disposed between each channel outlet and the remaining portion of the channel. As can be seen, all of the different channels shown have channel outlets with a cross-sectional area larger than the cross-sectional area of the remaining portion of the channel.

[0109] Figure 8 shows a partial cross-sectional view of an apparatus according to another embodiment of the present invention. The apparatus 1 has a first inlet 2 for supplying a first phase, which opens into a first chamber 4 having a rounded cross-section. In the illustrated embodiment, the first chamber 4 has the shape of a spherical dome, the radius at the base of the dome being smaller than the radius of a virtual global sphere with corresponding dimensions. The second chamber 5 is at least partially defined by a container 19. The apparatus further comprises a dispersion outlet 6 for collecting a dispersion in which the first phase is dispersed in a second phase. The corresponding membranes for good visualization are not shown. The second inlet opening towards the second chamber 5 comprises, in the illustrated embodiment, a supply channel 34 arranged circumferentially around a central longitudinal axis 15, and / or the axis is perpendicular to the first and second faces of the membrane and intersects the centre of the membrane. The supply channel 34 comprises a plurality of openings 35 into the second chamber 5. The openings 35 are uniformly distributed along the circumference of the supply channel and are arranged in the direction of the dispersion outlet 7. In the illustrated embodiment, the supply channel 34 forms an annular structure arranged at the bottom of the second chamber 5, i.e. at the edge of the membrane and the container 19. In the illustrated embodiment, the supply channel has an angular cross-section. Alternatively, the supply channel may have a rounded, in particular circular, cross-section.

[0110] Figure 9 shows a cross-sectional view of another embodiment of the device according to the present invention. The device 1 has a first inlet 2 for supplying a first phase, which opens into a first chamber 4 having a rounded cross-section. In the embodiment shown, the first chamber 4 has the shape of a spherical dome. The membrane 7 separates the first chamber 4 from the second chamber 5. In contrast to the embodiment shown in Figure 2, the membrane is inclined with respect to the central longitudinal axis 15 of the device 1. The acute angle β in a cross-sectional view along the central longitudinal axis between the central longitudinal axis and the second surface of the membrane is between 45° and 89°, preferably between 70° and 88°, more preferably between 78° and 87°. The device 1 additionally comprises a gas outlet 36. The gas outlet and the membrane are arranged such that the gas in the first chamber is directed towards the gas outlet and removed from the first chamber 4 via the gas outlet 36, especially during the first filling while the first phase is being supplied to the first chamber. As can be seen, the gas outlet 36 is arranged at the upper end of the first chamber 4 formed by the membrane 7 and the chamber wall which is part of the base 14. Before the first chamber 4 is first filled with the first phase, gas, especially air, is present in the first chamber. When the first chamber 4 is filled with the first phase, the air is pushed out through the gas outlet 36. The arrangement of the membrane 7 and the gas outlet 36 enables substantially all of the gas to be removed from the first chamber 4. The remaining gas, especially air bubbles, has an adverse effect on the pressure distribution, so that the size and particle distribution become more uniform.

[0111] Figure 10 shows a membrane 7 according to another embodiment of the present invention. The membrane 7 comprises several intersecting solid support structures 37 without channels, which divide the membrane into several triangular channel-containing parts 38. Such solid support structures can be integral with the membrane 7 or can comprise additional elements arranged on the first and / or second surface of the membrane.

Explanation of reference numerals

[0112] 1. Device 2. First inlet 3. Second injection port 4. First chamber 5. Second chamber 6. Dispersion outlet 7. Membrane 8. First surface 9. Second surface 10. Channel 11. Channel inlet 12. Channel outlet 13. Electrode 14. Base 15. Central axis 16. Spacer ring 17. Seal ring 18. Clamping means 19. Container 20. Membrane holder 21. Container holder 22. Groove 23. Pad 24. First reservoir 25. Second reservoir 26. Flow restrictor 27a, b. Pressure regulator 28. Flow meter 29. Product container 31. Rinse reservoir 30. Waste container 32. Pressure source 33. Heater or cooler 34. Supply channel 35. Opening 36. Gas outlet 37. Solid support structure 38. Section 39. Reading unit 40. Control unit 41. Transmitter unit 42. Analysis unit 43. Tag 44. Membrane seal ring 45. Membrane storage device M. Main section

Claims

1. A single-layer film (7) for generating a dispersion in which a first phase is dispersed in a second phase, the single-layer film (7) having a first surface (8) and a second surface (9) opposite to the first surface (8), and a plurality of channels (10) extending from the first surface to the second surface through the single-layer film, each channel having a channel inlet (11) disposed on the first surface (8), a channel outlet (12) disposed on the second surface (9), and a main section (M) disposed between the channel inlet (11) and the channel outlet (12), the channel outlet including a shape deviating from the shape of the main section, The single-layer film (7) in which each channel (10) of the single-layer film (7) has a rounded cross-section when cut perpendicular to the length direction of the channel and has no edges at least within the channel and the channel outlet.

2. The single-layer film (7) according to claim 1, wherein the cross-sectional area of the channel outlet (12) is larger than the cross-sectional area of the remaining portion of the channel.

3. The cross-sectional area of the remaining portion of each channel is 0.125 μm 2 to 4 mm 2 The single-layer film (7) according to claim 1 or 2, wherein the single-layer film (7) is in the range of

4. The single-layer film (7) according to any one of claims 1 to 3, wherein the single-layer film (7) has a thickness of 0.05 mm to 20 mm.

5. The single-layer film (7) according to any one of claims 1 to 4, wherein the single-layer film (7) includes at least one solid support structure without channels that divides the single-layer film (7) into two or more channel-containing portions (38).

6. The single-layer film (7) according to any one of claims 1 to 5, wherein the single-layer film (7) includes a tag (43).

7. The single-layer film (7) according to any one of claims 1 to 6, wherein the single-layer film (7) includes a membrane seal ring (44) that completely surrounds the periphery of the single-layer film in the circumferential direction.

8. An apparatus (1) for generating a dispersion in which a first phase is dispersed in a second phase, the apparatus (1) comprising: a. A first inlet (2) for supplying a first phase, which opens into a first chamber (4); b. A second inlet (3) for supplying a second phase, which opens into a second chamber (5); c. A dispersion outlet (6) for collecting a dispersion in which the first phase is dispersed in the second phase. d. The single-layer film (7) according to any one of claims 1 to 7, which separates the first chamber (4) and the second chamber (5), and includes a first surface (8) facing the first chamber (4) and a second surface (9) facing the second chamber (5). e. The apparatus (1) comprising the single-layer film (7), wherein the single-layer film (7) comprises a plurality of channels (10) extending from the first surface (8) to the second surface (9) of the single-layer film (7) that provides a fluid connection between the first chamber (4) and the second chamber (5), and each channel (10) comprises a channel inlet (11) disposed on the first surface (8) and a channel outlet (12) disposed on the second surface (9).

9. The apparatus (1) according to claim 8, wherein the first chamber (4) is configured such that the pressure along the first surface (8) of the single-layer film (7) is isobaric.

10. The apparatus (1) according to claim 8 or 9, wherein the first chamber (4) has a rounded cross-section.

11. The apparatus (1) according to claim 10, wherein the first chamber (4) is hemispherical.

12. The apparatus (1) according to any one of claims 8 to 11, wherein the second surface (9) of the single-layer film (7) has a total opening area formed by channels (10) that is larger than the total opening area of the first surface (8).

13. The apparatus (1) according to any one of claims 8 to 12, wherein each channel (10) comprises an end region at the channel outlet (12) that has a cross-sectional area larger than the cross-sectional area of the remaining portion of each respective channel (10).

14. The apparatus (1) according to any one of claims 8 to 13, wherein the first inlet (2) is disposed at an angle of 90° or less with respect to the channels (10) of the single-layer film (7).

15. The apparatus (1) according to any one of claims 8 to 14, comprising a membrane holder (20) for attaching the single-layer film (7).

16. The apparatus (1) according to claim 15, wherein the membrane holder (20) comprises clamping means (18) for attaching the single-layer film (7), and the membrane holder (20) and / or the clamping means (18) are configured to accommodate single-layer films (7) having different thicknesses.

17. The device according to any one of claims 8 to 16, wherein the device comprises a base (14), and the first chamber (4) is partially formed by the base (14).

18. The device (1) according to any one of claims 15 to 17, wherein the base (14) and / or the membrane holder comprises at least one sealing portion (17) for sealing the single-layer membrane (7) against the base (14) and / or against the membrane holder (20).

19. The device (1) according to any one of claims 8 to 18, wherein the first chamber (4) comprises a gas outlet (36), and the gas outlet (36) and the single-layer membrane (7) are arranged such that gas in the first chamber is directed towards the gas outlet (36) while the first phase is supplied to the first chamber (4), and is removed from the first chamber (4) through the gas outlet (36).

20. The device (1) according to any one of claims 8 to 19, wherein the device comprises a heater and / or a cooler (33) for heating and / or cooling the first phase and / or the second phase.

21. The device (1) according to any one of claims 8 to 20, wherein the device (1) comprises a first reservoir (24) for the first phase and / or a second reservoir (25) for the second phase such that the flow rate through the single-layer membrane (7) is adjustable.

22. The device (1) according to claim 21, wherein a flow restrictor (26) is arranged between the second reservoir (25) and the second chamber (5).

23. The device (1) according to any one of claims 8 to 22, wherein the second inlet (3) comprises a supply channel (34) arranged at least partially circumferentially about a central longitudinal axis, and / or the axis is perpendicular to the first and second surfaces of the single-layer membrane and intersects the center of the single-layer membrane, and the supply channel comprises one or more openings to the second chamber.

24. The device (1) according to any one of claims 8 to 23, wherein the single-layer membrane (7) comprises a tag (43), and the device (1) further comprises a reading unit (39) configured to acquire data from the tag (43) and a control unit (40) configured to process the data from the tag (43).

25. The apparatus (1) according to any one of claims 8 to 24, further comprising a transmitter unit (41) configured to transmit data to a receiver.

26. The apparatus (1) according to any one of claims 8 to 25, further comprising an analysis unit (42) provided with a sensor for determining and controlling quality values.

27. A method of generating an emulsion in which a first phase is dispersed in a second phase, using the apparatus according to any one of claims 8 to 26, comprising: The first phase is supplied to a first chamber through a first inlet, The second phase is supplied to a second chamber through a second inlet, The first phase flows from the first chamber into the second chamber through a plurality of channels of a single-layer membrane, forming an emulsion in which the first phase is dispersed in the second phase.

28. The method according to claim 27, wherein the pressure along the first surface of the single-layer membrane is isobaric.

29. The method according to claim 27 or 28, wherein the mass flow rate through each channel is equal across the entire single-layer membrane.

30. The method according to any one of claims 27 to 29, wherein an overpressure of up to 10 bar is applied to the first phase in the first chamber.

31. The method according to any one of claims 27 to 30, wherein the pressure of the second phase in the second chamber is from 0.01 bar to 10 bar.

32. The method according to any one of claims 27 to 31, wherein the pressure of the second phase is reduced by a flow restrictor before supplying the second phase to the second chamber.

33. The method according to any one of claims 27 to 32, wherein a reading unit acquires data from tags on the single-layer membrane, and the acquired data is provided to a control unit that processes the data.

34. The method according to any one of claims 27 to 33, wherein the data is transmitted by a transmitting unit to a receiver.

35. The method according to any one of claims 27 to 34, wherein the generated emulsion contains monodisperse droplets, and at least one of the generated monodisperse droplets is analyzed by an analysis unit provided with a sensor.

36. The method according to any one of claims 27 to 35, wherein the emulsion generated by dispersing the first phase in the second phase is further processed to generate capsules and particles.

37. A system for generating a dispersion having a plurality of core droplets, comprising at least two devices according to any one of claims 8 to 26 connected in series. **Claim 38**: The method according to claim 36, wherein the capsules and the particles are any one of microcapsules, microparticles, nanocapsules, and nanoparticles.

Images