Device and method for generating droplets

Abstract

Disclosed herein is a device (1) for producing a dispersion of a first phase in a second phase, the device comprising: a first inlet (2) for supplying the first phase, which opens into a first chamber (4); a second inlet for supplying the second phase, which opens into the second chamber; and a dispersion outlet (6) for collecting the dispersion. In addition, the device comprises a membrane (7), which separates the first chamber (4) and the second chamber (5) and comprises a first side (8) facing the first chamber (4) and a second side (9) facing the second chamber (5). The membrane (7) comprises a plurality of channels (10) extending from the first side (8) to the second side (9), which provide a fluid connection between the first chamber (4) and the second chamber (5). Each channel (10) comprises a channel inlet (11) arranged on the first side (8) and a channel outlet (82) arranged on the second side (9). The first chamber (4) is generally configured so that the flow rate of the first phase through all individual channels (10) is substantially equal.

Description

Technical Field

[0001] The present invention relates to a device, a monolayer membrane and a method for producing a dispersion of a first phase in a second phase. In particular, the device is a microfluidic brush emulsifier, which operates according to the principle of stepwise emulsification (also known as microchannel emulsification). Background Art

[0002] Monodisperse droplets in the size range from micrometers to millimeters are widely used in the fields of pharmaceuticals, cosmetics, diagnostics, food and materials science. In emulsions, monodispersity increases stability, allows precise control of volume in multiple chemical or biological reactions, and enables the generation of periodic structures. Microfluidics technology provides a sophisticated platform for the precise formation of monodisperse droplets. These monodisperse droplets can be further solidified to produce so-called microcapsules, which are used for the encapsulation of active ingredients, such as drugs, fragrances, flavorings, peptides, living materials (such as bacteria or bacteriophages, etc.), fertilizers, pesticides and other effective substances that are beneficial to health.

[0003] Currently, most industrial methods for producing microcapsules use spray drying, high-speed rotational ultrasonic treatment with high shear forces, mixing and / or shaking. It is worth noting that this method usually has the disadvantage of poor size control. However, especially in selective drug delivery, precise size control is a crucial factor.

[0004] Conventional microfluidic membranes according to the prior art are made from bulk materials as starting materials. As a processing step, holes are micro-drilled, lasered, wet etched or etched by deep reactive ion etching. These methods limit the possible size and shape of the final membrane, since the channels are processed along the final flow direction of the channels. A disadvantage of the devices of the prior art is that only a small fraction of the channels effectively generate droplets, which greatly reduces the efficiency of the emulsification. It is therefore desirable to improve this efficiency, especially for large-scale industrial applications of droplet generating devices.

[0005] An emulsification device is known from the prior art, which comprises a two-dimensional array of parallel droplet makers (WO 2014 / 186440 A2). Such a two-dimensional microfluidic device limits the production of high throughput. In such a device, a maximum rate of 25 ml / h can be achieved for the production of monodisperse emulsions. Summary of the invention

[0006] The methods known so far for producing monodisperse droplets are significantly limited. The known methods either allow the production of droplets with precise size control and therefore reproducible quality (which is however severely limited by the overall operating capacity), or can be performed at high operating capacity, but with poor reproducible quality and size control. Typically, the maximum production rate 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] It is therefore a general object of the present invention to improve the state of the art regarding the generation of monodisperse droplets, preferably thereby at least partially avoiding the disadvantages of the prior art.

[0008] In an advantageous embodiment, a method and an apparatus for carrying out the method are provided which allow for high run rates and high reproducibility, in particular with regard to droplet size control.

[0009] In a further advantageous embodiment, a method and a device for carrying out the method are provided, which apply a uniform pressure to the employed first phase.

[0010] In a further embodiment, a membrane is provided that allows high run capacity while maintaining high reproducibility.

[0011] The general object is achieved by the subject matter of the independent claims. Further advantageous embodiments are given by the dependent claims, the description and the drawings.

[0012] According to a first aspect, the present invention relates to a device for producing a dispersion of a first phase in a second phase, the device comprising: a first inlet for supplying the first phase, the first inlet leading to a first chamber; a second inlet for supplying the second phase, the second inlet leading to a second chamber; and a dispersion outlet for collecting the dispersion. In addition, the device comprises a membrane, the membrane separating the first chamber from the second chamber, and the membrane comprising a first side facing the first chamber and a second side facing the second chamber. The membrane comprises a plurality of channels extending from the first side to the second side, the channels providing a fluid connection between the first chamber and the second chamber. Each channel comprises a channel inlet arranged on the first side and a channel outlet arranged on the second side. The first chamber can generally be configured so that the flow rate of the first phase through all individual channels is substantially equal. In the prior art, the uneven pressure distribution (especially the uneven pressure distribution of the first phase) enables only a small portion of the channels to effectively produce droplets. However, the equal pressure distribution on the first side allows the first phase to flow stably into the second phase and allows droplets with reproducible quality to be produced at a high throughput of up to 5 liters / hour.

[0013] The membrane can generally be a single-layer membrane. Therefore, such a membrane is made of a uniform material and does not contain any phase interface or transition region except for a 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 aspect and embodiment disclosed herein.

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

[0015] The dispersion produced is generally a stable dispersion and / or microdispersion. That is, the dispersion includes droplets of the first phase in the second phase. The first phase and the second phase are generally fluids, especially liquids. In addition, the first phase and the second phase can also be dispersions, especially emulsions. The first phase and the second phase are generally immiscible. Therefore, if the first phase is a polar phase, especially an aqueous phase, the second phase is non-polar, especially oil-based. Similarly, if the first phase is non-polar, the second phase is polar. Generally, the first phase contains not only a carrier liquid, but also active ingredients, such as drugs, peptides, antibodies, DNA, RNA, fragrances, flavorings, odorants, pigments, dyes, bacteria, viruses, bacteriophages, agricultural chemical ingredients, non-drug classification substances, etc. In certain embodiments, the first phase can be composed of active ingredients. The term "first phase" is generally a phase dispersed in the second phase in the method according to the present invention. Therefore, in some embodiments, the first phase can be referred to as a "phase to be dispersed". The second phase can generally be a continuous phase, in which droplets of the first phase are dispersed.

[0016] In some embodiments, the second chamber can be made of glass or a transparent polymer (e.g., PTFE, polymethyl (meth)acrylate, or polyoxymethylene), or made of a metal (e.g., steel, aluminum, or titanium). Typically, the device can include a container (e.g., a glass container) that partially forms the second chamber. The container can form the second chamber together with the membrane. In some embodiments, the first chamber can be made of a metal (e.g., aluminum or steel), or made of a transparent polymer (e.g., PTFE, polymethyl (meth)acrylate, or polyoxymethylene).

[0017] Typically, the dispersion outlet may be connected to a product vessel. In some embodiments, the dispersion outlet may be in fluid communication with a three-way valve that may be switched between a product vessel and a waste vessel.

[0018] In some embodiments, the first chamber is configured so that: in an operating state, the pressure along the first side of the membrane is substantially isobaric. For example, the first inlet may include a nozzle for providing an isobaric pressure distribution on the first side of the membrane. In particular, a spray nozzle may be used. Alternatively, the first chamber may be shaped so as to provide an isobaric pressure distribution on the first side of the membrane.

[0019] In a further embodiment, the first chamber has a rounded cross section relative to the cross-sectional plane, which is perpendicular to the membrane and rotationally symmetrical relative to the central longitudinal axis. The term "rounded cross section" used herein refers to a continuous curve without an increment, particularly a curve having a radius of at least 1 mm, particularly at least 5 mm, particularly at least 10 mm in a cross section perpendicular to the membrane. It should be understood that the curved portion in the cross-sectional view can be described as a portion of a circle with the radius. Therefore, the side walls of the first chamber can converge toward each other continuously in the upstream direction. The central longitudinal axis is an axis extending in the longitudinal direction of the device (which is arranged at the center of the device) and / or an axis perpendicular to the membrane and intersecting the center of the membrane. For example, the first chamber can have a U-shaped cross section, or can be concavely rounded or semicircular. The rounded cross section is usually edgeless and therefore excludes edges, which will cause uneven pressure distribution when the first phase is forced through the membrane. Preferably, the first chamber can have the shape of a spherical dome. Generally, the shape of the first chamber is preferably substantially rotationally symmetrical relative to the central longitudinal axis.

[0020] In certain embodiments, the dispersion outlet may be arranged substantially on a central longitudinal axis and / or an axis perpendicular to the membrane and intersecting the center of the membrane. Preferably, the second chamber tapers toward the dispersion outlet. For example, at least a portion of the second chamber may be arched or conical toward the dispersion outlet. These embodiments ensure that no droplets are trapped and that all droplets are directly collectible via the dispersion outlet.

[0021] In some embodiments, the first chamber has the shape of a hemisphere or a truncated cone. Typically, the hemisphere or truncated cone is open toward the membrane, that is, the maximum radius is usually closest to the membrane. The term "hemispherical" used here also includes other spherical parts, such as a third of a sphere. Therefore, in some embodiments, the shape of the first chamber is a spherical dome or a spherical cap. Preferably, if the first chamber has the shape of a spherical dome, and / or in particular a hemispherical shape, the first inlet can be arranged near or in the polar region of the spherical dome of the first chamber (particularly the hemispherical first chamber). The advantage of this shape is that the material flow of the first phase is evenly distributed on the first side of the membrane, thereby helping to provide a uniform pressure distribution near each channel. For example, the first inlet can be arranged substantially perpendicular to the central longitudinal axis, i.e. substantially parallel to the first side of the membrane, or also parallel to the central longitudinal axis, i.e. perpendicular to the first side of the membrane.

[0022] In a further embodiment, the second side of the membrane comprises a total open area that is greater than the total open area of ​​the first side. Such a membrane has the advantage of producing high quality droplets even at flow rates up to 5 l / h. In some embodiments, the flow rate per channel may be between 1 µl / h and 50 ml / h, preferably between 10 µl / h and 5 ml / h.

[0023] In certain embodiments, each channel includes a channel outlet having a cross-sectional area greater than the cross-sectional area of ​​the rest of the corresponding channel. In the longitudinal direction, i.e., in the flow direction, the channel outlet has a typical length of several micrometers, such as 200 μm to 20 mm, preferably 500 μm to 5 mm. The channel outlet may be, for example, funnel-shaped, V-shaped or U-shaped. In some embodiments, the channel outlet may have an elliptical profile. In particular, the channel outlet is not rotationally symmetric and therefore has a length / width ratio of 3 or higher. Therefore, the channel outlet may not have a circular or square cross-section. Such a channel outlet can separate droplets without external force. Therefore, the formation of droplets of the first phase in the second phase is decoupled and is therefore substantially independent of the flow rate. According to the Young-Laplace equation, the pressure at the immiscible liquid interface is higher at the channel outlet than in the second reservoir. Therefore, a pressure gradient along the flow direction is generated, which causes the fluid thread to separate into separate droplets. Therefore, a pressure gradient is generated at the end of the channel, which contributes to the separation of the fluid boundary layer and is therefore conducive to the formation of a single droplet. When reaching the channel outlet, the pressure gradient of the dispersed phase inside and outside the channel causes the droplets to separate without external forces. This type of nozzle is advantageous because it decouples the flow rate from the emulsification process.

[0024] In some embodiments, the first inlet is arranged at an angle of substantially 90 ° or less relative to the channel of the membrane. Typically, all channels are arranged substantially parallel to each other. This has a beneficial effect, that is, the first phase is not directly pushed onto the membrane, thereby further being able to provide a uniform pressure distribution on each channel of the membrane. For example, the angle between the first inlet and the channel of the membrane can be between 60 ° and 90 °, particularly between 75 ° and 90 °. Preferably, the first inlet is substantially transverse to (preferably perpendicular to) a plurality of channel arrangements of the membrane. Therefore, in such an embodiment, the first inlet can be parallel to the first side of the membrane.

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

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

[0027] Preferably, if the container is a glass container, a shock-absorbing pad may be provided between the glass container and the container support to avoid damaging the glass container and to seal the glass container.

[0028] In some embodiments, the film holder includes a clamping device for mounting the film, and the film holder and / or the clamping device are configured to accommodate films with various thicknesses. Typically, the clamping device can be adjustable. Examples of clamping devices include screws, clips, bolts, locks, etc.

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

[0030] In a further embodiment, the base and / or the membrane holder comprises at least one seal to seal the membrane against the base and / or against the membrane holder. The sealing ring may be configured so that it completely surrounds the periphery of the membrane circumferentially. The sealing ring may also include a gas outlet that is in fluid communication with the first chamber and is configured to vent any gas present in the first chamber out of the first chamber.

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

[0032] In some embodiments, the first chamber includes a gas outlet, in particular a fluid switch, such as a valve. The gas outlet and the membrane are arranged so that: during the supply of the first phase to the first chamber (in particular during the first / initial filling of the first chamber with the first phase), the gas in the first chamber is directed to the gas outlet and removed from the first chamber via the gas outlet. In some examples, the membrane is inclined relative to the central longitudinal axis of the device. Therefore, in a cross-sectional view along the central longitudinal axis, the angle between the central longitudinal axis and the first and / or second side of the membrane is different from 90°. For example, the acute angle between the second side of the membrane and the central longitudinal axis can be between 45° and 89°, preferably between 70° and 88°, and more preferably between 78° and 87°. In such an embodiment, the gas outlet can be arranged at the top edge of the first chamber, which is formed by the membrane and another chamber wall. This ensures that any residual gas (in particular air) present in the first chamber (for example before using the device) rises to the membrane and is guided to the top edge due to the inclined arrangement of the membrane, thereby being guided to the gas outlet. Typically, the channels of the membrane are too narrow for air to pass through, and therefore the gas outlets described in the above embodiments are able to remove any remaining gas that would otherwise negatively affect uniform droplet size and distribution, or prevent the first fluid from reaching all microchannels, thereby reducing throughput. Typically, the gas outlets may be in fluid communication with the ambient 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 may be beneficial because the solidification of the dispersed droplets produced can be easily affected by temperature changes (e.g., by cooling the dispersion). Typically, at least one heater can provide sufficient thermal energy to heat the first phase and / or the second phase to 100° C., 125° C., or 150° C. The heater may, for example, comprise a heating bath, such as a water bath or an oil bath. Alternatively, the heater may be an infrared radiator, a heating coil, or any other suitable heater.

[0034] In a further embodiment, the device 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 reservoir and the second reservoir can be pressurized. For example, the reservoir can be fluidically connected to a pressure source, such as a compressor. Alternatively, the reservoir can be a syringe and pressurized by a common syringe pump and / or a plunger or peristaltic pump, a gear pump or any other pumping system.

[0035] The dispersion outlet can be for example connected with product vessel and / or waste vessel fluid.Alternately or additionally, post-processing vessel can be arranged between the second reservoir and product vessel or waste vessel.In certain embodiments, the second reservoir can further be used as post-processing vessel.

[0036] In some embodiments, a flow restrictor is arranged between the second reservoir for the second phase and the second chamber. Such a flow restrictor is beneficial because the second chamber generally does not provide a significant flow resistance for the second phase. Thus, by using a flow restrictor, the device is more stable because unintentional pressure differences, such as those caused by fluctuating gas pressure, can be avoided.

[0037] In a further embodiment, the second inlet includes a supply channel, which is at least partially arranged circumferentially around a central longitudinal axis, i.e., an axis perpendicular to the first and second sides of the film and intersecting the center of the film. The supply channel includes one or more openings leading to the second chamber. At least partially arranged circumferentially around the above-mentioned axis means that the supply channel can have a partially circular profile, such as a semicircle or a third of a circle, etc. Preferably, the supply channel is completely circumferentially arranged around the central longitudinal axis, i.e., an axis perpendicular to the film and intersecting the center of the film. In such an embodiment, the supply channel forms an annular structure. Preferably, the supply channel includes a plurality of openings leading to the second chamber, and these openings are substantially uniformly distributed along the circumference of the supply channel in particular. Typically, one or more openings of the supply channel can be arranged in the direction of the dispersion outlet, i.e., so that the opening faces the dispersion outlet. The embodiment including the supply channel has the advantage that the second phase can be introduced into the second chamber evenly and smoothly without causing harmful turbulence, which has a negative impact on the uniform shape and size distribution of the droplets produced. In some embodiments, one or more openings of the supply channel are arranged so that a vortex is generated when the second phase is provided to the second chamber. In particular, one or more openings may be tubular and the longitudinal axis of each tubular opening may be inclined relative to the central longitudinal axis of the device. Typically, all tubular openings are uniformly inclined. The generation of vortices is beneficial because, firstly, the surface stabilizer that may typically be contained in the first phase and / or the second phase may be more evenly distributed, which will therefore enhance the stability of the dispersion formed, and secondly, because the transport of the generated dispersion to the dispersion outlet is accelerated, which is particularly beneficial if the densities of the first phase and the second phase are substantially equal.

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

[0039] Alternatively, the second inlet may constitute a single inlet leading directly into the second chamber, preferably from a lateral side of the second chamber.

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

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

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

[0043] In a further embodiment, the film comprises a label, preferably a computer readable label. The label can be a 2D or 1D label, a barcode, a hologram, an RFID tag or a chip. The device can also include a readout unit configured to retrieve data from the label and a control unit configured to process the data from the label. The data can be associated with the desired quality value of the monodisperse droplets produced, such as particle size and size distribution and its lower and upper limits, which can be retrieved via the readout unit. In addition, the data can be associated with process parameters, such as the pressure applied to the first chamber and / or the second chamber, the flow rate or pressure of the first phase and / or the second phase, the temperature of the first phase and / or the second phase, the material used, the measured quality value (especially by the analysis unit), the viscosity of the first phase and / or the second phase, the interfacial tension, the contact angle, the duration of droplet generation, etc. The data can also be related to the parameters of the film itself, i.e., the channel outlet shape, the channel size (e.g., diameter, aspect ratio, length), and the film thickness and / or diameter, surface function (e.g., hydrophobic or hydrophilic treatment), the film material (e.g., steel glass or polymer), the use date, etc.

[0044] The readout unit and the control unit are not part of the membrane. The readout unit can be, for example, an optical scanner, a camera, etc. Processing data by the control unit can, for example, include: retrieving specific data related to process parameters, such as the pressure applied to the first chamber and / or the second chamber, the flow rate of the first phase and / or the second phase, the temperature of the first phase and / or the second phase, etc.; and adjusting these parameters when operating the device, in particular automatically adjusting these parameters. This allows the storage of optimal parameters for each specific membrane or membrane type. Depending on the specific membrane properties (such as thickness, total opening area, channel outlet shape, etc.), certain process parameters should ideally be optimized. Instead of optimizing each membrane separately, optimized parameters for each membrane type can be used. These optimized parameters can be stored directly on a specific membrane via a tag as data, or can be stored in the device itself, i.e., in a storage unit. In the latter case, the tag of the membrane is associated with a specific code, which is associated with a specific data set stored in the storage unit, such as process data or a desired quality value. The user then only has to insert the film into the device and the readout unit can retrieve the data from the tag, send the data to the control unit, which can then adjust the corresponding process parameters based on the data retrieved directly from the film or by retrieving a specific set of process parameters associated with a specific code on the film and stored in the storage unit. The readout unit can be positioned so that the tag can be read when the film is inserted into the film holder, i.e. when it is positioned between the first chamber and the second chamber. Alternatively, the readout unit can be located in any suitable position of the device. The user can then scan the tag of the film before introducing the film into the film holder. The readout 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 (particularly process data, such as actually applied process parameters, such as the pressure applied to the first chamber and / or the second chamber, the flow rate of the first phase and / or the second phase, the temperature of the first phase and / or the second phase, etc.) to the receiver. The process data described here may also include log entries, i.e. information about the duration of use, the location of use, user ID, etc. The transmission may be performed by any method known to those skilled in the art, such as via Bluetooth. ® , WiFi, Ethernet, online transmission, etc. For example, the transmission can take place in real time, ie: the process parameters are directly transmitted when the device is in use.

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

[0047] In some embodiments, the receiver may be a film storage unit contained in the film. In such embodiments, the transmitter unit may transmit the process parameters actually used to the film storage unit.

[0048] In some embodiments, the device may include an analysis unit having 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, for example, be configured to measure and / or determine the diffraction of light, i.e. to determine the refractive index of the product to be analyzed.

[0049] In a preferred embodiment, the analysis unit may include a detection chamber configured to enable the determination of the quality value of the generated dispersion. The detection chamber may preferably be configured to accommodate only a monodisperse droplet of a monolayer or a single monodisperse droplet. For example, the detection chamber may include or consist of a transparent material. The detection chamber may be configured so that the monodisperse droplets generated during the analysis are maintained in a stable state or an unstable state. The detection chamber may also be a microchannel, the diameter of which is generally greater than the diameter of the monodisperse droplets generated. For example, the diameter may be less than 5000 μm, or less than 2000 μm, or less than or less than 1000 μm, or less than 500 μm. In such an embodiment, when the monodisperse droplets generated are in the microchannel, they can be analyzed by the sensor. It should be understood that the sensor is generally arranged and positioned so that the droplets can be analyzed.

[0050] The analysis unit is arranged downstream of the membrane. For example, the analysis unit can be in fluid communication with the channel branching from the second chamber, or the analysis unit can be arranged downstream of the dispersion outlet. Downstream of the dispersion outlet, the device can include a fluid connector, which can be controlled in particular by a switch, which is in fluid communication with the analysis unit. For example, the control unit can be configured so that: the switch is operated automatically or on demand in such a way that, in particular when the device is running, a limited number of monodisperse droplets produced are directed and enter the analysis unit. Therefore, the analysis unit allows direct online quality control while producing monodisperse droplets.

[0051] It should be understood that, typically, the control unit, the transmission unit, the storage unit, the readout unit and the analysis unit are operatively coupled to each other.

[0052] In some embodiments, the analyzing unit is operatively coupled to the control unit, the sending unit and / or the storage unit. Thus, the obtained quality values ​​(e.g. particle size and size distribution of the generated monodisperse droplets) can be stored in the storage unit, sent or directly retrieved by the membrane as described above.

[0053] In some embodiments where the apparatus comprises a transmitter unit as described above, the transmitter unit may be configured for transmitting the quality parameter to the receiver.The quality parameter may be transmitted in real time at regular time intervals or on demand, respectively.

[0054] In some embodiments, the control unit can be configured to monitor the quality parameter and detect whether the quality parameter is below or exceeds a predetermined upper and / or lower threshold value. The threshold value associated with the data can be retrieved from the membrane, i.e. the threshold value can be stored directly on the membrane via a tag, or the tag contains a specific code associated with a specific upper and lower threshold value (e.g. an upper and lower limit of the droplet size) stored in the storage unit. In such an embodiment, an alarm can be triggered when the quality parameter is below or exceeds a predetermined upper and / or lower threshold value. The alarm can be, for example, an acoustic signal, a visual signal and / or a tactile signal. Additionally or alternatively, if the quality parameter is below or exceeds a predetermined threshold value, the control unit can cut off the device, i.e. prohibit the supply of an additional first phase and / or second phase.

[0055] In a second aspect, the invention includes a membrane for producing a dispersion of a first phase in a second phase, the membrane comprising a first side and a second side opposite thereto, and a plurality of channels extending from the first side to the second side through the membrane. Each channel comprises a channel inlet arranged at the first side, a channel outlet arranged at the second side, and a main section arranged between the channel inlet and the channel outlet, wherein the channel outlet comprises a shape different from the shape of the main section.

[0056] In some typical embodiments, the shape of the channel outlet is asymmetric. For example, relative to a cross-sectional plane perpendicular to the flow direction 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 usually has a constant diameter over the entire length of the main section.

[0058] In some embodiments, the total open area of ​​the second side of the membrane is greater than the total open area of ​​the first side.

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

[0060] The membranes described in any embodiment of the second aspect of the invention may generally be used in the devices described herein.

[0061] The membrane may typically be a monolayer membrane. That is, the membrane is made of a single piece. Preferably, such a membrane is made of a bulk material and, apart from the channels of the membrane, does not contain any phase interfaces or transition regions. Such a membrane is advantageous for the quality of the droplets produced, since any phase interfaces and transitions are detrimental to droplet formation and droplet stability.

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

[0063] In a further embodiment, the channel outlet may be wedge-shaped. In particular, the channel outlet may comprise an elliptical cross-section relative to a transverse plane perpendicular to the extending channel, ie 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 convex or concave towards the channel outlet. Furthermore, each channel may include a constriction having a cross-section smaller than the cross-section of the rest of the channel, and wherein the constriction is arranged near the channel outlet. Thus, the constriction is arranged between the channel outlet and the rest of the channel.

[0065] In some embodiments, each channel outlet may have an elliptical profile. Thus, the channel outlet may have an elliptical cross-section relative to a plane transverse to the extended channel and parallel to the first side or the second side of the membrane. Channel outlets having an elliptical profile have a beneficial effect on the quality of the droplets formed, because any edges in the channel may result in unstable and non-uniform droplets.

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

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

[0068] In further embodiments, the membrane comprises 0.06 to 600,000 channels / cm 2 , preferably 20 to 30,000 channels / cm 2 .

[0069] In some embodiments, the membrane is made of glass or a polymeric material such as polymethyl (meth)acrylate or PTFE, or of 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 in an acid (e.g. hydrofluoric acid) or a base (e.g. potassium hydroxide). In the case of a steel membrane or a plastic membrane, the membrane can be produced by micromachining (using methods such as drilling, milling, turning or laser melting, etching, etc.).

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

[0072] In a further embodiment, the cross-sectional area of ​​each channel outlet is 0.12 to 36000000 μm 2 , preferably 12 to 5760000 µm 2 In particular, the total open area of ​​the second side of the membrane may be 300% to 1500%, preferably 400% to 900% greater than the total open area of ​​the channel at any other given location (eg the main section and / or the channel inlet).

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

[0074] In certain embodiments, each channel of the film has a rounded cross section relative to the transverse plane. That is, at least in the channel and / or the channel outlet, each channel is substantially edgeless. Such a channel is beneficial because the edges may have an adverse effect on the pressure distribution, flow characteristics and the reproducibility of the dispersed droplets produced. The transverse plane is coplanar with the film and the first and second sides of the film. Typically, the channel outlet and the rest of the channel may have a rounded cross section.

[0075] In a further embodiment, the thickness of the membrane is 0.05 mm to 20 mm, in particular between 0.1 mm and 20 mm, in particular 0.1 mm to 5 mm, in particular 0.5 mm to 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 rest of the channel.

[0076] In some embodiments, the membrane includes at least one solid support structure without a channel, which divides the membrane into two or more sections containing channels. The solid support structure increases the stability of the membrane. This solid support structure can be integrated with the membrane, or can constitute additional elements, which are arranged on the top of the first surface and / or the second surface of the membrane. If there are several solid support structures, these solid support structures can extend parallel to the first side and / or the second side of the membrane (i.e., transverse to the extension channel). The solid support structure can be a straight beam. Typically, the support structure is not provided with a channel. Usually only a small part of the total surface area of ​​the first side and / or the second side of the membrane is part of the support structure. The total surface area of ​​at least one support structure (or all support structures combined) can be less than 1:10, preferably less than 1:15, and particularly less than 1:20 compared to the total surface area of ​​the section containing the channel. The support structure can be arranged so that some sections containing the channel each have a triangular shape, preferably at least 6, particularly at least 10. The solid support structure strengthens the membrane, is conducive to the handling of the membrane and avoids rupture, because the membrane may become relatively fragile due to the large total opening area of ​​the channel. In a further embodiment, the film comprises a label, preferably a computer readable label. The label can be a 2D or 1D label, a barcode, a hologram, an RFID tag or a chip. The label can be computer readable. Preferably, the label comprises data that can be associated with the desired quality value of the monodisperse droplets produced, such as particle size and size distribution and its lower and upper thresholds, which can be retrieved via a readout unit. In addition, the data can be associated with process parameters, such as the pressure applied to the first chamber and / or the second chamber, the flow rate of the first phase and / or the second phase, the temperature of the first phase and / or the second phase, the materials used, etc. The data can also be associated with the parameters of the film itself, i.e., the channel outlet shape, channel size (e.g., diameter, aspect ratio, length) and film thickness. The data can either be stored directly in the label, or the label can include a specific code associated with specific data stored in a device (particularly stored in a device as described in any aspect and embodiment of this article), which is used in conjunction with the film.

[0077] In some embodiments, the film may include a film storage unit configured to receive and store data sent by the transmitter device. The film storage unit may be an electronic circuit, a microprocessor, etc., so that the film can store the process parameters actually used obtained from the device (in particular from the transmitter device). Thus, the film can be returned to the manufacturer, who can retrieve the process parameters and analyze them.

[0078] In some embodiments, the membrane may include a membrane sealing ring that completely surrounds the periphery of the membrane circumferentially. Such a membrane sealing ring may have a C-shaped cross-section that completely enables, on the one hand, to completely surround the periphery of the membrane and also surrounds a small portion of the first side and the second side of the membrane. The membrane sealing ring may preferably be made of a suitable polymeric material (e.g., rubber, silicone, etc.).

[0079] According to another aspect, the present invention includes a method of producing a dispersion of a first phase in a second phase using an apparatus according to any embodiment described herein. The method includes the steps of providing an apparatus as described in any embodiment disclosed herein, supplying a first phase into a first chamber through a first inlet, and supplying a second phase into a second chamber through a second inlet, wherein the first phase flows from the first chamber through a plurality of channels of a membrane into the second chamber to form a dispersion of the first phase in the second phase.

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

[0081] In some embodiments, the dispersion produced in the second chamber is collected through the dispersion outlet. Preferably, the dispersion is continuously collected during the production of the dispersion in the second chamber.

[0082] In some embodiments, the first phase and / or the second phase may contain a surface stabilizer for stabilizing the dispersion produced by the first phase in the second phase. Preferably, the surface stabilizer is contained only in the second phase. For example, the surface stabilizer may be a surfactant, such as an anionic, cationic or amphoteric surfactant. The surface stabilizer may also be a soap or a suitable protein. Additionally or alternatively, depending on the application, the surface stabilizer may be a solid particle, preferably a hydrophobic hydrophilic or Janus type particle, which is configured to provide a pickering emulsion. For example, the solid particle may be colloidal silica. In some embodiments, the amount of the surface stabilizer in the first phase and / or the second phase is higher than the critical micelle concentration, particularly between 0.001 and 5 wt%, particularly between 0.01 and 5 wt%, particularly between 0.1 and 5 wt%.

[0083] In some embodiments, the pressure along the first side of the membrane is substantially isobaric.Thus, the pressure at each of the plurality of channels may be substantially uniform.

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

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

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

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

[0088] In some embodiments, the readout unit retrieves data from the tag on the membrane, and the retrieved data is provided to the control unit, which processes the data. Typically, the readout can be performed before providing the first phase and / or the second phase. The data can be associated with the desired quality values ​​of the monodisperse droplets produced, such as particle size and size distribution and their lower and upper thresholds, which can be retrieved via the readout unit. In addition, the data can be associated with process parameters, such as the pressure applied to the first chamber and / or the second chamber, the flow rate of the first phase and / or the second phase, the temperature of the first phase and / or the second phase, the materials used, etc. The data can also be associated with the parameters of the membrane itself, i.e., the channel outlet shape, channel size (e.g., diameter, aspect ratio, length), and membrane thickness. Processing the data by the control unit can, for example, include: retrieving specific data related to process parameters, such as the pressure applied to the first chamber and / or the second chamber, the flow rate of the first phase and / or the second phase, the temperature of the first phase and / or the second phase, etc.; and adjusting these parameters when operating the device, in particular automatically adjusting these parameters. Depending on the specific membrane characteristics (e.g. thickness, total open area, channel outlet shape, etc.), certain process parameters should ideally be optimized. Instead of optimizing each membrane individually, optimized parameters for each membrane type can be used. These optimized parameters can be stored as data directly on the specific membrane via a tag, or can be stored within the device itself, i.e. in a storage unit. In the latter case, the tag of the membrane is associated with a specific code, which is associated with a specific set of data stored in the storage unit, such as process data or desired quality values. The user then only needs to insert the membrane into the device, and the read-out unit can retrieve the data from the tag, transmit the data to the control unit, and the control unit can then adjust the corresponding process parameters based on the data retrieved directly from the membrane or by retrieving a specific set of process parameters associated with the specific code on the membrane and stored in the storage unit.

[0089] In some embodiments, data is sent by the sending unit to the receiver. The data may be actual process data, such as process parameters actually applied, such as pressure applied to the first chamber and / or the second chamber, flow rate of the first phase and / or the second phase, temperature of the first phase and / or the second phase, etc. The process data described herein may also include log entries, i.e. information about duration of use, location of use, user ID, etc. The sending may be performed by any method known to those skilled in the art, such as via Bluetooth. ® , WiFi, Ethernet, online transmission, etc. For example, the transmission may take place in real time, ie the process parameters are directly transmitted when the device is in use, ie when the first phase and / or the second phase is provided.

[0090] Alternatively, the actual process data may be recorded and stored in a storage unit. The control unit may retrieve the stored process data, for example on demand or at regular time intervals. Optionally, the data may then be provided to a 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 a storage unit and retrieved and transmitted by the transmitter unit at regular time intervals or on demand.

[0091] In some embodiments, the receiver may be a film storage unit contained in the film. In such embodiments, the transmitter unit may transmit the process parameters actually used to the film storage unit.

[0092] In some embodiments, the generated dispersion comprises monodisperse droplets, and at least one of the generated monodisperse droplets is analyzed in an analysis unit having a sensor. The analysis can be performed online, i.e. during the supply of the first phase and / or the second phase, and after the supply of the first phase and / or the second phase is 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, for example, be configured to measure and / or determine the diffraction of light, i.e. determine the refractive index of the product to be analyzed.

[0093] In a preferred embodiment, the analysis unit may include a detection chamber configured to enable the determination of the quality value of the generated dispersion. The detection chamber may preferably accommodate only a monolayer of generated monodisperse droplets or a single monodisperse droplet. For example, the detection chamber may include or consist of a transparent material. During the analysis, the detection chamber may accommodate the generated monodisperse droplets in a stable state or in an unstable state. The detection chamber may also be a microchannel, the diameter of which is generally greater than the diameter of the generated monodisperse droplets. For example, the diameter may be less than 5000 μm, or less than 2000 μm, or less than or less than 1000 μm, or less than 500 μm. In such an embodiment, when the generated monodisperse droplets are in the microchannel, they can be analyzed by the sensor. It should be understood that the sensor is generally arranged and positioned so that the droplets can be analyzed.

[0094] In some embodiments, the analysis unit is operatively coupled to the control unit and / or the storage unit. Thus, the obtained quality values ​​(eg particle size and size distribution of the generated monodisperse droplets) can be stored in the storage unit or directly retrieved from the membrane as described above.

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

[0096] In some embodiments, the quality parameter is monitored by the control unit. If it is detected that the quality parameter is below or exceeds a predetermined upper and / or lower threshold, an alarm may be triggered and / or the supply of the first phase and / or the second phase may be immediately stopped. The alarm may be, for example, an audible signal, a visual signal and / or a tactile signal.

[0097] The resulting dispersion of the first phase in the second phase can be further processed to produce capsules and particles, such as microcapsules, microparticles, nanocapsules, nanoparticles. Typical methods include: thermal curing by heating or by cooling; chemically, UV or thermally induced polymerization; solvent extraction; chemical reaction; interfacial reaction; gelation; crosslinking; radiation; complex coacervation and other methods known to those skilled in the art. Microcapsules or microparticles may have an average diameter of 1 to 1000 μm, and nanoparticles or nanocapsules may 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 greater than 1000 μm, an average diameter of up to 5 mm or up to 3 mm.

[0098] According to another aspect, the present invention relates to a system for producing a dispersion with multi-core droplets, the system comprising at least two devices according to any one of the embodiments described herein connected in series. Thus, a first dispersion with a first group of dispersed droplets is formed in the first device, which is then provided to the first chamber of the second device, which is arranged after the first device in the flow direction. The first group of dispersed droplets flows through the channel of the membrane of the second device, thereby forming multi-core droplets in the second phase. As understood by those skilled in the art, multi-core droplets are droplets comprising an inner core and an additional layer surrounding the inner core. Each of the inner core and the monolayer can be made of different materials. However, if separated by at least one different material, it is also possible that at least some of the layers and / or the inner core are made of the same material. Additionally or alternatively, the emulsion can be added to the device according to any embodiment described herein, in particular to the first phase and / or the second phase to form a multiple emulsion by methods known to those skilled in the art (e.g., shaking, ultrasonic treatment, high shear emulsification, spray drying).

[0099] According to another aspect, the present invention relates to a device for producing a dispersion of a first phase in a second phase, the device comprising a first inlet for supplying the first phase, the first inlet leading to a first chamber; a second inlet for supplying the second phase, the second inlet leading to a second chamber; a dispersion outlet for collecting the dispersion of the first phase in the second phase; a membrane holder for holding a membrane, the membrane being capable of separating the first chamber from the second chamber, wherein the first chamber has a rounded cross-section relative to the cross-sectional plane, and is rotationally symmetrical relative to a central longitudinal axis intersecting the center of the first chamber and the center of the second chamber. This aspect of the invention may also be combined with one or more embodiments described herein, in particular with one or more embodiments described with respect to the first aspect of the invention. In some embodiments, the device may also include a membrane as described in any aspect and embodiment described herein, the membrane being arranged so that it separates the first chamber from the second chamber, and comprising a first side facing the first chamber and a second side facing the second chamber. The membrane may also be held by a membrane holder. BRIEF DESCRIPTION OF THE DRAWINGS

[0100] The invention described herein will be more fully understood from the detailed description given below and the accompanying drawings, which should not be considered to limit the invention described in the appended claims. The accompanying drawings show:

[0101] Figure 1 : A schematic diagram of an apparatus for producing a dispersion of a first phase in a second phase according to a first embodiment of the present invention;

[0102] Figure 2 : Figure 1 A cross-sectional view of the device shown in;

[0103] Figure 3 : Figure 1 An exploded partial cross-sectional view of the device shown in;

[0104] Figure 4 : A schematic diagram of a device 1' according to another embodiment of the present invention;

[0105] Figure 5 : A schematic enlarged view of the second side of the membrane according to the first embodiment of the present invention;

[0106] Figure 6 : Figure 5 A partial cross-sectional view of the membrane shown in FIG. 1 along the AA axis;

[0107] Figure 7 : Schematic partial representation of different channel outlet geometries according to other embodiments of the present invention;

[0108] Figure 8 : A partial cross-sectional view of a device according to another embodiment of the present invention;

[0109] Fig. 9 : A cross-sectional view of a device according to another embodiment of the present invention;

[0110] Fig.10 : Schematic diagram of a membrane according to another embodiment of the present invention. DETAILED DESCRIPTION

[0111] Figure 1 A device 1 for producing a dispersion of a first phase in a second phase is depicted. The device 1 comprises a container 19 made of glass and a base 14 made of metal. The base 14 comprises a first inlet (not shown, see Figure 2 ), the first inlet leads to the first chamber. The first chamber is formed in part by the base 14 and the membrane 7 (see Figure 2 ). The container 19 comprises: a second inlet 3 for supplying the second phase, which leads to the second chamber; and a dispersion outlet 6 for collecting the dispersion produced in the second chamber. The second chamber is formed by the container 19 and the membrane 7 (see Figure 2 ). The device 1 further comprises a membrane holding structure 20 fixedly connected to the base 14. Furthermore, the device comprises a container holding structure 21 fixedly connected to the membrane holding structure 20 via a clamping device 18. Thus, the container 19 is fixedly connected to the base 14.

[0112] Figure 2 A cross-sectional view of the device 1 is shown. The device 1 comprises a base 14 having a first inlet 2 for supplying a first phase. The inlet 2 leads to a first chamber 4, which is partly formed by the base 14. The device 1 also comprises a container 19 having a second inlet 3 for supplying a second phase and a dispersion outlet 6 for collecting a dispersion of the first phase in the second phase. The second inlet 3 leads to a second chamber 5, which is partly formed by the container 19. The first chamber and the second chamber are separated by a membrane 7. From Figure 2, it can be easily seen that the first chamber has a rounded cross section relative to a corresponding cross section along the central longitudinal axis 15 and perpendicular to the membrane 7. In the particular embodiment shown, the first chamber 4 has a semicircular cross section and can therefore have the shape of a hemisphere. The first inlet 2 is arranged in the region of the pole 13 of the hemisphere. The second chamber 5 tapers towards the dispersion outlet 6, which is arranged on the longitudinal axis 15, which extends in the longitudinal direction of the device, intersecting the center of the first and second chambers, perpendicular to the membrane 7 and intersecting the center of the membrane. It can be seen that the longitudinal axis 15 constitutes the central axis of the device in the longitudinal direction. In the embodiment shown, the second chamber is arched towards the dispersion outlet 6. Therefore, the second chamber 6 has a U-shaped cross section. The first inlet 2 is arranged at an angle α of substantially 90° relative to the central axis 15 and the passage of the membrane, which is generally parallel to the axis 15. The device 1 includes a membrane holder 20 and a container holder 21, which are fixedly connected to each other via a releasable clamping device 18. The membrane 7 is mounted on the membrane holder 20 by clamping the membrane between the membrane holder 7 and the base 14. The membrane holder 20 is fixedly connected to the base 14 via the clamping means 18. In order to securely fix the glass container 19 between the membrane holder 20 and the container holder 21, a pad 23, in a specific case a foam pad, can be arranged between the container 19 and the container holder 21. The membrane holder 20 comprises a groove 22 for receiving the container 19.

[0113] Figure 3 An exploded view of a partially deleted device 1 is shown. It can be seen that the first chamber is partially formed by the base 14 and has the shape of a hemisphere. The first inlet 2, which is arranged at an angle of substantially 90° relative to the central axis 15, is arranged at the pole of the hemisphere. The base 14 includes a spacing ring 16, which enables the use of different membranes with different thicknesses, and the membrane holder 20 includes a sealing ring 17. The membrane 7 is arranged between the rings 16 and 17. The design of the device 1 with an adjustable clamping device 18 allows the use of membranes of various thicknesses. The membrane holder 20 also includes a circumferential groove 22 for receiving the lower end portion of the container 19. The clamping device 18 connects the membrane holder 20 to the container holder 21 fixedly and releasably.

[0114] Figure 4A schematic diagram of a device 1 according to a preferred embodiment of the present invention is shown. The second chamber 5 is formed by a container 19 and a membrane 7, which separates the first chamber 4 from the second chamber 5. The container 19 includes a dispersion outlet 6, which is in fluid communication with a product container 29 and a waste container 30. In general, the fluid flow rate can be controlled by a valve, such as a three-way valve. The device 1 also includes a first reservoir 24, which is in fluid communication with the first chamber 4, for providing the first phase to the first chamber 4 via the first inlet 2. A flow meter for measuring the fluid flow of the first phase is provided between the first reservoir 24 and the first inlet 2. The first reservoir 24 is in fluid communication with a pressure source 32. In addition, a pressure regulator 27a is arranged between the first reservoir 24 and the pressure source 32. In addition to the first reservoir 24, the device 1 includes a flushing reservoir 31, which is also in fluid communication with both the first chamber 4 and the pressure source 32. The flushing reservoir 31 is configured to provide a flushing solution to the first chamber 4 after the intended use of the device 1 in order to clean the device 1. Typically, if a flushing solution is provided to the first chamber 4, a three-way valve disposed between the product vessel 29 and the waste vessel 30 and the dispersion outlet 6 is configured so that the flushing solution can flow into the waste vessel 30. The device 1 also includes a heater 33, which is configured to heat the first and second chambers during the generation of the dispersed phase. In addition, the second chamber 5 is fluidly connected to the second reservoir 25 for supplying the second phase to the second chamber 5. The restrictor 26 and the flow meter 28 are arranged between the second chamber 5 and the second reservoir 25. In the embodiment shown, the restrictor 26 is arranged behind the flow meter 28 in the flow direction. The second reservoir 25 is also connected to the pressure source 32 fluid. In addition, the second pressure regulator 27b is arranged between the second reservoir 25 and the pressure regulator 27a. In a representative experiment, the first reservoir is pressurized with an overpressure of 0.08 atm, and the second reservoir is pressurized with an overpressure of 0.4 atm. A 1 L product vessel can be filled with a dispersion generated by the first phase in the second phase in only 12 minutes. The device 1 also includes a readout unit 39 and a control unit 40, the readout unit 39 being configured to retrieve data from the label of the film 7, and the control unit 40 being configured to process the data from the label. Generally, the readout unit can be arranged at any suitable position. For example, the user can scan the label of the film before placing the film between the first chamber and the second chamber. Optionally, the readout unit and the label can generally be arranged so that when the film is located between the first chamber 4 and the second chamber 5, the label can be directly read out. The device 1 also includes a transmitter unit 41, which is configured to send data to the receiver. Generally, the transmitter unit 41, the control unit 40 and the readout unit 39 can be functionally connected. The device 1 also includes an analysis unit 42 with a sensor, which is used to determine and control quality values, in particular the size and size distribution of the monodisperse droplets produced. The analysis unit 42 is located downstream of the film 7, in this case downstream of the dispersion outlet 6.

[0115] Figure 5 A single-layer membrane 7 for producing a dispersion of a first phase in a second phase is shown, and the membrane 7 can be used in a device as described in any embodiment disclosed herein. The membrane 7 has a first side 8 (not shown) and a second side 9, and the second side 9 faces the second chamber in an operating state. A plurality of microchannels 10 extend through the membrane 7. Each channel 10 has an elliptical profile. The membrane 7 also has a computer-readable label 43 attached to the second side 9. In addition, the membrane 7 includes a membrane sealing ring 44, which completely surrounds the periphery of the membrane circumferentially. In some cases, the membrane 7 may additionally include a membrane storage unit 45, which is configured to receive and store data sent by the transmitter device.

[0116] Figure 6 The cross-sectional view along AA shows Figure 5 A single-layer membrane 7 of thickness T is shown. The membrane includes a first side 8 and a second side 9. A plurality of channels 10 (drawn in an exaggerated size) each extend from the first side 8 of the membrane to the second side 9 of the membrane. Each channel includes a channel inlet 11 arranged at the first side 8 and a channel outlet 12 arranged at the second side 9. Disposed between each channel inlet and channel outlet is a main section M. It can be easily seen that the second side 9 includes a total opening area that is greater than the total opening area of ​​the first side 8. In addition, the shape of each channel outlet 12 is different from the shape of the rest of the channel (i.e., the main section M and the channel inlet 11). The cross-sectional area of ​​each channel outlet 12 is greater than the cross-sectional area of ​​the rest of the corresponding channel 10. In the embodiment shown, the channel outlet 12 is wedge-shaped.

[0117] Figure 7 Shown are selected schematic partial cross-sectional views of channels with different channel outlet shapes. For example, Figure 7 a) Shows the wedge-shaped channel outlet. Figure 7 b) shows the angled channel exit. Figure 7 c) and 7d) show the following channel outlets, where the channel wall is convex ( Figure 7 c) or concave ( Figure 7 d) curved. Figure 7 e) to 7g) show channels with a constriction which is arranged near the channel outlet and between the respective channel outlet and the remainder of the channel. It can be seen that the cross-sectional area of ​​the channel outlet of all the different channels shown is larger than the cross-sectional area of ​​the remainder of the channel.

[0118] Figure 8A partial cross-sectional view of a device according to another embodiment of the invention is shown. The device 1 has a first inlet 2 for supplying a first phase, the first inlet 2 leading to 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 radius at the base of the dome being smaller than the radius of the corresponding imaginary spherical body. The second chamber 5 is at least partially defined by a container 19. The device also includes a dispersion outlet 6 for collecting the dispersion produced by the first phase in the second phase. For better visualization, the corresponding membrane is not shown. The second inlet leading to the second chamber 5 comprises, in the embodiment shown, a supply channel 34, which is arranged circumferentially around the central longitudinal axis 15 and / or an axis perpendicular to the first and second sides of the membrane and intersecting the center of the membrane. The supply channel 34 comprises a plurality of openings 35 leading to the second chamber 5. The openings 35 are evenly distributed along the circumference of the supply channel and are arranged in the direction of the dispersion outlet 7. In the embodiment shown, the supply channel 34 forms an annular structure, which is arranged at the bottom of the second chamber 5, i.e. at the edge of the membrane and the container 19. In the embodiment shown, the supply channel has an angular cross-section. Alternatively, the supply channel can have a rounded cross section, in particular a circular cross section.

[0119] Fig. 9 A cross-sectional view of another embodiment of the device according to the invention is shown. The device 1 has a first inlet 2 for supplying a first phase, the first inlet 2 opening 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. A membrane 7 separates the first chamber 4 from the second chamber 5. Figure 2 In contrast to the embodiment shown, the membrane is inclined relative to the central longitudinal axis 15 of the device 1. In a cross-sectional view along the central longitudinal axis, the acute angle β between the central longitudinal axis and the second side of the membrane is between 45° and 89°, preferably between 70° and 88°, more preferably between 78° and 87°. The device 1 further comprises a gas outlet 36. The gas outlet and the membrane are arranged such that: during the supply of the first phase to the first chamber (in particular during the first filling), the gas in the first chamber is directed to the gas outlet and removed from the first chamber 4 via the gas outlet 36. It can be seen that the gas outlet 36 is arranged at the top edge of the first chamber 4, which is formed by the membrane 7 and the chamber wall, which is part of the base 14. Before the initial filling of the first chamber 4 with the first phase, gas, in particular air, is present in the first chamber. When the first chamber 4 is filled with the first phase, the air is pushed out of the gas outlet 36. Due to the arrangement of the membrane 7 and the gas outlet 36, substantially all gas can be removed from the first chamber 4. Since residual gas, in particular bubbles, has an adverse effect on the pressure distribution, the size and particle distribution become more uniform.

[0120] Fig.10A membrane 7 according to another embodiment of the invention is depicted. The membrane 7 comprises a number of intersecting solid support structures 37 which are not provided with channels and which divide the membrane into a number of triangular channel-containing segments 38. Such solid support structures may be integral with the membrane 7 or may comprise additional elements arranged on the first and / or second surface of the membrane.

[0121] Reference numerals list

[0122] 1 Device

[0123] 2 First Entrance

[0124] 3 Second Entrance

[0125] 4. Room 1

[0126] 5. Second Room

[0127] 6 Dispersion outlet

[0128] 7 Membrane

[0129] 8 First side

[0130] 9 Second side

[0131] 10 channels

[0132] 11 Channel Entrance

[0133] 12 channel exit

[0134] 13 Pole

[0135] 14 Base

[0136] 15 Central axis

[0137] 16 Spacer ring

[0138] 17 Sealing ring

[0139] 18 Clamping device

[0140] 19 Container

[0141] 20 Membrane holder

[0142] 21 Container holder

[0143] 22 grooves

[0144] 23 pads

[0145] 24 First Storage

[0146] 25 Second storage

[0147] 26 Current Limiter

[0148] 27a,b Pressure regulator

[0149] 28 Flow Meter

[0150] 29 Product containers

[0151] 30 Waste container

[0152] 31 Flush reservoir

[0153] 32 Stressors

[0154] 33 Heater or cooler

[0155] 34 Supply Channel

[0156] 35 Opening

[0157] 36 Gas outlet

[0158] 37 Solid support structure

[0159] 38 sections

[0160] 39 Readout unit

[0161] 40 Control components

[0162] 41 Transmitter Unit

[0163] 42 Analysis Units

[0164] 43 Tags

[0165] 44 membrane seal

[0166] 45 Membrane Storage Unit

[0167] M main section.

Claims

1. A single-layer membrane (7) for producing a dispersion of a first phase in a second phase, the membrane comprising a first side (8) and a second side (9) opposite thereto and a plurality of channels (10) extending through the membrane from the first side to the second side, wherein each channel comprises a channel inlet (11) arranged at the first side (8), a channel outlet (12) arranged at the second side (9) and a main section (M) arranged between the channel inlet (11) and the channel outlet (12), wherein the channel outlet comprises a shape deviating from the shape of the main section, and wherein each channel (10) of the membrane (7) has a rounded cross-section relative to a transverse plane and is edgeless at least in the channel and the channel outlet.

2. The single-layer film (7) according to claim 1, characterized in that The cross-sectional area of ​​the channel outlet (12) is larger than the cross-sectional area of ​​the rest of the channel.

3. The single-layer film (7) according to claim 1 or 2, characterized in that: The cross-sectional area of ​​the rest of each channel is 0.125 μm 2 Up to 4mm 2 within the range.

4. The single-layer film (7) according to claim 1 or 2, characterized in that: The thickness of the film (7) is 0.05 mm to 20 mm.

5. The single-layer film (7) according to claim 1 or 2, characterized in that: The membrane (7) comprises at least one solid support structure without channels, the solid support structure dividing the membrane (7) into two or more sections (38) containing channels.

6. The single-layer film (7) according to claim 1 or 2, characterized in that: The membrane comprises a label (43).

7. The single-layer film (7) according to claim 1 or 2, characterized in that: The membrane (7) comprises a membrane sealing ring (44) which completely surrounds the periphery of the membrane circumferentially.

8. The single-layer film (7) according to claim 1 or 2, characterized in that: The cross-sectional area of ​​the rest of each channel is 10 μm 2 Up to 0.5mm 2 within the range.

9. The single-layer film (7) according to claim 1 or 2, characterized in that: The thickness of the film (7) is 0.5 mm to 20 mm.

10. The single-layer film (7) according to claim 1 or 2, characterized in that: The film includes a computer readable label.

11. An apparatus (1) for producing a dispersion of a first phase in a second phase, the apparatus (1) comprising: a. a first inlet (2) for supplying a first phase, the first inlet (2) leading to the first chamber (4); b. a second inlet (3) for supplying a second phase, said second inlet (3) leading to a second chamber (5); c. a dispersion outlet (6) for collecting the dispersion of the first phase in the second phase; d. A single-layer membrane (7) according to any one of claims 1 to 10, wherein the single-layer membrane (7) separates the first chamber (4) and the second chamber (5), the membrane (7) comprising a first side (8) facing the first chamber (4) and a second side (9) facing the second chamber (5), in, e. A plurality of channels (10) extending from the first side (8) to the second side (9) of the membrane (7) provide a fluid connection between the first chamber (4) and the second chamber (5), each channel (10) comprising a channel inlet (11) disposed on the first side (8) and a channel outlet (12) disposed on the second side (9); f. The first chamber (4) is configured such that the flow rate of the first phase through each individual channel (10) is uniform.

12. The device (1) according to claim 11, characterized in that The first chamber (4) is configured such that the pressure along the first side (8) of the membrane (7) is isobaric.

13. The device (1) according to claim 11 or 12, characterized in that The first chamber (4) has a rounded cross section.

14. The device (1) according to claim 13, characterized in that The first chamber (4) has a hemispherical shape.

15. The device (1) according to claim 11 or 12, characterized in that The second side (9) of the membrane (7) has a total open area formed by the channels (10), which is greater than the total open area of ​​the first side (8).

16. The device (1) according to claim 11 or 12, characterized in that Each channel (10) comprises an end region at the channel outlet (12), the cross-sectional area of ​​the end region being larger than the cross-sectional area of ​​the remainder of the corresponding channel (10).

17. The device (1) according to claim 11 or 12, characterized in that The first inlet (2) is arranged at an angle of 90° or less relative to the channel (10) of the membrane (7).

18. The device (1) according to claim 11 or 12, characterized in that The device comprises a membrane holder (20) for mounting a membrane (7).

19. The device (1) according to claim 18, characterized in that The membrane holder (20) comprises a clamping device (18) for mounting the membrane (7), the membrane holder (20) and / or the clamping device (18) being configured to accommodate membranes (7) having different thicknesses.

20. The device (1) according to claim 11 or 12, characterized in that The device comprises a base (14), and in that the first chamber (4) is partly formed by the base (14).

21. The device (1) according to claim 20, characterized in that The base (14) and / or the membrane holder comprises at least one seal (17) for sealing the membrane (7) against the base (14) and / or against the membrane holder (21).

22. The device (1) according to claim 11 or 12, characterized in that The first chamber (4) comprises a gas outlet (36), and the gas outlet (36) and the membrane (7) are arranged such that: during supply of the first phase to the first chamber (4), gas within the first chamber is directed to the gas outlet (36) and removed from the first chamber (4) via the gas outlet (36).

23. The device (1) according to claim 11 or 12, characterized in that The device comprises a heater and / or a cooler (33) to heat and / or cool the first phase and / or the second phase.

24. The device (1) according to claim 11 or 12, characterized in that The device comprises a first reservoir (24) for the first phase and / or a second reservoir (25) for the second phase, so that the flow rate through the membrane (7) is adjustable.

25. The device (1) according to claim 24, characterized in that A flow restrictor (26) is arranged between the second reservoir (25) and the second chamber (5).

26. The device (1) according to claim 11 or 12, characterized in that The second inlet (3) comprises a supply channel (34), which is at least partially arranged circumferentially around a central longitudinal axis and / or an axis perpendicular to the first and second sides of the membrane and intersecting the center of the membrane, and the supply channel comprises one or more openings leading to the second chamber.

27. The device (1) according to claim 11 or 12, characterized in that The film (7) comprises a tag (43), and in that the device (1) further comprises a read-out unit (39) configured to retrieve data from the tag (43) and a control unit (40) configured to process the data from the tag (43).

28. The device (1) according to claim 11 or 12, characterized in that The apparatus further comprises a transmitter unit (41) configured to transmit data to the receiver.

29. The device (1) according to claim 11 or 12, characterized in that The device also comprises an analysis unit (42) with sensors for determining and controlling quality values, namely the size and size distribution of the monodisperse droplets produced.

30. The device (1) according to claim 14, characterized in that The first inlet (2) is arranged adjacent to a pole (13) of the hemispherical first chamber.

31. The device (1) according to claim 17, characterized in that The first inlet (2) is arranged transversely to the plurality of channels (10) of the membrane (7).

32. The device (1) according to claim 27, characterized in that The film (7) comprises an RFID tag or a barcode.

33. The device (1) according to claim 11 or 12, characterized in that The device further comprises an evaluation unit (42) with a sensor, the evaluation unit having an optical sensor.

34. A method of producing a dispersion of a first phase in a second phase using an apparatus according to any one of claims 11 to 33, wherein - the first phase is supplied into the first chamber through the first inlet, and - the second phase is supplied into the second chamber through the second inlet, wherein - the first phase flows from the first chamber into the second chamber through the plurality of channels of the membrane to form a dispersion of the first phase in the second phase.

35. The method according to claim 34, characterized in that The pressure along the first side of the membrane is isobaric.

36. The method according to claim 34 or 35, characterized in that The mass flow through each channel is equal across the membrane.

37. The method according to claim 34 or 35, characterized in that An overpressure of up to 1.2 atm is applied to the first phase in the first chamber.

38. The method according to claim 34 or 35, characterized in that The pressure of the second phase in the second chamber is 0.01 to 10 atm.

39. The method according to claim 34 or 35, characterized in that Before supplying the second phase into the second chamber, the pressure of the second phase is reduced by a flow restrictor.

40. The method according to claim 34 or 35, characterized in that A readout unit retrieves data from the tag on the film, and the retrieved data is provided to a control unit, which processes the data.

41. The method according to claim 34 or 35, characterized in that Data is sent from the sending unit to the receiver.

42. The method according to claim 34 or 35, characterized in that The generated dispersion comprises monodisperse droplets, at least one of which is analyzed in an analyzing unit having a sensor.

43. The method according to claim 34 or 35, characterized in that The resulting dispersion of the first phase in the second phase is further processed to produce capsules and particles.

44. The method according to claim 34 or 35, characterized in that The pressure of the second phase in the second chamber is 0.01 to 1 atm.

45. The method according to claim 34 or 35, characterized in that The resulting dispersion of the first phase in the second phase is further processed to generate at least one of: microcapsules, microparticles, nanocapsules, nanoparticles.

46. ​​A system for producing a dispersion having multi-core droplets, the system comprising at least two devices according to any one of claims 11 to 33 connected in series.

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