EP1931453A1

EP1931453A1 - Apparatus and method for producing a mixture of two phases that are insoluble in each other

Info

Publication number: EP1931453A1
Application number: EP06792143A
Authority: EP
Inventors: Stefan Haeberle; Jens DUCRÉE; Roland Zengerle
Original assignee: Hann-Schickard-Gesellschaft fuer Angewandte Forschung eV
Current assignee: Hann-Schickard-Gesellschaft fuer Angewandte Forschung eV
Priority date: 2005-10-07
Filing date: 2006-09-19
Publication date: 2008-06-18
Also published as: WO2007042126A1; DE102005048259A1; DE102005048259B4; US20090197977A1

Abstract

An apparatus for producing a mixture of two phases that are insoluble in each other comprises a first fluid channel (134) and a second fluid channel (130), which open out into a contact region (132). Also provided is a third fluid channel (138), which opens out into the contact region. The apparatus comprises a device which is configured to impart a rotation on the fluid channels, wherein a first phase is supplied to the contact region centrifugally through the first fluid channel and a second phase, which is insoluble in the first phase, is supplied to the contact region through the second fluid channel, wherein the rotation is used to cause centrifugal-hydrodynamically induced compressive and/or shearing forces in the contact region to make drops break away in one of the supplied phases, in order to produce the mixture of the first and second phases.

Description

Apparatus and method for producing a mixture of two intractable phases

description

The present invention relates to an apparatus and a method for producing a mixture of two intractable phases, for example emulsions or foams.

Emulsification is a key step in a variety of production processes in the food, cosmetics and pharmaceutical industries. In emulsification, two intractable liquids, such as oil and water, are mixed to produce a batch in which one liquid is dispersed in the form of small droplets in the other.

Apparatuses used to prepare emulsions fall into two broad groups, namely turbulence inducing systems and controlled droplet generation systems.

With respect to turbulence-induced systems, for example, rotor-stator systems are used for industrial use where a rotor is used to stir in the fluids to produce the batch. Such systems are available, for example, from Microtec Co., Ltd. (http://nition.com/en). Furthermore, high-pressure homogenizers, for example from Niro Inc. (http://www.niroinc.com "), or ultrasound-based systems, for example Dr. Hielscher GmbH (http://www.hielscher.com), are used These devices can be used universally to disperse multiple immiscible phases by inducing large shear forces into the phase boundaries to achieve intermixing and varying the size distribution of the disperse phase However, this method is very strong because stochastically distributed tearing effects in turbulent flows are responsible for the drop generation. Another disadvantage of these mechanical dispersing processes is the energy input into the phase mixture. As a result, the temperature of the emulsion is increased and heat-sensitive components, as they are often found in pharmaceutical production, can be destroyed.

The disadvantages of the turbulence-inducing systems, namely a broad droplet size distribution and a heating of the emulsion, can be circumvented by systems in which structures in the order of the droplets to be generated are used for a geometrically controlled droplet generation.

A well-known example for the production of monodisperse emulsions is a membrane reactor, which is disclosed, for example, by the Fraunhofer Institute for Interfacial Engineering and Bioprocess Engineering (http://www.igb.fraunhofer.de). An example of such a membrane reactor is shown in Fig. 1, wherein a continuous phase 10 is passed between two porous membranes 12 and 14 through whose micropores 16 a phase 18 to be dispersed is forced into the continuous phase. The disperse phase is then sheared from the perpendicular to it flowing, continuous phase at the exit from the pores 16 and it forms drops 20. Thereby, an emulsion 22 of the continuous phase 10 and the disperse phase 18 is generated.

More recently, the production of stable microemulsions exhibiting small droplet size distributions has been disclosed by microfluidic systems, see T. Thorsen, RW Roberts, FH Arnold and SR Quake, Phys. Rev. Lett. 86, p. 4.163-4166 (2001). The generation of double emulsions by microfluidic systems has also been disclosed, see AS Utada, E. Lorenceau, DR Link, PD Kaplan, HA Stone, DA Weitz, Science, 308, Pp. 537-541 (2005). In the case that the droplet size is adjusted to the range of channel dimensions, a continuous flow is subdivided into separate fluid compartments, each of which is a tiny reaction vessel where fast diffused and even convection-assisted mixing takes place. See A. Günther, M Jhunjhunwala, M. Thalmann, MA Schmidt and KF Jensen, Langmuir, 21, pp. 1.547-1555 (2005), and LS Roach, H. Song, RF Ismagilov, Anal. Chem., 77, pp. 785-796 (2005).

By such techniques, emulsions having a very narrow distribution of drop sizes, so-called monodisperse emulsions, can be prepared.

Such microfabricated fluidic structures in the sub-millimeter range, which are referred to as microfluidic systems, allow the controlled production and manipulation of individual drops, so that emulsions with a very narrow-band distribution of droplet sizes and thus highly monodisperse emulsions can be produced.

T. Nisiako, T. Toru and H. Toshiro, "Rapid Preparation of Monodispersed Droplets with Confluent Laminar Flows", in Proceedings of the Sixth International Conference on Microelectromechanical Systems (MEMS 2003, pp. 331-334) a first phase 30 is passed as a continuous phase through a first fluid channel 32 to a connection point 34, while through a further fluid channel 36 a second phase 38 as a disperse phase to the In order to supply the phases, syringes and syringe pumps are used at the contacting point because of the special hydrodynamic conditions, for example the high shear forces, in the microchannels to a sequence of droplet breaks of the disperse in the continuous Phase, so that in an outlet channel 40, an emulsion of the first and the second phase is generated.

QY Xu and M. Nakajima, "The generation of highly monodisperse droplets through the breakup of hydrodynamically focused microthreads in a microfluidic device", Applied Physics Letters, Vol. 85, No. 17, pp. 3,726-3,728, 2004 Such a channel structure is shown in Fig. 3 and comprises a central channel 42 over which a disperse phase, e.g., soybean oil, is supplied, and two lateral channels 44 and 46 via which a continuous phase, e.g. SDS (sodium-dodecyl sulfate) solution is used to supply the phases using micro-syringe pumps for pumping the disperse phase and the continuous phase, at the juncture of the three channels 42, 44 and 46, at which there is contact between them Due to the special hydrodynamic conditions in the microchannels, a controlled droplet demolition occurs the dispersions into the continuous phase in the downstream fluid region.

With regard to the physical principles of droplet formation in the channels shown in FIGS. 2 and 3, reference is made to the aforementioned publications by Nisiako and Xu.

Regardless of the methods mentioned above for producing emulsions, microfluidic systems are known from the prior art which use centrifugal forces to handle liquids, see J. Ducree, HP. Schlosser, S. Haeberle, T. Glatzel, T. Brenner, R. Zengerle, Proc. μTAS 2004, Malmö, Sweden, pp. 554-556. Droplet-based analyzes and corresponding micro-processing techniques are also described, for example, by S. Okushima, T. Nisisako, T. Torii, T. Higuchi, Proc. of μTAS 2004, Malmo, Sweden, pp. 258-260. The object of the present invention is to provide an apparatus and a method for producing a mixture of two intractable phases, which allow a controlled and reproducible droplet size.

This object is achieved by a device according to claim 1 and a method according to claim 10.

The present invention provides an apparatus for producing a mixture of two intractable phases with the following features:

a first fluid channel opening into a contact area;

a second fluid channel opening into the contact area;

a third fluid channel opening into the contact area; and

a device configured to impart rotation to the first fluid channel, the second fluid channel, and the third fluid channel, wherein a first phase is supplied centrifugally through the first fluid channel to the contact region and a second phase insoluble in the first phase the centrifugal-hydrodynamically induced pressure and / or shear forces in the contact region cause drop separation in one of the supplied phases to produce the mixture of first and second phases.

The present invention further provides a method for producing a mixture of two intractable phases comprising the steps of: centrifugally feeding a first phase through a first fluid channel to a contact region;

Supplying a second phase through a second fluid channel to the contact area,

wherein the centrifugal feeding is effected by a rotation of the first fluid channel, the second fluid channel and the contact region, wherein the centrifugally hydrodynamically induced pressure and / or shear forces in the contact region cause a droplet break in one of the supplied phases to the first batch and second phase; and

centrifugally discharging the batch from the contact area through a fluid channel.

The present invention is thus based on exploiting centrifugal force over known techniques to contact at least two immiscible phases in a rotating system to produce emulsions when the two phases are liquids. Liquid phases are thereby fed centrifugally through the rotation to the contact area.

Foams, for example monodisperse liquid-gas-phase dispersions, can also be produced according to the invention if one phase is a liquid and one phase is a gas. Feeding a gaseous phase into a liquid phase is not directly possible by centrifugal pumping because the gas phase would be pumped radially inward instead of outward in the presence of the much denser liquid phase. In order to produce liquid-gas dispersions, in embodiments of the invention, therefore, a device is provided which allows a supply of the gas via the associated fluid channels or channels. Such a device could be formed for example by a co-rotating pump (on-board pump). Further, aspiration of the gas according to the water jet pump principle could be done at a radially outward location of the high velocity channel of the liquid stream.

The present invention thus deals with the production of droplets or emulsions in rotating channels as well as the processing of immiscible phases in rotating modules. According to the invention, at least one and in the case of two liquids, both phases are transported by centrifugal forces in fluid channels and the phases are combined at at least one location, whereby a controlled drop break of at least one phase takes place. This process can be repeated serially and in parallel.

The pump according to the invention by means of the centrifugal force allows continuous operation, d. H. a pulse-free force field on the interacting fluids. In this case, the rotational frequency is stabilized in the continuous rotational movement over the moment of inertia of the rotor with respect to speed fluctuations of the drive. Oscillations as in a drive via syringe pumps or positive displacement pumps are thereby avoided.

This means constant conditions for all droplet break-off processes and thus reproducibility of the processes or the droplets produced. Here, the pumping of highly viscous media by means of centrifugal force is possible. In preferred embodiments, the phases are continuously metered into an inlet region of the fluid channels, such an inlet region being able to be formed, for example, by a reservoir on an upper side of a rotor. The liquids can then be supplied via suitable guide structures in the rotor to closed channels, which represent the fluid channels whose radially outer ends open into the contact area. In further embodiments of the invention, a continuous, radial ejection of Processed liquid from the rotor into a collecting device. Alternatively, the liquid can be collected in a cavity on the rotor, optionally together with a targeted discharge thereof. Thus, according to the invention, no pressure-tight fluid interfaces are necessary, since media to be processed can be directed in the free jet into the process module and, if appropriate, can be led out of it.

In preferred embodiments, the channel structure of the present invention comprises three feed channels in the form of a "sheath-flow" structure in which the phase to be dispersed is contacted with the continuous phase at a contacting site from two opposite sides in which at least two miscible or immiscible phases are enclosed in one drop, to achieve this, a mixture of two miscible or immiscible phases can be fed via one of the feed channels. In addition, double emulsions can also be produced according to the sheath-flow principle by adding further phases in, for example two, further supply channels for contacting be added. These can be used, for example, for encapsulating an internal phase relative to the continuous medium (vesicle).

The channel structures required to implement the invention may either be formed directly in a rotor, for example a disk, or may be formed in a module which is inserted into a rotor. Further processing of the drops on the rotor or the rotating module, for example a renewed splitting of the drops, is also possible. In addition, through an integrated extraction of the phases, For example, by sedimentation and / or decantation, new process flows are made possible. In addition to the production of emulsions, the present invention also permits the preparation of dispersions of gases and liquids, ie foams.

The use according to the invention of the centrifugal force for producing a mixture of two phases insoluble in one another enables precise control and reproducibility of the droplet size via hydrodynamic boundary conditions defined by geometric structures. In addition, identical structures can be operated in parallel, which leads to a parallelization on the process module. In the invention, new "centrifugal" conditions of drop separation are present, allowing access to new ranges of experimental parameters, such as droplet size, droplet frequency, droplet spacing for given viscosities, densities, and surface / interfacial tensions of the liquids to be dispersed By centrifugal pumping a heat input into the liquids are completely avoided.

In order to allow the centrifugal liquid transport open respectively radially outer ends of the channels through which liquids are supplied to a contact region in the contact region, while radially inner ends of the channel or the channels, which serve for the discharge of liquids or a liquid-gas emulsion , enter the contact area. By "radially outer" end is meant an end that is radially further out than another end of the respective channel so that centrifugally driven liquid transport from the other end to the radially outer end is possible. radially inner end is understood to mean an end which is radially inward than another end of the respective channel, so that a centrifugally driven liquid transport from the radially inner end to the other end is possible. These terms thus represent is not an absolute condition to the effect that the channels could not have arcs whose arc sections are radially further outward or inward than the respective junctions, as long as a centrifugal liquid transport, as described above, is possible.

The present invention thus provides a novel centrifugal microfluidic process for the continuous production of highly monodispersed mixtures of two intractable phases, for example water droplets in an oil flow. The present invention can be readily integrated on centrifugal platforms with other processing techniques, such as centrifugal droplet sedimentation, enabling novel applications in the field of droplet-based analysis and microprocessing technology.

Preferred embodiments of the present invention will be explained in more detail below with reference to the accompanying drawings. Show it:

Fig. 1 shows a membrane reactor according to the prior art;

2 and 3 channel structures according to the prior art;

4 shows a schematic cross-sectional view of an embodiment of a device according to the invention;

5 is a schematic plan view of a channel structure according to an embodiment of the present invention;

Figs. 6 to 8 are schematic diagrams for explaining the functionality of the present invention; and Fig. 9 shows experimental results of an implementation of the invention.

Referring to FIG. 4, the basic structure of an embodiment of the present invention is explained below, wherein an exemplary channel structure for generating a mixture of two non-detachable phases is described below with reference to FIG. 5.

The embodiment shown in Fig. 4 of the present invention comprises a drive unit 100, which is formed for example by a rotary motor with an associated control. The device further comprises a rotational body 102, which is rotatable about a rotational axis Z by the drive unit 100. In this case, the drive unit 100 comprises a suitable device for holding the rotational body 102. The device further comprises a first fluid injection module 104 and a second fluid injection module 106. In addition, a fluid collecting device 108 is provided which surrounds the rotational body 102 in an annular manner.

At least one channel structure, which makes it possible to generate a mixture of two non-detachable phases, is provided in the rotary body 102. In preferred embodiments, however, a plurality of corresponding channel structures 110, which are arranged in the rotational body in a star shape and extending radially outward, are preferably provided, which can be fed via separate or common reservoirs. The rotary body 102 is in the illustrated embodiment of a substrate 102, which may be formed of any suitable material, such as plastic, silicon, glass or the like. In the substrate 102, the channel structures 110 are structured. The substrate 102a is provided with a lid 102b which has openings 112 for fluid communication with fluid reservoirs 114 and 116, which are formed on the rotary body 102 has. The reservoirs 114 and 116 are annularly formed on the rotary body 102 so as to allow continuous filling via the fluid injection devices 104 and 106 during rotation. The reservoirs are also shaped so as to avoid centrifugal overflowing up to a certain rotational frequency, which should be above the speed required for droplet production.

The channel structures 110 are open radially outwardly so that liquid may be expelled from them radially outwardly into the catcher 108 by centrifugal force. The catcher 108 may further be provided with suitable drainage means to remove the generated batch from the same, as indicated by an arrow 120. Also, the dispersion can be collected in a co-rotating reservoir.

In operation, a first liquid is continuously introduced into the reservoir 114 by the fluid injection device 104, while a second liquid is continuously introduced into the reservoir 116 by the fluid injection device 106. The reservoirs 114 and 116 are designed to hold the liquids in the reservoirs during rotation of the rotary body 102 about the rotation axis Z perpendicular to it. During the rotation of the rotary body 102 about the axis Z, the liquids reach the channel structures 110 by centrifugal force assisted by gravitational force, where they are driven radially outward by the centrifugal force F _z . The outgoing from the reservoirs 114 and 116 fluid channels open in each case at a radially outer end in a contact region, in which further opens a radially inner end of a third fluid channel. Where the fluids meet in the contact area, caused by the rotation centrifugally-hydrodynamically induced pressure and / or shear forces a drop break in one of the supplied Liquids, so that an emulsion of the two liquids is centrifugally driven outward through the third channel and is ejected into the catcher 108 at the radially outer end of the rotary body.

The device which was described with reference to FIG. 4 thus comprises a drive unit and a process module, the process module consisting of at least two fluid inlets or at least two reservoirs and a microstructured substrate which is perpendicular to the axis of rotation about a rotation axis Z Can rotate substrate surface. The fluid inputs are designed so that a continuous supply of several liquid streams under rotation is possible.

In the example shown in FIG. 4, the fluids are continuously ejected from the process module into the catcher 108 after processing, and optionally discharged via a suitable device 120. Alternatively, the fluids could be collected after processing in further reservoirs on the module.

In the embodiment shown in FIG. 4, the channel structures are formed in the rotor 102. Alternatively, the channel structures could be integrated in a channel module that can be inserted into a rotor. The rotor could then include, for example, the reservoir structures and / or catch reservoirs and / or structures that enable radial ejection of the processed fluids.

As has been stated, the fluids, in the preferred embodiment, non-dissolvable fluids, are coupled via vertical communication channels or openings 112 in the lid 102b to the substrate and coupled into the microchannels of the channel structure which causes the formation of an emulsion. Under rotation, the fluids are transported centrifugally to the outside, wherein the to be dispersed Phases are passed in separate and differently shaped microchannels to a contact point.

An embodiment of such a channel structure for effecting a suspension of two intractable phases is shown in FIG. More specifically, Figure 5 shows schematically a section of the rotor 102 with the channel structure for generating a mixture of two phases insoluble in one another. The channel structure has a fluid channel 130, the radially outer end of which opens into a contacting point or a contacting region 132, and two fluid lines 134 and 136, whose radially outer ends likewise open into the contacting region 132. The radially outer ends of the fluid channels 134 and 136 open into the contact region with respect to the fluid channel 130 from two opposite sides, so that the fluid channel 130 is arranged between the fluid channels 134 and 136. A radially inner end of an outlet channel 138 also opens into the contacting region 132, preferably with respect to the fluid channel 130. The fluid channel 130 is connected, for example, to the reservoir 106 in order to obtain the phase to be dispersed therefrom. For example, the fluid channels 134 and 136 are connected to the reservoir 104 to receive the continuous phase therefrom. Upon rotation of the rotor 102, as indicated by a rotational frequency v in FIG. 5, a centrifugal flow is caused in the fluid channels 130, 134, and 136. More specifically, in the fluid channel 130, the fluid to be dispersed _is supplied via a fluid flow Φ _d , while via the channels 134 and 136, the continuous fluid with a fluid flow Φ _{c is} supplied. The channel structure shown in FIG. 5 illustrates a so-called "sheath-flow" structure. The phase to be dispersed Φ _d is contacted in the contacting region 132 to the continuous phases Φ _c from both sides, thereby inducing a drop of demolition. The different design, ie length and cross section, of the channels defines the hydrodynamic resistances R _d and R _{c of} the supply channels and the hydrodynamic resistance R _{aUs of} the discharge channel 138, as indicated on the left side of FIG. 5. By means of these hydrodynamic resistances and by the rotational speed, the flow velocities of the two phases at the contacting point 132 can be controlled. Together with the pulse-free centrifugal pumping, the droplet break-off at the contacting point can thus be controlled with high precision and repeatability.

In FIG. 5, two torn off drops 140, which have a droplet diameter d and a distance Δ from one another, are shown purely schematically.

Four phases of drop breakage are shown in a stroboscopic frame sequence in FIGS. 6a-6d. The sequence was recorded using water as the phase to be dispersed and sunflower oil as the continuous phase.

As has been described, the disperse phase supplied by the fluid channel 130 by centrifugal force F _{v is} contacted from two sides with flows of the continuous phase fed through the channels 134 and 136 and directed into a common channel 138. This takes place at a defined angle of attack in order to achieve a constricting effect of the two side streams on the disperse phase coming from the central channel 130 and to promote the drop separation at the contacting point.

In addition to the channel arrangement and the wetting property of the channels is important. The continuous phase Φ _c preferably wets the channels in comparison to the dispersive phase Φ _d . Thus, the dispersive phase must be actively drawn out of the center channel 130 by the centrifugal force F ₂ . From a certain size onwards in the contact Due to the constricting effect of the side streams Φ _c and the interfacial tension between the two phases, the front of the dispersive phase Φ _d projects to a drop break, as shown in FIGS. 6b-6d. The generated droplet 140 is then guided via the outlet channel 138 and preferably a channel region 150 with a significantly lower flow resistance (see FIG. 5) adjoining it in the direction of the outer edge of the rotary body 102 and ejected through the channel end open at this end. Alternatively, the same can be collected in a reservoir on the rotary body 102, for which purpose an outlet opening can be provided, see opening 152 in FIG. 5.

Both the droplet size and the type of multiphase flow can be adjusted by targeted changes in the geometric parameters of the channel structure and the rotation frequency. In this regard, Figures 7a-7c show different "sheath-flow" channel structures with respective inlet channels 130, 134 and 136 when operating at different rotational frequencies v. By varying the geometric parameters and rotational frequencies, different types of emulsion can be made As shown in Figures 7a-7c, three different forms of multiphase flows have been produced, as shown in Figures 7a and 7b, there are isolated droplets 160, ie, spatially isolated droplets flowing in suspension, and pinched droplets 162, ie, droplets which are in the vertical position against the channel walls, as shown in Fig. 7c In addition, it is possible to produce a segmented flow, that is, drops in the vertical and the horizontal (transverse to the flow) This may be assisted, for example, by moving downstream in the exhaust duct a taper is provided, as shown in the left portion of the outlet channel 164 in Fig. 7c. FIGS. 7d-7f respectively show the same channels as FIGS. 7a-7c when operating at higher frequencies.

The microchannels can be formed in a polymer substrate, for example made of COC (cyclic olefin copolymer), in which the continuous phase (for example nonpolar oil) exhibits wetting properties which are higher than the phase to be dispersed (for example water). Thus, the water plug must be actively pulled by centrifugal force from the central channel 130, against the force F _{σ of} the surface tension. At low rotational frequencies, the water plug thus rests in the middle channel, so that the working area over which droplet formation takes place has a lower limit frequency vi _ow . Above this lower limit frequency, the water plug leaves the middle channel and breaks off as soon as the mass of the droplet exceeds a critical mass. The upper limit of the working range v _hOc h is determined by the point at which, due to the droplet diameter d and the drop spacing Δ, the droplets start to touch and _grow together. In this regard, operation in Figs. 7d and 7e is above the cut-off frequency for generating individually separated drops since there has been contact between drops, see reference numeral 170, or drop coalescence, see reference numeral 172.

With regard to the production of the droplets can be retained, that the droplet formation process _c through the hydrodynamic resistances R, Rd and R _au sr the radial positions of the feed channels and the outlet channel as well as the geometry of the drop-carrying channel and the rotational speed is influenced. The channel geometries to be used for different fluids for the production of emulsions or foams as well as rotational speeds are readily determinable for experts by appropriate calculations or simulations. An example of a way to further process the generated drops on the rotating platform is shown in Figs. 8a and 8b. In this case, a droplet guide channel 180, which may be formed, for example, by the region 150 in FIG. 5, merges into a fluid channel 182 whose radially outer end opens into a second contact region 184. Further, in another contact region 184 radially outer ends of supply ducts 186 and 188. About open the feed channels 186 and 188 a continuous phase Φ _c is supplied, while a drop of 140-containing emulsion is fed via the channel 182nd Thus, the continuous phase Φ _c acts from the outside on a drop 140 'located in the contact area 184, so that this drop can be subdivided into two separate drops 190. This process is also initiated by a "sheath-flow" structure and can be controlled precisely, whereby the frequency is set a bit too high according to FIG. 8b, since there is no clean splitting into two drops, but rather an additional satellite drop is produced.

The droplet formation method of the invention was tested using surfactant-free sunflower oil and ink-dyed water (2% by volume).

Two parameters, a characteristic droplet area A and the droplet distance Δ, which is a measure of the droplet production rate, were experimentally evaluated. The diameter d as well as the volume of the droplets was partially approximated from A because the droplets were partially crushed to an unknown extent between the upper and lower channel walls, the channel having a depth of about 200 microns.

Three different functions could be realized by varying the design of the structure. In this regard, fully free-flowing and isolated droplets can be made using a high Φ _c and a small _ro be generated. Vertical crimped droplet trains can be realized while a segmented flow may be implemented by a constriction in the droplet carrying channel using a small flow rate Φ _c and a large R _from. As already stated, in addition to the channel geometry, the frequency of the rotation also influences the distance and the diameter of the droplet, the droplet production rate increasing as the rotational frequencies increase, while the size thereof decreases. The results relating to the droplet diameter d and the droplet spacing Δ are shown in FIGS. 9a and 9b as a function of the rotational frequency v. Curves 200 and 202 refer to isolated droplets, while curves 204 and 206 refer to pinched droplets.

The present invention thus provides an apparatus and a method enabling the generation of monodisperse droplet trains (CV <2%). The experiments carried out allow droplet generation with droplet volumes between 5 and 22 nL within a working range, the size and spacing of which can be controlled by channel geometry and rotational frequency. Furthermore, the present invention allows another important operation, namely the hydrodynamic splitting of droplets. The centrifugal platform also provides new capabilities in multi-phase microfluidic applications, with particular emphasis on sedimentation.

Exemplary post-processing of blends produced in accordance with the present invention may include bead polymerization of dispersed drops, which may result in solid-liquid emulsions having monodisperse solid phase particles.

Preferred exemplary embodiments have been explained above with reference to a so-called "sheath-flow" channel structure, but the present invention is not limited to such a channel structure but can also be used with alternative channel structures that facilitate droplet detachment can be implemented, for example, by a T-shaped channel structure as shown in FIG. 2 of the present application.

Claims

claims

1. A device for generating a Geraenges of two intractable phases, with the following features:

a first fluid channel (134) opening into a contact region (132);

a second fluid channel (130) opening into the contact area (132);

a third fluid channel (138) opening into the contact area (132); and

means (100) configured to apply rotation to the first fluid channel (134), the second fluid channel (130), and the third fluid channel (138), wherein a first phase through the first fluid channel (134) is centrifugal the contact region (132) is supplied and a second insoluble in the first phase phase through the second fluid channel (130) to the contact region (132) is supplied, wherein by the rotation centrifugally-hydrodynamically induced pressure and / or shear forces in the Kontaktbe - rich (132) cause a drop break in one of the supplied phases to produce the mixture of first and second phases.

2. Apparatus according to claim 1, further comprising a fourth fluid channel (136) in the contact area

(132) opens, wherein the second fluid channel (130) between the first (134) and the fourth (136) fluid channel opens into the contact region, so that a phase flow from the first and fourth fluid channel (134, 136) from opposite sides a phase flux from the second fluid channel (130) strikes, whereby a drop break of the phase flow from the second fluid channel (130) is effected.

3. Apparatus according to claim 1 or 2, further comprising means for metering (104, 106, 114, 116) at least one of the phases into an inlet region of at least one of the fluid channels during rotation.

4. Apparatus according to any one of claims 1 to 3, further comprising means (108) for continuously receiving the generated batch from the third fluid channel (138, 150).

5. A device according to any one of claims 1 to 4, wherein the fluid channels (130, 132, 134, 136, 150) are formed in a module (102), the mixture being expelled radially from the module, and wherein the Device further comprising means (108) for collecting the radially ejected from the module (102) batch.

6. Device according to one of claims 1 to 4, wherein the fluid channels (130, 132, 134, 136, 150) are formed in a module, and in which the module is inserted into a rotor or in which the module is a rotor ,

The apparatus of claim 6, wherein the rotor has a receiving reservoir for receiving the generated batch.

8. Apparatus according to claim 6, wherein the rotor comprises a plurality of channel structures of first, second, third and, if present, fourth fluid channel, which are arranged in a star shape from a radially inner region to a radially outer region thereof.

9. Device according to one of claims 1 to 8, wherein a radially outer end of the third fluid channel (138, 150) opens into a further contact region (184), in which further the radially outer end of at least one further fluid channel (186, 188), so that centrifugally-hydrodynamically induced pressure and / or shear forces in the further contact region (184) caused by the rotation cause a further splitting of the drops (140) in the mixture fed through the third fluid channel.

10. Device according to one of claims 1 to 8, wherein a radially outer end of the third fluid channel (138, 150) opens into a further contact area, in which further opens the radially outer end of at least one further fluid channel, so caused by the rotation centrifugal hydrodynamically induced pressure and / or shear forces in the further contact region (184) cause the generation of a mixture of the mixture of first and second phases and a third phase supplied via the at least one further fluid channel.

11. Device according to one of claims 1 to 10, wherein the phases are liquids, wherein the device is designed such that the phases are supplied centrifugally to the contact region or the contact regions.

The apparatus of any one of claims 1 to 10, wherein one of the phases is a gas, the apparatus further comprising means for supplying the gas through the fluid channel (s) to the contact area (s).

13. A method of producing a mixture of two intractable phases comprising the steps of: centrifugally feeding a first phase through a first fluid channel (134) to the contact region (132);

Supplying a second phase through a second fluid channel (130) to a contact region (132),

wherein the centrifugal feeding is effected by a rotation of the first fluid channel (134), the second fluid channel (136) and the contact region (132), wherein the rotation centrifugally-hydrodynamically induced pressure and / or shear forces in the contact region a drop break in one of supplied phases to produce the mixture of first and second phase; and

centrifugally discharging the batch from the contact area through a third fluid channel (138, 150).

14. The method of claim 13, further comprising a step of supplying a third phase through a fourth fluid channel to the contact region, the second fluid channel between the first fluid channel and the fourth fluid channel. 136) opens into the contact region (132) so that a phase flow from the first and fourth fluid channels (134, 136) from opposite sides meets a phase flow from the second fluid channel (130), whereby a drop break of the phase flow from the second fluid channel (130 ) is effected.

15. The method of claim 13, further comprising a step of metering at least one of the phases into inlet regions of at least one of the fluid channels during rotation.

16. The method according to any one of claims 13 to 15, further comprising a step of transporting the generated Has a mixture in a receiving reservoir (108) by centrifugal force.

17. The method according to any one of claims 13 to 16, further comprising a step of centrifugally feeding the

Blended through the third fluid channel (138, 150) to a further contact area (184), and a step of centrifugally supplying a further phase to the further contact area (184), so that caused by the rotation centrifugally hydrodynamically induced pressure and / or shear forces cause further splitting of the drops in the mixture supplied through the third fluid channel in the further contact area.

18. A method according to any one of claims 13 to 16, further comprising a step of centrifugally feeding the batch through the third fluid channel (138, 150) to a further contact area, and comprising a step of centrifugally feeding a further phase to the further contact area, so that centrifugally-hydrodynamically induced pressure and / or shear forces in the further contact area caused by the rotation cause the production of a mixture of the mixture of the first and second phases and of the further phase.

19. The method according to any one of claims 13 to 18, wherein by the second fluid channel (130) a combination of two miscible or immiscible phases is supplied to the contact region, so that in the contact region multiphase drops are generated.

20. A method according to any one of claims 13 to 19, wherein the phases are liquids which are supplied through the fluid channels centrifugally to the contact region or regions so that the mixture is an emulsion.

21. The method according to any one of claims 13 to 19, wherein a phase is a liquid and a phase is a gas, so that the mixture is a foam.