Apparatus and method for producing a fluid mixture

Abstract

The present invention relates to an apparatus (1) for generating a fluid mixture, the apparatus comprising: a first mixing chamber (20) having: a first inlet opening (201) through which a first fluid (F1) can be introduced into the first mixing chamber (20) in a first fluid flow direction (R1); a second inlet opening (202) through which a second fluid (F2) can be introduced into the first mixing chamber (20) in a second fluid flow direction (R2); and an outlet opening (203) for generating an intermediate fluid mixture (F1) comprising the first fluid (F1) and the second fluid (F2). 12 It can flow through the outflow opening along the direction of the fluid mixture flow (R) 12 The outflow channel (207) is formed upstream of the outflow opening (203), and the outflow channel is transverse to the flow direction of the fluid mixture (R). 12 The cross-section defined along the direction of fluid mixture flow (R) 12 - The flow opening (203) decreases towards the outlet; - The second mixing chamber (40) has: a first inlet opening (401), an intermediate fluid mixture (F 12 It can flow along the direction of the fluid mixture flow (R) through the first inlet opening. 12 The first fluid (F1), the second fluid (F2), and the third fluid (F3) are introduced into the second mixing chamber (40); the third fluid (F3) can be introduced into the second mixing chamber (40) via the second inlet opening (402) along the third fluid flow direction (R3); and the fluid mixture (F1), comprising the first fluid (F1), the second fluid (F2), and the third fluid (F3) is discharged through the outlet opening (403). 123 It can be discharged through the outflow opening.

Description

Technical Field

[0001] This invention generally relates to an apparatus and a corresponding method for generating fluid mixtures. The fluid mixture can be a mixture of two fluids (liquids), but for the purposes of this application, it can also be a dispersion. A dispersion is a heterogeneous mixture of at least two substances that are immiscible or poorly miscible with each other. Here, the dispersed phase is distributed in a dispersion medium. Currently, the apparatus and method are particularly used for preparing suspensions or emulsions, in which a liquid is used as the dispersion medium and a solid as the dispersed phase, and in which not only the dispersed phase but also the dispersion medium is liquid.

[0002] Therefore, this invention relates to combining or mixing at least three separate fluids with each other. Depending on the type of fluid used, particles may be generated during the process, such as those distributed in the liquid, resulting in a suspension overall. Particles can be understood as solids forming a dispersed phase. In many applications, small-diameter particles are desirable. Particles in the nanometer size range are also called nanoparticles. These nanoparticles can be important in chemical, biochemical, or pharmaceutical processes. This invention particularly relates to apparatus and methods for generating such nanoparticles or particles in the micrometer range. Background Technology

[0003] An example of a pharmaceutically significant suspension is a drug formulated in liposome form. Here, particle or vesicle size and polydispersity index are key physical parameters affecting the therapeutic index of drugs formulated in liposome form. It is known that smaller liposomes have slower blood clearance, thereby improving drug bioavailability. Therefore, there is a need to produce particles of the pharmaceutically required size and with high quality, i.e., a low polydispersity index.

[0004] To produce nanoparticles, devices known as microfluidics or microfluidic mixers are employed. Microfluidic mixers typically have very small microchannels that generate low Reynolds numbers, thus often producing laminar flow without significant turbulence, which is detrimental to fluid mixing. Here, the flow channels are considerably long relative to their cross-sectional dimensions. These channels are expensive to manufacture and can easily become clogged during operation. Their application in mass production can also be difficult or even impossible. Summary of the Invention

[0005] The objective of this invention is to provide apparatus and methods for generating fluid mixtures (having nanoparticles with specific particle sizes and defined size distributions) that are as undisturbed as possible. In particular, the objective is also to provide apparatus and methods that can be used not only on a laboratory scale (i.e., a few nanoliters per minute) but also in batch production (i.e., a few liters per minute).

[0006] According to the invention, this objective is achieved by a device having the features of claim 1. The design of the invention is given in the dependent claims.

[0007] Accordingly, the apparatus for generating a fluid mixture first includes a first mixing chamber having: a first inlet opening through which a first fluid can be introduced into the first mixing chamber along a first fluid flow direction; a second inlet opening through which a second fluid can be introduced into the first mixing chamber along a second fluid flow direction; and an outlet opening through which an intermediate fluid mixture comprising the first and second fluids can be discharged along the fluid mixture flow direction. An outlet channel is formed upstream of the outlet opening, the cross-section of which, transverse to the fluid mixture flow direction, decreases towards the outlet opening along the fluid mixture flow direction. The outlet channel forms a downstream end section of the first mixing chamber. The outlet channel prevents the formation of a so-called stagnant zone in the first mixing chamber.

[0008] Furthermore, the device includes a second mixing chamber having a first inlet opening through which an intermediate fluid mixture can be introduced into the second mixing chamber in the direction of fluid mixture flow; a second inlet opening through which a third fluid can be introduced into the second mixing chamber in the direction of third fluid flow; and an outlet opening through which a fluid mixture comprising the first fluid, the second fluid, and the third fluid can be discharged. Therefore, the second mixing chamber is located downstream of the first mixing chamber, wherein the first and second mixing chambers are fluidly connected such that an intermediate fluid mixture exiting from the outlet opening of the first mixing chamber enters the second mixing chamber through the first inlet opening of the second mixing chamber.

[0009] To introduce fluid into the mixing chamber, a conveying device may be provided. Specifically, the device includes a first conveying device that is fluidly connected to the first mixing chamber via a first inlet opening and is configured to guide the first fluid into the first mixing chamber along a first fluid flow direction (variable in time and space).

[0010] Here, the first conveying device includes a fluid component having an outflow opening that is fluidly connected to a first inflow opening of a first mixing chamber. Specifically, the outflow opening of the fluid component can correspond to the first inflow opening of the first mixing chamber.

[0011] The fluid component includes at least one mechanism for targeted directional change of a first fluid, which flows through the fluid component. For targeted directional change, alternating vortices generated, for example, by colliding fluid flows within the fluid component or by disturbances within the fluid component, can be used. In this type of mechanism for generating targeted directional change, sufficient space must be provided for generating and subsequently eliminating the vortex structure. In particular, the at least one mechanism is configured and structured to create spatial oscillations of the first fluid at the outlet opening. In one embodiment, the mechanism for targeted directional change of the first fluid can be configured to induce oscillations of the first fluid in an oscillation plane.

[0012] Therefore, the first fluid is guided into the first mixing chamber not as a (quasi)static flow but as an oscillating fluid flow, which moves periodically and temporally. In addition to a longitudinal flow component along the direction of the first fluid flow, the first fluid also has a temporally varying transverse flow component (transverse to the direction of the first fluid flow). This generates turbulence in the first mixing chamber, enabling a high mixing quality. Accordingly, the first fluid enters the first mixing chamber oscillatingly or dynamically from the first conveying device. Thus, the first fluid acquires a constantly changing velocity component transverse to its main flow direction (the transverse flow component or the direction of the first fluid flow).

[0013] Furthermore, the device includes a first interactive channel disposed between a first mixing chamber and a second mixing chamber. The first interactive channel connects the outflow opening of the first mixing chamber and the first inflow opening of the second mixing chamber to each other, and has a cross-section transverse to the flow direction of the fluid mixture, said cross-section being constant at least within a portion directly downstream of the outflow opening of the first mixing chamber. Accordingly, the outflow opening of the first mixing chamber or the inflow opening of the first interactive channel is the downstream end of the outflow channel. Because the cross-section of the outflow channel decreases towards the outflow opening along the flow direction of the fluid mixture, the cross-section of the outflow channel is smallest at the outflow opening of the first mixing chamber or at the inflow opening of the first interactive channel. This location is further characterized by forming the upstream end of the portion (of the first interactive channel) with a constant cross-section.

[0014] For example, the first interaction channel in the segment can be designed tubularly. The first interaction channel can have a length that is at least three times its width at the height of the outlet opening of the first mixing chamber. The length here is the extension of the first interaction channel along the flow direction of the fluid mixture from the outlet opening of the first mixing chamber to the first inlet opening of the second mixing chamber. The width here is the transverse extension of the first interaction channel in the oscillating plane along the flow direction of the fluid mixture.

[0015] The first interactive channel can be used to continue the mixing process downstream of the outflow opening of the first mixing chamber; and if particles are generated during the mixing process, the particles can grow in the first interactive channel (in a manner controlled by the length of the first interactive channel). The section of the first interactive channel with a constant cross-section serves to keep the intermediate fluid mixture as undisturbed as possible in order to allow for a defined reaction time for the intermediate fluid mixture, while homogenizing the flow without flow separation effects.

[0016] According to one embodiment, the first interactive channel extends at least partially along a longitudinal axis, which is particularly parallel to the direction of fluid mixture flow. Similarly (alternatively or additionally), the first interactive channel can have a meandering section. The bend(s) caused by the meandering shape can induce suppression of the formation of so-called stagnant zones.

[0017] Additionally, the first interaction channel may have a section in which the cross-section transverse to the flow direction of the fluid mixture increases downstream.

[0018] The transition between the first interactive channel and the second mixing chamber (i.e., the location of the outflow opening of the first interactive channel or the first inflow opening of the second mixing chamber) can be characterized by a sudden increase in cross-section (transverse to the flow direction of the fluid mixture). Here, the second inflow opening of the second mixing chamber can be located in the region of the sudden increase in cross-section.

[0019] In addition, the device includes: a second conveying device fluidly connected to a first mixing chamber via a second inlet opening and configured to guide a second fluid into the first mixing chamber in a second fluid flow direction; and a third conveying device fluidly connected to a second mixing chamber via a second inlet opening and configured to guide a third fluid into the second mixing chamber in a third fluid flow direction.

[0020] The flow direction of the third fluid (i.e., the flow direction of the third fluid entering the second mixing chamber) and the flow direction of the fluid mixture (i.e., the direction of the intermediate fluid mixture consisting of the first and second fluids entering the second mixing chamber) can form an angle of less than or equal to 90°. This limits the shear rate of the fluid in the second mixing chamber. Consequently, the particles present in the intermediate fluid mixture experience the smallest possible mechanical load when they encounter the third fluid. Accordingly, particle damage or particle agglomeration / agglomeration due to particle fusion or adhesion can be avoided. This has a positive effect on the polydispersity index of the particles. To enhance this effect, it is advantageous to choose very similar values ​​for the velocities of the third fluid and the intermediate fluid mixture. This can be achieved by selecting suitable process parameters. With the aid of the apparatus according to the invention and the method also shown below, it is possible to produce high-quality particles (i.e., particles with a low polydispersity index) of the size required for pharmaceutical manufacturing, as mentioned at the beginning.

[0021] Preferably, the angle between the direction of the fluid mixture flow and the direction of the third fluid flow is less than 45°, and particularly between 5° and 40°. The smaller the angle, the lower the shear rate of the fluid.

[0022] According to one embodiment, the third conveying device is configured to guide the third fluid as a (quasi)static flow into the second mixing chamber. This similarly limits the shear rate of the fluid in the second mixing chamber. The second conveying device can also be configured to guide the second fluid as a (quasi)static flow into the first mixing chamber.

[0023] The third conveying device has a conveying channel that extends along the direction of the third fluid flow and opens into a second inlet opening of the second mixing chamber. Here, the conveying channel is particularly linear in shape. The conveying channel, or its shape, is mostly predetermined by the fluid flow direction of the third fluid as it enters the second mixing chamber.

[0024] The mechanism for targeted directional change of the first fluid is configured to cause the first fluid to oscillate in an oscillating plane. The delivery channel extends in a plane parallel to or corresponding to the oscillating plane. Thus, the intermediate fluid mixture and the third fluid move in a common plane.

[0025] As already mentioned, the fluid component includes at least one mechanism for targeted directional change of the first fluid, which flows through the fluid component. This design of the first conveying device causes a targeted directional change of the first fluid, such that the first fluid moves in a time-varying manner within the first mixing chamber, wherein the first fluid has a motion component along the direction of the first fluid flow and a motion component transverse to the direction of the first fluid flow.

[0026] According to one embodiment, a fluid component includes a flow chamber having an inflow opening in addition to the previously mentioned outflow opening, and the flow chamber is permeable by a first fluid that enters the flow chamber through the inflow opening and exits through the outflow opening. According to one embodiment, the inflow and outflow openings of the fluid component can have different widths. Specifically, the flow chamber has a main flow channel connecting the inflow and outflow openings of the flow chamber (or fluid component) to each other, and at least one secondary flow channel serving as a mechanism for targeted directional changes of the first fluid. In the fluid component, movable parts that generate oscillations can be eliminated, thus avoiding the associated costs and expenses. Furthermore, by eliminating movable parts, vibration and noise generation are relatively low.

[0027] As a mechanism for targeted directional change of the first fluid, the flow chamber can have at least one secondary flow channel as already mentioned. The secondary flow channel can be traversed by a portion of the first fluid (i.e., the secondary flow). The portion of the first fluid that does not enter the secondary flow channel but exits from the fluid member is called the main flow. At least one secondary flow channel can have an inlet near the outflow opening of the fluid member and an outlet near the inflow opening of the fluid member. Viewed along the direction of the first fluid flow (from the inflow opening to the outflow opening), at least one secondary flow channel can be positioned adjacent to (not behind or in front of) the main flow channel. In particular, two secondary flow channels can be provided, extending laterally adjacent to the main flow channel (viewed along the direction of the first fluid flow), with the main flow channel positioned between these two secondary flow channels. According to a preferred embodiment, the secondary flow channels and the main flow channel are arranged in a row transverse to the direction of the first fluid flow and extend respectively along the direction of the first fluid flow.

[0028] Preferably, at least one secondary flow channel is separated from the main flow channel by a block. The block can have different shapes. Therefore, when viewed along the first fluid flow direction (from the inlet opening to the outlet opening), the cross-section of the block can taper. Furthermore, the block can have rounded edges. Sharp edges can be provided at the block, particularly near the inlet opening and / or the outlet opening.

[0029] According to one embodiment, at least one secondary flow channel can have a greater or lesser depth than the main flow channel. (Here, depth is the extension transverse to the oscillation plane of the first fluid). This can thus affect the oscillation frequency of the first fluid exiting the fluid component. When other parameters remain substantially constant, the oscillation frequency decreases by reducing the component depth in the region of at least one secondary flow channel (compared to the main flow channel). Conversely, when the component depth in the region of at least one secondary flow channel is increased (compared to the main flow channel) while other parameters remain substantially constant, the oscillation frequency increases.

[0030] Another possibility for influencing the oscillation frequency of the first fluid exiting the fluid component can be achieved by using at least one separator, preferably located at the inlet of at least one secondary flow channel. The separator assists in separating the secondary flow from the flow of the first fluid. Here, the separator should be understood as an element extending into the flow chamber at the inlet of at least one secondary flow channel (transverse to the flow direction present in the secondary flow channel). The separator can be configured as a deformed portion (especially a recess) of the secondary flow channel wall, or as a protrusion constructed in other ways. Therefore, the separator can be configured in a (circular) conical or pyramidal shape. Besides influencing the oscillation frequency, using such a separator also makes it possible to change the so-called oscillation angle. The oscillation angle is the angle swept by the oscillating fluid jet (between its two maximum deflections). If multiple secondary flow channels are provided, then a separator can be provided for each of the secondary flow channels or only a portion of the secondary flow channels.

[0031] The cross-sections of the inflow and outflow openings of the fluid component (but also the first and second mixing chambers) can have any shape, such as square, rectangle, polygon, circle, oval, etc.

[0032] According to one embodiment, on the one hand, the first inflow opening of the first conveying device and the first mixing chamber, and on the other hand, the second inflow opening of the second conveying device and the first mixing chamber, are arranged relative to each other such that the first fluid flow direction and the second fluid flow direction form an angle of 45° to 90° in a plane parallel to the first fluid flow direction. A substantially 45° angle is particularly preferred. This can positively influence the mixing quality and the mixing path length or mixing duration. For production reasons, the angle can also be substantially 90°.

[0033] Provided that the mechanism for the targeted directional change of the first fluid is configured to cause the first fluid to oscillate in an oscillating plane, the second inflow opening of the second conveying device and the first mixing chamber can be configured such that the flow direction of the second fluid and the oscillating plane of the first fluid form an angle of 30° to 150° in a plane transverse to the flow direction of the first fluid. Preferably, the angle is substantially 90°.

[0034] Regarding the second conveying device, it can be proposed that the second conveying device is configured to guide the second fluid as a (quasi)static flow into the first mixing chamber. Therefore, the second conveying device can be configured as a pipe, the longitudinal axis of which (or its downstream elongated end section) pre-determines the second fluid flow direction. By means of a pump, the second fluid can be guided into the first mixing chamber through the pipe and a second inlet opening.

[0035] Alternatively, the second conveying device (as the first conveying device already is) can also include a fluid component. This fluid component can operate on the same principle as the fluid component of the first conveying device. Therefore, the fluid component can have at least one mechanism for targeted directional change of a second fluid flowing through it, the mechanism being particularly designed to create spatial oscillations of the fluid at the outlet opening. The remaining features of the fluid component of the first conveying device can also be transferred to the fluid component of the second conveying device. Thus, in the first mixing chamber, the oscillating first fluid and the oscillating second fluid meet each other. The fluid component of the second conveying device can have a smaller oscillation angle compared to the fluid component of the first conveying device. Both oscillation angles can also be equally large.

[0036] The first mixing chamber can have a longitudinal axis, defined as extending along the direction of the first fluid flow or the direction of the fluid mixture flow. According to one embodiment, the cross-section of the first mixing chamber, transverse to the longitudinal axis, increases along the longitudinal axis in at least one section. For example, starting from the first inlet opening of the first mixing chamber, the cross-section can increase in the upstream end section of the first mixing chamber with increasing distance from the first inlet opening. Therefore, the upstream end section can form an inlet channel of the first mixing chamber (widening downstream). Here, an outlet channel can be directly connected to the inlet channel. Alternatively, an intermediate section of the first mixing chamber can be provided between the inlet channel and the outlet channel, in which the cross-section of the first mixing chamber is substantially constant.

[0037] If the mechanism for targeted directional change of the first fluid is configured to induce oscillation of the first fluid in the oscillation plane, then the expansion of the first mixing chamber in the oscillation plane and transversely to the longitudinal axis increases in the inflow channel from the first inflow opening of the first mixing chamber with increasing distance from the first inflow opening, or the expansion of the first mixing chamber in the oscillation plane and transversely to the longitudinal axis decreases in the outflow channel with increasing distance from the first inflow opening. In particular, the expansion of the first mixing chamber also increases in the inflow channel downstream of the second inflow opening of the first mixing chamber. Therefore, in the inflow channel, the limiting walls of the first mixing chamber (viewed in the oscillation plane) form an angle preferably guided by the oscillation angle of the oscillating first fluid. This angle can be at most 10° smaller or at most 10° larger than the oscillation angle, or a value between these two. Particularly preferred is that this angle is at most 5° smaller or at most 5° larger than the oscillation angle, or a value between these two. Therefore, it is possible to avoid adverse effects on the oscillation of the first fluid in the first mixing chamber. The oscillation angle of the first fluid can be at least 5°, preferably at least 25°, and particularly preferably at least 40°. For many applications, an oscillation angle between 25° and 50°, and particularly between 30° and 45°, is suitable. A typical maximum value for the oscillation angle is 75°. In the outflow channel, the boundary walls of the mixing chambers (viewed in the oscillation plane) also form an angle that is preferably smaller than the angle between the boundary walls of the first mixing chambers in the inflow channel. Particularly preferred is that the angle of the outflow channel is at most 15° smaller than the angle of the inflow channel. Additionally, the transverse extension of the first mixing chamber to the oscillation plane can also increase in the inflow channel with increasing distance from the first inflow opening, or the transverse extension of the first mixing chamber to the oscillation plane can decrease in the outflow channel with increasing distance from the first inflow opening.

[0038] The relative dimensions of the inflow and outflow channels of the first mixing chamber can be designed according to the application.

[0039] According to one embodiment, a second inflow opening of the first mixing chamber is offset downstream of a first inflow opening of the first mixing chamber along the longitudinal axis of the first mixing chamber. Preferably, the second inflow opening is formed within an inflow channel (i.e., within the boundary wall of the inflow channel). Viewed along the longitudinal axis, the spacing between the first and second inflow openings can correspond to at least half the width of the first inflow opening of the first mixing chamber, wherein the width is parallel to the oscillation plane of the first fluid and defined transversely to the longitudinal axis of the first mixing chamber.

[0040] The first inlet and outlet openings of the first mixing chamber can be formed on opposite sides of the first mixing chamber. Therefore, the first inlet opening can form the upstream end of the first mixing chamber, while the outlet opening can form the downstream end. In particular, the first inlet and outlet openings can be located on a longitudinal axis. The first inlet and outlet openings can be defined at a position where the cross-section of the first mixing chamber transverse to its longitudinal axis is minimized, said longitudinal axis being the longitudinal axis through which the entering first fluid or the exiting intermediate fluid mixture passes.

[0041] Furthermore, it is conceivable that the first mixing chamber has a volume greater than the volume of the fluid component or the flow chamber of the fluid component. Specifically, not only the width (the extension transverse to the longitudinal axis of the mixing chamber and located in the oscillation plane of the first fluid) but also the length (the extension along the longitudinal axis) of the first mixing chamber can be greater than the width (the extension transverse to the direction of the first fluid flow and located in the oscillation plane of the first fluid) or the length (the extension along the direction of the first fluid flow) of the flow chamber of the fluid component. This volume relationship prevents the formation of undesirably high pressures in the first mixing chamber. Alternatively, the volume of the first mixing chamber can be smaller than the volume of the flow chamber of the fluid component. In this case, the width and / or length of the first mixing chamber can be smaller than the width or length of the flow chamber of the fluid component.

[0042] Similar to the first interactive channel, the second interactive channel can be connected downstream to the outflow opening of the second mixing chamber.

[0043] The second mixing chamber and / or the second interactive channel extend along axes corresponding to the flow direction of the generated fluid mixture. These axes form angles with the third fluid flow direction and the fluid mixture flow direction (of the intermediate fluid mixture). According to one embodiment, the angle between the axis and the third fluid flow direction (in the oscillating plane) is not as large as the angle between the axis and the fluid mixture flow direction. In particular, the angle between the axis and the third fluid flow direction can be greater than the angle between the axis and the fluid mixture flow direction. These two angles are preferably less than 180°. For example, the angle between the axis and the third fluid flow direction can be 170° to 179°. For example, the angle between the axis and the fluid mixture flow direction can be 160° to 169°. The total angle between the axis and the third fluid flow direction, the angle between the axis and the fluid mixture flow direction, and the other angle between the fluid mixture flow direction and the third fluid flow direction is 360°.

[0044] When using this apparatus, for example in the method for generating a fluid mixture described further below, the volumetric flows of the first, second, and third fluids can be selected such that the velocity vector of the intermediate fluid mixture at the first inlet opening of the second mixing chamber and the velocity vector of the third fluid at the second inlet opening of the second mixing chamber are generally designed such that the velocity vector of the fluid mixture is parallel to the axis of the second mixing chamber or the second interactive channel. Therefore, the angle between the velocity vector of the fluid mixture and the flow direction of the third fluid (the velocity vector of the third fluid) can be between 170° and 179°. Furthermore, the angle between the velocity vector of the fluid mixture and the flow direction of the fluid mixture (the velocity vector of the intermediate fluid mixture) can be between 160° and 169°.

[0045] A pump device can be used to deliver a first fluid, a second fluid, and a third fluid to a first delivery device, a second delivery device, and a third delivery device, respectively. For example, the pump device can be configured as a syringe pump or a circulating pump. An HPLC pump or a diaphragm pump can be used instead of a syringe pump.

[0046] The apparatus for generating fluid mixtures has been described so far using a first mixing chamber and a second mixing chamber. However, it is conceivable that the apparatus may include at least one additional mixing chamber with a corresponding conveying device. Here, the at least one additional mixing chamber can be arranged according to the described principle such that the first inflow opening of the nth mixing chamber is fluidly connected to the outflow opening of the (n-1)th mixing chamber. This results in a cascaded arrangement of n mixing chambers.

[0047] The objective mentioned at the beginning is also achieved by a device having the features of claim 9.

[0048] Accordingly, the apparatus for generating a fluid mixture first includes a first mixing chamber having: a first inlet opening through which a first fluid can be introduced into the first mixing chamber in a first fluid flow direction; a second inlet opening through which a second fluid can be introduced into the first mixing chamber in a second fluid flow direction; and an outlet opening through which an intermediate fluid mixture comprising the first fluid and the second fluid can be discharged in a fluid mixture flow direction. The apparatus further includes a second mixing chamber having: a first inlet opening through which an intermediate fluid mixture can be introduced into the second mixing chamber in a fluid mixture flow direction; a second inlet opening through which a third fluid can be introduced into the second mixing chamber in a third fluid flow direction; and an outlet opening through which a fluid mixture comprising the first fluid, the second fluid, and the third fluid can be discharged. Therefore, the second mixing chamber is disposed downstream of the first mixing chamber, wherein the first and second mixing chambers are fluidly connected such that an intermediate fluid mixture exiting from the outlet opening of the first mixing chamber enters the second mixing chamber (directly) through the first outlet opening of the second mixing chamber.

[0049] To introduce fluid into the mixing chamber, a conveying device may be provided. Specifically, the device also includes a first conveying device that is fluidly connected to the first mixing chamber via a first inlet opening and is configured to guide the first fluid into the first mixing chamber along a first fluid flow direction.

[0050] Furthermore, a second conveying device and a third conveying device may be provided. The second conveying device is fluidly connected to the first mixing chamber via a second inlet opening and is configured to guide the second fluid into the first mixing chamber along the second fluid flow direction. The third conveying device is fluidly connected to the second mixing chamber via a second inlet opening and is configured to guide the third fluid into the second mixing chamber along the third fluid flow direction.

[0051] The first conveying device includes a fluid component. The fluid component includes an outlet opening and at least one mechanism for targeted directional change of a first fluid, the outlet opening being fluidly connected to a first inlet opening of a first mixing chamber, the first fluid flowing through the fluid component, and the mechanism being particularly used to create spatial oscillations of the first fluid at the outlet opening.

[0052] The device is characterized in that the first inlet opening of the second mixing chamber has a cross-section transverse to the flow direction of the fluid mixture, said cross-section being smaller than the cross-section of the second inlet opening of the second mixing chamber. The cross-section of the second inlet opening of the second mixing chamber is defined transversely to the flow direction of the third fluid. Alternatively or additionally, the device is characterized in that the sum of the cross-sections of the first inlet opening and the second inlet opening of the second mixing chamber is similar to (when the flow direction of the third fluid and the flow direction of the fluid mixture are in the same plane) or larger than the cross-section of the outlet opening of the second mixing chamber (when the flow direction of the third fluid and the flow direction of the fluid mixture are not in the same plane). Therefore, the average velocity of the intermediate fluid mixture at the first inlet opening of the second mixing chamber is greater than the average velocity of the third fluid at the second inlet opening of the second mixing chamber. This results in the following hydrodynamic effect: the pulsation of the intermediate fluid mixture entering the second mixing chamber is greater than the pulsation of the third fluid flow entering the second mixing chamber. The aforementioned pulsation difference enables the fluid mixture flow direction at the first inlet opening of the second mixing chamber and the third fluid flow direction at the second inlet opening of the second mixing chamber to form a relatively large angle, such as 90°, without significant shearing of the intermediate fluid mixture in the second mixing chamber. Due to the feasibility of choosing 90° for the aforementioned angle, the second mixing chamber in the region of the second inlet opening and the third conveying device can be structurally simple to design.

[0053] Feasible design schemes and implementation methods for the fluid component have been described above. Therefore, the mechanism for targeted directional change of the first fluid can also be configured to induce oscillation of the first fluid in the oscillation plane.

[0054] According to one embodiment, the second mixing chamber has an extension parallel to the oscillation plane and transverse to the flow direction of the fluid mixture, and this extension is constant. This extension can be referred to as the width of the second mixing chamber. Here, the width of the second mixing chamber can be observed to be constant over its entire length (the extension along the flow direction of the fluid mixture).

[0055] Alternatively, the second mixing chamber may have an extension parallel to the oscillation plane and transverse to the flow direction of the fluid mixture, the extension being the same size as the extension of the outflow opening of the first mixing chamber and / or the first inflow opening of the second mixing chamber, parallel to the oscillation plane and transverse to the flow direction of the fluid mixture. Furthermore, the first inflow opening and the outflow opening of the second mixing chamber can have the same width, for example, corresponding to the width of the second mixing chamber. This also simplifies the structural design of the second mixing chamber.

[0056] According to one embodiment, the second mixing chamber has an extension transverse to the oscillation plane, which is greater than the transverse extension of the first inlet opening of the second mixing chamber. This transverse extension can be referred to as depth. Accordingly, the depth of the second mixing chamber can be greater than the depth of the first inlet opening. The depth of the second mixing chamber can be observed to be constant over its entire length (the extension along the flow direction of the fluid mixture). In particular, the cross-section of the first inlet opening of the second mixing chamber (transverse to the flow direction of the fluid mixture) can be smaller than the cross-section of the second mixing chamber (transverse to the flow direction of the fluid mixture). The change in cross-section can be particularly abrupt, and is achieved, for example, by a stepped shape that abruptly changes the depth. This stepped shape, while potentially causing a recirculation zone (also called a dead zone) to form directly downstream of the first inlet opening in the second mixing chamber, thereby impairing the function of the second mixing chamber, allows the second inlet opening to be positioned directly downstream of the first inlet opening, i.e., in the region of the potential recirculation zone, such that a third fluid flows through the potential recirculation zone. Therefore, although the residence time of the third fluid in the second mixing chamber may be uncertain, the residence time of the intermediate fluid mixture is not uncertain, so that the function of the second mixing chamber is not ultimately impaired.

[0057] According to one embodiment, a first interactive channel is provided between a first mixing chamber and a second mixing chamber, the first interactive channel connecting the outflow opening of the first mixing chamber and the first inflow opening of the second mixing chamber to each other. The first interactive channel has a cross-section transverse to the flow direction of the fluid mixture, the cross-section being at least partially constant. In particular, the cross-section of the first interactive channel can be smaller than the cross-section of the second mixing chamber. Here, the depth of the first interactive channel (the extension transverse to the oscillation plane) can be smaller than the depth of the second mixing chamber, while its width (the extension parallel to the oscillation plane and transverse to the flow direction of the fluid mixture) can be the same size. In particular, the depth of the second mixing chamber can be (constant and) twice the depth of the first interactive channel (in the section directly upstream of the second mixing chamber). The ratio of the depths (first interactive channel / second mixing chamber) can here follow the ratio of the volume flow of the intermediate fluid mixture to the sum of the volume flows in the two mixing chambers. Preferably, the ratio of the depths (first interactive channel / second mixing chamber) corresponds to the ratio of the volume flows (intermediate fluid mixture / (intermediate fluid mixture + third fluid)).

[0058] According to one embodiment, the depth (extension transverse to the oscillation plane) of the first interaction channel is less than the width (extension parallel to the oscillation plane and transverse to the flow direction of the fluid mixture). The width-to-depth ratio can be in the range of 1.5 to 100, preferably between 2 and 10.

[0059] The first interactive channel can have a length that is at least three times the width of the first interactive channel at the height of the outlet opening of the first mixing chamber. The length here is the extension of the first interactive channel along the flow direction of the fluid mixture from the outlet opening of the first mixing chamber to the first inlet opening of the second mixing chamber. The width here is the transverse extension of the first interactive channel in the oscillating plane along the flow direction of the fluid mixture.

[0060] The transition between the first interactive channel and the second mixing chamber (i.e., the location of the outflow opening of the first interactive channel or the first inflow opening of the second mixing chamber) can be characterized by a sudden change in cross-section (transverse to the flow direction of the fluid mixture). For example, at the transition, the depth and / or width can change abruptly.

[0061] The transition between the first mixing chamber and the first interaction channel (i.e., the location of the outflow opening of the first mixing chamber or the inflow opening of the first interaction channel) can be defined by providing a section (the outflow channel of the first mixing chamber) upstream, wherein the cross-section of the section decreases toward the outflow opening along the flow direction of the fluid mixture, and the cross-section is minimized at the outflow opening of the first mixing chamber or at the inflow opening of the first interaction channel.

[0062] To keep the structure as simple as possible, the first interaction channel can extend along a longitudinal axis, which is particularly parallel to the direction of the first fluid flow or the direction of the fluid mixture flow. However, it is also conceivable that the first interaction channel includes meandering sections.

[0063] Another option is to connect the second interactive channel to the outflow opening of the second mixing chamber.

[0064] The design of the first conveying device, the second conveying device, and the first mixing chamber has been described above in conjunction with other embodiments, and can also be applied to the following embodiments in which the first inflow opening of the second mixing chamber has a smaller cross-section than the second inflow opening of the second mixing chamber.

[0065] The equipment according to the invention can be manufactured by means of cutting or removal production methods, replication methods, such as replication methods by means of injection molding, or additive methods (3D printing). For production, methods using specific cutting edges (e.g., milling) or removal methods (e.g., electrical discharge ablation) are also applicable.

[0066] The device according to the invention can be manufactured from a variety of materials. Considered materials are plastics (PEEK, PVDF, COC), metals or alloys (stainless steel, aluminum), glass, or ceramics.

[0067] The present invention also relates to a method for generating a fluid mixture. The method is carried out using an apparatus according to the invention. To perform the method, an apparatus according to the invention, a first fluid, a second fluid, and a third fluid, according to one of the embodiments described herein, are first provided. The first fluid is introduced into a first mixing chamber via a first conveying device in a first volumetric flow. Simultaneously, the second fluid is introduced into the first mixing chamber via a second conveying device in a second volumetric flow, and the third fluid is introduced into the second mixing chamber via a third conveying device in a third volumetric flow.

[0068] In the first mixing chamber, the first fluid and the second fluid have the opportunity to mix and form an intermediate fluid mixture (with particles). The formation of (nano)particles can be achieved by altering the solubility of substances dissolved in the second fluid through contact / dilution with the first fluid. Nanoparticles precipitate out via nanoprecipitation. Due to the design of the first conveying device causing spatial oscillations in the first fluid, the velocities of the first and second fluids, or the velocity difference between them, fluctuate dramatically in the first mixing chamber, resulting in so-called turbulent mixing. The residence time of the two fluids in the first mixing chamber can vary depending on the application.

[0069] In the second mixing chamber, the intermediate fluid mixture generated in the first mixing chamber is combined with the third fluid. Through the design of the second mixing chamber in the regions of its first and second inlet openings, the shear rate in the second mixing chamber is low, resulting in particularly minimal turbulent mixing (more precisely, quasi-laminar mixing). This allows the mechanical load on the particles to be kept as low as possible. The mixing process in the second mixing chamber serves to stabilize the particles in the intermediate fluid mixture.

[0070] The particle size and size distribution can be influenced by the volumetric flow of the first and second fluids, the oscillation frequency of the oscillating first fluid, and the geometry of the first and second mixing chambers. In particular, the width (the extension in the oscillation plane transverse to the direction of the first fluid flow / fluid mixture flow) plays a role. The oscillation frequency of the oscillating first fluid can be at least 100 Hz, and typically greater than 2000 Hz.

[0071] Subsequently, a fluid mixture comprising a first fluid, a second fluid, and a third fluid is discharged from the second mixing chamber via an outlet opening in the second mixing chamber.

[0072] According to one embodiment, the volumetric flow is set such that the first volumetric flow is greater than the second volumetric flow, or the first and second volumetric flows are equal in size. With respect to the second mixing chamber, the third volumetric flow can be set such that the volumetric flow of the intermediate fluid mixture entering the second mixing chamber is greater than or equal to the third volumetric flow. However, depending on the application, the third volumetric flow can also be greater than the volumetric flow of the intermediate fluid mixture entering the second mixing chamber. The volumetric flow of the intermediate fluid mixture is derived from the volumetric flows of the first and second fluids. It is conceivable that the first, second, and third volumetric flows are constant over the duration of the mixing process.

[0073] The volumetric flow of the first, second, and third fluids can be controlled by a pumping device that pumps the first, second, and third fluids into a first or second mixing chamber via a first, second, or third conveying device. The pressure of the introduced fluids can range from a few millibars (mbar) to several hundred bar, depending on the application (relative to ambient pressure). For applications in the mass production of (lipid) nanoparticles, the input pressure can be between 1 bar and 50 bar, preferably between 1 bar and 25 bar, and particularly preferably between 1 bar and 10 bar. For emulsion production, the pressure can be several hundred bar. A pressure range between 2 bar and 500 bar is preferred. A pressure range between 10 bar and 250 bar is particularly preferred.

[0074] In order to apply the method on an industrial scale, the introduction of the first fluid into the first mixing chamber, the introduction of the second fluid into the first mixing chamber, and the introduction of the third fluid into the second mixing chamber can be carried out continuously, respectively.

[0075] According to one embodiment, the method is performed using a liquid or suspension as the first fluid. The second fluid is also either a liquid or a suspension. In the case of a suspension, the two fluids can, for example, differ (only) in particle size. Through turbulence present in the first mixing chamber, the particle size in the suspension (as both the first and second fluids) can, for example, be altered. This also affects the particle size distribution.

[0076] Typically, the first and second fluids can differ or be the same in terms of chemical composition and / or the concentration of their respective components. For example, the first fluid can comprise an aqueous buffer solution, and the second fluid can comprise a polymer, a pharmaceutical active ingredient, or a polymer-active ingredient-conjugate or lipid, respectively, in a solvent. The aqueous buffer solution (first fluid) can be, for example, an acetate buffer, a citrate buffer, a phosphate buffer, or a TRIS buffer. The buffer solution can contain one or more nucleic acids (DNA, RNA, or mRNA). The buffer solution can have a pH of 3 to 7, preferably 3 to 6. The aqueous solution (first fluid) can also contain a surfactant, such as poloxamer or polyvinyl alcohol. The solvent of the second fluid can be water-miscible (e.g., ethanol, acetonitrile, acetone) or water-insoluble (e.g., ethyl acetate, chloroform).

[0077] Considerable is that the first fluid is a suspension comprising a solvent and nucleic acids. The second fluid can comprise a lipid mixture and is suitable for encapsulating the nucleic acids of the first fluid during the mixing process, and acts as a carrier or transporter for nucleic acids in the intermediate fluid mixture thus obtained. The nucleic acids can be DNA, RNA, or mRNA.

[0078] The first fluid and the third fluid can be the same or different in terms of chemical composition and / or the concentration of their respective components.

[0079] Depending on the application, a third fluid can have specific functions. Therefore, a third fluid can be used to set the pH value, particle density, or solvent content in an intermediate fluid mixture, and / or include surfactants.

[0080] Typically, the chemical composition of the fluid used also determines the particle size of the resulting fluid mixture. At the first inlet opening of the first mixing chamber, the oscillating first fluid has a Reynolds number Re greater than 500, preferably greater than 1000, and particularly preferably greater than 2000. At the first inlet opening of the second mixing chamber, the intermediate fluid mixture has a Reynolds number Re greater than 50, preferably greater than 100, and particularly preferably greater than 200. The Reynolds number Re is here determined according to Re = (u... i ×h i ) / v is determined, where u i It is the flow velocity at the corresponding inflow opening, h i is the height or depth of the corresponding inflow opening, and v is the kinematic viscosity of the fluid (mixture).

[0081] The method can be used to prepare lipid nanoparticles, polymer nanoparticles, or liposomes. Attached Figure Description

[0082] The present invention will now be described in detail with reference to the accompanying drawings and embodiments.

[0083] The attached diagram shows:

[0084] Figure 1 A cross-section is shown through a device for generating a fluid mixture according to one embodiment;

[0085] Figure 2 A cross-section is shown through a portion of a device for generating a fluid mixture according to another embodiment, wherein the portion shows, in particular, a first mixing chamber and a first conveying device;

[0086] Figures 3 to 5 Show Figure 2 The equipment in the diagram is shown in cross-sectional views along lines A'-A'', B'-B'', and C'-C''.

[0087] Figure 6 A cross-section is shown through a device for generating a fluid mixture according to another embodiment;

[0088] Figure 7 The diagram illustrates the time-dependent deflection of the oscillating first fluid as it enters the first mixing chamber of the apparatus used to generate the fluid mixture;

[0089] Figure 8 A cross-section is shown through a device for generating a fluid mixture according to another embodiment;

[0090] Figure 9 A cross-section is shown through a device for generating a fluid mixture according to another embodiment;

[0091] Figure 10 A cross-section is shown through a device for generating a fluid mixture according to another embodiment;

[0092] Figure 11 Show Figure 10 A cross-sectional view of the device along line D'-D'';

[0093] Figure 12 A schematic diagram of a second mixing chamber according to another embodiment is shown; and

[0094] Figure 13 A schematic diagram of a method for generating a fluid mixture is shown. Detailed Implementation

[0095] The equipment and components shown in the accompanying drawings are not to scale. Variations of the embodiments shown, different from those shown in the following drawings, are also possible.

[0096] exist Figure 1 The image schematically illustrates an apparatus 1 for generating a fluid mixture according to an embodiment of the present invention.

[0097] The device 1 includes a first mixing chamber 20, a first interactive channel 30, a second mixing chamber 40, a second interactive channel 50, a first conveying device 60, a second conveying device 70, and a third conveying device 80. Figure 2 A first mixing chamber 20 and a first conveying device 60 according to another embodiment of the apparatus are shown. Although Figure 2 The first mixing chamber 20 and the first conveying device 60 of the equipment are Figure 1 The implementation differs in minor details, but the remaining components (first interaction channel 30, second mixing chamber 40, second interaction channel 50, second conveying device 70, and third conveying device 80) are compatible with... Figure 1 The components are the same. Figures 3 to 5 Show each Figure 2 The cross-sectional view of device 1 along lines A'-A'', B'-B'', and C'-C''. Because there are many identical points, Figure 1 and Figure 2 The implementation methods are described together below. Distinctions are discussed where appropriate.

[0098] The first mixing chamber 20 has a first inlet opening 201, a second inlet opening 202, and an outlet opening 203. A first fluid F1 can be introduced into the first mixing chamber 20 via the first inlet opening 201, and a second fluid F2 can be introduced into the first mixing chamber 20 via the second inlet opening 202. In the first mixing chamber 20, the first fluid and the second fluids F1 and F2 form an intermediate fluid mixture F. 12 The intermediate fluid mixture can be discharged through the outflow opening 203 of the first mixing chamber 20.

[0099] The first conveying device 60 is connected to the first mixing chamber 20 (fluid) via the first inlet opening 201 and is used to introduce the first fluid F1 into the first mixing chamber 20. The second conveying device 70 is connected to the first mixing chamber 20 (fluid) via the second inlet opening 202 and is used to introduce the second fluid F2 into the first mixing chamber 20.

[0100] The first interactive channel 30 is connected downstream to the outflow opening 203. The first interactive channel has an inflow opening 301 and an outflow opening 302. The inflow opening 301 of the first interactive channel 30 coincides with the outflow opening 203 of the first mixing chamber 20, such that the intermediate fluid mixture F... 12 It can flow from the first mixing chamber 20 into the first interaction channel 30.

[0101] The second mixing chamber 40 has a first inlet opening 401, a second inlet opening 402, and an outlet opening 403. The first inlet opening 401 coincides with the outlet opening 302 of the first interactive channel 30. Intermediate fluid mixture F 12 The intermediate fluid mixture F3 can be introduced into the second mixing chamber 40 via the first inlet opening 401, and the third fluid F3 can be introduced into the second mixing chamber 40 via the second inlet opening 402. In the second mixing chamber 40, the intermediate fluid mixture F... 12 A fluid mixture F is formed with the third fluid F3. 123 The fluid mixture can be discharged through the outflow opening 403 of the second mixing chamber 40.

[0102] The second interactive channel 50 is connected downstream to the outflow opening 403. The second interactive channel has an inflow opening 501 and an outflow opening 502. The inflow opening 501 of the second interactive channel 50 coincides with the outflow opening 403 of the second mixing chamber 40. The resulting fluid mixture F 123 It can be removed from device 1 via outflow opening 502. According to one embodiment, device 1 does not have a second interaction channel, and the resulting fluid mixture F... 123 It can be removed from the device 1 through the outflow opening 403 of the second mixing chamber 40.

[0103] The first conveying device 60 includes a fluid component 10 having two secondary flow channels (feedback channels) 104a and 104b as mechanisms for generating a spatially and / or temporally movable first fluid F1, and particularly for constituting spatial oscillations of the first fluid F1. Figure 1 The fluid component 10 with secondary flow channels 104a and 104b shown is merely exemplary. In principle, other fluid components, such as so-called feedbackless components, can also be used.

[0104] The energy used to generate a spatially and / or temporally movable fluid jet is derived from the input pressure of the first fluid F1 (also referred to as the first phase A) at the inflow opening of the flow chamber 100. The input pressure can be values ​​up to 1000 bar. Typically, the input pressure is below 400 bar. Preferably, the input pressure is between 0.5 bar and 200 bar, particularly preferably between 1 bar and 25 bar. For applications involving the generation of liquid nanoparticles, these values ​​are typically below 10 bar. Using the fluid component 10 has the advantage that an additional energy source is not required, thereby reducing the complexity and error-proneness of the device. Furthermore, it is therefore guaranteed that no additional external energy is input into the fluid. The input of additional / external energy may damage sensitive components of the fluid (e.g., long-chain molecules) and should therefore be avoided.

[0105] The fluid component 10 includes a flow chamber 100 through which a first fluid (flow) F1 can pass. The fluid component 10 has the function of causing oscillation of the first fluid F1, such that the first fluid F1 oscillates in time and / or position as it enters the first mixing chamber 20 through the first inflow opening 201. The time frequency of the oscillation is typically from 1 Hz to 10 kHz, preferably from 10 Hz to 10 kHz, and particularly preferably from 100 Hz to 5 kHz.

[0106] The flow chamber 100 includes an inflow opening 101 and an outflow opening 102, the inflow opening having an inflow width b. 101 The first fluid flow F1 enters the flow chamber 100 through the inlet opening, and the outlet opening has an outlet width b. 102 The first fluid flow F1 exits the flow chamber 100 via the outflow opening. The inflow opening 101 and the outflow opening 102 are respectively defined at locations where the cross-section (transverse to the fluid flow direction) traversed by the fluid member 10 as it enters or exits the flow chamber 100 is minimized. The width b of the inflow opening or outflow opening 101, 102 is... 101 and b 102 The extension corresponding to the inflow opening or outflow opening 101, 102, transverse to the fluid flow direction and within the oscillation plane of the first fluid F1 (described later).

[0107] The outflow opening 102 of the flow chamber 100 of the fluid component 10 corresponds here to the first inflow opening 201 of the first mixing chamber 20.

[0108] Inflow width b 101 Sizes ranging from 0.5 μm to 5000 μm are possible. The minimum dimensions of the narrowest cross-sections within the fluid component 10 can be selected based on the desired volumetric flow. With the input pressure (at the inflow opening 101 of the flow chamber 100) remaining constant, a larger volumetric flow, for example, with an inflow width b, results in a higher volumetric flow. 101 and / or inflow height h 101 The size must be larger. Typical dimensions range from 100μm to 1500μm. Width b 101 Typical values ​​are 100μm, 150μm, 300μm, 600μm and 1200μm.

[0109] Inlet opening 101 and outlet opening 102 are disposed on opposite sides of the fluid member 10 in terms of flow. Flow chamber 100, more specifically the main flow channel 103 of flow chamber 100, connects inlet opening 101 and outlet opening 102 to each other without obstruction. In an embodiment not shown, inlet opening 101 and outlet opening 102 can be connected by means of a non-obstructive flow chamber.

[0110] A first fluid flow F1 moves substantially along the longitudinal axis A of the fluid component 1 (which connects the inlet opening 101 and the outlet opening 102) from the inlet opening 101 to the outlet opening 102 within the flow chamber 100. The longitudinal axis A forms the axis of symmetry of the fluid component 1. The longitudinal axis A lies in two mutually perpendicular planes of symmetry, S1 and S2, with respect to which the fluid component 1 is mirror-symmetric.

[0111] To selectively change the direction of fluid flow, the flow chamber 100 includes two secondary flow channels 104a and 104b in addition to the main flow channel 103. The main flow channel 103 and the two secondary flow channels 104a and 104b extend substantially along the longitudinal axis A of the fluid member 10, with the main flow channel 103 (viewed transversely to the longitudinal axis A) positioned between the two secondary flow channels 104a and 104b. Directly behind the inflow opening 101, the flow chamber 100 divides into the main flow channel 103 and the two secondary flow channels 104a and 104b, which converge again directly in front of the outflow opening 102. In the embodiment shown here, the two secondary flow channels 104a and 104b are symmetrically arranged about the plane of symmetry S2. Figure 4 The secondary flow channel can also be located outside the flow plane shown. This channel can be implemented, for example, by a pipe also located outside the plane of symmetry S1, or by a channel at an angle relative to the flow plane (plane of symmetry S1).

[0112] The main channel 103 connects the inflow opening 101 and the outflow opening 102 to each other in a substantially straight line, so that the fluid flow F1 flows substantially along the longitudinal axis A of the fluid member 10.

[0113] Secondary flow channels 104a and 104b, starting from the inflow opening 101, initially extend in opposite directions at an angle of approximately 90° relative to the longitudinal axis A in the first section. Subsequently, the secondary flow channels 104a and 104b bend so that they extend substantially parallel to the longitudinal axis A (towards the outflow opening 102) (second section). To allow the secondary flow channels 104a and 104b to rejoin the main flow channel 103, the secondary flow channels 104a and 104b change direction again at the ends of the second section, so that they point substantially towards the longitudinal axis A (third section). Figure 1 and Figure 2In this embodiment, the direction of the secondary flow channels 104a and 104b changes by approximately 120° when transitioning from the second section to the third section. However, the direction change between these two sections of the secondary flow channels 104a and 104b can also be chosen at an angle different from the angle mentioned herein, or even follow a completely different direction.

[0114] The secondary flow channels 104a and 104b are mechanisms for influencing the direction of the first fluid flow F1 through the flow chamber 100. For this purpose, the secondary flow channels 104a and 104b each have inlets 104a1 and 104b1 formed through their ends facing the outlet opening 102, and outlets 104a3 and 104b3 formed through their ends facing the inflow opening 101. A small portion of the first fluid flow F1, i.e., the secondary flow, flows into the secondary flow channels 104a and 104b through the inlets 104a1 and 104b1. The remaining portion of the first fluid flow F1 (the so-called main flow) exits from the fluid member 10 via the outlet opening 102. The secondary flow exits from the secondary flow channels 104a and 104b at outlets 104a3 and 104b3, where it applies lateral (transverse to longitudinal axis A) pulsations to the first fluid flow F1 entering through inlet opening 101. Here, the direction of the first fluid flow F1 is influenced such that the main flow exiting at outlet opening 102 oscillates spatially, more specifically, in the plane in which the main flow channel 103 and the secondary flow channels 104a and 104b are disposed. The plane in which the main flow oscillates is also called the oscillation plane, and substantially corresponds to or is parallel to the plane of symmetry S1. Figure 3 ).

[0115] In the embodiment shown here, the secondary flow channels 104a and 104b each have a nearly constant cross-section along their entire length (from inlet 104a1, 104b1 to outlet 104a2, 104b2). Conversely, the cross-sectional dimensions of the main flow channel 103 substantially increase continuously in the main flow direction (i.e., from inlet opening 101 to outlet opening 102). Figure 1 and Figure 2 In both embodiments, the shape of the main channel 103 is exemplary mirror-symmetric with respect to the planes of symmetry S1 and S2.

[0116] However, the cross-section of the main channel 103 can also be reduced downstream in principle.

[0117] The main channel 103 is separated from each secondary channel 104a, 104b via blocks 11a and 11b. Figure 1 and Figure 2In this embodiment, the two blocks 11a and 11b are arranged symmetrically about the mirror plane S2. However, in principle, the blocks can also be configured differently and oriented asymmetrically. In the case of asymmetrical orientation, the shape of the main channel 103 is also asymmetrical with respect to the mirror plane S2. The symmetrical implementation of the two blocks 11a and 11b is preferred.

[0118] exist Figure 1 and Figure 2 The shapes of blocks 11a and 11b shown are exemplary only and can be modified. Blocks 11a and 11b have rounded edges. Sharp edges are also possible. The embodiment with rounded edges is preferred. Figure 1 and Figure 2 Blocks 11a and 11b differ in shape on their side facing the main channel 103. Figure 1 In the middle, this side is almost flat, while... Figure 2 In the middle, the side has an arched portion.

[0119] A funnel-shaped extension 106 connects upstream to the inflow opening 101 of the flow chamber 100, and the extension tapers downstream toward the inflow opening 101. In principle, an extension 106 with a substantially constant cross-section or a partially widened cross-section is also feasible. The funnel-shaped extension can also be referred to as an inflow channel. The flow chamber 100 also tapers, more specifically, in the region of the outflow opening 102 downstream of the inner blocks 11a, 11b. The taper is formed by the outflow channel 107 and begins at the inlets 104a1, 104b1 of the secondary flow channels. Here, the extension 106 and the outflow channel 107 taper such that only their width, i.e., their extension perpendicular to the longitudinal axis A in the plane of symmetry S1, decreases downstream. In this embodiment, the taper does not affect ( Figure 3 The depth of the extension 106 and the outflow channel 107 (i.e., the extension perpendicular to the longitudinal axis A in the plane of symmetry S2). Alternatively, the extension 106 and the outflow channel 107 can also taper in width and depth, respectively. Furthermore, the extension 106 can taper only in depth or width, while the outflow channel 107 can taper not only in width but also in depth, and vice versa. The shapes of the extension 106 and the outflow channel 107 are in... Figure 1 The diagram is shown only by way of example. Here, the width decreases linearly downstream, with the boundary walls of the extension 106 and the outflow channel 107 (viewed in the oscillating plane) forming an angle ε or φ. Other shapes of the tapering section are possible. The length l of the inflow channel of the funnel-shaped extension 106... 106 For example, corresponding to the inflow width b 101 At least 1.5 times, i.e., applicable l 106 ≥1.5×b101 According to a preferred embodiment, the length l of the funnel-shaped extension 106 is... 106 Greater than width b 101 7.5 times. In width b 101 Given a fixed value, the following applies: the smaller the angle ε, the longer the inflow opening 106 should be.

[0120] The inflow opening 101 and the outflow opening 102 each have an idealized rectangular cross-section. The inflow and outflow openings each have the same depth (an extension perpendicular to the longitudinal axis A in the plane of symmetry S2). Figure 3 However, its width b 101 b 102 (The extension perpendicular to the longitudinal axis A in the plane of symmetry S1,) Figure 2 The two aspects differ. In principle, the corners of the cross-section can be rounded, and the opposing surfaces of the inflow or outflow openings 101 and 102 do not necessarily have to extend parallel to each other.

[0121] The outflow opening 102 of the flow chamber 100 of the fluid component 10 is in Figure 1 and Figure 2 The first inflow opening 201 corresponds to the first mixing chamber 20. At either the outflow opening 102 or the first inflow opening 201 (of the same shape and size), the tapering outflow channel 107 of the fluid member 10 and the widening inflow channel 206 of the first mixing chamber 20, described later, meet each other, forming an edge in the transition region. This transition region is preferably rounded. The rounded portion can have a radius 109, which is smaller than the minimum width b. 101 (Width of inflow opening 101) and b 11 (The smallest cross-section A between inner blocks 11a and 11b in the main channel 103) 11 The width to which it belongs, Figure 2 The extreme value of the resulting sharp-edged outlet 102 is a radius of zero. Due to its high mechanical stability, a radius of 109 is preferred. Width b 101 b 11 and b 102 They are approximately the same size. For example, the width can be approximately 0.3 mm. Thus, the radius 109 of the outlet opening 102 can be approximately 0.025 mm.

[0122] Downstream of the first inflow opening 201 of the first mixing chamber 20, an inflow channel 206 is connected. The inflow channel 206 has a cross-section that increases downstream (transverse to the direction of the first fluid flow or the longitudinal axis L of the first mixing chamber 20). Here, the width of the inflow channel 206 (an extension in the oscillation plane and transverse to the longitudinal axis L) increases downstream. The width increases linearly. However, the increase in width can also follow a polynomial. Viewed in the oscillation plane, the walls defining the inflow channel 206 form an angle δ. This angle δ can have different measures. Advantageously, an angle δ is chosen in relation to the oscillation angle α. Here, a deviation of +40° to -10° from the oscillation angle α is feasible, i.e., α-10° < δ < α+40°. A particularly preferred value for the angle δ is α-5° < δ < α+20°. The oscillation angle α here corresponds to the natural oscillation angle of the oscillating first fluid F1, which may occur even without the inflow channel 206 and the first mixing chamber 20. Figure 1 and Figure 2 In the implementation, the angle δ is different. That is, the first inflow opening 201 can be defined in the inflow channel 206 at a location where the inflow channel has a minimum cross-section (transverse to the first fluid flow direction R1) or a minimum width (parallel to the oscillation plane and transverse to the first fluid flow direction R1).

[0123] The width b of the first mixing chamber 20 20 Defined by two approximately parallel and flat surfaces, these two surfaces act as boundary walls in the intermediate section of the first mixing chamber 20. The intermediate section, along the first fluid flow direction R1, is formed between the inflow channel 206 and the outflow channel 207 of the first mixing chamber 20. In principle, the boundary walls can also be designed in a different manner (than flat and parallel).

[0124] The outflow channel 207 is connected to the downstream end of the intermediate section. The cross-section of the outflow channel (transverse to the first fluid flow direction or the longitudinal axis L of the mixing chamber 20) decreases downstream along the longitudinal axis L. Here, the width of the outflow channel 207 (the extension in the oscillating plane and transverse to the longitudinal axis L) decreases downstream. The width decreases linearly here. However, the decrease in width can also follow a polynomial. Viewed in the oscillating plane, the walls that limit the outflow channel 207 form an angle ω. Figure 1 and Figure 2 In the implementation of this method, the angle ω is not of a certain size.

[0125] The downstream end of the outflow channel 207 is formed by an outflow opening 203. That is, the outflow opening 203 is defined in the outflow channel 207 at a location where the outflow channel has a minimum cross-section (transverse to the flow direction R of the fluid mixture). 12) or minimum width (parallel to the oscillation plane and transverse to the direction of fluid mixture flow R) 12 The intermediate fluid mixture F, consisting of the first fluid and the second fluids F1 and F2. 12 It exits the first mixing chamber 20 through its outflow opening 203.

[0126] If the first mixing chamber 20 transitions into the first interactive channel 30 without any change in cross-section, then the length l of the first mixing chamber 20... 20 According to the diameter D of the second inflow opening 202 of the first mixing chamber 20 202 Defined as 20 times. That is, applicable to: l 20 ~20×D 202 .

[0127] The outflow opening 203 has a cross-section A 203 The cross-section is, for example, rectangular, thus having a width b. 203 and height h 203 In principle, a non-rectangular cross-section of the outflow opening 203 is also feasible. Cross-section A 203 The minimum cross-section (A) of the fluid component 10 is greater than that of the fluid component. 101 A 11 Or A 102 Cross section A 203 The cross-section A of the second inflow opening 202 of the first mixing chamber 20 is equal to or greater than that of the second inflow opening 202. 102 and the minimum cross-section (A) of fluid component 10 101 A 11 Or A 102 The sum of ).

[0128] The outflow channel 207 exhibits the following hydrodynamic effect: the vortices generated by the fluid component 10 contract to a smaller cross-section. Because, according to Helmholtz's vortex theorem, the circulation within the vortex must remain constant, the contraction of the vortex causes an increase in vortex velocity, thereby increasing the transverse velocity in the fluid. This higher velocity leads to faster mixing of the fluid and also to faster decomposition of the vortices, which in turn results in better mixing at a smaller scale. This vortex decomposition essentially determines the length l of the first interactive channel 30 connected to the first mixing chamber 20. 30 Therefore, the outflow channel 207 of the first mixing chamber 20 significantly contributes to the rapid mixing of fluids F1 and F2. To utilize this effect, the maximum cross-sectional area A of the first mixing chamber 20 is... 20 (where A) 20 =b 20 ×h 20 See Figure 2 and Figure 3 ) and the cross-section A of the outflow opening 203203 (where A) 203 =b 203 ×h 203 See Figure 2 and Figure 3 The ratio of ) must be chosen such that, if applicable, 2 20 / A 203 <100, Preferred 2 20 / A 203 <50, Special Selection 3 20 / A 203 <20.

[0129] In one embodiment (not shown), multiple outflow openings 203 may be provided, which open into parallel interactive channels 30 and subsequently into parallel second mixing chambers. Here, the cross-sectional area A of each outflow opening 203 is shown. 203 The sum is greater than the minimum cross-section of fluid component 10 (A 101 A 11 Or A 102 ).

[0130] The second inflow opening 202 is formed in the inflow channel 206. Alternatively, the second inflow opening 202 can be formed in the outflow channel 207. It is conceivable to provide more than one second inflow opening (for introducing the second fluid F2 or other fluids). Preferably, at least one of the second inflow openings 202 is located in the inflow channel 206.

[0131] exist Figure 1 and Figure 2 In this design, the second inflow opening 202 is circular; however, a non-circular shape for the second inflow opening 202 is also feasible. The cross-section of the second inflow opening 202 is approximately the same size as the cross-section of the first inflow opening 201.

[0132] The distance between the second inflow opening 202 and the first inflow opening 201 along the first fluid flow direction R1 is... Figure 2 Chinese use l 202 This indicates that the length l is advantageous. 202 At least the width b corresponding to the first inflow opening 201 (or outflow opening 102) 201 That is, l 202 ≥b 201 A particularly advantageous feature is the length l 202 At least the width b corresponding to the first inflow opening and the second inflow opening 201, 202 201 and width b 202 The sum, or corresponding to the width b 201 At least twice that, i.e., applicable to l 202 ≥(b​​​201 +b 202 ) or l 202 ≥2×b 201 .

[0133] Figure 3 Show Figure 2 The cross-sectional view of device 1 along line A'-A" (perpendicular to) Figure 2 (The cross-sectional plane in the diagram). Accordingly, in this embodiment, the upstream ends of the fluid member 10, the first mixing chamber 20, and at least the first interaction channel 30 have a constant height h. Height (also referred to as depth) is an extension transverse to the oscillation plane of the first fluid F1. In an embodiment not shown, the height h may not be constant. Particularly in the regions of inflow channels 106 and 206 and outflow channels 107 and 207, the height h may differ from the height in the rest of the device.

[0134] Figure 3 As shown, the second conveying device 70 enters the second inflow opening 202 of the first mixing chamber 20. The second conveying device 70, configured to introduce the second fluid F2 into the first mixing chamber 20, includes a conveying channel 701 extending along the longitudinal axis and pre-defined fluid flow direction R2 for the second fluid F2. Figure 3 The delivery channel 701 is connected to the first mixing chamber 20 via the second inflow opening 202. The delivery channel 701 (viewed in the plane of symmetry S2 or in a plane perpendicular to the oscillation plane and extending along the longitudinal axis L) forms an angle β with the oscillation plane of the fluid component 10 or with the plane of symmetry S1. In this embodiment, the angle β = 90°. In principle, other values ​​of the angle can be used. The angle β affects the mixing quality and / or the mixing path length or mixing time.

[0135] Figure 4 Show Figure 2 The diagram shows a cross-sectional view of device 1 along line B'-B''. In this cross-sectional view, the cross-sections of the main flow channel 103 and the secondary flow channels 104a and 104b of the fluid component 10 are visible. In this embodiment, the height h of channels 103, 104a, and 104b is... 103 h 104a h 104b They are the same size. However, in principle, the stated heights can also be different from each other. Figure 4 The cross-sections of the main flow channel and the secondary flow channels 103, 104a, and 104b are simplified by using sharp edges. However, the corners can be rounded with radii.

[0136] Figure 5 Show Figure 2The device 1 is shown in a cross-sectional view along line C'-C''. In this cross-sectional view, the cross-section of the inflow channel 206 penetrating the first mixing chamber 20 is visible. The corners are again shown simplified, without a radius, although such a radius may exist. The spacing of the lateral boundary walls of the inflow channel 206 (parallel to the oscillation plane and transverse to the longitudinal axis L) is along the entire height h. 206 The spacing is constant within the range of h. However, the spacing can also be adjusted along the height h. 20 6. Changes.

[0137] exist Figure 5 As can also be seen, the second inflow opening 202 of the first mixing chamber 20 is formed in its inflow channel 206. Viewed in a plane transverse to the longitudinal axis L, the delivery channel 701 forms an angle η with the oscillation plane. In the illustrated embodiment, the angle η = 90°. In principle, other values ​​of the angle can be used, for example, between 30° and 150°. An angle η of 90° is preferred.

[0138] The mixing of the first fluid and the second fluids F1 and F2 in the first mixing chamber 20 is characterized by the following: the fluid component 10 generates a mainstream direction transverse to the first fluid flow direction R1 (i.e., substantially in the Y direction). Figure 1 The violent velocity fluctuations of the two fluid flows cause rapid mixing of the two fluid flows through chaotic advection.

[0139] Furthermore, large-scale eddies are generated by the fluid component 10, which gradually decompose into smaller eddies through hydrodynamic processes and are ultimately dissipated through viscous processes. In addition to the dissipation of eddies, this cascading of eddies also causes the fluids F1 and F2 to mix at increasingly smaller scales. This mixing (mostly) occurs in the first mixing chamber 20.

[0140] The first interactive channel 30 is connected to the outflow opening 203 of the first mixing chamber 20. Mixing continues continuously in the first interactive channel 30 until the characteristic mixing time t is reached. mix Then, the two fluids F1 and F2 are thoroughly and uniformly mixed. The mixing time t... mix It is capable of operating within a range of 0.1ms to 1000ms (0.1ms to 1ms, 1ms to 1000ms). Typically, the mixing time t... mix The mixing time is between 0.1 ms and 500 ms (1 ms to 500 ms), and particularly between 0.1 ms and 100 ms (1 ms to 100 ms). Mixing should be completed in the first interactive channel 30. For this purpose, the length l of the first mixing chamber 20 is... 20 The length l of the first interaction channel 30 30The ability to select such a large value allows particles transported at an average velocity to be mixed within a mixing time t. mix It passes completely through the first mixing chamber 20 and the first interaction channel 30.

[0141] exist Figure 1 In the first interactive channel 30, starting from its inflow opening 301, there is initially a section with a constant cross-section. Downstream, a section is connected where the cross-section increases downstream. This section is related to the flow direction R of the fluid mixture. 12 Symmetrical. Downstream of this section is another segment with a constant cross-section, which in turn is followed by a segment in which the cross-section increases downstream. This segment is relative to the flow direction R of the fluid mixture. 12 Asymmetry.

[0142] The first interactive channel 30 can be widened once or multiple times (by increasing the cross-section, especially by widening it transversely to the direction of fluid mixture flow R). 12 And the increase is parallel to the oscillation plane). Alternatively, the first interactive channel 30 can be gradually narrowed once or multiple times (the cross-section decreases, especially the width is transverse to the direction of fluid mixture flow R). 12 And the decrease is parallel to the oscillation plane). Through the cross-section A of the first interactive channel 30 30 Along the direction of fluid mixture flow R 12 This change enables improved mixing of pulsating flow at lower Reynolds numbers (<10) and reduces mixing pulsations generated through fluid member 10 at significantly higher Reynolds numbers (<100). The cross-sectional change occurs without the formation of separation (so-called dead zones), which would cause indeterminate residence times of the intermediate fluid mixture in the first interaction channel 30. This is achieved by adjusting the angle λ... 30 This is achieved by angles less than 10°. The angle is between the centerline of the interaction channel 30 and the boundary wall of the interaction channel 30 at (along the fluid mixture flow direction R)... 12 (Observation) Defined in the widened section. If the first interactive channel 30 (along the flow direction R of the fluid mixture) 12 (Observation) If the width is expanded multiple times, then there are multiple angles λ. 30 ,exist Figure 1 For example, the upstream angle λ 30ia and λ 30ib and the downstream angle λ 30ii Preferably, the angle λ 30 Less than 8°. Advantageously, angle λ 30 Between 2° and 6°. In the illustrated variant of the implementation, symmetrical widening of the upstream portion is achieved in the interaction channel 30, where the angle λ... 30ia and λ 30ib They are the same size.

[0143] exist Figure 1 In the middle, the interactive channel 30 is linear (along the direction of fluid mixture flow R). 12 (Extended) In principle, the interaction channel may also not be straight, and may have, for example, at least one meandering segment, as in... Figure 6 As exemplarily illustrated in the diagram. Depending on the fluids F1 and F2 to be mixed, this meandering section allows for an extension of the residence time in the interaction channel 30, thereby enabling secondary mixing. This is particularly useful for a specific intermediate fluid mixture F1 and F2. 12 This is advantageous because the intermediate fluid mixture requires a certain maturation time, thus having a longer mixing time t. mix .

[0144] In order to achieve the mixing time t mix Afterwards, the particle growth is terminated and the particles are further stabilized, resulting in an intermediate fluid mixture F (containing the particles). 12 It merges with the third fluid F3 in the second mixing chamber 40. For this purpose, the intermediate fluid mixture F... 12 The third fluid F3 enters the second mixing chamber 40 through the first inflow opening 401 from the first interaction channel 30, and enters the second mixing chamber 40 through the second inflow opening 402. The third fluid F3 flows out from the conveying channel 801 of the third conveying device 80. The intermediate fluid mixture F3 is mixed in the second mixing chamber 40. 12 When mixed with the third fluid F3, the particles are subjected to the least possible mechanical stress to avoid particle damage and particle fusion and adhesion (agglomeration and aggregation). For this purpose, the intermediate fluid mixture F... 12 The magnitude and direction are very similar to those of the third fluid F3.

[0145] The method for generating a fluid mixture according to the claims may require: an intermediate fluid mixture F 12 The average velocity U is at the outflow opening 302 of the first interactive channel 30. 302 The third fluid F3 has an average velocity U at the second inflow opening 402 of the second mixing chamber 40. 402 ; and fluid mixture F 123 The average velocity U is at the outflow opening 403 of the second mixing chamber 40. 403 The ratio applicable to the speed is 0.8. 402 / U 302 <1.2 and 0.8 403 / U 302 <1.2. The desired velocity ratio is possible considering the intermediate fluid mixture F 12 ​​In the case of volumetric flow of the third fluid F3, the cross-sectional dimensions of the outflow openings 302 and 403 and the second inflow opening 402 are set. If the intermediate fluid mixture F... 12 If the volumetric flow of fluid F3 is twice as large as that of the third fluid F3, then the cross-section of the outflow opening 302 should be chosen to be twice as large as the cross-section of the second inflow opening 402 (A). 302 =2A 402 Furthermore, the cross-section of the outflow opening 403 should be selected to be three times larger than the cross-section of the second inflow opening 402 (A). 403 =3A 402 When the heights of the outflow openings 302 and 403 and the second inflow opening 402 are the same, the ratio of the cross sections is transferred to the corresponding width.

[0146] In summary, the outflow opening A of the second mixing chamber 40 403 The cross-section roughly corresponds to the outflow opening A 302 (First inflow opening A) 401 The cross-section of the second inflow opening A 402 The sum of the cross-sections. When the direction of the third fluid F3 is R3 and the intermediate fluid mixture F... 12 Direction R 12 This is especially true when the object is in or parallel to the plane of oscillation.

[0147] The transition from the first interaction channel 30 to the second mixing chamber 40 (i.e., the location of the outflow opening 302 of the first interaction channel 30 and the first inflow opening 401 of the second mixing chamber 40) is characterized by its cross-section (transverse to the flow direction R of the fluid mixture). 12 The cross-section suddenly increases in size. In this region where the cross-section suddenly increases in size, the conveying channel 801 of the third conveying device 80 enters the second mixing chamber 40. The conveying channel 801 extends (straight) along the third fluid flow direction R3. Here, the third fluid flow direction R3 and the fluid mixture flow direction R... 12 An angle ζ is formed, which is less than or equal to 90°, preferably less than 45°, and particularly preferably between 5° and 40°.

[0148] The resulting fluid mixture F 123 The fluid flows from the outlet opening 403 of the second mixing chamber 40 into the second interaction channel 50, and exits the device 1 through the outlet opening 502 of the second interaction channel 50.

[0149] Figure 6 Device 1 according to another embodiment is shown. This device is related to... Figures 1 to 5The difference in the implementation method lies particularly in the shape of the first interaction channel 30. Therefore, the first interaction channel 30 has a meandering section, which (exemplarily exemplarily here) has a 180° deflection portion 303 and two 90° deflection portions 304. The meandering section extends the first interaction channel 30, such that the intermediate fluid mixture F 12 The dwell time in the first interactive channel 30 (and) Figure 1 Compared to the previous implementation method, the implementation time is extended.

[0150] In the variant of the described embodiment, the interaction channel 30 has a constant channel width b in the deflection sections 303 and 304. 300 .

[0151] The straight-formed segment 305 connects to the meandering segment directly downstream of the final deflection segment 304. The straight-formed segment 305 has a length of l. 305 The length is the channel width b. 300 At least three times larger (l) 305 ≥3×b 300 The preferred channel width is b. 300 At least five times larger (l) 305 ≥5×b 300 The linearly shaped section 305 is used to make the intermediate fluid mixture F 12 The velocity distribution map is homogenized.

[0152] Downstream of the linearly formed segment 305, there is an asymmetrical segment 307. The asymmetrical segment 307 takes into account the intermediate fluid mixture F. 12 The asymmetrical flow velocity distribution is shown. The asymmetrical section 307 prevents the formation of a recirculation zone. The widening is achieved through the angle λ. 30 accomplish.

[0153] A further linearly shaped segment 308 is provided directly downstream of the asymmetrical segment 307. The length of the segment is l. 308 The desired mixing time t depends on the fluids F1 and F2 to be mixed. mix This process is necessary to produce particles with the desired size and shape. Approximately 10 ms of mixing time is required to produce lipid nanoparticles.

[0154] In this variant of the implementation, the cross-section A of the first inflow opening 201 of the first mixing chamber 20 is... 201 The cross-section A of the second inflow opening 202 of the first mixing chamber 20 202 Around 25% larger.

[0155] It is also worth considering with Figure 6The different implementations of the method are as follows: the first interaction channel 30 does not include the deflection parts 303 and 304, but only includes the linearly formed section 305, the widened symmetrical section 307 and the linearly formed section 308 (directly connected to the first mixing chamber 20).

[0156] The second interactive channel 50 (typically) runs along the fluid mixture F. 123 The direction of the axis extends. Fluid mixture F 123 The direction of the fluid mixture F 123 velocity vector The fluid mixture F is obtained. 123 velocity vector The sum of the following velocity vectors corresponds to the intermediate fluid mixture F. 12 velocity vector at the first inflow opening 401 ; and the velocity vector of the third fluid F3 at the second inflow opening 402 The axis of the second interactive channel 50 and the direction of fluid mixture flow R 12 Enclosed at an angle ε, the angle is in Figure 6 In the implementation, the angle is less than 180°. The axis of the second interactive channel 50 and the third fluid flow direction R3 form an angle κ, which is within... Figure 6 In this implementation, the angle is less than 180°. Angles ε and κ are not of equal size here; in particular, angle κ is larger than angle ε. For example, angle κ is between 170° and 179° (174°), and angle ε is between 160° and 169° (166°). The flow direction R of the fluid mixture... 12 The angle ζ between the fluid and the direction of the third fluid flow R3, as well as the angles ε and κ, total 360°.

[0157] exist Figure 7 The diagram schematically illustrates the deflection of a moving (oscillating) first fluid F1 (at the outlet opening 102 of the fluid member 10) over time. Accordingly, the first fluid F1 oscillates periodically between two maximum deflections, exemplarily approximately +25° and -25°. Here, the dashed line represents an idealized sinusoidal curve. Additional intermediate oscillations are advantageous to improve the mixing quality in the first mixing chamber 20. The curve shown as a solid line includes such intermediate oscillations. For example, intermediate oscillations are present at approximately ±5°. This time-varying curve (as shown as a solid line) can, for example, be obtained by means of... Figure 1 or Figure 2The fluid component 10 generates the oscillation angle α. The oscillation angle α can be selected based on the desired mixing mass, the fluid to be mixed, and its volume. The oscillation angle α can be determined in different ways. For example, it can be determined based on the ratio of the velocity components at the center of the cross-section of the outlet opening 102 according to the relationship α = 2*arctan(v / u), where u is the velocity component in the flow direction, and v is the velocity component transverse to the flow direction in the oscillation plane.

[0158] In the first mixing chamber 20, the first fluid F1 preferably has a turbulence Tu greater than 0.05. 20 Particularly preferably, the turbulence intensity is between 0.1 and 0.5. Generally, turbulence intensity represents the change in velocity relative to the average velocity. Here, turbulence intensity is specifically defined as the maximum time fluctuation σ of the local velocity F1 in the first mixing chamber 20. u,max,20 The average velocity u of the first fluid F1 at the first inflow opening 201 201 The merchant: Tu 20 =σ u,max,20 / u 201 To determine the maximum time fluctuation, the time variance σ of the velocity was determined using transient numerical flow simulation (CFD) of the first fluid F1. u Identify σ in mixing chamber 20 u The maximum value of space.

[0159] In the second mixing chamber 40, the turbulence Tu 40 According to Tu 40 =σ u,max,40 / u 401 Limited, where σ u,max,40 It is F in the mixing chamber 40 12 The maximum variance of the velocity, and u 401 It is an intermediate fluid mixture F 12 The velocity at the first inflow opening 401 of the second mixing chamber 40. Preferably, the turbulence Tu 40 Less than 0.1, preferably less than 0.05, and especially preferably less than 0.025.

[0160] In the first mixing chamber 20 of the proposed embodiment, in order to rapidly mix the first fluid and the second fluids F1 and F2, a Kolmogorov scale Lk (the length scale of the smallest eddy in turbulent flow) of less than 20 μm can be achieved, preferably less than 10 μm and particularly preferably less than 5 μm, through the corresponding fluid component 10. The Kolmogorov scale Lk can be estimated from the results of turbulent CFD (Reynolds Averaged Navier Stokes, RANS). For this purpose, the turbulent dissipation rate ε, calculated as the transport volume in the so-called k-ε turbulence model, is compared with the fluid mixture F... 12 The kinematic viscosity ν is related as follows: .

[0161] In contrast to the mixing in the first mixing chamber 20, the mixing in the second mixing chamber 40 should be carried out with minimal shearing of the intermediate fluid mixture F. 12 This is done in a manner that... For this purpose, the velocity u at the first inflow opening 401 of the second mixing chamber 40 (or at the outflow opening 302 of the first interactive channel 30) is... 401 The velocity u at the second inflow opening 402 of the second mixing chamber 40 402 The relative difference should be as small as possible. Absolutely speaking, the turbulence in the second mixing chamber 40 should also be less than the turbulence in the first mixing chamber 20. For this purpose, the absolute velocity in the second mixing chamber 40 can be smaller than that in the first mixing chamber 20. Preferably, u is suitable. 401 201 U is the preferred choice. 401 201 / 2, where u 401 It is an intermediate fluid mixture F 12 The velocity at the first inflow opening 401 of the second mixing chamber 40, and u 201 It is the velocity of the first fluid F1 at the first inflow opening 201 of the first mixing chamber 20.

[0162] Figure 8 Another embodiment of device 1 is shown. This embodiment is similar to... Figures 1 to 6 The difference in the implementation methods lies primarily in the design of the first conveying device 60 and the number of the third conveying devices 80a, 80b, 80c, and 80d. Therefore, the fluid component 10 of the first conveying device 60 has only one secondary flow channel 104. This secondary flow channel 104 is annularly formed and located upstream of the main flow channel 103. The four third conveying channels 801a, 801b, 801c, and 801d lead into the second mixing chamber 40.

[0163] exist Figure 8 ​​In this design, the secondary flow channel 104 has a substantially constant cross-section over its entire length (between points 104a1 and 104b1). A corresponding enlarged portion of the cross-section is provided in the region at each secondary flow channel inlet or outlet (at points 104a1 and 104b1). In principle, the size of the cross-section can also be as large as it is over the entire length of the secondary flow channel 104.

[0164] At the transition between the secondary flow channel 104 and the main flow channel 103, the fluid component 10 has a width b 11 (Extension parallel to the oscillation plane and transverse to the first fluid flow direction R1). Preferably, the inflow width b 101 Less than width b 11 The width of the main channel 103 first increases and then decreases downstream from the transition region towards the secondary channel 104. Figure 1 and Figure 2 Compared to the fluid component 10, the fluid component 10 at the same input pressure P 10IN This results in a higher oscillation frequency. The higher oscillation frequency shortens the mixing time of the first fluid F1 and the second fluid F2 in the first mixing chamber 20 and the immediately following first interaction channel 30.

[0165] exist Figure 8 In the middle, the length l of the first mixing chamber 20 20 (The extension along the first fluid flow direction R1) is less than the length l of the fluid component 10. 10 It should be considered that in a more easily manufactured variant of this embodiment, the length l 10 Including length l 106 In this case, the length l 10 The flow path 104 is defined by a point on the boundary wall outside the secondary flow path 104, extending to the outlet opening 102, where the point is furthest from the outlet opening 102 along the axis X. The main flow path 103 and the secondary flow path 104 are in the same plane. According to an alternative, the secondary flow path 104 can be in a plane parallel to the plane of the main flow path 103. In this case, the length l... 10 Excluding length l 106 In this case, the length l 10 It extends from the inflow opening 101 to the outflow opening 102. Alternatively, a length l can be considered. 20 Greater than length l 10 .

[0166] The third fluid F3 is introduced into the second mixing chamber 40 via multiple third delivery channels 801a, 801b, 801c, and 801d. Figure 8The example provided consists of four third conveying channels 801a, 801b, 801c, and 801d. Other numbers are also possible. Two more upstream third conveying channels 801a and 801c are arranged symmetrically with respect to each other (with respect to the second mixing chamber 40), while two more downstream third conveying channels 801b and 801d are arranged asymmetrically with respect to each other (or along the fluid mixture flow direction R). 12 (Staggered) The conveyor channels 801a, 801b, 801c, and 801d are respectively part of the third conveyor devices 80a, 80b, 80c, and 80d. However, the conveyor channels 801a, 801b, 801c, and 801d can also be part of a common third conveyor device and be supplied by a common inlet that branches into the respective conveyor channels 801a, 801b, 801c, and 801d.

[0167] Multiple third delivery channels 801a, 801b, 801c, and 801d cause: the application of third fluid F3 to the intermediate fluid mixture F 12 The pulsation on the surface (about Figures 1 to 6 The implementation method is relatively small because the pulsations are spatially distributed.

[0168] The cross-section is designed so that the average velocities at the inflow and outflow openings are as similar as possible. For example, in an intermediate fluid mixture F... 12 The average velocity u302 at the outflow opening 302 of the first interactive channel 30 and the average velocity u of the third fluid F3 at the second inflow openings 402a and 402c of the second mixing chamber 40 402a and u 402c The ratio is: 0.8 402a / u 302 <1.2 and 0.8 402c / u 302 <1.2. The volumetric flow through the second inflow openings 402a and 402c, and the intermediate fluid mixture F 12 The volumetric flow through the first inflow opening 401 determines the size of the cross-section at the aforementioned opening. If the volumetric flows through the second inflow openings 402a and 402c are the same and are each half the size of the volumetric flow through the first inflow opening 401, then the cross-sections of the second inflow openings 402a and 402c are correspondingly the same and are each half the size of the cross-section of the first inflow opening 401.

[0169] Figure 9 Another embodiment of device 1 is shown. This embodiment is similar to... Figures 1 to 6 and Figure 8 The difference in the implementation method lies particularly in the design of the first conveying device 60. Therefore, in Figure 9 ​​In the first conveying device 60, there are two inlet openings 101a and 101b, but no secondary flow channel. An extension 106 is provided upstream of the inlet openings 101a and 101b, which, when viewed in the fluid flow direction, divides into two channels 106a and 106b. Channels 106a and 106b open into the inlet openings 101a and 101b. Channels 106a and 106b are used to regulate the fluid flow of the first fluid F1. The shapes of these two channels 106a and 106b are... Figure 9 The following is merely an example. The downstream ends of channels 106a and 106b toward inflow openings 101a and 101b are formed by straight end segments. Channels 106a and 106b are arranged mirror-symmetrically about the longitudinal axis of device 1, as are inflow openings 101a and 101b. Inflow openings 101a and 101b form a transition between channels 106a and 106b and the main channel 103. The downstream, straight end segments of channels 106a and 106b form an angle σ. The angle σ is a value between 95° and 175°. The vertex of angle σ is downstream of inflow openings 101a and 101b. Angle σ is measured upstream of the vertex. The smaller the angle σ, the longer the fluid member 10.

[0170] Figure 9 The implementation method differs from the others in the design of the first interactive channel 30 and the conveying channel 801 of the third conveying device 80. Therefore, the first interactive channel 30 has a section 307, the cross-section of which decreases downstream. Section 307 is closer to the outflow opening 302 than to the inflow opening 301. Similarly, the conveying channel 801 has a section 807, the cross-section of which decreases downstream. These cross-sectional changes have the effect of reducing relative velocity fluctuations and achieving a more uniform velocity distribution across the cross-section. Furthermore, it allows for better control of the intermediate fluid mixture F. 12 The velocity of the third fluid F3 at the point of convergence allows for more precise definition of the mixing conditions. This achieves precise definition, thereby limiting, the shear during the mixing of the two fluid flows. To reduce fluid velocity fluctuations and equalize velocity distribution, the cross-section of the outflow opening 302 can be reduced by 2 to 100 times, preferably 2 to 20 times, and particularly preferably 2 to 10 times, compared to the maximum cross-section of the first interaction channel 30. Similarly, the cross-section of the second inflow opening 402 can be reduced by 2 to 100 times, preferably 2 to 20 times, and particularly preferably 2 to 10 times, compared to the maximum cross-section of the conveying channel 801 of the third conveying device 80.

[0171] Combination Figure 6 The implementation schemes for angles ε and κ can also be adapted to Figure 9 .

[0172] Device 1 in Figure 10The implementation methods shown are similar to Figure 1 The difference in the implementation method lies particularly in the design of the fluid component 10, the first interactive channel 30, and the relative arrangement of the third conveying device 80 with respect to the second mixing chamber 40. This relative arrangement is designed such that the intermediate fluid mixture F... 12 The third fluid F3 and the third fluid meet each other at an angle of approximately 90°, or cause the fluid mixture to flow in the direction R. 12 The third fluid flow direction R3 forms an angle of approximately 90°. In the remaining embodiments of device 1, this angle is denoted by ζ and is less than 90°. Figure 10 In the middle, the direction R3 of the third fluid F3 does not extend in the oscillation plane or extends parallel to the oscillation plane.

[0173] The first interaction channel 30 is tubularly configured to have a constant cross-section and a constant width along its extension between the inlet opening 301 and the outlet opening 302. The second mixing chamber 40 is formed through an elongated portion of the first interaction channel 30, wherein the width remains constant. However, the depth of the second mixing chamber 40 is greater than the depth of the first interaction channel 30. Specifically, in Figure 10 In the implementation method (see also) Figure 11 The depth of the second mixing chamber 40 is twice the depth of the first interaction channel 30. Consequently, the first inlet opening 401 of the second mixing chamber 40 has a smaller cross-section (depth) compared to the outlet opening 403. The ratio of the depth of the first inlet opening 401 to the depth of the outlet opening 403 depends on the intermediate fluid mixture F. 12 and fluid mixture F 123 The ratio of volumetric flow. Preferably, the ratio of depth t 401 / t 403 Greater than or equal to F 123 Volume flow and F 12 The ratio of volumetric flow.

[0174] The second mixing chamber 40 has a length (R along the direction of fluid mixture flow) 12 (extension) and width (transverse to the direction of fluid mixture flow R) 12 (and extending transversely to the third fluid flow direction R3), the length and width respectively correspond to the diameter of the second inflow opening 402 of the second mixing chamber 40. The width of the second mixing chamber 40 corresponds to the width of the first inflow opening 401. The ratio of the width of the second mixing chamber 40 to the diameter of the second inflow opening 402 can be from 1:1 to 2:1. Here, the second inflow opening 402 has, for example, a circular cross-section. Alternatively, the cross-section can be angular or oval.

[0175] like Figure 11 In Figure 10As shown in the observation, the depth t of the outflow opening 302 of the first interactive channel 30 is... 302 The depth t of the outflow opening 403 of the second mixing chamber 40 is significantly smaller than that of the second mixing chamber 40. 403 Cross section A 302 The width b at the outflow opening 302 302 and depth t 302 Formation. Cross-section A 403 The width b at the outflow opening 403 403 and depth t 403 Formed. In the variant embodiment, the cross-section A of the second inflow opening 402 of the second mixing chamber 40 is... 402 Through the diameter d at the outlet opening 402 402 form.

[0176] In this variant of the implementation, the cross-section of the second inflow opening 402 is significantly larger than the cross-section of the first inflow opening 401 (corresponding to the outflow opening 302). Consequently, the average velocity at the second inflow opening 402 is significantly lower than the average velocity at the first inflow opening 401. This results in the following hydrodynamic effect: the intermediate fluid mixture F (entering the second mixing chamber 40 via the first inflow opening 401)... 12 The pulsation upon entering the second mixing chamber 40 is significantly greater than that of the third fluid F3 (entering the second mixing chamber 40 via the second inflow opening 402) upon entering the second mixing chamber 40. Although the intermediate fluid mixture F 12 The third fluid F3 and the third fluid F3 meet each other at approximately a right angle, but due to the different pulsations, only an intermediate fluid mixture F is produced. 12 The minimum shear.

[0177] In summary, the outflow from opening A 403 The cross-section is smaller than the cross-section A at the outlet opening 302. 302 Cross section A at the second inflow opening 402 402 The sum. When the direction of the third fluid F3 is R3 and the intermediate fluid mixture F 12 Direction R 12 This is the case when the angle is certain and the plane of oscillation is not within the plane of oscillation. Figure 10 and Figure 11 In the variant of the implementation shown, direction R3 is orthogonal to the oscillation plane.

[0178] In contrast to the variant of the implementation where direction R3 is in the oscillation plane, in Figure 10 and Figure 11 In the implementation method, cross section A 403 It should be larger than cross-section A 401 (A) 403 >A401 The preferred area relationship is as follows: 1.1 A 403 401 +A 402 <10A 403 The following area relationship is particularly preferred: 1.9 A 403 401 +A 402 <7.9 A 403 .

[0179] exist Figure 10 and Figure 11 Another feature of the embodiment shown is the cross-section (transverse to the direction of fluid mixture flow R). 12 The sudden widening at the first inflow opening 401. According to... Figure 11 In the embodiment shown with section D'-D'', the widened portion of the cross-section is stepped. The step extends towards the conveying channel 801. The inflow of the third fluid F3 into the mixing chamber 40 is in the intermediate fluid mixture F 12 The direction of fluid mixture flow R 12 The upper observation point is downstream of the step. According to basic fluid mechanics principles, such a step should be avoided because it leads to the formation of a recirculation zone (dead water zone), which causes fluid mixture F... 123 The uncertain residence time in the mixing chamber 40 impairs its function. However, in Figure 10 In the embodiment shown, the depth t at the mixing chamber 40 or the outflow opening 403 is... 403 Depth t at the outflow opening 302 302 The design is such that the potential recirculation zone is traversed only by the third fluid F3. Therefore, only the third fluid F3 is recirculated, and the residence time of the third fluid in the mixing chamber 40 is insignificant. The depth t at the outlet opening 403... 403 Depth t at the outflow opening 302 302 The ratio of fluid F 12 It is related to the velocity ratio of fluid F3. Figure 10 and Figure 11 In the variant of the implementation shown, the depth corresponds to t. 403 =1.8 t 302 The width is constant, b 302 =b 403 .

[0180] Figure 10 and Figure 11 The implementation method described herein will be used for gently mixing intermediate fluid mixture F 12 The hydrodynamic aspects of the third fluid F3 are combined with the minimized construction. ​​

[0181] Figure 12 Another implementation is shown. This implementation is similar to... Figure 10 and Figure 11 The difference in the implementation method lies particularly in the design of the first interaction channel 30 and the second mixing chamber 40.

[0182] The second mixing chamber 40 is tubularly configured with a bend. Specifically, the bend is L-shaped, having two sections arranged at a 90° angle relative to each other and each opening into an open end. The end of the first section of the tubular mixing chamber 40 forms a second inlet opening 402, through which the third fluid F3 enters the mixing chamber 40. The end of the second section of the tubular mixing chamber 40 forms an outlet opening 403, through which the fluid mixture F... 123 It exits from the mixing chamber 40 via the outflow opening.

[0183] The first interaction channel 30 is also tubular and has a smaller diameter than the second mixing chamber 40. The tubular interaction channel 30 and the second section of the tubular mixing chamber 40 are concentrically arranged and extend along an axis on which the outlet opening 403 is also located. The first interaction channel 30 extends into the mixing chamber 40 in the region of the bend. For this purpose, an opening is provided in the wall of the mixing chamber 40, the shape and size of which correspond to the cross-section of the interaction channel 30. The outlet opening 302 of the first interaction channel 30, which is also the first inlet opening 401 of the mixing chamber 40, is located upstream of the outlet opening 403. Intermediate fluid mixture F 12 It enters the mixing chamber 40 through the first inflow opening 401.

[0184] In the mixing chamber 40, the intermediate fluid mixture F 12 In a circular jet with an average velocity u 302 The flow continues, and the third fluid F3 flows through the concentric annular gap at an average velocity u. 401 The flow occurs at the height of the first inflow opening 401. Here, a velocity ratio of 0.5 applies. 401 / u 302 <2. The velocity is set here via the diameter / cross-section of the tube (forming the first interaction channel 30 and the second mixing chamber 40) to produce the desired velocity ratio in the volumetric flow required for the process. For example, if the third fluid F3 and the intermediate fluid mixture F are to be mixed in a 3:1 ratio... 12 The volume flow, and if the cross-section of the tube forming the first interactive channel 30 and the second mixing chamber 40 is circular, then the ratio of the outer tube diameter to the inner tube is selected as 2:1, thereby creating an area ratio of the annular gap to the inner tube of 3:1.

[0185] ​ Figure 13 The diagram schematically illustrates a process for continuously mixing multiple (three or more) fluids to produce a fluid mixture according to one embodiment. The steps shown with dashed or dotted lines are merely optional method steps.

[0186] The method is characterized by combining different mixing techniques with each other at very short time intervals using the device 1 according to the invention. This achieves high reproducibility and minimizes the risk of errors, thereby ensuring the consistent quality of the resulting fluid mixture and reducing costs.

[0187] In the first mixing chamber 20, the first fluid and the second fluids F1 and F2 are rapidly / turbulently mixed (turbulence greater than 0.1) to produce an intermediate fluid mixture F. 12 The intermediate fluid mixture undergoes quasi-laminar mixing with a low shear rate (turbulence less than 0.1) in the second mixing chamber 40 together with the third fluid F3 (and other fluids).

[0188] exist Figure 13 The first method steps, denoted by P1.1, P2.1, and P3.1, involve a first fluid F1 and are performed in parallel with method steps P1.2 and P2.2 involving a second fluid F2 and method steps P1.3 and P2.3 involving a third fluid F3. According to an embodiment, these method steps can also be performed in parallel with optional method steps P1.4 and P2.4 involving other fluids.

[0189] During the aforementioned method steps, the first fluid F1, the second fluid F2, the third fluid F3 (and other fluids) exist in separate forms.

[0190] First, in method steps P1.1, P1.2, and P1.3 (and optionally P1.4), the volumetric flow rates (velocities) of the first fluid F1, the second fluid F2, and the third fluid F3 (and other fluids) are set. The volumetric flow rates are set based on the mixing ratio of fluids F1 and F2. In cases where particles are generated during mixing, the particle size can also be influenced and set by the ratio of the volumetric flow rates.

[0191] The ratio of the flow rate of the first fluid F1 to the flow rate of the second fluid F2 is greater than or equal to 1:1 (e.g., 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, or 10:1, and values ​​between therewith). In other cases, the ratio of the flow rate of the second fluid F2 to the flow rate of the first fluid F1 is greater than 1:1 (e.g., 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, or 10:1, and values ​​between therewith).

[0192] In the subsequent method steps P2.1, P2.2 and P2.3 (and optionally P2.4), the inlet pressure of the first fluid F1 (at the inlet opening 101 of the fluid member 10), the inlet pressure of the second fluid F2 (at the second inlet opening 202 of the first mixing chamber 20), and the inlet pressure of the third fluid F3 (at the second inlet opening 402 of the second mixing chamber 40) (and optionally the inlet pressures of other fluids) are set by means of suitable pump equipment (depending on the volume, for example, syringe pumps, multi-plunger pumps, diaphragm pumps, gear pumps, circulation pumps, hose pumps or other displacement pumps). The first fluid, the second fluid and the third fluid F1, F2, F3 (and optionally other fluids) are guided into the first conveying device, the second conveying device or the third conveying device 60, 70, 80 (and optionally other conveying devices).

[0193] After the first fluid F1 is introduced into the first conveying device 60, the flow characteristics of the first fluid F1 are adjusted by means of the conveying device 60 in method step P3.1. Therefore, in P3.1, oscillation of the first fluid F1 is generated by means of the fluid member 10. The oscillation frequency is generally higher than 100 Hz. An oscillation frequency of several kilohertz, for example 2000 Hz, is advantageous. Since the oscillation frequency can vary drastically depending on the dimensions of the fluid member 10, it is common to express the oscillation frequency in a dimensionless manner as the Strouhal number (St). For this purpose, the oscillation frequency f is divided by the average velocity u at the outlet opening 102 of the fluid member 10 102 , and multiplied by the width b of the outlet opening 102 of the fluid member 10 102 , that is, St=f*b 102 / u 102 . The Strouhal number defined in this way can be in the range of 0.001<St<1, preferably 0.005<St<0.5, particularly preferably 0.01<St<0.05. Thus, the first fluid F1 with passive oscillation is provided at the outlet opening 102 of the fluid member 10. The oscillation angle α of the first fluid F1 can be at least 5°, preferably at least 25°, particularly preferably at least 40°. For many applications, an oscillation angle between 25° and 50°, in particular between 30° and 45°, is suitable. A typical maximum value of the oscillation angle is 75°.

[0194] In method step P4, the oscillating first fluid jet F1 provided by the first conveying device 60 and the (quasi-)static second fluid jet F2 provided by the second conveying device 70 are guided into the first mixing chamber 20 via the first inlet opening or the second inlet opening 201, 202, and are combined there into an intermediate fluid mixture F 12The collision occurs at angles β and η, which have been described in detail above in conjunction with device 1. When the method is applied in industrial-scale or batch production, the first fluid and the second fluids F1 and F2 are guided into the first mixing chamber 20 in a continuous volumetric flow.

[0195] In method step P5, the fluid mixture F that exits from the first mixing chamber 20 via the outflow opening 203 at the end of the mixing process P4 is... 12 Guided to the length l connected downstream 30 In the first interaction channel 30, mixing continues until the characteristic mixing time t is reached. mix The two fluids F1 and F2 are then mixed sufficiently uniformly. As long as particles (e.g., lipid nanoparticles, polymer nanoparticles, liposomes) or crystals are generated during the mixing process P4, the particles have time to mature in the first interaction channel 30.

[0196] The intermediate fluid mixture F exiting from the first interaction channel 30 12 In method step P6.1, it is guided into the second mixing chamber 40 and merged with the third fluid F3 (and optionally with other fluids in turn). In this case, the third fluid F3 and the other fluids can be different or the same.

[0197] To achieve gentle mixing, the third fluid F3 and the intermediate fluid F are mixed. 12 The mixing is carried out under specific hydrodynamic criteria, which are illustrated below with different embodiments. To keep the shear rate in the second mixing chamber 40 as low as possible, the third fluid F3 and the intermediate fluid mixture F... 12 The velocities, in terms of both magnitude and direction, must be as similar as possible. Once particles are generated during mixing process P4, process step P6.1 can be used to stabilize the particles. Gentle mixing with a low shear rate minimizes the mechanical stress on the particles, thereby achieving better particle quality.

[0198] In one embodiment variation, improved stability of the particles (e.g., lipid nanoparticles) is achieved by diluting the particle stream (intermediate fluid mixture F) with an aqueous solution, such as a buffer solution (third fluid F3). 12 In some variations of the method, the diluent (third fluid F3) is the same buffer solution used in the first fluid F1. In other variations, the diluent (third fluid F3) is different from the buffer solution used in the first fluid F1. In this case, the intermediate fluid mixture F... 12A reduced solvent content leads to improved stability of the nanoparticles. For some nanoparticles, a solvent content below 50% results in improved particle stability. In another embodiment variation, a solvent content below 25% results in improved nanoparticle stability. In yet another embodiment variation, a solvent content below 10% results in improved nanoparticle stability.

[0199] In one embodiment variation, the stability of particles (e.g., lipid nanoparticles) is improved by increasing, decreasing, or neutralizing the particle flow (intermediate fluid mixture F) from the mixing process P4 through dilution with a corresponding medium (third fluid F3). 12 pH value (e.g., through acidic or alkaline buffer solutions).

[0200] In one variant of the implementation, the stability of the particles (e.g., polymer nanoparticles) is improved by: feeding the particle stream (intermediate fluid mixture F) from the mixing process P4... 12 Add a diluent (third fluid F3) containing a surfactant. The surfactant can be, for example, poloxamer or polyvinyl alcohol, but is not limited to these substances.

[0201] In one embodiment variation, the previously mentioned embodiment variations can be combined, wherein multiple fluids (e.g., two; but not limited to two) are sequentially fed to the particulate stream (intermediate fluid mixture F) from mixing process P4. 12 Therefore, for example, a third fluid F3 is first fed to the particle stream, and then another fluid is fed to the resulting fluid mixture F. 123 .

[0202] intermediate fluid mixture F 12 The ratio between the flow rate of the intermediate fluid F3 and the flow rate of the third fluid F3 is greater than or equal to 1:1 (e.g., 1:1, 2:1, 3:1, 4:1, or 5:1, and values ​​between these). In other cases, the flow rate of the intermediate fluid F3 is greater than or equal to the flow rate of the intermediate fluid mixture F... 12 The ratio between the flow rates is greater than 1:1 (e.g., 2:1, 3:1, 4:1 or 5:1 and values ​​in between).

[0203] In method step P7.1, at the end of the mixing process P6.1, the fluid mixture F exits from the second mixing chamber 40 via the outflow opening 403 of the second mixing chamber 40. 123 Guided to the length l connected downstream 50 In the second interaction channel 50, mixing from the second mixing chamber 40 continues.

[0204] The second mixing process in the second mixing chamber 40 can be cascaded (optional method steps P6.2 and P7.2) by connecting multiple second mixing chambers 40 (optionally grouped with second interaction channels 50 respectively) in series. In P6.2 and P7.2, similar to P6.1 and P7.1, one or more other fluids are combined with the fluid mixture generated from the previous mixing process. The fluid added in the optional steps can be the same as or different from the third fluid F3.

[0205] Method step P7.1 (optionally P7.2) is followed by method step P8, in which the resulting fluid mixture is removed from device 1. Method step P8 may be followed by heat treatment (e.g., cooling) of the resulting fluid mixture and / or separation of a component (e.g., solvent) from the fluid mixture.

[0206] To perform the method, process parameters should be specified. These process parameters are related to the dimensions of the equipment. The dimensions of the equipment affect the fluid velocity, which in turn imposes limitations on the volumetric flow. Figure 1 For reference, the device in the first mixing chamber has a first inflow opening 201 with a width b. 201 and height h 201 The applicable one is h. 201 =b 201 .

[0207]

[0208] The volumetric flow of other fluid flows is derived from the corresponding volumetric flow ratio for a specific implementation of the process.

[0209] The accompanying drawings illustrate different embodiments of device 1, each corresponding to a specific combination of the fluid component 10, the first mixing chamber 20, the first interaction channel 30, the second mixing chamber 40, and the second interaction channel 50. Besides the combinations specifically shown, the components mentioned in each embodiment can be combined with each other. It is also possible to omit the second interaction channel.

[0210] Different types of fluid components can be used. The fluid component can have a secondary flow channel or other mechanism as a means for targeted directional changes.

[0211] In the specification, the terms height h and depth t are used synonymously to refer to the extension of the oscillating plane transverse to the first fluid.

[0212] List of reference numerals

[0213] F1 First Fluid

[0214] F2 Second Fluid

[0215] F3 Third Fluid

[0216] F 12 intermediate fluid mixture

[0217] F 123 fluid mixture

[0218] R1 First fluid flow direction

[0219] R2 Second fluid flow direction

[0220] R3 Third Fluid Flow Direction

[0221] R 12 Fluid mixture flow direction

[0222] 1. Equipment for generating fluid mixtures

[0223] 10 fluid components

[0224] 11a, 11b internal blocks

[0225] 100 flow chambers

[0226] 101 Inflow Opening

[0227] 102 outflow opening

[0228] 103 Mainstream Channels

[0229] 104a, 104b secondary flow channels

[0230] 106 Extension

[0231] 107 outflow channel

[0232] 20 First Mixing Chamber

[0233] 201 First Inflow Opening

[0234] 202 Second Inflow Opening

[0235] 203 outflow opening

[0236] 206 Inflow Channel

[0237] 207 outflow channel

[0238] 30 First Interactive Channel

[0239] 301 Inflow Opening

[0240] 302 outflow opening

[0241] 303 deflection section

[0242] 304 deflection section

[0243] Sections of the first interactive channel, 305, 307, and 308.

[0244] 40 Second mixing chamber

[0245] 401 First Inflow Opening

[0246] 402 Second Inflow Opening

[0247] 403 outflow opening

[0248] 50 Second Interactive Channel

[0249] 501 Inflow Opening

[0250] 502 flow outlet

[0251] 60 First Conveying Equipment

[0252] 70 Second Conveying Equipment

[0253] 701 Conveyor Channel

[0254] 80 Third Conveying Equipment

[0255] 801 Conveyor Channel

Claims

1. An apparatus (1) for generating a fluid mixture, the apparatus comprising: - A first mixing chamber (20), the first mixing chamber having: a first inflow opening (201), a first fluid (F1) being able to be introduced into the first mixing chamber (20) via the first inflow opening along a first fluid flow direction (R1); A second inlet opening (202) allows the second fluid (F2) to be introduced into the first mixing chamber (20) along the second fluid flow direction (R2); and an outlet opening (203) contains an intermediate fluid mixture (F1) comprising the first fluid (F1) and the second fluid (F2). 12 ) can flow through the outflow opening along the direction of the fluid mixture flow (R) 12 The outflow channel (207) is formed upstream of the outflow opening (203), and the outflow channel is transverse to the flow direction of the fluid mixture (R). 12 The cross-section defined by the fluid mixture flow direction (R) 12 The diameter decreases toward the outflow opening (203). - A second mixing chamber (40), the second mixing chamber having: a first inflow opening (401), the intermediate fluid mixture (F 12 ) can flow along the direction of the fluid mixture flow (R) through the first inflow opening. 12 ) is introduced into the second mixing chamber (40); The third fluid (F3) can be introduced into the second mixing chamber (40) through the second inlet opening (402) along the third fluid flow direction (R3); and the outflow opening (403), comprising the fluid mixture (F1), the second fluid (F2), and the third fluid (F3). 123 It can be discharged through the outflow opening, and - A first conveying device (60), which is fluidly connected to the first mixing chamber (20) via the first inflow opening (201) and configured to guide the first fluid (F1) into the first mixing chamber (20) along the first fluid flow direction (R1), wherein the first conveying device (60) includes a fluid member (10) having: • An outflow opening (102), which is fluidly connected to a first inflow opening (201) of the first mixing chamber (20), and • At least one mechanism (104a, 104b) for targeted direction change of the first fluid (F1), the first fluid flowing through the fluid member (10), the mechanism for targeted direction change of the first fluid (F1) being configured to cause spatial oscillation of the first fluid (F1) at the outflow opening (102), wherein the mechanism (104a, 104b) for targeted direction change of the first fluid (F1) is configured to cause oscillation of the first fluid (F1) in the oscillation plane. - A second conveying device (70), which is fluidly connected to the first mixing chamber (20) via the second inlet opening (202) and is configured to guide the second fluid (F2) into the mixing chamber (20) along the second fluid flow direction (R2), and - A third conveying device (80) is fluidly connected to the second mixing chamber (40) via the second inlet opening (402) and configured to guide the third fluid (F3) into the second mixing chamber (40) along the third fluid flow direction (R3), wherein the third conveying device (80) has a conveying channel (801) extending along the third fluid flow direction (R3) and opening into the second inlet opening (402) of the second mixing chamber (40), wherein the conveying channel (801) extends in a plane parallel to the oscillation plane. A first interactive channel (30) is provided between the first mixing chamber (20) and the second mixing chamber (40). The first interactive channel connects the outflow opening (203) of the first mixing chamber (20) and the first inflow opening (401) of the second mixing chamber (40) to each other, and the first interactive channel has a transverse direction to the flow direction of the fluid mixture (R). 12 The cross-section of the first mixing chamber (20) is constant at least in the section located directly downstream of the outflow opening (203) of the first mixing chamber (20).

2. The device (1) according to claim 1, characterized in that, The first interactive channel (30) has a section that is transverse to the flow direction of the fluid mixture (R) 12 The cross-section of the ) increases downstream.

3. The device (1) according to claim 1 or 2, characterized in that, The third conveying device (80) is configured to guide the third fluid (F3) as a (quasi) static flow into the second mixing chamber (40).

4. The device (1) according to any one of the preceding claims, characterized in that, The conveying channel (801) is straight.

5. The device (1) according to any one of the preceding claims, characterized in that, The first conveying device (60) is configured to cause a targeted change in direction of the first fluid (F1), such that the first fluid (F1) moves in a time-varying manner within the first mixing chamber (20), wherein the first fluid (F1) has a motion component along the first fluid flow direction (R1) and a motion component transverse to the first fluid flow direction (R1), wherein the first fluid (F1) moves in a time-varying manner particularly periodically within the first mixing chamber (20).

6. The device (1) according to any one of the preceding claims, characterized in that, The fluid component (10) includes a flow chamber (100) through which the first fluid (F1) flows, and the flow chamber has a main channel (103) that connects the inflow opening (101) of the fluid component (10) and the outflow opening (102) of the fluid component to each other. And at least one secondary flow channel (104a, 104b) as a mechanism for targeted directional change of the first fluid (F1).

7. The device (1) according to any one of the preceding claims. Its features are, The first mixing chamber (20) has a longitudinal axis (L) extending along the first fluid flow direction (R1), and The cross section of the mixing chamber (20) defined transversely to the longitudinal axis (L) begins at the first inflow opening (201) of the first mixing chamber (20) and increases in size at the upstream end section of the first mixing chamber (20) forming the inflow channel (206) as the distance from the first inflow opening (201) increases.

8. The device (1) according to any one of the preceding claims, characterized in that, The outflow opening (403) of the second mixing chamber (40) is connected to a second interactive channel (50).

9. An apparatus (1) for generating a fluid mixture, the apparatus comprising: - A first mixing chamber (20), the first mixing chamber having: a first inflow opening (201), a first fluid (F1) being able to be introduced into the first mixing chamber (20) via the first inflow opening along a first fluid flow direction (R1); The second inlet opening (202) allows the second fluid (F2) to be introduced into the first mixing chamber (20) along the second fluid flow direction (R2), and the outlet opening (203) contains an intermediate fluid mixture (F1) comprising the first fluid (F1) and the second fluid (F2). 12 ) can flow through the outflow opening along the direction of the fluid mixture flow (R) 12 Export, - A second mixing chamber (40), the second mixing chamber having: a first inflow opening (401), the intermediate fluid mixture (F 12 ) can flow along the direction of the fluid mixture flow (R) through the first inflow opening. 12 ) is introduced into the second mixing chamber (40); The third fluid (F3) can be introduced into the second mixing chamber (40) through the second inlet opening (402) along the third fluid flow direction (R3); and the outflow opening (403), comprising the fluid mixture (F1), the second fluid (F2), and the third fluid (F3). 123 It can be discharged through the outflow opening. - A first conveying device (60), which is fluidly connected to the first mixing chamber (20) via the first inflow opening (201) and configured to guide the first fluid (F1) into the first mixing chamber (20) along the first fluid flow direction (R1), wherein the first conveying device (60) includes a fluid member (10) having: • An outflow opening (102), which is fluidly connected to a first inflow opening (201) of the first mixing chamber (20), and • At least one mechanism (104a, 104b) for targeted direction change of the first fluid (F1), the first fluid flowing through the fluid member (10), the mechanism for targeted direction change of the first fluid (F1) being particularly used to create spatial oscillation of the first fluid (F1) at the outflow opening (102), The first inflow opening (401) of the second mixing chamber (40) has a transverse direction to the flow direction of the fluid mixture (R). 12 The cross-section of the second inflow opening (402) of the second mixing chamber (40) is smaller than the cross-section of the second inflow opening (402) of the second mixing chamber (40), wherein the cross-section of the second inflow opening (402) of the second mixing chamber (40) is defined transversely to the third fluid flow direction (R3), and / or The sum of the cross-sections of the first inflow opening (401) and the second inflow opening (402) of the second mixing chamber (40) is similar to or larger than the cross-section of the outflow opening (403) of the second mixing chamber (40).

10. The device (1) according to claim 9, characterized in that, The mechanisms (104a, 104b) for targeted directional changes of the first fluid (F1) are configured to cause the first fluid (F1) to oscillate in an oscillating plane.

11. The device (1) according to claim 10, characterized in that, The second mixing chamber (40) has a shape parallel to the oscillation plane and transverse to the flow direction of the fluid mixture (R). 12 The extension of ), wherein the extension is constant.

12. The device (1) according to claim 10 or 11, characterized in that, The second mixing chamber (40) has a shape parallel to the oscillation plane and transverse to the flow direction of the fluid mixture (R). 12 The extension of the first mixing chamber (20) outflow opening (203) and / or the second mixing chamber (40) in the second mixing chamber (40) is parallel to the oscillation plane and transverse to the flow direction of the fluid mixture (R). 12 The expansion is as large as that of ).

13. The device (1) according to any one of claims 10 to 12, characterized in that, The second mixing chamber (40) has an extension transverse to the oscillation plane, which is greater than the transverse extension of the first inflow opening (401) of the second mixing chamber (40) to the oscillation plane.

14. The device (1) according to any one of the preceding claims, characterized in that, The device (1) further includes: - A second conveying device (70), which is fluidly connected to the first mixing chamber (20) via the second inlet opening (202) and is configured to guide the second fluid (F2) into the mixing chamber (20) along the second fluid flow direction (R2), and - A third conveying device (80) is fluidly connected to the second mixing chamber (40) via the second inlet opening (402) and is configured to guide the third fluid (F3) into the second mixing chamber (40) along the third fluid flow direction (R3).

15. The device (1) according to any one of claims 9 to 14, characterized in that, The first conveying device (60) is configured to cause a targeted change in direction of the first fluid (F1), such that the first fluid (F1) moves in a time-varying manner within the first mixing chamber (20), wherein the first fluid (F1) has a motion component along the first fluid flow direction (R1) and a motion component transverse to the first fluid flow direction (R1), wherein the first fluid (F1) moves in a time-varying manner particularly periodically within the first mixing chamber (20).

16. The device according to any one of claims 9 to 15, characterized in that, The fluid component (10) includes a flow chamber (100) through which the first fluid (F1) flows, and the flow chamber has a main channel (103) that connects the inflow opening (101) of the fluid component (10) and the outflow opening (102) of the fluid component to each other. And at least one secondary flow channel (104a, 104b) as a mechanism for targeted directional change of the first fluid (F1).

17. The device (1) according to any one of claims 9 to 16. Its features are, The first mixing chamber (20) has a longitudinal axis (L) extending along the first fluid flow direction (R1), and The cross-section of the first mixing chamber (20) defined transversely to the longitudinal axis (L) begins at the first inflow opening (201) of the first mixing chamber (20) and increases in size at the upstream end segment of the first mixing chamber (20) forming the inflow channel (206) with increasing distance from the first inflow opening (201), and / or The cross-section decreases in the downstream end section of the first mixing chamber (20) forming the outflow channel (207) as the distance from the first inflow opening (201) increases.

18. The device (1) according to claims 10 and 17. Its features are, The expansion of the first mixing chamber (20) in the oscillation plane and transverse to the longitudinal axis (L) begins from the first inflow opening (201) of the first mixing chamber (20), particularly downstream of the second inflow opening (202) of the first mixing chamber (20), and increases in the inflow channel (206) with increasing distance from the first inflow opening (201), or The extension of the first mixing chamber (20) in the oscillation plane and transverse to the longitudinal axis (L) in the outflow channel (207) decreases as the distance from the first inflow opening (201) increases.

19. The device (1) according to any one of claims 9 to 18, characterized in that, A first interactive channel (30) is provided between the first mixing chamber (20) and the second mixing chamber (40), the first interactive channel connecting the outflow opening (203) of the first mixing chamber (20) and the first inflow opening (401) of the second mixing chamber (40) to each other, and the first interactive channel has a transverse direction to the flow direction of the fluid mixture (R). 12 The cross-section of the cross-section is at least partially constant.

20. The device (1) according to claim 19, characterized in that, Compared to the second mixing chamber (40), the first interaction channel (30) has a transverse direction (R) to the flow direction of the fluid mixture. 12 (a smaller cross-section).

21. The device (1) according to claim 10 and any one of claims 19 and 20, characterized in that, The first interaction channel (30) has an extension transverse to the oscillation plane, which is smaller than the corresponding extension of the second mixing chamber (40), wherein, in particular, the first interaction channel (30) is parallel to the oscillation plane and transverse to the flow direction of the fluid mixture (R). 12 The expansion of the second mixing chamber (40) is the same as the corresponding expansion of the second mixing chamber (40).

22. The device (1) according to claim 10 and any one of claims 19 to 21, characterized in that, The first interactive channel (30) has an extension transverse to the oscillation plane, the extension being smaller than that parallel to the oscillation plane and transverse to the fluid mixture flow direction (R). 12 An extension of ).

23. A method for generating a fluid mixture, the method comprising the following steps: - Provides the device (1), first fluid (F1), second fluid (F2) and third fluid (F3) according to any one of claims 1 to 22. Simultaneously, the first fluid (F1) is introduced into the first mixing chamber (20) via the first conveying device (60) in a first volumetric flow, the second fluid (F2) is introduced into the first mixing chamber (20) via the second conveying device (70) in a second volumetric flow, and the third fluid (F3) is introduced into the second mixing chamber (40) via the third conveying device (80) in a third volumetric flow. - A fluid mixture (F1) comprising the first fluid (F1), the second fluid (F2), and the third fluid (F3) 123 It is discharged from the second mixing chamber (40) through the outflow opening (403) of the second mixing chamber (40).

24. The method according to claim 23, characterized in that, The first volume flow is greater than the second volume flow, or the first volume flow is the same as the second volume flow.

25. The method according to claim 23 or 24, characterized in that, The intermediate fluid mixture (F) 12 The volume flow enters the second mixing chamber (40) in a volume flow that is greater than or equal to the third volume flow.

26. The method according to any one of claims 23 to 25, characterized in that, The first fluid (F1) is continuously introduced into the first mixing chamber (20), the second fluid (F2) is introduced into the first mixing chamber (20), and the third fluid (F3) is introduced into the second mixing chamber (40).

27. The method according to any one of claims 23 to 26, characterized in that, The first fluid (F1) and the third fluid (F3) may be the same or different.

28. The method according to any one of claims 23 to 27, characterized in that, The third fluid (F3) is used to set the intermediate fluid mixture (F 12 pH value, particle density or solvent content, and / or include surfactants.

29. The method according to any one of claims 23 to 28, characterized in that, The first fluid (F1) and the second fluid (F2) differ in chemical composition and / or the concentration of their respective components.

30. The method according to any one of claims 23 to 29, Its features are, The first fluid (F1) comprises an aqueous buffer solution, particularly an aqueous buffer solution in combination with one or more nucleic acids, and The second fluid (F2) comprises a polymer, a pharmaceutical active ingredient, or a polymer-active ingredient-conjugate or lipid in a solvent.

Images