Apparatus and method for preparing a mixed fluid by mixing fluids.

Abstract

Provided is an apparatus and method for mixing fluids to prepare a mixed fluid, which is less prone to malfunction and is suitable for mass preparation of mixed fluids and particles having specified properties. [Solution] The device 1 comprises a mixing chamber 20 having a first inlet opening 201 through which a first fluid 7 can be introduced, a second inlet opening 2011 through which a second fluid 8 can be introduced, and an outlet opening 202 through which a mixed fluid 9 comprising the first fluid 7 and the second fluid 8 can be discharged, a first supply section 40 fluidly connected to the mixing chamber 20 via the first inlet opening 201 and configured to convey the first fluid 7 into the mixing chamber 20 along a first fluid flow direction F1, and a second supply section 50 fluidly connected to the mixing chamber 20 via the second inlet opening 2011 and configured to convey the second fluid 8 into the mixing chamber 20 along a second fluid flow direction F2. The first supply section 40 has a fluid component 10, an outlet opening 102 fluidly connected to the first inlet opening 201 of the mixing chamber 20, and at least one means 104a, 104b for changing the direction of the first fluid 7 flowing through the fluid component 10 in a specific direction, in particular so as to generate spatial oscillations of the fluid 7 at the outlet opening 102.

Description

[Technical Field]

[0001] The present invention relates to an apparatus and corresponding method for preparing a mixed fluid by mixing fluids. The preparation of mixed fluids plays an important role in fields such as chemistry, microbiology, biochemistry, pharmaceuticals, medical technology, and food technology. In such cases, it is important that the prepared mixed fluid has predetermined properties. For example, in mixing processes that produce particles (in the nanometer range), a predetermined particle size associated with a predetermined particle size distribution may be desired. The apparatus and method according to the present invention are suitable for preparing (nano) particles. [Background technology]

[0002] Microfluidic systems for preparing nanoliter-scale mixed fluids and (nano)particles, which require precise control of temperature, residence time, and dissolved substance concentration, are known from prior art. [Overview of the project] [Problems that the invention aims to solve]

[0003] In such systems, the length of the flow path is long relative to the cross-sectional area, resulting in relatively high flow-related resistance. These systems are not only expensive but also prone to clogging. Furthermore, performing large-scale preparations with such systems is difficult, or even impossible.

[0004] The object of the present invention is to provide an apparatus and method for mixing fluids to prepare a mixed fluid that is less prone to malfunction and is suitable for the large-scale preparation of mixed fluids or particles having predetermined characteristics. Specifically, the aim is to enable the preparation of mixed fluids using the same mixing technique, whether on a laboratory scale (i.e., nanoliters per minute) or on a large scale (i.e., liters per minute).

[0005] The prepared mixed fluid may be, for example, a solution for intravenous nutrition, a drug for oral administration, a drug for transdermal administration, etc. [Means for solving the problem]

[0006] In the present invention, the above objective is achieved by an apparatus having the configuration of claim 1. The dependent claims specify embodiments of the present invention.

[0007] According to the description, an apparatus for mixing fluids to prepare a mixed fluid first comprises a mixing chamber having a first inlet opening into which a first fluid can be introduced, a second inlet opening into which a second fluid can be introduced, and an outlet opening from which the mixed fluid, including the first and second fluids, can be discharged. The apparatus further comprises a first supply device configured to fluidly connect to the mixing chamber via the first inlet opening and transport the first fluid into the mixing chamber along a first fluid flow direction, and a second supply device configured to fluidly connect to the mixing chamber via the second inlet opening and transport the second fluid into the mixing chamber along a second fluid flow direction.

[0008] In this case, the first supply device consists of a fluid component, and the fluid component has an outlet opening that is fluid-connected to the first inlet opening of the mixing chamber. Specifically, the outlet opening of the fluid component may correspond to the first inlet opening of the mixing chamber.

[0009] The fluid component is characterized by comprising at least one means for changing the direction of the first fluid flowing through the fluid component to a specific direction. For changing the direction to a specific direction, alternating vortices, i.e., vortices formed by collisions between fluid flows within the fluid component or vortices formed by obstructions within the fluid component, may be used. This type of means for changing the direction to a specific direction requires sufficient space for the vortex structure to develop and then dissipate. Specifically, the at least one means for generating the spatial oscillation of the first fluid is provided and formed at the outlet opening.

[0010] In other words, the first fluid is delivered into the mixing chamber as an oscillating fluid flow rather than a (quasi) steady flow. The first fluid has a longitudinal flow component as well as a transverse flow component that changes over time. As a result, turbulence can be generated in the mixing chamber, improving the mixing quality within the chamber. Therefore, the apparatus is characterized in that the first fluid flows into the mixing chamber from the first supply device in an oscillating or dynamical manner. In other words, the velocity component of the first fluid that crosses its main flow direction is constantly changing. At this time, the oscillating first fluid flowing into the mixing chamber may have a Reynolds number greater than 600 or about 1000, or even greater than 1000. The oscillation frequency of the oscillating first fluid may be 100 Hz or more, typically greater than 2000 Hz.

[0011] An advantage of the apparatus according to the present invention is that it has relatively low flow resistance. Therefore, the apparatus according to the present invention can be used for mixing processes of very small volumes, such as in the microliter range, as well as for mixing processes for large-scale preparation (for example, mixing processes of several liters per minute).

[0012] In one embodiment, the fluid component comprises a flow chamber through which the first fluid can flow, having an inlet opening as well as the outlet opening described above. The fluid flows into the flow chamber from the inlet opening and out through the outlet opening. In one embodiment, the inlet opening and the outlet opening of the fluid component may have different widths. Specifically, the flow chamber has a main flow path connecting the inlet opening of the flow chamber (or the fluid component) and the outlet opening of the flow chamber (or the fluid component) to each other, and at least one auxiliary flow path as a means for changing the direction of the first fluid to a specific direction. In the device according to the present invention, movable parts that generate oscillations can be omitted, thus eliminating the associated costs and expenses. Moreover, by omitting movable parts, the generation of vibrations and noise is relatively small.

[0013] The flow chamber may have the above-described at least one auxiliary flow channel as a means for changing the direction of the first fluid to a specific direction. An auxiliary flow, which is part of the first fluid, may flow through the auxiliary flow channel. The portion of the first fluid that flows out of the fluid component without flowing into the auxiliary flow channel is referred to as the main flow channel. The at least one auxiliary flow channel may have an inlet located near the outlet opening of the fluid component and an outlet located near the inlet opening of the fluid component. The at least one auxiliary flow channel may be located alongside the main flow channel (neither behind nor in front of) along the first fluid flow direction (from the inlet opening to the outlet opening). Specifically, two auxiliary flow channels may be provided extending laterally to the main flow channel (along the first fluid flow direction), with the main flow channel located between the two auxiliary flow channels. In one preferred embodiment, the auxiliary flow channels and the main flow channel are arranged in a row transverse the first fluid flow direction and each extends along the first fluid flow direction.

[0014] Preferably, the at least one auxiliary channel and the main channel are separated by a block. The shape of this block can vary. For example, the cross-section of the block may be tapered along the first fluid flow direction (from the inlet opening to the outlet opening). Alternatively, the block may have rounded edges. The block may also have pointed edges, particularly near the inlet opening and / or near the outlet opening.

[0015] In one embodiment, the depth of the at least one auxiliary channel may be shallower or deeper than the main channel (where depth is the extent that extends across the oscillation plane of the first fluid). This makes it possible to influence the oscillation number of the first fluid flowing out of the fluid component. If the depth of the region of the at least one auxiliary channel in the component is made shallower (compared to the main channel) while most other parameters remain the same, the oscillation frequency will be lower. Similarly, if the depth of the region of the at least one auxiliary channel in the component is made deeper (compared to the main channel) while most other parameters remain the same, the oscillation frequency will be higher.

[0016] At least one diversion fluid may also be one of the other options used to influence the oscillation frequency of the first fluid flowing out of the fluid component. Preferably, the diversion fluid is provided at the inlet of the at least one auxiliary channel. The diversion fluid facilitates the separation of the auxiliary flow from the flow of the first fluid. Here, the diversion fluid should be interpreted as a member that protrudes into the flow chamber (across the flow direction occurring within the auxiliary channel) at the inlet of the at least one auxiliary channel. The diversion fluid may be provided as a deformation (particularly a recess) or other type of protrusion formed in the wall of the auxiliary channel. For example, the diversion fluid may be configured in a cone or pyramidal shape. In addition to influencing the oscillation frequency, using this type of diversion fluid also makes it possible to change what is known as the oscillation angle. The oscillation angle is the angle of variation (between two maximum displacements) of the oscillating fluid jet. If there are multiple auxiliary channels, diversion fluid may be provided in each of the auxiliary channels, or in only some of the auxiliary channels.

[0017] The cross-sectional areas of the inlet and outlet openings of this device may be any shape, such as a square, rectangle, polygon, circle, or ellipse.

[0018] In one embodiment, the first supply device and the first inlet opening of the mixing chamber, and the second supply device and the second inlet opening of the mixing chamber are arranged relative to each other such that the first and second fluid flow directions are separated by an angle of 0° to 90°. Preferably, the angle is in the range of 35° to 55°. Most preferably, the angle is substantially 45°. As a result, a positive effect on mixing quality, mixing path length, and mixing time may occur. For manufacturing technology reasons, the angle may be substantially 90°.

[0019] If the means for changing the direction of the first fluid to a specific direction is configured to oscillate the first fluid in a oscillating plane, the second supply device and the second inlet opening of the mixing chamber may be positioned such that the second fluid flow direction and the oscillating plane of the first fluid straddle an angle of 30° to 150° in a plan view across the first fluid flow direction, preferably such an angle is substantially 90°.

[0020] The longitudinal axis of the mixing chamber may be defined to extend along the first fluid flow direction. In one embodiment, the cross-sectional area of ​​the mixing chamber across the longitudinal axis varies along the longitudinal axis. For example, the cross-sectional area may increase and / or decrease as the longitudinal axis of the mixing chamber progresses. In this case, the change in the dimensions of the cross-sectional area can be configured such that no areas known as watertight regions (Totwassergebiete) are formed within the mixing chamber. For example, the cross-sectional area may increase at the upstream end of the mixing chamber, starting from the first inlet opening of the mixing chamber and moving away from the first inlet opening, and / or decrease at the downstream end of the mixing chamber, moving away from the first inlet opening. This allows the upstream end to form an inlet channel (expanding downstream) of the mixing chamber, and the downstream end to form an outlet channel (tapering downstream). In this case, the outlet channel may be directly adjacent to the inlet channel. As a variation, an intermediate portion of the mixing chamber having a substantially constant cross-sectional area may be provided between the inlet channel and the outlet channel.

[0021] If the means for changing the direction of the first fluid to a specific direction is configured to oscillate the first fluid in a oscillation plane, the extent of the mixing chamber across the longitudinal axis in the oscillation plane may increase in the inlet channel, starting from the first inlet opening of the mixing chamber and moving away from the first inlet opening, or the extent of the mixing chamber across the longitudinal axis in the oscillation plane may decrease in the outlet channel, moving away from the first inlet opening. That is, preferably, in the inlet channel, the angle between the boundary walls of the mixing chamber (in view of the oscillation plane) is the angle of the oscillating first fluid toward the oscillation plane. This angle may be up to 10° less than or up to 10° greater than the oscillation angle, or may take a value between these two numbers. Most preferably, the angle may be up to 5° less than or up to 5° greater than the oscillation angle, or take a value between these two numbers. This prevents undesirable effects on the oscillation of the first fluid in the mixing chamber. The oscillation angle of the first fluid may be 5° or more, preferably 25° or more, and very preferably 40° or more. For most applications, an oscillation angle of 25° to 50°, particularly 30° to 45°, is suitable. Generally, the maximum value of the oscillation angle is 75°. The angle between the boundary walls of the mixing chamber (viewed from the oscillation plane) in the outlet channel is smaller than the angle between the boundary walls of the mixing chamber in the inlet channel. Very preferably, the angle in the outlet channel is up to 15° smaller than the angle in the inlet channel. Furthermore, the extent of the mixing chamber across the oscillation plane may increase in the inlet channel as it moves away from the first inlet opening, or the extent of the mixing chamber across the oscillation plane may decrease in the outlet channel as it moves away from the first inlet opening.

[0022] The (relative) sizes of the inlet and outlet channels of the mixing chamber can be set according to the application.

[0023] In one embodiment, the second inlet opening of the mixing chamber is offset from the first inlet opening of the mixing chamber along the longitudinal axis of the mixing chamber. Preferably, the second inlet opening is located within the inlet flow path (i.e., the boundary wall of the inlet flow path). The distance between the first and second inlet openings along the longitudinal axis may be at least half the width of the first inlet opening of the mixing chamber, which is determined by crossing the longitudinal axis of the mixing chamber parallel to the oscillation plane of the first fluid.

[0024] The first inlet opening and the outlet opening in the mixing chamber may be formed on opposite sides of the mixing chamber. For example, the first inlet opening may form the upstream end of the mixing chamber, and the outlet opening may form the downstream end. Specifically, the first inlet opening and the outlet opening may be located on the longitudinal axis.

[0025] Furthermore, the volume of the mixing chamber may be made larger than the volume of the fluid component or the volume of the flow chamber of the fluid component. Specifically, the width (extending range of the mixing chamber across the longitudinal axis on the oscillation plane of the first fluid) and length (extending range along the longitudinal axis) of the mixing chamber may be made larger than the width (extending range across the first fluid flow direction on the oscillation plane of the first fluid) and length (extending range along the first fluid flow direction) of the flow chamber of the fluid component, respectively. By using such a volume ratio, it is possible to prevent the construction of undesirable high pressure in the mixing chamber. As a variation, the volume of the mixing chamber may be made smaller than the volume of the flow chamber of the fluid component. In this case, the width and / or length of the mixing chamber may be made smaller than the width and length of the flow chamber of the fluid component.

[0026] The second supply device may be configured to deliver the second fluid into the mixing chamber as a (quasi) steady flow. Therefore, the second supply device may be configured, for example, as a pipe whose longitudinal axis (or the elongated downstream end) defines the direction of the second fluid flow. The second fluid may be delivered into the mixing chamber by a pump device through the pipe and the second inlet opening.

[0027] As a variation, the second supply device may also include a fluid component (as previously described with respect to the first supply device). The fluid component may operate in the same manner as the fluid component of the first supply device. That is, the fluid component may have at least one means for changing the direction of the second fluid flowing through the fluid component, in particular, in a specific direction, so as to generate in-space oscillations of the fluid at the outlet opening. Other features of the fluid component of the first supply device may also be applied to the fluid component of the second supply device. In this way, the oscillating first fluid and the oscillating second fluid merge with each other in the mixing chamber. The oscillation angle of the fluid component of the second supply device may be smaller than that of the fluid component of the first supply device. Alternatively, these two oscillation angles may be of the same magnitude.

[0028] The first and second fluids can be supplied to the first and second supply devices, respectively, using a pumping device. Preferably, the pumping device delivers a constant volumetric flow rate. For example, the pumping device may be configured as a syringe pump or a transport pump. Instead of a syringe pump, an HPLC pump or a membrane pump may be used.

[0029] In further embodiments, the apparatus comprises a second mixing chamber in addition to the (first) mixing chamber described above. The second mixing chamber has a first inlet opening, a second inlet opening, and an outlet opening (as previously described with respect to the first mixing chamber). The second mixing chamber is fluidly connected to the first mixing chamber. Specifically, the second mixing chamber is adjacent to the outlet opening of the first mixing chamber in a downstream direction. In this case, the first inlet opening of the second mixing chamber may correspond to the outlet opening of the upstream first mixing chamber. That is, the first and second mixing chambers are directly connected to each other without the use of additional (e.g., tubular) transition members. The second mixing chamber may serve to introduce a further (third) fluid into the mixed fluid prepared in the first mixing chamber. When particles are prepared by a mixing process using the apparatus according to the present invention, the particles may be constructed in layers in the second mixing chamber, for example, with the third fluid forming the outermost layer of the particles. The relative arrangement and shape (inlet flow path, outlet flow path) of the first and second inlet openings of the first mixing chamber (which is the upstream mixing chamber) may also be applied to the second mixing chamber. The volume (and furthermore, width and length) of the second mixing chamber may be set to be larger than that of the first mixing chamber.

[0030] In further embodiments, an interaction channel having at least one bend is adjacent downstream of the outlet opening of the first or second mixing chamber. The at least one bend prevents the formation of what is known as a watertight area. The interaction channel may be configured in the form of a pipe. The interaction channel may serve to continue the mixing process downstream of the outlet opening of the mixing chamber. If the mixing process prepares particles, the particles may grow within the interaction channel (depending on the length of the interaction channel).

[0031] According to the apparatus of the present invention, the fluids to be mixed can be brought together relatively compactly and at an angle. In this process, at least the first fluid moves locally back and forth on a single plane, which can be described as oscillation. The second fluid then collides with this moving (oscillating) fluid at an angle. In addition to improving the controllability of the mixing, it is advantageous to perform the mixing process in a relatively small volume space for recovering the prepared mixed fluid.

[0032] The present invention further relates to a method for preparing a mixed fluid by mixing fluids. The method is carried out using an apparatus according to the present invention. To carry out the method, first, the apparatus according to the present invention, a first fluid, and a second fluid are prepared. The first fluid is introduced into the mixing chamber from the first supply device at a first volumetric flow rate. At the same time, the second fluid is introduced into the mixing chamber from the second supply device at a second volumetric flow rate. In the mixing chamber, an opportunity is provided for the mixing of the first and second fluids, and possibly for the formation of particles in the process. At this time, the residence time of each fluid in the mixing chamber may vary depending on the application. Thereafter, the mixed fluid, including the first fluid and the second fluid, is discharged out of the mixing chamber from the outlet opening.

[0033] Therefore, the particle size and particle size distribution when preparing particles by mixing can be influenced by the selection of chemical substances for the first and second fluids, the oscillation frequency of the oscillating first fluid, and the geometry of the apparatus used for the mixing process.

[0034] If an interaction channel is adjacent to the downstream outlet opening of the mixing chamber, the mixing process can continue in the interaction channel. If particles are prepared during the mixing process, these particles may grow further within the interaction channel.

[0035] In one embodiment, the first volumetric flow rate is greater than the second volumetric flow rate. However, depending on the application, the first and second volumetric flow rates may be of the same magnitude. During the mixing process, the first and second volumetric flow rates may be kept constant. Preferably, during the mixing process, the first and second fluids are continuously introduced into the mixing chamber, respectively.

[0036] The volumetric flow rates of the first and second fluids are controlled by pumping devices that pump the first and second fluids from the first and second supply devices, respectively, into the mixing chamber. Depending on the application, the pressure of the introduced fluid may range from a few millibars (mbar) to several hundred bar (relative to ambient pressure). For large-scale preparation applications, the inflow pressure may exceed 2 bar. A pressure range of 2 bar to 350 bar is preferred, and 10 bar to 220 bar is extremely preferred.

[0037] Each fluid used may consist of only one chemical substance or a mixture of two or more chemical substances. The mixture may also contain a solvent. The method may be carried out using two distinct fluids, a first fluid and a second fluid. These two distinct fluids may differ in chemical composition and / or the concentration of their individual components. In the case of a suspension, the particle sizes of the two fluids may also differ. However, it is also possible that the first and second fluids are identical, i.e., there is no difference in the above-mentioned properties. Even if the suspensions (as the first and second fluids) are identical, turbulence generated in the mixing chamber can change, for example, the particle size of the particles in the suspension. This can also affect the particle size distribution, or what is known as the encapsulation rate.

[0038] In one embodiment, the method is carried out using a liquid or suspension as the first fluid. Here, a suspension should be interpreted as a mixture of a liquid and particles dispersed in the liquid. Furthermore, the second fluid may also be a liquid or suspension. However, it is also conceivable that at least one of these fluids may be in gaseous form.

[0039] The first fluid may, for example, contain a solvent and a pharmaceutical or therapeutic component. The second fluid may be a liquid suitable for surrounding the pharmaceutical or therapeutic component of the first fluid in a mixing process and functioning as a carrier or excipient for the pharmaceutical or therapeutic component in the resulting mixed fluid. The first fluid may be a suspension containing nucleic acids, and the second fluid may be a lipid mixture. The nucleic acids may be DNA, RNA, or mRNA.

[0040] Generally, the fluids used in this method may be aqueous solutions. Other options include lipophilic and hydrophilic additives (emulsifiers, surfactants) and lipids, such as triglycerides, monoglycerides, diglycerides, partial glycerides, semi-synthetic waxes, and synthetic waxes. This apparatus is also suitable for use with polyethylene glycol (PEG) as the first or second fluid.

[0041] Depending on the mixing process, the use of water-soluble organic solvents and / or non-water-soluble organic solvents (e.g., ethanol) may be required. Such solvents may be used as the first or second fluid, or may be contained within the first or second fluid. In the purification process of the prepared mixed fluid, most of the solvent can be removed.

[0042] The proposed apparatus for mixing fluids and the method using it can be applied to self-assembling structure formation, multi-stage particle formation, crystallization, multi-stage biochemical structure formation, multilayer particle formation and packing, precipitation, and the preparation of dispersions (particularly suspensions and emulsions). Furthermore, the apparatus and method are also suitable for the preparation of liquid crystal nanoparticles such as cubosomes and hexosomes. The prepared materials can be used, for example, in pharmaceuticals, process systems engineering, cosmetics, and food manufacturing.

[0043] The apparatus according to the present invention can be manufactured by cutting or machining methods, or by replication methods such as injection molding or additive methods (3D modeling). Similarly, methods using specific cutting tools (e.g., milling) or machining methods (e.g., electrical discharge machining) are also suitable for manufacturing.

[0044] The apparatus according to the present invention can be manufactured from a variety of materials. Plastic materials (PEEK, PVDF, COC), metals and alloys (stainless steel, aluminum), glass, or ceramics are all possible materials.

[0045] This device may be configured to exhibit fluid tightness and pressure resistance through a sealing system. The sealing system may consist of a direct sealing cover structure, an interposed sealing structure, or a contour-following structure seal. Advantageously, the sealing surface of the direct sealing cover structure or the interposed sealing structure may be made from a material with a surface roughness Ra ≤ 200 nm and a flatness E ≤ 5 μm. A surface roughness of Ra ≤ 50 nm and a flatness E ≤ 1 μm is highly advantageous. To provide a sealing surface with a predetermined roughness and flatness, the surface characteristics can be directly fabricated or adjusted through post-processing (grinding, polishing, ultra-precision machining).

[0046] The fluid-conducting components of this device may have a predetermined fine surface morphology. This has a favorable effect on the fluid flow behavior of the fluid flowing through the component. For example, the material of the fluid-conducting component may have a surface roughness Ra ≤ 0.5 μm, very preferably Ra ≤ 0.38 μm, so that fluid components do not accumulate on the component. In one embodiment, the surface of the fluid-conducting component is hydrophilic with a contact angle β ≤ 90°. The contact angle refers to the angle that a droplet on a solid surface makes with respect to that surface. The surface properties of the fluid-conducting component can be adjusted by the selection of the material (stainless steel, PEEK, or COC) and surface functionalization (plasma treatment, chemical functionalization, or microstructuring).

[0047] The present invention will be described in detail below with reference to the drawings and embodiments. [Brief explanation of the drawing]

[0048] [Figure 1] This is a cross-sectional view showing one embodiment of an apparatus for mixing fluids to prepare a mixed fluid. [Figure 2] This is a cross-sectional view of the device along the line A'-A'' in Figure 1. [Figure 3] This is a cross-sectional view of the device along the line B'-B'' in Figure 1. [Figure 4] This is a cross-sectional view of the device along the line C'-C'' in Figure 1. [Figure 5] This is a cross-sectional view showing a further embodiment of an apparatus for mixing fluids to prepare a mixed fluid. [Figure 6] This is a cross-sectional view showing a further embodiment of an apparatus for mixing fluids to prepare a mixed fluid. [Figure 7] This is a cross-sectional view showing a further embodiment of an apparatus for mixing fluids to prepare a mixed fluid. [Figure 8] This is a schematic diagram showing one embodiment of an interaction channel as part of a device for mixing fluids to prepare a mixed fluid. [Figure 9] This figure shows the time change in the displacement of a first oscillating fluid that flows into the mixing chamber of a device that mixes fluids to prepare a mixed fluid. [Figure 10] This is a schematic diagram of a method for preparing a mixed fluid by mixing fluids. [Figure 11] Figures a) to c) show the measured values ​​of the mixed fluid at various volumetric flow rates, obtained using the apparatus in Figure 5 and the method in Figure 10. [Figure 12] This is a cross-sectional view showing a further embodiment of an apparatus for mixing fluids to prepare a mixed fluid. [Figure 13] This is a cross-sectional view of the device along the line D'-D'' in Figure 12. [Figure 14] This is a schematic diagram of a method for preparing a mixed fluid by mixing fluids. [Modes for carrying out the invention]

[0049] Figure 1 schematically shows one embodiment of an apparatus 1 for mixing fluids to prepare a mixed fluid. Figures 2 to 4 are cross-sectional views of the apparatus 1 along lines A'-A'', B'-B'', and C'-C'', respectively.

[0050] Apparatus 1 comprises a mixing chamber 20, a first supply device 40, a second supply device 50, and an interaction channel 30.

[0051] At this time, the mixing chamber 20 forms the central component of the apparatus 1. The mixing chamber 20 has a first inlet opening 201, a second inlet opening 2011, and an outlet opening 202. The first fluid 7 can be introduced into the mixing chamber 20 from the first inlet opening 201. The second fluid 8 can be introduced into the chamber from the second inlet opening 2011. Inside the mixing chamber 20, the first and second fluids 7 and 8 form a mixed fluid 9. The mixed fluid 9 can be discharged from the outlet opening 202 of the mixing chamber 20.

[0052] The first supply device 40 is (fluid) connected to the mixing chamber 20 via the first inlet opening 201 and plays the role of introducing the first fluid 7 into the mixing chamber 20. The second supply device 50 is (fluid) connected to the mixing chamber 20 via the second inlet opening 2011 and plays the role of introducing the second fluid 8 into the mixing chamber 20. An interaction channel 30 is adjacent to the downstream direction of the outlet opening 202. An embodiment of the interaction channel 30 is illustrated in Figure 8 as an example and will be explained later.

[0053] The first supply device 40 has a fluid component 10 equipped with two auxiliary flow channels (feedback flow channels) 104a, 104b, which are means for causing movement in space and / or time in the first fluid 7, in particular means for causing oscillation of the first fluid 7 in space.

[0054] The energy required to cause motion in space and / or time in a fluid jet is equal to the inflow pressure P of the first fluid 7 (also referred to as the first phase A). 10IN It is obtained from. Using the fluid component 10 has the advantage of reducing the complexity and susceptibility to failure of the device because it does not require an additional energy source. In addition, it ensures that no external energy is added to the fluid 7 flowing through the fluid component 10. It is desirable to prevent the introduction of energy, because the introduction of energy can destroy delicate components in the fluid (e.g., long-chain molecules).

[0055] The fluid component 10 shown in Figure 1 has auxiliary flow channels 104a and 104b, but this is merely one example. In principle, other fluid components, such as those known as feedback-free components, can also be used.

[0056] The fluid component 10 comprises a flow chamber 100 through which the first fluid (fluid flow) 7 can flow. The fluid component 10 has the role of generating oscillations in the first fluid 7, causing the first fluid 7 to oscillate over time and / or locally when it flows into the mixing chamber 20 from the first inlet opening 201.

[0057] The flow-through chamber 100 has an inlet width b for the first fluid flow 7 to flow into the flow-through chamber 100 101 of the inlet opening 101 and an outlet width b for the first fluid flow 7 to flow out of the flow-through chamber 100 102 of the outlet opening 102. The inlet opening 101 and the outlet opening 102 are respectively formed at the locations where the cross-sectional area (across the fluid flow direction) through which the fluid flow passes when flowing into the flow-through chamber 100 or when re-flowing out of the flow-through chamber 100 in the fluid component 10 is the smallest. The respective widths b 101 , b 102 of the inlet opening and the outlet openings 101, 102 respectively correspond to the extension ranges of the inlet opening and the outlet openings 101, 102 of the first fluid 7 across the fluid flow direction on the rocking plane (described later).

[0058] At this time, the outlet opening 102 of the flow-through chamber 100 of the fluid component 10 corresponds to the first inlet opening 201 of the mixing chamber 20.

[0059] The dimension of the inlet width b 101 can be 0.5 μm to 5000 μm. The size of the narrowest cross-sectional area (the cross-section A of the outlet opening 102 102 or the smallest cross-sectional area A of the main flow path 103 between the internal blocks 11a, 11b 11 ) in the fluid component 10 of the apparatus 1 can be selected according to the desired volume flow rate. Assuming that the inflow pressure P 10IN is constant, the larger the volume flow rate, the larger the dimensions such as, for example, the inlet width b 101 and / or the inlet height h 101 need to be. General dimensions are 100 μm to 3500 μm, preferably 200 μm to 1500 μm.

[0060] The inlet opening 101 and the outlet opening 102 are located on two sides of the fluid component 10 that are opposite to each other in terms of the flow. The flow chamber 100, more precisely, the main flow path 103 of the flow chamber 100, connects the inlet opening 101 and the outlet opening 102 without any obstructions. In one modified example (not shown), the inlet opening 101 and the outlet opening may be connected by a flow chamber 100 with obstructions.

[0061] The first fluid flow 7 moves through the flow chamber 10 from the inlet opening 101 to the outlet opening 102, substantially along the longitudinal axis A of the fluid component 1 (which connects the inlet opening 101 and the outlet opening 102 to each other). The longitudinal axis A forms the axis of symmetry of the fluid component 1. The longitudinal axis A is located on two mutually orthogonal planes of symmetry S1 and S2 that define the mirror symmetry of the fluid component 1. As a variation, the fluid component 1 may be configured asymmetrically (mirror-symmetrically).

[0062] To change the direction of fluid flow to a specific direction, the flow chamber 100 has a main flow channel 103 in addition to two auxiliary flow channels 104a and 104b. The main flow channel 103 and the two auxiliary flow channels 104a and 104b extend substantially along the longitudinal axis A of the fluid component 10, with the main flow channel 103 located between the two auxiliary flow channels 104a and 104b (across the longitudinal axis A). Directly behind the inlet opening 101, the flow chamber 10 branches into the main flow channel 103 and the two auxiliary flow channels 104a and 104b, and then rejoins directly in front of the outlet opening 102. In this embodiment, the two auxiliary flow channels 104a and 104b are arranged symmetrically with respect to the plane of symmetry S2 (Figure 3). In one modified example not shown, the auxiliary flow channels are arranged asymmetrically. The auxiliary flow channels may be located outside the illustrated flow plane. Such a flow path may be realized, for example, by a pipe located outside the plane of symmetry S1, or it may extend as a flow path positioned at an angle to the flow plane (plane of symmetry S1).

[0063] The main flow path 103 connects the inlet opening 101 and the outlet opening 102 in a substantially straight line with each other so that the fluid flow 7 flows substantially along the longitudinal axis A of the fluid component 10. Generally, the volume of the main flow path 103 is 0.08 mm³. 3 ~260mm 3 This can be assumed. The volume of the main channel 103 is 0.3 mm 3 ~120mm 3 This is extremely preferable. In the illustrated embodiment, the volume of the main flow path 103 is approximately 0.67 mm 3 The fluid component 10 has a fluid holding volume of 0.5 mm³. 3 ~1.2mm 3 Furthermore, the minimum cross-sectional area A of the exit opening 102 102 Approximately 0.09 mm 2 In the illustrated embodiment, the cross-sectional area A of the entrance opening 101 is as shown. 101 Approximately 0.12 mm 2 That is the case.

[0064] Starting from the inlet opening 101, the auxiliary channels 104a and 104b begin to extend in opposite directions at an angle of approximately 90° with respect to the longitudinal axis A in the first section. Subsequently, the auxiliary channels 104a and 104b branch off so as to extend approximately parallel to the longitudinal axis A (towards the outlet opening 102) (second section). In order to rejoin the auxiliary channels 104a and 104b with the main channel 103, the auxiliary channels 104a and 104b change direction again at the end of the second section and substantially align themselves with the longitudinal axis A (third section). In the embodiment shown in Figure 1, the direction of the auxiliary channels 104a and 104b changes by approximately 120° at the transition from the second section to the third section. However, the change in direction between these two parts of the auxiliary channels 104a and 104b may be at an angle different from the angle described here, or even to follow a completely different trajectory.

[0065] The auxiliary channels 104a and 104b are means for influencing the direction of the first fluid flow 7 flowing through the flow chamber 100. For this purpose, each auxiliary channel 104a and 104b has an inlet section 104a1 and 104b1 formed by the end of the auxiliary channel 104a and 104b on the outlet opening 102 side, and an outlet section 104a3 and 104b3 formed by the end of the auxiliary channel 104a and 104b on the inlet opening 101 side. A small proportion of the first fluid flow 7 (auxiliary flow) flows from the inlet sections 104a1 and 104b1 into the auxiliary channels 104a and 104b. The remaining proportion of the first fluid flow 7 (referred to as the main flow) flows out of the fluid component 10 through the outlet opening 102. The auxiliary flow flows out from the auxiliary channels 104a and 104b at the outlet sections 104a3 and 104b3 and can impart a lateral impact (crossing the longitudinal axis A) to the first fluid flow 7 flowing in from the inlet opening 101. At this time, the first fluid flow 7 is affected in such a way that the main flow flowing out at the outlet opening 102 causes oscillation in space, and more specifically, causes oscillation in the plane where the main channel 103 and auxiliary channels 104a and 104b are located. The plane in which the oscillation of the main flow occurs is also called the oscillation plane and is either substantially coincides with the plane of symmetry S1 or is parallel to the plane of symmetry S1.

[0066] In this embodiment, the cross-sectional area of ​​each auxiliary channel 104a, 104b is substantially constant over the entire length of the auxiliary channels 104a, 104b (from the inlet sections 104a1, 104b1 to the outlet sections 104a2, 104b2). In contrast, the size of the cross-sectional area of ​​the main channel 103 increases substantially constant in the direction of the main flow (i.e., from the inlet opening 101 to the outlet opening 102). In this case, although this is merely an example, the shape of the main channel 103 is mirror-symmetric with respect to the symmetry planes S1, S2.

[0067] However, as a general rule, the cross-sectional area of ​​the main channel 103 may decrease in the downstream direction.

[0068] The main channel 103 and the auxiliary channels 104a and 104b are separated by blocks 11a and 11b. In this embodiment, the two blocks 11a and 11b are arranged symmetrically with respect to the mirror surface S2. However, in principle, the configuration may be changed to an asymmetrical orientation. In the case of an asymmetrical orientation, the shape of the main channel 103 will also be asymmetrical with respect to the mirror surface S2. As an embodiment, an embodiment in which the two blocks 11a and 11b are symmetrical is preferred.

[0069] The shapes of blocks 11a and 11b shown in Figure 1 are merely illustrative and may be modified. Blocks 11a and 11b in Figure 1 have rounded edges. Pointed edges are also possible. Embodiments with rounded edges are preferred.

[0070] A funnel-shaped neck (Ansatz) 106 is connected to the upstream direction of the inlet opening 101 of the flow chamber 100. This neck tapers in the direction toward the inlet opening 101 (downstream direction). In principle, the neck 106 can have a substantially constant cross-section or a partially wider cross-sectional area. The funnel-shaped neck may also be called the inlet passage. The flow chamber 100 also tapers downstream of the internal blocks 11a and 11b, particularly in the area of ​​the outlet opening 102. This taper is formed by the outlet passage 107, which originates from the inlet sections 104a1 and 104b1 of the auxiliary passage. In this case, the neck 106 and the outlet passage 107 taper in such a way that only their width, i.e., only their extent on the symmetrical plane S1 perpendicular to the longitudinal axis A, decreases downstream. In this embodiment, the tapering does not affect the depth of the neck portion 106 and the outlet channel 107 (i.e., the extending range perpendicular to the longitudinal axis A on the plane of symmetry S2) (Figure 2). As a modification, it is also possible to taper both the width and depth of the neck portion 106 and the outlet channel 107. Furthermore, it is possible to taper either the depth or width of only the neck portion 106 while simultaneously tapering both the width and depth of the outlet channel 107, or to taper either the depth or width of only the outlet channel 107 while simultaneously tapering both the width and depth of the neck portion 106. The shapes of the neck portion 106 and the outlet channel 107 shown in Figure 1 are merely examples. In this case, the reduction in width is linear in the downstream direction, and the boundary walls of the neck portion 106 and the boundary walls of the outlet channel 107 (in the aforementioned oscillation plane view) are separated by angles ε and φ, respectively. Other shapes are also possible for the tapering. In this embodiment, the length of the inlet channel (in this example, the funnel-shaped neck portion 106) is l 106 The entrance width is b 101 (l 106 ≥ 1.5 × b 101 In a preferred embodiment, the length of the funnel-shaped neck portion 106 is l 106 is width b 101 It is said to be more than three times that. 101 Assuming that is a given constant value, the smaller the angle ε, the more desirable it is to increase the length of the inlet channel 106.

[0071] The cross-sectional areas of the inlet opening 101 and the outlet opening 102 are both ideal rectangles. The depth (extension range perpendicular to the longitudinal axis A on the symmetrical plane S2) is the same for both (Figure 2), but the width b 101 ,b 102 The (extended range perpendicular to the longitudinal axis A on the symmetrical plane S1) is different (Figure 2). In principle, the corners of the cross-sectional area may be rounded, and the opposing surfaces defining the inlet opening 101 and the outlet opening 102 do not have to extend parallel to each other. To put it extremely, the inlet opening 101 and the outlet opening 102 may have a circular or elliptical cross-sectional area.

[0072] In this case, the outlet opening 102 of the flow chamber 100 of the fluid component 10 corresponds to the first inlet opening 201 of the mixing chamber 20. Generally (i.e., in any embodiment), the cross-sectional area A of the outlet opening 102 102 Cross-sectional area A 101 , cross-sectional area A 11 and cross-sectional area A 102 It is advantageous to have the smallest cross-sectional area among them or to have an area equal to the smallest cross-sectional area (A 102 ≤min(A 101 ,A 11 )). Most advantageously, the cross-sectional area A of the exit opening 102. 102 This is the smallest cross-sectional area in the flow chamber 100 of the fluid component 10. Cross-sectional area A of the outlet opening 102 102 and the cross-sectional area A of the first entrance opening 201 201 They are of the same size, width b 102 and width b 201 It is of the same scale, and the height h 102 and height h 201 The same scale is also observed. At the outlet opening 102, i.e., the first inlet opening 201, the tapered outlet flow path 107 of the fluid component 10 and the flared inlet flow path 206 of the mixing chamber 20 (described later) merge with each other, and an edge is formed in this transition region. This transition region may be rounded. The radius R 109 of the rounding is b 101 (The minimum width of the entrance opening 101) and b 11(Minimum cross-sectional area A of the main flow path 103 between internal blocks 11a and 11b) 11 It can be smaller than the minimum width of the corresponding width. R radius = zero is the limiting value at which the edge shape of the exit portion 102 becomes pointed. If mechanical stability is to be increased, it is preferable to have an R radius 109.

[0073] An inlet channel 206 is adjacent to the downstream side of the first inlet opening 201 of the mixing chamber 20. The cross-sectional area of ​​the inlet channel 206 (crossing the first fluid flow direction or the longitudinal axis L of the mixing chamber 20) increases in the downstream direction. Specifically, the width of the inlet channel 206 (the extent extending across the longitudinal axis L on the oscillation plane) increases in the downstream direction. In this case, the increase in width is linear. However, the increase in width may follow a polynomial. In the oscillation plane view, the walls defining the inlet channel 206 are separated by an angle δ. The dimensions of the angle δ can vary. Advantageously, the angle δ is selected according to the oscillation angle α. In this case, the displacement from the oscillation angle α can be +10° to -10°, i.e., α-10° < δ < α+10°. A value of α-5° < δ < α+5° is extremely preferable for the angle δ. Here, the oscillation angle α corresponds to the natural oscillation angle that occurs when the inlet flow path 206 and mixing chamber 20 are absent.

[0074] In the inlet channel 206, the cross-sectional area A of the mixing chamber 20 (crossing the longitudinal axis L) 200 This is constantly increasing. At this time, the cross-sectional area of ​​the entrance opening 201 is, for example, 0.09 mm². 2 The cross-sectional area increases by more than double along the longitudinal axis L to the center point of the second inlet opening 2011. At the center point of the second inlet opening 2011, the cross-sectional area is 0.26 mm². 2 In this embodiment, the cross-sectional area A of the second entrance opening 2011 is... 2011 This is 0.07 mm, which is smaller than the cross-sectional area of ​​the first entrance opening 201. 2 This is the result.

[0075] In the embodiment shown in Figure 1, the width b of the mixing chamber 20 20 However, the width b of the fluid component 10 10It is smaller than that. Furthermore, the length of the mixing chamber 20 is l 20 The length l of the fluid component 10 is 10 Shorter than. Each width is the extent that extends across the longitudinal axis A of the fluid component 10 or the longitudinal axis L of the mixing chamber 20 on the oscillation plane of the first fluid 7. Each length is the extent that extends along the longitudinal axis A of the fluid component 10 or the longitudinal axis L of the mixing chamber 20 on the oscillation plane of the first fluid 7.

[0076] In this illustrated embodiment, the width b of the mixing chamber 20 20 This boundary is defined by two substantially parallel surfaces that function as a boundary wall in the intermediate part of the mixing chamber 20. This intermediate part is the portion formed along the first fluid flow direction F1 between the inlet channel 20 and the outlet channel 207 of the mixing chamber 20. In principle, the boundary wall may have a different shape (other than flat or parallel), as shown in Figure 6, for example.

[0077] An outlet channel 207 is adjacent to the downstream end of the intermediate section. The cross-sectional area of ​​the outlet channel 207 (crossing the first fluid flow direction or the longitudinal axis L of the mixing chamber 20) decreases downstream along the longitudinal axis L. Specifically, the width of the outlet channel 207 (the extent extending across the longitudinal axis L on the oscillation plane) decreases downstream. This decrease in width is linear. However, the decrease in width may follow a polynomial. In the oscillation plane view, the walls defining the outlet channel 207 are separated by an angle ω. It is advantageous for angle ω to be smaller than angle δ. It is extremely advantageous for angle ω to be up to 15° smaller than angle δ. The downstream end of the outlet channel 207 is formed by an outlet opening 202. The mixed fluid 9 of the first and second fluids 7 and 8 escapes from the mixing chamber 20 through the outlet opening 202.

[0078] Cross-sectional area A of the exit opening 202 202 In this example, it is a rectangle, and the width b is just one example. 202 and height h 202 It has. In principle, the cross-sectional area of ​​the exit opening 202 can be other than rectangular. Cross-sectional area A 202The smallest cross-sectional area A is the means that causes the fluid jet 10 to move in space. 1min (A 101 , A 11 Or A 102 And that is, A 1min =min(A 101 ,A 11 ,A 102 It is larger than )). Cross-sectional area A 202 This is the cross-sectional area A of the second entrance opening 2011. 2011 1 / 2 of and cross-sectional area A 1min The sum of the whole is equal to or greater than the sum of the whole, that is, A 202 ≧A 1min +0.5 × A 2011 A 202 ≧A 1min +A 2011 That is extremely desirable.

[0079] In one embodiment not shown, a plurality of outlet openings 202 connected to separate interaction channels 30 may be provided. Alternatively, some of the plurality of outlet openings 202 may be connected to correspondingly provided interaction channels, while the others may be formed without interaction channels. In the case of multiple outlet openings 202, the above explanation applies to the cross-sectional area A. 202 This applies to the sum of identical terms.

[0080] Figure 2 is a cross-sectional view of the apparatus 1 along the line A'-A'' in Figure 1. According to the figure, at least the upstream end of the fluid component 10, the mixing chamber 20, and the interaction channel 30 in this embodiment is at a constant height h. Height (also referred to as depth) is the extent to which the first fluid 7 extends across the oscillation plane. In one embodiment not shown, the height h may be non-constant. Specifically, the height h of the inlet channels 106, 206 and the outlet channels 107, 207 may differ from the height of the rest of the apparatus.

[0081] A second supply device 50, provided for introducing the second fluid 8 into the mixing chamber 20, comprises a pipe 204. The pipe 204 extends along its longitudinal axis and defines the fluid flow direction F2 of the second fluid 8. The pipe 204 is connected to the mixing chamber 20 via a second inlet opening 2011 of the mixing chamber 20. The pipe 204 forms an angle β with respect to the oscillation plane of the fluid component 10, i.e., the oscillation plane S1 (in view of the plane of symmetry S2, i.e., in a plan view extending along the longitudinal axis L perpendicular to the oscillation plane). In this embodiment, angle β = 90°. In principle, the angle may take a different value. This will affect the mixing quality and / or the mixing path length or mixing time. To reduce pressure loss, a value of 45° ± 10° for angle β is preferable. When preparing particles in the mixing process, an angle greater than 90° is advantageous if the particle size is to be reduced.

[0082] Figure 3 is a cross-sectional view of the apparatus 1 along the line B'-B'' in Figure 1. In this cross-sectional view, the cross-sectional areas of the main flow path 103 and auxiliary flow paths 104a and 104b of the fluid component 10 are visualized. In this embodiment, the height h of the flow paths 103, 104a, and 104b is shown. 103 ,h 104a h 104b These are identical. However, in principle, they may be different from each other. In Figure 3, the cross-sectional areas of the main channel 103 and the auxiliary channels 104a and 104b are depicted as simple structures with sharp edges. However, it is also possible to provide rounded corners, i.e., to make them rounded.

[0083] Figure 4 is a cross-sectional view of the apparatus 1 along the line C'-C'' in Figure 1. In this cross-sectional view, the cross-section of the inlet channel 206 of the mixing chamber 20 is visualized. Here again, a simple shape without rounded corners is depicted, but rounded corners may be present. The distance between the lateral boundary walls of the inlet channel 206 (parallel to the oscillation plane and crossing the longitudinal axis L) is the height h 206 It remains constant overall. However, the distance is constant at height h 206 It may be variable according to the following.

[0084] In FIG. 4, it can be further seen that the second inlet opening 2011 of the mixing chamber 20 is formed in the inlet flow path 206 of the mixing chamber 20. In a plan view cutting across the longitudinal axis L, the pipe (supply flow path 204) and the swinging plane form an angle η. In the illustrated embodiment, the angle η = 90°. In principle, this angle may take another value, for example, it can be 30° to 150°. Particularly, in the case of an embodiment where there is one second inlet opening 2011, the angle η = 90° is preferred. However, it is also possible that the mixing chamber has a plurality of second inlet openings, and the mixing chamber is connected to a corresponding number of second supply devices (configured as pipes) through the plurality of second inlet openings. In the same embodiment (not shown), it may be advantageous for each angle η to take a value other than 90°. In an advantageous variant having a plurality of second inlet openings and the inlet flow paths 204 of the corresponding second supply devices, they are alternately formed on the cover surface of the mixing chamber 20 (depicted on the upper side in FIG. 4) and the base surface on the opposite side of the cover surface (depicted on the lower side in FIG. 4).

[0085] FIG. 5 shows the device 1 according to a further embodiment of the present invention. Specifically stated, in this embodiment, the structure of the fluid component 10 and the volume ratio between the flow-through chamber 100 of the fluid component 10 and the mixing chamber 20 are different from those in the embodiments of FIGS. 1 to 4.

[0086] The volume of the mixing chamber 20 is larger than the volume of the flow-through chamber 100 of the fluid component 10. Specifically described, in this embodiment, the width b of the mixing chamber 20 20 and the length l of the mixing chamber 20 20 are respectively larger than the width b of the fluid component 10 10 , the length l of the fluid component 10 10 . That is, the ratios of the formulas: b 20 >b 10 and l 20 >l 10 apply. In a preferred embodiment, the fluid conduction volume V 10 of the flow-through chamber 100 of the fluid component 10 is much smaller than the volume V 20 of the mixing chamber 20 (V 20 >V 10 ). Preferably, the formula: V 20 >2×V10 That applies.

[0087] In this embodiment, the second inlet opening 2011 is provided for the second fluid flow 8 (i.e., phase B). However, in principle, the mixing chamber 20 may also be provided with a further second inlet opening for introducing phase B or another phase into the mixing chamber.

[0088] In this embodiment as well, the second inlet opening 2011 for the second fluid flow 8 (i.e., phase B) is provided within the inlet flow path 206 of the mixing chamber 20. In principle, one or more second inlet openings 2011 can be freely positioned within the mixing chamber 20. Preferably, one or more second inlet openings 2011 are located within the inlet flow path 206 or the outlet flow path 207 of the mixing chamber 20. Most preferably, one or more second inlet openings 2011 are located within the inlet flow path 206.

[0089] In Figure 5, the distance along the longitudinal axis L between one or more second inlet openings 2011 and the first inlet opening 201 is length l 2011 It is represented as follows. Advantageously, length l 2011 The width b of the first entrance opening 201 is 201 This corresponds to more than half of, i.e., l 2011 ≥0.5 × b 201 This applies. For the most advantageous case, length l 2011 The width b of the first entrance opening 201 is 102 1 / 2 of and width b of the second entrance opening 2011 2011 (l 2011 ≥0.5 × (b 201 +b 2011 )) Also, to be advantageous, length l 2011 However, the width b of the first entrance opening 201 201 It is less than 5 times that. In summary, 5 × b 201 ≧l 2011 ≥0.5 × (b 102 +b 2011 ) applies.

[0090] In the embodiment shown in Figure 5, the second entrance opening 2011 is circular, and its width b corresponds to the diameter of the circle. 2011 It has. In principle, a second entrance opening 2011 with a shape other than circular is also possible. In this embodiment, the area A of the second entrance opening 2011 2011 However, the area A of the outlet opening 102 of the fluid component 10 102 It is slightly smaller than (Here, since the outlet opening 102 of the fluid component 10 corresponds to the first inlet opening 201 of the mixing chamber 20, the area A of the second inlet opening 2011 2011 Area A of the first entrance opening 201 201 (Slightly smaller compared to) Area A 102 The outlet width b 102 It is determined by the outlet depth. In the embodiment shown in Figure 5, the cross-sectional area A (crossing the longitudinal axis L) of the mixing chamber 20 in the inlet channel 206 is 20 Cross-sectional area A increases steadily. 20 is width b 20 and height h 20 The cross-sectional area A of the mixing chamber 20 in the region of the inlet channel 206 is determined by (the extent of the first fluid across the oscillation plane). 20 Cross-sectional area A 206 It can be called that, and the corresponding width and height is width b 206 and height h 206 It is called [this]. Advantageously, cross-sectional area A 20 From the first entrance opening 201 (along the longitudinal axis L) approximately l 2011 -(b 2011 The size changes abruptly at a distance of ( / 2). In this case, it is extremely advantageous that the abrupt change in size occurs at height h 20 This is achieved through an increase in [something].

[0091] In the case of the fluid component 10 shown in Figure 5, width b 101 , width b 11 and width b 102 These are considered to be of roughly the same size. For example, they may be about 0.3 mm. In this case, the radius R 109 of the outlet opening 102 may be about 0.025 mm.

[0092] Figure 6 shows a further embodiment of the present invention. This embodiment differs from the embodiments in Figures 1 to 5 in that the mixing chamber is composed of multiple parts. That is, the mixing chamber consists of multiple sub-chambers 20, 20' (in this example, two as an example) arranged front to back along the longitudinal axis L. Therefore, with respect to the fluid component 10 and the first fluid flow direction, there is an upstream sub-chamber 20 directly adjacent to the outlet opening 102 of the fluid component 10, and a downstream sub-chamber 20' directly adjacent to the outlet opening 202 of the upstream sub-chamber 20. The first inlet opening of the downstream sub-chamber 20' corresponds to the outlet opening of the upstream sub-chamber 20. In this case, each sub-chamber 20, 20' has an inlet flow path 206, 206' that widens in the downstream direction along the longitudinal axis L, and an outlet flow path 207, 207' that tapers in the downstream direction along the longitudinal axis L. Furthermore, a second inlet opening 2012 is formed in the inlet flow path of the downstream sub-chamber. These two sub-chambers can also be considered as a mixing chamber 20 with a constricted section in between. Therefore, the cross-sectional area A of the mixing chamber 20 is 20 It is configured to increase downstream to a predetermined point before and after the second inlet opening 2011, then remain constant and continue further, before decreasing again to a (local) minimum value. Downstream of this (local) minimum value, the cross-sectional area A 20 The volume then begins to increase again. A further inlet opening 2012 is located in this region. The subsequent mixing chamber 20 has the configuration described in relation to the embodiments in Figures 1 and 5. Cross-sectional area A 20 Of the parts having this characteristic, the portion that remains constant along the longitudinal axis L may or may not exist.

[0093] More advantageously, the first portion of the mixing chamber (or upstream sub-chamber 20), including the second inlet opening 2011, is configured to generate alternating vortices that amplify the movement of the first fluid 7 and, furthermore, the moving mixed fluid jet 9. In other words, the shape of the first portion of the mixing chamber (or upstream sub-chamber 20) is such that two boundary walls on both sides in the oscillating plan view each form a pocket-like structure that allows the jet of the first fluid 7, which is moving over time, to flow alternately and generate alternating vortices.

[0094] Figure 7 shows a further embodiment of the apparatus 1. This embodiment differs from the embodiments in Figures 1, 5, and 6, particularly in the shape of the mixing chamber 20 and the number of second inlet openings 2011. The mixing chamber 20 is provided with one second inlet opening 2011a for the second fluid 8 (phase B), as well as a further second inlet opening 2011b. In principle, this further second inlet opening 2011b may also serve to transport the second fluid 8 into the mixing chamber 20. As a variation, this further second inlet opening 2011b may serve to transport a further phase C or a third fluid into the mixing chamber 20. In Figure 7, there are two second inlet openings 2011. However, it is also possible to provide three or more second inlet openings.

[0095] The two second inlet openings 2011a and 2011b are formed in a common boundary wall of the inlet flow path 206. In principle, two or more second inlet openings 2011 may be formed on opposite sides of the mixing chamber 20. That is, one or more second inlet openings 2011 may be formed on the upper side of the device 1 (as shown in Figure 4), and one or more further second inlet openings 2011 may be formed on the lower side of the device 1, opposite to the upper side.

[0096] In Figure 7, two second inlet openings 2011 are provided adjacent to each other, and the distance l (along the longitudinal axis L) from the first inlet opening 201 is... 2011 They are identical. As a variation, the distance between the second entrance openings 2011 is l 2011 They may be different.

[0097] Advantageously, the distance b (crossing the longitudinal axis L) between the second entrance openings 2011 is advantageous. 2013 The distance b between the two second inlet openings 2011a and 2011b is selected to be small. 2013 The width b of the first entrance opening 201 201 It is smaller than that.

[0098] Each of the above embodiments includes an interaction channel 30 downstream of the outlet opening 202 of the mixing chamber 20. However, the interaction channel may or may not be present. The apparatus according to the present invention does not require such an interaction channel. Each of the above embodiments includes a predetermined number (at least one) of first / second inlet openings, outlet openings, and first / second supply devices. In practice, there may be two or more of each.

[0099] The interface of the apparatus 1 that comes into contact with the first fluid 7, the second fluid 8, or the mixed fluid 9 is advantageous if it has low surface roughness. The risk of fluid component deposition within the apparatus 1 is already extremely low due to the dynamic motion of the fluid jet. This effect can be improved by reducing surface roughness, thereby increasing the stability of continuous operation of the apparatus. It is extremely advantageous if the surface, in particular the surface of the mixing chamber, is lipophilic.

[0100] Various types of fluid components can be used. In such cases, means such as auxiliary channels may be provided as means for changing the direction to a specific direction. In this specification, the terms height h and depth t are used synonymously with the extent of the first fluid across the oscillation plane.

[0101] In the apparatus 1 according to the present invention, a wide range of volumetric flow rates, for example, from 20 ml / min to 200 ml / min, can be applied to the volumetric flow rates of the first fluid 7 and the second fluid 8, respectively. This volumetric flow rate is such that it does not significantly change the particle size when preparing particles in the mixing chamber 20. As a result, apparatus 1 exhibits excellent robustness against volumetric flow rate fluctuations that may occur for technical reasons. Furthermore, the system can be used for both laboratory-scale and large-scale preparations.

[0102] Figure 8 shows one embodiment of the interaction channel 30 as an example. The interaction channel 30 is an optional component of the apparatus 1. If provided, the interaction channel 30 is connected to the outlet opening 202 of the mixing chamber 20. The interaction channel 30 is pipe-shaped and has a plurality of bends 31 in Figure 8. The number of bends and their bending radii in Figure 8 are merely examples. Generally, the interaction channel 30 is formed in a shape that prevents the formation of stagnant areas and uncontrollable aggregation. The mixed fluid 9 flowing out from the outlet opening 202 is given further mixing opportunities by flowing through the interaction channel 30. If particles are prepared by the mixing process in the mixing chamber 20, the particles can grow through the interaction channel. The residence time of the prepared mixed fluid 9 or particles can be manipulated by the length of the interaction channel 30.

[0103] Figure 9 schematically illustrates the displacement of the moving (oscillating) first fluid 7 (at the outlet opening 102 of the fluid component 10) over time. It can be seen that the first fluid oscillates periodically between two maximum displacement values ​​(in this example, approximately ±25°). Here, the dashed line represents the trajectory of the moving fluid jet in the case of an ideal sine wave. To improve the mixing quality in the mixing chamber 20, it is advantageous to add intermediate oscillations. Such intermediate oscillations are represented by solid lines and are applied at approximately ±5°. This type of trajectory (including intermediate oscillations) over time can be formed by the fluid component 10, for example, as shown in Figures 6 and 7. In Figure 9, the oscillation angle α is approximately 50°. In principle, the oscillation angle may differ from this value. The oscillation angle is selected according to the desired mixing quality and mixing amount of the fluids to be mixed.

[0104] Figure 10 schematically shows the time series of the method according to the present invention for preparing a mixed fluid containing two fluids by mixing each fluid (in this example, two fluids as an example). The apparatus according to the present invention is used when carrying out this method.

[0105] The initial process steps labeled P1.1, P2.1, and P3.1 in Figure 10 relate to the first fluid 7 and are carried out in parallel with the process steps P1.2, P2.2, and P3.2 relating to the second fluid 8. During these process steps, the first fluid 7 and the second fluid 8 are isolated from each other.

[0106] First, in steps P1.1 and P1.2 of the method, the volumetric flow rates of the first fluid and the second fluid are set, respectively. As a result, the mixing ratio (and optionally the particle size if particles are prepared during the mixing process) can be set.

[0107] In the following steps P2.1 and P2.2, the inflow pressure P of the first fluid 7 10IN and the inflow pressure P of the second fluid 8 20IN The flow rate is set using an appropriate pumping device (depending on the volume, for example, a syringe pump, transport pump, etc.), and the first and second fluids 7 and 8 are delivered into the first supply device 40 and the second supply device 50, respectively. Here, the inflow pressure P of the first fluid 7 10IN This refers to the pressure at which the first fluid flows from the inlet opening 101 into the passage chamber 100 of the fluid component 10 (first supply device 40). Here, the inflow pressure P of the second fluid 8. 20IN This refers to the pressure at which the second fluid flows into the second supply device 50.

[0108] Each applied inlet pressure is within the range of a few millibars to several hundred bar (relative to ambient pressure). For large-scale preparation, for example, inlet pressures significantly exceeding 2 bar are applied. This pressure may take the three-digit value, such as 600 bar. A pressure range of 2 bar to 350 bar is preferred. A pressure range of 10 bar to 220 bar is extremely preferred.

[0109] After the first and second fluids 7 and 8 are introduced into their respective supply devices 40 and 50, their respective flow characteristics are adjusted by the supply devices 40 and 50 in method steps P3.1 and P3.2. For example, in P3.1, the fluid component 10 causes the first fluid 7 to oscillate. Generally, the oscillation frequency is greater than 100 Hz. Motion or oscillation frequencies of several thousand Hz, such as 2000 Hz, are advantageous. In this way, the passively oscillating first fluid 7 is delivered to the outlet opening 102 of the fluid component 10. The oscillation angle of the first fluid may be 5° or more, preferably 25° or more, and very preferably 40° or more. For most applications, an oscillation angle of 25° to 50°, particularly 30° to 45°, is preferred. Generally, the maximum value of the oscillation angle is 75°.

[0110] In a parallel process step P3.2, a (quasi)steady second fluid jet 8 is generated in the second supply device 50 by the corresponding pump device. As a modification, it is also possible to generate oscillations of the second fluid 8 in the second supply device 50 in process step P3.2. (For this purpose, the second supply device 50 is provided with fluid components 10 similar to those in the first supply device 40).

[0111] In step P4 of the method, the oscillating first fluid jet 7 prepared by the first supply device 40 and the (quasi)steady second fluid jet 8 prepared by the second supply device 50 are delivered into the mixing chamber 20 through the first inlet opening 201 and the second inlet opening 2011, respectively, where they merge. This collision occurs with angles β and η, which have already been described in detail in relation to the device 1. When this method is applied on an industrial process scale or in large-scale preparations, the fluids 7 and / or 8 are delivered into the mixing chamber 20 in a continuous volume flow.

[0112] Method step P7, in which the prepared mixed fluid 9 is removed from the apparatus 1, may be performed immediately after method step P4. In addition, method step P7 may include heat treatment (cooling) the prepared mixed fluid and / or separating any components (e.g., solvents, etc.) from the mixed fluid.

[0113] However, one or more intermediate steps P5 and / or intermediate steps P6 may be provided between P4 and P7.

[0114] In other words, the mixed fluid 9 that flows out of the mixing chamber 20 through the outlet opening 202 at the end of the mixing step P4 may be carried in the method step P5 into the interaction channel 30, which is adjacent to the downstream direction and gives the mixed fluid 9 further mixing opportunities. If particles are formed in the mixing step P4, these particles may grow in the interaction channel 30. The interaction channel 30 has already been described in detail in relation to the apparatus 1.

[0115] Optionally, step P6 may be performed after step P5. As a variation, step P7 may be performed immediately after step P5. In step P6, the prepared mixed fluid (containing or not containing particles) is mixed with a further medium (fluid), for example, for dilution. The medium may be selected depending on the properties of the prepared mixed fluid. This may be beneficial in subsequent processing, for example, when preparing nanoparticles.

[0116] The method described herein can be used in the field of chemistry to prepare mixed chemicals. It can also be used in microbiology, biochemistry, pharmacy, medical technology, and food technology. In preparing pharmaceutical or therapeutic microparticles, the method may be carried out using a solvent mixed with a pharmaceutical or therapeutic substance and / or a fluid mixed with one or more particle-containing pharmaceutical or therapeutic substances as the first and / or second fluid 8.

[0117] Therefore, this method can be used to encapsulate RNA of a predetermined particle size in a lipid layer. In this case, the first fluid 7 may be an aqueous solution containing RNA (e.g., mRNA), and the second fluid 8 may be a lipid or a lipid mixture.

[0118] Figure 11 shows the measured values ​​of the mixed fluid prepared using the apparatus in Figure 5 and the method in Figure 10. This mixed fluid contains particles prepared by the mixing process. Specifically, an mRNA batch was used as the first fluid, and a lipid mixture was used as the second fluid. The mixing process formed mRNA particles surrounded by a lipid layer. This procedure was performed multiple times with varying volume flow rates (13.3 ml / min, 40 ml / min, 60 ml / min). In all cases, the volume flow rate of the first fluid was three times that of the second fluid. The volume flow rates specified in Figure 11 all correspond to the sum of the first and second fluids. The volume flow rates depend, for example, on the composition of the lipid mixture.

[0119] Figure 11 shows the measured values ​​for each characteristic variable—encapsulation efficiency (graph a), particle size (graph b), and polydispersity index (abbreviated as PDI) (graph c)—for three different volumetric flow rates, represented by three graphs a), b), and c). Encapsulation efficiency is expressed as a percentage of the proportion of mRNA present in particle form. The polydispersity index represents the particle size distribution of mRNA particles. Here, a polydispersity index of 0 means that all particles have the same particle size. The values ​​on the x-axis of each graph simply represent different samples collected at different time points.

[0120] Graph a) shows that the encapsulation efficiency is consistently 95% to 100%, regardless of the volumetric flow rate setting. (Similar efficiencies are obtained when the volumetric flow rate is above or below the values ​​shown in Figure 11). When preparing mRNA particles surrounded by a lipid layer industrially, a value exceeding 85% is expected as a standard. The method according to the present invention can easily meet this standard.

[0121] Here, regarding particle size (graph b), it is clear that a particle size of approximately 90 nm is obtained when the volumetric flow rate is low at 13.3 ml / min, and the particle size decreases to approximately 70 nm when the volumetric flow rate is increased to 40 ml / min. Conversely, even if the volumetric flow rate is further increased to 60 ml / min, the particle size does not decrease any further. By selecting an appropriate volumetric flow rate, mRNA particles surrounded by a lipid layer can be prepared with a particle size within the standard particle size range (dashed line) by the method according to the present invention. In this case, the scale of the volumetric flow rate may depend on the composition of the lipid mixture.

[0122] The particle size distribution of the prepared particles (graph c) is relatively narrow, and the effect of volumetric flow rate on the particle size distribution is negligibly small. From graph c), it can be seen that the particle size distribution of mRNA particles surrounded by the lipid layer also falls within the range of industry standards by the method according to the present invention.

[0123] Figures 12 and 13 show further embodiments of apparatus 1. Similar to the apparatus in Figures 1 to 4, apparatus 1 comprises a first supply device 40 and a second supply device 50, each connected to the mixing chamber 20, and an interaction channel 30 adjacent to the outlet opening 202 of the mixing chamber 20.

[0124] At this time, the first supply device 40 is equipped with a fluid component 10 as a means for dynamically changing the direction of the first fluid 7 toward the target. As a result, the fluid flow of the first fluid 7 moves within the mixing chamber 20 having a kinetic component along the first fluid flow direction F1 and a kinetic component crossing the first fluid flow direction F1. Here, the first fluid flow direction F1 is the main flow direction F within the mixing chamber 20. H20 This corresponds to the movement of the first fluid 7 in this case, which may be variable over time. Main flow direction F in the mixing chamber 20 H20This direction is from the first inlet opening 201 of the mixing chamber 20 toward the outlet opening 202 of the mixing chamber 20. The movement of the fluid flow of the first fluid 7 within the mixing chamber 20 may also be a periodic motion that varies over time. This motion may be considered as oscillation, vibration, rotation, or pulsation of the fluid flow. The supply device 40 in Figure 12 may be equipped with the fluid component 10 of the device 1 in Figure 1 as the fluid component 10. That is, the dimensions (length, width, height, depth, diameter) of the fluid component 10 (and its components) in Figure 12 may be as described above with respect to the fluid component 10 (and its components) in Figure 1.

[0125] The embodiment in Figure 12 differs from the embodiment in Figure 1, particularly in the structure upstream of the inlet opening 101 of the fluid component 10 (part of the first supply device 40) and the structure downstream of the outlet opening 202 of the mixing chamber 20. In the embodiment of Figure 1, the funnel-shaped neck portion 106 is provided upstream of the inlet opening 101 and extends only on the oscillating plane in which the first fluid 7 moves within the fluid component 10. As a result, the first fluid 7 flows only along the first fluid flow direction F1 on the oscillating plane before reaching the inlet opening 101. In contrast, in the embodiment of Figure 12, the inlet passage 1614 is provided upstream of the neck portion 106. The inlet passage 1614 extends substantially perpendicular to the oscillating plane, that is, perpendicular to the neck portion 106. In this case, the neck portion 106 is directly adjacent to the inlet passage 1614. In Figure 13, the transition between the inlet channel 1614 (or the downstream end of the inlet channel 1614) and the neck portion 106 (or the upstream end of the neck portion 106) is represented by reference numeral 161. The neck portion 106 and the inlet channel 1614 can be formed as a single unit. Specifically, the inlet channel 1614 is formed in a boundary wall that extends parallel to the oscillating plane and defines the neck portion 106, and can completely penetrate this boundary wall by crossing the oscillating plane. In other words, the first fluid 7 flowing through the inlet channel 1614 and the neck portion 106 undergoes a change of direction of approximately 90°.

[0126] In the embodiment shown in Figure 12, the same thing happens downstream of the outlet opening 202 of the mixing chamber 20. The downstream direction of the outlet channel 3024 is directly adjacent to the interaction channel 30. In Figure 13, the transition between the interaction channel 30 (or the downstream end of the interaction channel 30) and the outlet channel 3024 (or the upstream end of the outlet channel 3024) is represented by reference numeral 302. In this case, the interaction channel 30 extends only on the oscillation plane, and the outlet channel 3024 extends substantially perpendicular to the oscillation plane. The interaction channel 30 and the outlet channel 3024 can be formed as a single unit. Specifically, the outlet channel 3024 can be formed as a boundary wall extending parallel to the oscillation plane and defining the interaction channel 30, and can completely penetrate the boundary wall so as to cross the oscillation plane. In other words, the prepared mixed fluid 9 flowing through the interaction channel 30 and the outlet channel 3024 undergoes a substantially approximately 90° change of direction.

[0127] The inlet channel 1614 and the outlet channel 3024 each have a constant diameter and are cylindrical in shape, as an example. Here, the diameter d of the inlet channel 1614 is... 161 The diameter is 0.45 mm, and the diameter of the outlet channel 3024 is d 302 d is 0.5 mm. As an alternative, these two diameters may be of the same magnitude. In one advantageous embodiment, diameter d 302 is, d 161 and b 2011 (d) is greater than or equal to the maximum value of (width of the second entrance opening 2011) 302 ≥ max(b 2011 d 161 )) d 161 and d 302 The appropriate dimensional ratio depends on the properties of each fluid to be mixed, the interactions between the fluids (e.g., collisions), the chemical reactions between the fluids, and the ratio of the amounts of each fluid to be mixed.

[0128] In one advantageous embodiment, no steps are formed in the transition section 161 between the inlet channel 1614 and the neck section 106, or in the transition section 302 between the interaction channel 30 and the outlet channel 3024. In this case, the wall of the inlet channel 1614 (interaction channel 30) transitions directly to the wall of the neck section 106 (outlet channel 3024) without any steps. However, steps may be formed in the above-mentioned transition sections 161 and 302. Therefore, in Figure 12, a step is shown in the transition section 161 between the inlet channel 1614 and the neck section 106, as an example, and the diameter d of the inlet channel 1614 is shown. 161 However, the width b of the neck portion 106 106 It is smaller than (the extended range across the longitudinal axis L on the oscillation plane). In contrast, in Figure 12, the diameter d of the outlet channel 3024 302 and the width b of the interaction channel 30 300 The extent of the vibration (extending across the longitudinal axis L on the aforementioned vibration plane) is the same.

[0129] The inlet channel 1614 is fluidly connected to the inlet opening 101 of the fluid component 10 via the neck portion 106. In one advantageous embodiment, the length of the neck portion 106 is l 106 (Diameter d of the inlet channel 1614) 161 The extension from the center point along the longitudinal axis L to the entrance opening 101 is width b 101 Twice the diameter and d 161 (l 106 ≥ 2 × b 101 +2×d 161 ).

[0130] In the embodiment shown in Figure 12, the width b of the entrance opening 101 101 The minimum cross-sectional area A of the main flow path 103 between internal blocks 11a and 11b 11 width b 11 They are of similar size, and their respective values ​​are 0.38 mm.

[0131] The outlet opening 202 of the mixing chamber 20 is fluidly connected to the outlet channel 3024 via the interaction channel 30. At least a portion of the interaction channel 30 has a width b 300The (extended range across the fluid flow direction on the oscillation plane) is constant. In the embodiment shown in Figure 12, the width b 300 The diameter d of the outlet opening 202 of the mixing chamber 20 and the outlet channel 3024 are constant at approximately 0.5 mm along the entire length of the interaction channel 30. 302 The length along the longitudinal axis L (or the fluid flow direction) between the center point and the interaction channel l is the length of the interaction channel 30. 30 In that case, length l 30 It can take on various values. Preferably, length l 30 is diameter d 302 It is twice the size of (l 30 ≥ 2 × d 302 ). When preparing lipid nanoparticles using this device, 30 ≥ 5 × d 302 This is advantageous. In the case where the interaction channel 30 is not linear, as in the embodiment shown in Figure 8, the length along the center line of the interaction channel 30 is length l. 30 It is said that...

[0132] In the embodiment shown in Figure 12, the cross-section of the second inlet opening 2011 of the mixing chamber 20 is circular. Here, width b 2011 The (extended range across the longitudinal axis L on the aforementioned oscillation plane) is 0.3 mm as an example, and the cross-sectional area of ​​the second inlet opening 2011 is approximately 0.07 mm². 2 The distance along the longitudinal axis L between the center point of the first inlet opening 201 and the second inlet opening 2011 of the mixing chamber 20 is 1.01 mm. Advantageously, the part depth h of the region between the first and second inlet openings 201 and 2011 of the mixing chamber 20 is... 206 (The extended range that crosses the oscillation plane) is width b 2011 It is less than 3 times (h 206 ≤ 3 × b 2011 ). Preferably, h 206 ≤2.75 × b 2011 That is the case.

[0133] The cross-sectional area A of the mixing chamber 20 (crossing the longitudinal axis L) at the height of the center point of the second entrance opening 2011. 20,b2011m It is approximately 0.25 mm 2This is the cross-sectional area A of the mixing chamber 20 (crossing the longitudinal axis L) at the height immediately before the second inlet opening 2011, which is further upstream (with reference to the first fluid flow direction F1) within the mixing chamber 20. 20,b2011a It is approximately 0.21 mm 2 This is the cross-sectional area A of the mixing chamber 20 (crossing the longitudinal axis L) at the height immediately after the second inlet opening 2011, which is further downstream (with reference to the first fluid flow direction F1) within the mixing chamber 20. 20,b2011e It is approximately 0.3 mm 2 The depth of the mixing chamber 20 is the same in these three regions. Also, the cross-sectional area A 20,b2011a and cross-sectional area A 20,b2011e They may be of the same size, or the cross-sectional area A 20,b2011a Cross-sectional area A 20,b2011e It may be larger than this. Cross-sectional area A 20,b2011m is the cross-sectional area A 20,b2011a and cross-sectional area A 20,b2011e It can take any value between and . The specific size ratio can be set according to the desired application. In one advantageous embodiment, the cross-sectional area A of the mixing chamber 20 20,b2011e This refers to the cross-sectional area A of the first and second inlet openings 201, 2011 of the mixing chamber 20. 201 and cross-sectional area A 2011 It is greater than or equal to the sum of (A 20,b2011e ≧A 201 +A 2011 Condition: A 20,b2011e ≧A 201 +A 2011 In addition, condition: A 20,b2011e ≤3.5 × A 201 The following may also apply: satisfying both conditions and the component depth h in the region of the inlet channel 206 of the mixing chamber 20. 206 By keeping the (extended range across the oscillation plane) constant, the mixing of the first fluid 7 and the second fluid 8 can be optimized.

[0134] In the embodiment shown in Figure 12, the volume V of the fluid component 10 10 Approximately 0.67 mm 3 Volume V 10This refers to the space between the inlet opening 101 and the outlet opening 102 of the fluid component 10 through which the first fluid 7 can flow. At this time, the volume V of the main flow path 103 of the fluid component 10 is 103 It is approximately 0.32 mm 3 The volume V of the mixing chamber 20. 20 Approximately 1.68 mm 3 Volume V 20 This refers to the space between the first and second inlet openings 201, 2011 of the mixing chamber 20 and the outlet opening 202 of the mixing chamber 20 through which the first fluid 7, the second fluid 8, or the prepared mixed fluid 9 can flow. The inlet openings 201, 2011 and the outlet opening 202 are the points in the mixing chamber 20 where the cross-sectional area of ​​the fluid flow (crossing the fluid flow direction) during inflow and re-outflow is smallest, respectively. Specifically, volume V 20 This does not include the space upstream of the point where the cross-sectional area is smallest, where only one of the fluids 7 or 8 is supplied to the mixing chamber 20. Specifically, volume V 20 This does not include the space downstream of the point where the cross-sectional area is smallest, from which the mixed fluid 9 is discharged. Also, the total volume V of the first supply device 40. 40 It is approximately 1.017 mm 3 Here, volume V 40 This refers to the space between the upstream end of the inlet channel 1614 and the outlet opening 102 of the fluid component 10 through which the first fluid 7 can flow. The volume V of the mixing chamber 20. 20 The volume V of the supply device 40 40 Making it larger than (V) will result in a more favorable mixing outcome. 20 >V 40 , or V 20 >V 40 >V 10 >V 103 The specific volume details described above relate to one embodiment of apparatus 1 shown in Figure 12. Depending on the desired application, apparatus 1 may be enlarged or reduced while maintaining the volume ratio defined for this embodiment.

[0135] Figure 13 is a cross-sectional view of the apparatus 1 along the line D'-D'' in Figure 12. The figure further shows a cover 60 and an optional component, a seal 70, which extend on planes parallel to the oscillation plane and are located on the opposite side of the second inlet opening 2011 of the apparatus 1. Although only a cross-sectional view of the cover 60 is shown here, the cover 60 extends throughout the entire apparatus 1. For clarity, gaps are shown between the cover 60, the seal 70, and the main body 2 of the apparatus 1 on which the fluid conduction functional elements 40, 50, 20, and 30 are formed, but these gaps do not actually exist.

[0136] The cover body 60 seals the fluid conduction functional elements 40, 20, and 30 from the outside. In the illustrated embodiment, the inlet channel 1614 upstream of the inlet opening 101 of the fluid component 10, the supply channel 2014 connected to the second inlet opening 2011 of the mixing chamber 20, and the outlet channel 3024 of the interaction channel 30 are formed in the main body 2 as perforations perpendicular to the oscillation plane. However, in principle, these perforations may also be formed in the cover body 60, or they may be formed only in the cover body 60.

[0137] In the embodiments shown in Figures 1 to 4, the main body 2 and the cover 60 are formed as a single unit, and the fluid conduction functional element is incorporated into the material block. In principle, this structure is also possible in the embodiments shown in Figures 12 and 13. Similarly, the above structure (a structure in which the main body 2, cover 60, and seal 70 are separate components) may also be applied to the embodiments shown in Figures 1 to 4.

[0138] The seal 70 may be made from an elastic material. In particular, when the inflow pressure P exceeds 5 bar in the first supply device 40 (specifically, the inlet passage 1614) 10IN For applications of device 1 where the following is added, it is advantageous to use an elastic material. The embodiment of device 1 shown in Figures 12 and 13 is, for example, the inflow pressure P of the suction passage 1614. 10IN (First fluid 7) is set to 0.5 bar to 90 bar, and the inflow pressure P of the supply channel 2014 is set. 20INThe (second fluid 8) can be operated at 0.5 bar to 90 bar. Generally, the inflow pressure is in the range of 0.75 bar to 65 bar. When apparatus 1 in Figures 12 and 13 is used in a method for preparing lipid nanoparticles, the inflow pressure P 10IN ,P 201N Inlet pressures of 1 to 30 bar can be used in this method. Generally, the inlet pressure is in the range of 2 to 6 bar.

[0139] The supply channel 2014 is formed immediately upstream (with respect to the second fluid flow direction F2) of the second inlet opening 2011 of the mixing chamber 20. The supply channel 2014 is formed as a cylindrical bore, with a diameter d 2014 The width b of the second entrance opening 2011 2011 This matches. However, diameter d 2014 is width b 2011This may differ from the above. In the embodiments of Figures 12 and 13, the edge of the second inlet opening 2011 is pointed. In principle, it may be configured with other features such as a C-chamfer or R-chamfer. However, it is extremely advantageous for the second inlet opening 2011 to be configured with a pointed edge without burrs. The supply channel 2014 may be fluidly connected to a pipe member 204 or a tubular body (Figure 13). In this case, the diameter of the pipe member 204 or the tubular body is larger than the diameter of the supply channel 2013. As a result, a step 2020 is created in the transition region. In Figure 13, the step 2020 is configured with a pointed edge. However, the transition between the pipe member 204 or the tubular body and the supply channel 2014 may be smoothly configured (without a step), or a chamfer may be formed on the step 2020. As previously described in relation to the embodiments in Figures 1 to 4, the supply channel 2014 (or the pipe member 204 connected to the supply channel 2014) and the oscillating plane are separated by angles β and η. Here, angle β is the angle measured on a plane that extends parallel to the longitudinal axis L and perpendicular to the oscillating plane. On the other hand, angle η is the angle measured on a plane that extends perpendicular to the longitudinal axis L and perpendicular to the oscillating plane. The specifications for the magnitudes of angles β and η in the embodiments in Figures 1 to 4 also apply to the embodiments in Figures 12 and 13.

[0140] Specifically, the above-described geometric relationship of the apparatus 1, including the supply channel 1614, the supply channel 2014, and the outlet channel 3024, does not include fluid supply means connected to the supply channel 1614 or the supply channel 2014, nor does it include any device for recovering the mixed fluid that has exited the outlet channel 3024.

[0141] Figure 13 shows the length h of the supply channel 2014. 2014 This is shown. Length h 2014 is width b 2011 It is more than 2.5 times (h 2014 ≥2.5 × b 2011 ). Preferably, formula: h 2014 ≥4.2 × b 2011 This applies.

[0142] In the embodiments shown in Figures 12 and 13, the fluid component 10 and the mixing chamber 20 have the same height (extension range across the oscillation plane) (h 10 =h 20 ). Height h 10 and height h 20 This height is set to a constant 0.3 mm over the entire extent of the fluid component 10 or the mixing chamber 20. In other words, the height h of the outlet opening 102 of the fluid component 10. 102 It is also 0.3 mm. As a result, dimension b 102 ,h 102 All of the values ​​are 0.3 mm, A 1min This forms the height h and depth h, and since both terms refer to the extent that extends across the oscillation plane, they are used synonymously in this application.

[0143] Given the geometric specifications described above, the total volume V9 of the prepared mixed fluid 9 (measurable in the outlet channel 3024) can be between 10 ml / min and 90 ml / min. Of the total volumetric flow rate V9, the volume fraction of the first fluid 7 can be 75%, and the volume fraction of the second fluid 8 can be 25%. Therefore, the inflow pressure P of the inlet channel 161 or supply channel 2013 is... 10IN and P 20IN When the pressure is between 2 bar and 6 bar, the overall volumetric flow rate V9 is between 10 ml / min and 90 ml / min, and vice versa.

[0144] In the apparatus 1 according to the present invention, the volumetric flow rate of the first fluid 7, the volumetric flow rate of the second fluid 8, the overall volumetric flow rate V9 of the mixed fluid, and the inflow pressure P are... 10IN ,P 20IN This makes it possible to adjust the pressure over a wide process range without significantly changing the quality of the mixed fluid 9 or the particles being prepared. Moreover, the apparatus 1 is relatively unaffected by pressure pulsations in the first and second fluids. In other words, the method of preparing the mixed fluid using the apparatus 1 is also relatively unaffected by these pressure pulsations. For example, pressure increasing means used in process steps P2.1, P2.2 (V2.1, V2.2, and optionally V2.3~V2.5) of the method shown in Figure 10 (Figure 15) cause pressure pulsations.

[0145] The volumetric flow rates of the first fluid and the second fluid are determined by the inflow pressure P. 10IN ,P 20IN Assuming constant pressure, the width b of the outlet opening 102 of the fluid component 10. 102 and / or height h 102 It can be changed by altering the formula:E 102 =b 102 / h 102 The ratio of lengths E is determined by 102 It is 1. However, E 102 The value may be anything other than 1.

[0146] The above describes various embodiments of the apparatus 1, and defines predetermined geometric dimensions (length, width, height, depth, and diameter) for each embodiment. These relate to a specific example of each embodiment of the apparatus 1. Depending on the desired application, the apparatus 1 may be scaled up or down while maintaining the ratio of the basic geometric dimensions defined for a particular embodiment. In other words, the individual geometric dimensions can be adjusted according to the mixing task.

[0147] Figure 15 schematically shows a time series of the method according to the present invention for preparing a mixed fluid 9 containing two or more fluids by mixing two or more fluids. The method in Figure 15 (and the method in Figure 10) can use the apparatus 1 of the embodiments in Figures 12 and 13. However, it is also possible to use the apparatus 1 of any other embodiment (Figures 1 to 8). Each influent substance used in this method may exist in either an absolute gaseous form or a solid form at room temperature. The influent substance can then be converted to a desired fluid form by temperature control and / or adjustment of the influent pressure before and / or within the apparatus 1 so that it is mixed in a liquid form, preferably in the mixing chamber 20 and the fluid component 10.

[0148] In Figure 15, the process steps within the boxes bordered by dotted lines are arbitrary process steps.

[0149] The first method steps V1.1, V1.2, and optional method steps V1.3, V1.4, V1.5 are carried out in parallel. Here, the first fluid 7 and the second fluid 8 (or their components), as well as three additional fluids (if used), are prepared separately. In these method steps, the volumetric flow rate (and volumetric flow rate ratio) of each fluid used is adjusted. This allows for setting the mixing ratio (and optionally, particle size if particles are prepared by mixing). Specifically, using the apparatus 1 according to the present invention, the particle size of the prepared particles can be adjusted by changing the volumetric flow rate ratio of the fluids used, without significantly changing the monodispersity (i.e., polydispersity index close to 0) of the resulting particle size distribution. For example, in the preparation of mRNA nanoparticles, it is possible to set the mixing ratio to consist of both by setting the volumetric fraction of the first fluid 7 to 75% in step V1.1 and the volumetric fraction of the second fluid 8 to 25% in step V1.2. In this case, the first fluid 7 may be an aqueous mRNA solution, and the second fluid 8 may be a lipid mixture. When preparing mRNA nanoparticles, if the overall volumetric flow rate V9 is 10 ml / min, the volumetric flow rate V7 of the first fluid 7 may be set to a constant 7.5 ml / min, and the volumetric flow rate V8 of the second fluid 8 may be set to a constant 2.5 ml / min. The three further fluids may include, for example, an organic solvent whose volumetric flow rate is adjusted in step V1.4. This organic solvent may be removed in a later step.

[0150] In the second method steps V2.1, V2.2, and optional method steps V2.3, V2.4, V2.5, the inflow pressure P of the first fluid 7 (or its components) 10IN and the inflow pressure P of the second fluid 8 (or its components) 20IN This is set using an appropriate pumping device (depending on the volume, for example, a syringe pump, a transport pump, etc.). Here, the inflow pressure P of the first fluid 7 is set. 10IN This refers to the pressure at which the first fluid flows from the inlet opening 101 into the passage chamber 100 of the fluid component 10 (first supply device 40). Here, the suction pressure P of the second fluid 8 is... 20IN This refers to the pressure at which the second fluid flows into the second supply device 50.

[0151] In the second method steps V2.1, V2.2, and the optional method steps V2.3, V2.4, V2.5, the temperature of the influent material used may be controlled as needed. The influent pressure may also be adjusted to impart the desired properties to the influent material. For example, the viscosity of the influent material can be adjusted. Depending on the type of influent material, the temperature and / or influent pressure can affect the mixing ratio and the results of the mixing process.

[0152] The third method step V3 is an optional method step. In this step, the fluids treated in V1.2, V1.3, V2.2, and V2.3 are mixed (assuming they have not yet become the first or second fluid) to prepare the first fluid 7 or the second fluid 8. The apparatus according to the present invention may be used for method step V3. However, in principle, a different mixing apparatus may be used for method step V3.

[0153] In the fourth method steps V4.1, V4.2, and optional method steps V4.3, V4.4, the first and second fluids 7, 8, and optionally additional fluids, are delivered into the first or second supply devices 40, 50, respectively. In method steps V4.1, V4.2, and optional method steps V4.3, V4.4, the flow characteristics are adjusted by the supply devices 40, 50. That is, in V4.1, the fluid component 10 causes the first fluid 7 to oscillate. Generally, the oscillation frequency is greater than 100 Hz. Oscillation frequencies of several thousand Hz, such as 2000 Hz, are advantageous. In this way, the passively oscillating first fluid 7 is delivered to the outlet opening 102 of the fluid component 10. The oscillation angle of the first fluid may be 5° or more, preferably 25° or more, and very preferably 40° or more. For most applications, an oscillation angle of 25° to 50°, particularly 30° to 45°, is preferable. Generally, the maximum value of the oscillation angle is 75°. By using the first supply device 40 (particularly the fluid component 10) shown in Figures 1 to 7 and Figures 12 and 13, it is possible to attenuate undesirable pressure fluctuations that may occur in the second method step, thus providing the advantage that this method is relatively less susceptible to the effects of such pressure fluctuations.

[0154] In a parallel process step V4.2, a (quasi)steady second fluid jet 8 is generated in an accelerated state within the second feeder 50 by the corresponding pump device. Depending on the specific task or desired mixing quality, it may be advantageous to reduce the velocity of the second fluid 8. As a variation, in process step V4.2, the second feeder 50 can also generate oscillations in the second fluid 8. (For this purpose, the second feeder 50 will be provided with fluid components 10 similar to those in the first feeder 40).

[0155] Step V5 involves combining and interacting the first and second fluids in the mixing chamber 20, and corresponds to step P4 in Figure 10. In step V5, the components of the mixed fluid 9 interact with each other, for example, causing a precipitation reaction or (if particles are formed in mixing step V5) particle growth. Optionally, one or more additional fluids from V4.3, etc., can be combined with the first and second fluids to produce, for example, a chemical reaction. In this case, the method can be carried out using the apparatus 1 in Figure 7. Step P9, in which the prepared mixed fluid 9 is removed from the apparatus 1, may be performed immediately after step V5.

[0156] One or more intermediate steps V6 and / or V7 and / or V8 may be provided between step V5 and step V9.

[0157] In an optional process step V6, the components of the mixed fluid 9 may continue to interact with each other from V5 onward. Process step V6 is carried out in an interaction channel 30 (specially provided for this process) adjacent to the downstream side of the mixing chamber 20. The interaction channel 30 can improve mixing and / or adjust the particle size of the prepared particles.

[0158] Optionally, step V7 may be performed after step V5 or step V6. In this step, the prepared mixed fluid 9 (containing or not containing particles) is mixed with a further medium (fluid) from, for example, V4.4, for purposes such as dilution. The medium may be selected depending on the properties of the prepared mixed fluid. This may be beneficial in subsequent processing, for example, when preparing nanoparticles.

[0159] Optionally, a post-treatment step V8 of the prepared mixed fluid may be performed after step V5, step V6, or step V7. This post-treatment may include, for example, counting the prepared particles, measuring the particle size of the prepared particles, or verifying the quality of the particles formed in the mixed fluid 9. Dialysis and / or filtration may also be considered.

[0160] In the final step V9, the prepared mixed fluid 9 is removed from the apparatus 1. Furthermore, the present invention includes the following aspects. [Aspect 1] Apparatus (1) for mixing fluids to prepare a mixed fluid, - Mixing chamber (20), A first inlet opening (201) through which a first fluid (7) can be introduced into the mixing chamber (20), A second inlet opening (2011) through which a second fluid (8) can be introduced into the mixing chamber (20), A mixing chamber (20) having an outlet opening (202) through which the mixed fluid (9) containing the first fluid (7) and the second fluid (8) can be discharged, - A first supply device (40) is configured to fluidly connect to the mixing chamber (20) via the first inlet opening (201) and transport the first fluid (7) into the mixing chamber (20) along the first fluid flow direction (F1), - A second supply device (50) is configured to fluidly connect to the mixing chamber (20) via the second inlet opening (2011) and transport the second fluid (8) into the mixing chamber (20) along the second fluid flow direction (F2), The first supply device (40) has a fluid component (10), and the fluid component (10) is - An outlet opening (102) fluid-connected to the first inlet opening (201) of the mixing chamber (20), and - At least one means (104a, 104b) for changing the direction of the first fluid (7) flowing through the fluid component (10) to a specific direction, in particular, so as to cause the fluid (7) to oscillate in space at the outlet opening (102), A device (1) that is equipped with the following. [Aspect 2] The apparatus (1) according to Embodiment 1, wherein the fluid component (10) comprises a flow chamber (100) through which the first fluid (7) can flow, and the flow chamber (100) is characterized in that it has a main flow path (103) connecting an inlet opening (101) and an outlet opening (102) of the fluid component (10) to each other, and at least one auxiliary flow path (104a, 104b) as means for changing the direction of the first fluid (7) to a specific direction. [Aspect 3] Apparatus (1) according to embodiment 1 or 2, characterized in that the first supply device (40) and the first inlet opening (201) of the mixing chamber (20), and the second supply device (50) and the second inlet opening (2011) of the mixing chamber (20) are arranged relative to each other such that the first fluid flow direction (F1) and the second fluid flow direction (F2) are separated by an angle of 0° to 90°, preferably 35° to 55°, and most preferably 45°. [Aspect 4] Apparatus (1) according to any one of embodiments 1 to 3, wherein the means (104a, 104b) for changing the direction of the first fluid (7) to a specific direction is configured to oscillate the first fluid (7) on a oscillating plane, and the second supply device (50) and the second inlet opening (2011) of the mixing chamber (20) are arranged such that the second fluid flow direction (F2) and the oscillating plane of the first fluid (7) straddle an angle (η) of 30° to 150°, preferably 90°, in a plan view where the second fluid flow direction (F2) and the oscillating plane of the first fluid (7) intersect the first fluid flow direction (F1), characterized in that Apparatus (1). [Aspect 5] Apparatus (1) according to any one of embodiments 1 to 4, characterized in that the longitudinal axis (L) of the mixing chamber (20) extends along the first fluid flow direction (F1), and the cross-sectional area of ​​the mixing chamber (20) determined so as to cross the longitudinal axis (L) changes along the longitudinal axis (L). [Aspect 6] Apparatus (1) according to Embodiment 5, characterized in that the cross-sectional area increases at the upstream end portion of the mixing chamber (20) that forms the inlet passage (206), starting from the first inlet opening (201) of the mixing chamber (20) and / or decreases at the downstream end portion of the mixing chamber (20) that forms the outlet passage (207), as it moves away from the first inlet opening (201). [Aspect 7] Apparatus (1) according to Embodiment 6, wherein the means (104a, 104b) for changing the direction of the first fluid (7) to a specific direction is configured to oscillate the first fluid (7) on a oscillating plane, and the extent of the mixing chamber (20) that crosses the longitudinal axis (L) on the oscillating plane increases in the inlet passage (206) as it moves away from the first inlet opening (201) of the mixing chamber (20), or decreases in the outlet passage (207) as it moves away from the first inlet opening (201). [Aspect 8] Apparatus (1) according to embodiment 6 or 7, characterized in that the second inlet opening (2011) of the mixing chamber (20) is offset from the first inlet opening (201) of the mixing chamber (20) along the longitudinal axis (L) of the mixing chamber (20) and is located within the inlet flow path (206). [Aspect 9] Apparatus (1) according to Embodiment 8, characterized in that the distance between the first and second inlet openings (201, 2011) along the longitudinal axis (L) is equal to or equal to 1 / 2 or more of the width (b201) of the first inlet opening (201) of the mixing chamber (20) that is determined by crossing the longitudinal axis parallel to the oscillation plane. [Aspect 10] Apparatus (1) according to any one of embodiments 1 to 9, characterized in that the volume of the mixing chamber (20) is greater than the volume of the fluid component (10) or the volume of the flow chamber (100) of the fluid component (10). [Aspect 11] In the apparatus (1) described in any one of embodiments 1 to 10, the second supply device (50) is configured to transport the second fluid (8) into the mixing chamber (20) as a (quasi) steady flow, or the second supply device (50) has a fluid component (10), and the fluid component (10) is - An outlet opening (102) fluid-connected to the second inlet opening (2011) of the mixing chamber (20), and - At least one means (104a, 104b) for changing the direction of the second fluid (8) flowing through the fluid component (10) to a specific direction, in particular, so as to cause the fluid (8) to oscillate in space at the outlet opening (102), Apparatus (1) characterized by comprising the following: [Aspect 12] Apparatus (1) according to any one of embodiments 1 to 11, wherein a second mixing chamber (20') is adjacent to the outlet opening (202) of the mixing chamber (20) in the downstream direction, and the second mixing chamber (20') has a first inlet opening (201'), a second inlet opening (2011'), and an outlet opening (202'), and the first inlet opening (201') of the second mixing chamber (20') corresponds to the outlet opening (202) of the upstream mixing chamber (20). [Aspect 13] Apparatus (1) according to any one of embodiments 1 to 12, characterized in that an interaction channel (30) having at least one bent portion is adjacent to the outlet opening (202, 202') of the mixing chamber (20) or the second mixing chamber (20') in the downstream direction. [Aspect 14] A method for preparing a mixed fluid by mixing fluids, - A step of preparing the apparatus (1), first fluid (7), and second fluid (8) according to any one of embodiments 1 to 13 and embodiment 20, - A step of introducing the first fluid (7) into the mixing chamber (20) from the first supply device (40) at a first volumetric flow rate, and at the same time introducing the second fluid (8) into the mixing chamber (20) from the second supply device (50) at a second volumetric flow rate, - A step of discharging the mixed fluid (9), which includes the first fluid (7) and the second fluid (8), out of the mixing chamber (20) through the outlet opening (202), A method that includes [a certain feature]. [Aspect 15] A method according to the method of embodiment 14, characterized in that the first volumetric flow rate is greater than the second volumetric flow rate, or the first volumetric flow rate and the second volumetric flow rate are of the same magnitude. [Aspect 16] A method according to embodiment 14 or 15, characterized in that the first fluid (7) and the second fluid (8) are, each, a liquid or a suspension containing a liquid and particles dispersed in the liquid. [Aspect 17] A method according to any one embodiment of embodiments 14 to 16, characterized in that the introduction of the first fluid into the mixing chamber and the introduction of the second fluid into the mixing chamber occur in succession. [Aspect 18] A method according to any one embodiment of embodiments 14 to 17, characterized in that the first fluid (7) and the second fluid (8) have different chemical compositions and / or concentrations of individual components. [Aspect 19] A method according to any one embodiment of embodiments 14 to 18, characterized in that the first fluid (7) contains RNA, particularly mRNA, and the second fluid (8) contains a lipid mixture. [Aspect 20] Apparatus (1) according to any one embodiment from embodiments 1 to 13, wherein the first supply device (40) is configured to change the direction of the first fluid (7) in a specific direction such that the movement of the first fluid (7) in the mixing chamber (20) becomes variable over time, and the first fluid (7) has a motion component along the first fluid flow direction (F1) and a motion component across the first fluid flow direction (F1), and the movement of the first fluid (7) in the mixing chamber (20) is particularly variable over time, periodically, in particular.

Claims

1. Apparatus (1) for mixing fluids to prepare a mixed fluid, - Mixing chamber (20), A first inlet opening (201) through which a first fluid (7) can be introduced into the mixing chamber (20), A second inlet opening (2011) through which a second fluid (8) can be introduced into the mixing chamber (20), A mixing chamber (20) having an outlet opening (202) through which the mixed fluid (9) containing the first fluid (7) and the second fluid (8) can be discharged, - A first supply device (40) is configured to fluidly connect to the mixing chamber (20) via the first inlet opening (201) and transport the first fluid (7) into the mixing chamber (20) along the first fluid flow direction (F1), - A second supply device (50) is configured to fluidly connect to the mixing chamber (20) via the second inlet opening (2011) and transport the second fluid (8) into the mixing chamber (20) along the second fluid flow direction (F2), The first supply device (40) has a fluid component (10), and the fluid component (10) is - An outlet opening (102) fluid-connected to the first inlet opening (201) of the mixing chamber (20), and - A flow chamber (100) through which the first fluid (7) can flow, A main flow path (103) connecting the inlet opening (101) and the outlet opening (102) of the fluid component (10), and In the outlet opening (102), an inlet section (104a1, 104b1) and an outlet section (104a2, 104b2) are provided to generate in-space oscillation of the first fluid (7) within the oscillation plane. The passage chamber (100) comprises at least one auxiliary passage (104a, 104b) having, A portion of the first fluid (7) can pass through the at least one auxiliary channel (104a, 104b), flows into the at least one auxiliary channel (104a, 104b) at the inlet (104a1, 104b1), escapes from the at least one auxiliary channel (104a, 104b) at the outlet (104a2, 104b2), and applies a lateral impact to the first fluid (7) flowing in from the inlet opening (101). Apparatus (1), wherein the mixing chamber (20) has a longitudinal axis (L) extending along the first fluid flow direction (F 1), and the second inlet opening (2011) of the mixing chamber (20) is offset from the first inlet opening (201) of the mixing chamber (20) by a certain length (l 2011) along the longitudinal axis (L) of the mixing chamber (20), and this length (l 2011) is 5 times or less the width (b 201) of the first inlet opening (201), and this width (b 201) is determined as an extending range that crosses the longitudinal axis (L) of the mixing chamber (20) parallel to the oscillation plane of the first fluid (7).

2. The apparatus (1) according to claim 1, characterized in that the cross-sectional area of ​​the mixing chamber (20), which is determined so as to cross the longitudinal axis (L), changes along the longitudinal axis (L).

3. The apparatus (1) according to claim 2, wherein the cross-sectional area increases at the upstream end portion of the mixing chamber (20) that forms the inlet passage (206), starting from the first inlet opening (201) of the mixing chamber (20) and moving away from the first inlet opening (201), and / or the cross-sectional area decreases at the downstream end portion of the mixing chamber (20) that forms the outlet passage (207), moving away from the first inlet opening (201).

4. The apparatus (1) according to claim 3, characterized in that the extent of the mixing chamber (20) that crosses the longitudinal axis (L) on the oscillating plane increases in the inlet flow path (206) as it moves away from the first inlet opening (201) of the mixing chamber (20), or the extent of the mixing chamber (20) that crosses the longitudinal axis (L) on the oscillating plane decreases in the outlet flow path (207) as it moves away from the first inlet opening (201).

5. The apparatus (1) according to claim 3, characterized in that the second inlet opening (2011) of the mixing chamber (20) is provided within the inlet flow path (206).

6. In the apparatus (1) according to claim 5, the distance between the first and second inlet openings (201, 2011) along the longitudinal axis (L) is the width of the first inlet opening (201) of the mixing chamber (20) and is determined by crossing the longitudinal axis parallel to the oscillation plane (b ２０１ Apparatus (1), characterized by being equivalent to 1 / 2 or more of ).

7. In the apparatus (1) according to claim 1, the second supply device (50) is configured to transport the second fluid (8) into the mixing chamber (20) as a (quasi) steady flow, or the second supply device (50) has a fluid component (10), and the fluid component (10) is - An outlet opening (102) fluid-connected to the second inlet opening (2011) of the mixing chamber (20), and - At least one auxiliary flow path (104a, 104b) for causing the second fluid (8) flowing through the fluid component (10) to oscillate in space at the outlet opening (102), Apparatus (1) characterized by comprising the following:

8. The apparatus (1) according to claim 1, characterized in that an interaction channel (30) having at least one bent portion is adjacent to the outlet opening (202) of the mixing chamber (20) in the downstream direction.

9. A method for preparing a mixed fluid by mixing fluids, - The process of preparing the apparatus (1), the first fluid (7), and the second fluid (8) described in claim 1. To what extent, - A step of introducing the first fluid (7) into the mixing chamber (20) from the first supply device (40) at a first volumetric flow rate, and at the same time introducing the second fluid (8) into the mixing chamber (20) from the second supply device (50) at a second volumetric flow rate, - A step of discharging the mixed fluid (9), which includes the first fluid (7) and the second fluid (8), out of the mixing chamber (20) through the outlet opening (202), A method that includes [a certain feature].

10. The method according to claim 9, characterized in that the first volumetric flow rate is greater than the second volumetric flow rate, or the first volumetric flow rate and the second volumetric flow rate are equal in amount.

11. The method according to claim 9, characterized in that the first fluid (7) and the second fluid (8) have different chemical compositions and / or concentrations of individual components.

12. A method according to claim 9, characterized in that the first fluid (7) contains RNA and the second fluid (8) contains a lipid mixture.

13. In the apparatus (1) according to claim 1, the first supply device (40) is configured to generate oscillation of the first fluid (7) in the space within the oscillation plane at the outlet opening (102) so that the movement of the first fluid (7) within the mixing chamber (20) becomes variable over time, and the first fluid (7) flows in the first fluid flow direction (F １ ) and the motion component along the first fluid flow direction (F １ The apparatus (1) has a motion component that crosses the first fluid (7), and the movement of the first fluid (7) within the mixing chamber (20) is characterized in that it is periodically variable over time.

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