Fluid mixing device, fluid mixing method, and nanoparticle manufacturing method

Abstract

A fluid mixing device 1 comprises two fluid introduction flow paths 10a, 10b, and a mixing flow path 20 communicating with the downstream ends of the fluid introduction flow paths 10a, 10b. Respective communication ports 11a, 11b of the fluid introduction flow paths 10a, 10b with respect to the mixing flow path 20 are separated in a direction orthogonal to an extending direction of the mixing flow path 20. The fluid introduction flow path 10a extends toward the communication port 11a at an angle θ1 of 30° or less with respect to the extending direction of the mixing flow path 20.

Description

Fluid mixing device, fluid mixing method, and method for producing nanoparticles

[0001] The present invention relates to a fluid mixing device, a fluid mixing method, and a method for producing nanoparticles.

[0002] Devices for mixing fluids are used in a wide range of fields such as medicine, pharmacy, and materials science. For example, in Patent Document 1, a fluid mixing device is used to produce nanoparticles that can be used as carriers in drug delivery systems. In the fluid mixing device of Patent Document 1, the first fluid to be mixed is introduced into the mixing channel through the central fluid introduction channel, and the second fluid to be mixed is introduced into the mixing channel through the fluid introduction channels on both sides thereof.

[0003] Inside the mixing channel of the fluid mixing device of Patent Document 1, it is considered that the first fluid and the second fluid can be rapidly mixed by forming micro vortices (micro whirls) that are symmetric with respect to the central fluid introduction channel. Therefore, in such a fluid mixing device, three fluid introduction channels are required to mix the fluids.

[0004] Further, as a fluid mixing device having two fluid introduction channels, face-to-face collision type micro mixers such as a T-shaped micro mixer and a V-shaped micro mixer are known (Non-Patent Document 1).

[0005] U.S. Patent No. 10864162

[0006] Nagare, Japan Society of Fluid Mechanics, February 2015, Vol. 34, No. 1, P3 - P9

[0007] In a fluid mixing device such as that of Patent Document 1, three fluid introduction channels are required, so the structure inevitably becomes complicated. Further, in a fluid mixing device such as that of Non-Patent Document 1, since the fluids introduced from the two fluid introduction channels are collided at high speed to mix the fluids, it is necessary to arrange one fluid introduction channel and the other fluid introduction channel substantially opposite to each other. Therefore, it is difficult to mix fluids in a narrow space with limited width, and it is difficult to miniaturize the device.

[0008] One of the objectives of the present invention is to provide a fluid mixing device that has a simple structure, can mix fluids in a narrow space with a limited width, and can be miniaturized, as well as a method for mixing fluids and a method for producing nanoparticles.

[0009] To achieve the above objective, the fluid mixing device according to the present invention is a fluid mixing device having two fluid introduction channels and a mixing channel communicating with the downstream end of each of the fluid introduction channels, wherein the respective communication ports of the fluid introduction channels to the mixing channels are spaced apart in a direction perpendicular to the extending direction of the mixing channels, and at least one of the fluid introduction channels extends toward the communication port at an angle of 30 degrees or less with respect to the extending direction of the mixing channel.

[0010] Such fluid mixing devices can have a simple structure because they only require two fluid introduction channels to introduce fluid into the mixing channel. Furthermore, in such fluid mixing devices, the fluid introduction channel and the mixing channel can be housed in a narrow space with a limited width, enabling fluid mixing in a confined space.

[0011] Furthermore, in such a fluid mixing device, because the communication ports are spaced apart, when a first fluid is introduced into the mixing channel through one fluid introduction channel and a second fluid is introduced into the mixing channel through the other fluid introduction channel, the first fluid flowing near the side wall on the side of the mixing channel on the side of the one fluid introduction channel moves away from the side wall and approaches the side wall on the side of the mixing channel on the side of the other fluid introduction channel, thereby efficiently mixing the first fluid and the second fluid. Conventionally, it is thought that the first fluid and the second fluid form separate flows and mix at their boundary, and the fluid flowing near the side wall of the mixing channel is far from the boundary and therefore difficult to mix. However, in the present invention, the first fluid flowing near the side wall on the side of the mixing channel on the side of the one fluid introduction channel moves away from the side wall and approaches the side wall on the side of the mixing channel on the side of the other fluid introduction channel, thereby making it easier for the first fluid and the second fluid to mix.

[0012] Furthermore, such fluid mixing devices can rapidly and uniformly mix the fluids introduced from each fluid introduction channel into the mixing channel within the mixing channel. Therefore, such fluid mixing devices are suitably used as a method for mixing fluids.

[0013] Furthermore, such a fluid mixing device can rapidly and uniformly mix the fluids introduced from each fluid introduction channel into the mixing channel, allowing for the simple production of desired nanoparticles based on the materials contained in each fluid. Therefore, such a fluid mixing device is suitably used as a method for producing nanoparticles.

[0014] Each of the fluid introduction channels may extend toward the communication port such that the angle between the central axis of one fluid introduction channel and the central axis of the other fluid introduction channel is 60 degrees or less. This configuration allows the fluid introduction channels and mixing channels to be housed in a narrower space with a limited width. In particular, by making the angle between the central axis of one fluid introduction channel and the central axis of the other fluid introduction channel substantially 0 degrees (each fluid introduction channel being approximately parallel), the fluids can be mixed substantially in a space as narrow as the width of the mixing channel.

[0015] An expanded channel with a larger cross-sectional area than the fluid introduction channel may be connected to the upstream side of the fluid introduction channel. This configuration prevents clogging of the fluid flowing through the fluid introduction channel and allows the fluid to be introduced into the mixing channel at a desired flow velocity through the fluid introduction channel.

[0016] Preferably, the distance between each of the aforementioned communication ports is 0.5 times or more the width of the mixing channel. In this way, the communication ports are spaced apart, so that when the first fluid is introduced into the mixing channel through one fluid introduction channel and the second fluid is introduced into the mixing channel through the other fluid introduction channel, the first fluid flowing near the side wall on the side of the mixing channel on the side of the one fluid introduction channel moves away from the side wall and approaches the side wall on the side of the mixing channel on the other fluid introduction channel, thereby making it easier for the first fluid and the second fluid to mix.

[0017] Furthermore, the fluid mixing method according to the present invention comprises the steps of introducing a first fluid into a mixing channel through one of two fluid introduction channels, and introducing a second fluid into the mixing channel through the other fluid introduction channel, wherein the first fluid flowing near the side wall of the mixing channel on the side of the one fluid introduction channel moves away from the side wall and approaches the side wall of the mixing channel on the side of the other fluid introduction channel, thereby mixing the first fluid and the second fluid.

[0018] In the fluid mixing method according to the present invention, the first fluid, which flows near the side wall on the side of the mixing channel on one side of the fluid introduction channel, moves away from the side wall and approaches the side wall on the side of the mixing channel on the other side of the mixing channel, thereby efficiently mixing the first fluid and the second fluid. Conventionally, it is thought that the first fluid and the second fluid form separate flows and mix at their boundary, and the fluid flowing near the side wall of the mixing channel is far from the boundary and therefore difficult to mix. However, in the present invention, the first fluid, which flows near the side wall on the side of the mixing channel on one side of the fluid introduction channel, moves away from the side wall and approaches the side wall on the side of the mixing channel on the other side of the mixing channel, thereby promoting rapid and uniform mixing of the first fluid and the second fluid.

[0019] The first fluid and the second fluid may be introduced into the mixing channel such that the Reynolds number in the mixing channel is equal to or greater than a predetermined value. In the fluid mixing method according to the present invention, when the Reynolds number in the mixing channel is equal to or greater than a predetermined value, the first fluid flowing near the side wall on the side of the mixing channel on one side of the fluid introduction channel moves away from the side wall and approaches the side wall on the other side of the mixing channel on the fluid introduction channel side, thereby making it easier for the first fluid and the second fluid to mix.

[0020] The first fluid may be passed through one fluid introduction channel and the second fluid through the other fluid introduction channel such that the flow rate of the second fluid in the other fluid introduction channel is greater than the flow rate of the first fluid in the one fluid introduction channel. By passing the first and second fluids through their respective fluid introduction channels in this way, the first fluid flowing near the side wall on the side of the mixing channel on the one fluid introduction channel side moves away from the side wall and approaches the side wall on the other fluid introduction channel side of the mixing channel, making it easier for the first and second fluids to mix.

[0021] Furthermore, the method for producing nanoparticles according to the present invention comprises the steps of introducing a first fluid containing at least one material into a mixing channel through one of two fluid introduction channels, and introducing a second fluid into the mixing channel through the other fluid introduction channel, wherein the first fluid flowing near the side wall on the side of the mixing channel on the one fluid introduction channel side moves away from the side wall and approaches the side wall on the other fluid introduction channel side of the mixing channel.

[0022] In the nanoparticle manufacturing method according to the present invention, the first fluid flowing near the side wall on the side of the mixing channel on one side of the fluid introduction channel moves away from the side wall and approaches the side wall on the side of the mixing channel on the other side of the fluid introduction channel, thereby efficiently mixing the first fluid and the second fluid. Conventionally, it is thought that the first fluid and the second fluid form separate flows and mix at their boundary, and the fluid flowing near the side wall of the mixing channel is far from the boundary and therefore difficult to mix. However, in the present invention, the first fluid flowing near the side wall on the side of the mixing channel on one side of the fluid introduction channel moves away from the side wall and approaches the side wall on the side of the mixing channel on the other side of the fluid introduction channel, thereby promoting rapid and uniform mixing of the first fluid and the second fluid. As a result, desired nanoparticles can be easily manufactured.

[0023] The first fluid and the second fluid may be introduced into the mixing channel such that the Reynolds number in the mixing channel is equal to or greater than a predetermined value. In the nanoparticle manufacturing method according to the present invention, when the Reynolds number in the mixing channel is equal to or greater than a predetermined value, the first fluid flowing near the side wall on the side of the mixing channel on one side of the fluid introduction channel moves away from the side wall and approaches the side wall on the other side of the mixing channel on the fluid introduction channel side, thereby making it easier for the first fluid and the second fluid to mix. As a result, the mixing efficiency of the first fluid and the second fluid is improved, and nanoparticles can be manufactured more efficiently.

[0024] The first fluid may be passed through one fluid introduction channel and the second fluid through the other fluid introduction channel such that the flow rate of the second fluid in the other fluid introduction channel is greater than the flow rate of the first fluid in the one fluid introduction channel. By passing the first and second fluids through their respective fluid introduction channels in this way, the first fluid, which flows near the side wall on the side of the mixing channel on the side of the one fluid introduction channel, moves away from the side wall and approaches the side wall on the side of the mixing channel on the side of the other fluid introduction channel, making it easier for the first and second fluids to mix. As a result, the mixing efficiency of the first and second fluids is improved, and nanoparticles can be produced more efficiently.

[0025] The aforementioned material may contain lipids. In the nanoparticle production method according to the present invention, for example, phospholipids, cholesterol, etc., can be used as materials.

[0026] The second fluid may contain at least one water-soluble material. In the nanoparticle production method according to the present invention, the water-soluble material may contain at least one of a protein and a peptide. For example, by mixing a first fluid in which phospholipids are dissolved with a second fluid in which apolipoprotein AI (apoA-I) is dissolved, a reconstituted high-density lipoprotein (rHDL) having a fine particle size that can be used as a carrier in a drug delivery system or as a pharmaceutical product can be produced.

[0027] Figure 1 is an exploded perspective view of a fluid mixing device according to one embodiment of the present invention. Figure 2 is a plan view of the fluid mixing device shown in Figure 1. Figure 3A is a partially enlarged view of the fluid mixing device shown in Figure 2. Figure 3B is a partially enlarged view showing a modified example of the fluid mixing device shown in Figure 2. Figure 4 is a view of the fluid mixing device shown in Figure 1 immersed in a constant temperature water bath. Figure 5A is a conceptual diagram showing an example of the flow state of the first and second fluids flowing through the mixing channel under predetermined conditions in the fluid mixing device shown in Figure 2. Figure 5B is a conceptual diagram showing an example of the flow state of the first and second fluids flowing through the mixing channel under other conditions in the fluid mixing device shown in Figure 2. Figure 5C is a conceptual diagram showing an example of the flow state of the first and second fluids flowing through the mixing channel under yet another condition in the fluid mixing device shown in Figure 2. Figure 6A is a photograph showing the flow state of the first and second fluids flowing through the mixing channel under predetermined conditions in the fluid mixing device shown in Figure 2. Figure 6B is a photograph showing the flow state of the first and second fluids flowing through the mixing channel under other conditions in the fluid mixing device shown in Figure 2. Figure 6C is a photograph showing the flow state of the first and second fluids flowing through the mixing channel under other conditions in the fluid mixing device shown in Figure 2. Figure 7A is a photograph showing the flow state of the first and second fluids flowing through the mixing channel under other conditions in the fluid mixing device shown in Figure 2. Figure 7B is a photograph showing the flow state of the first and second fluids flowing through the mixing channel under other conditions in the fluid mixing device shown in Figure 2. Figure 8 is a plan view of a fluid mixing device according to another embodiment. Figure 9 is a partially enlarged view of the fluid mixing device shown in Figure 8. Figure 10 is a photograph showing the flow state of the first and second fluids flowing through the mixing channel under predetermined conditions in the fluid mixing device shown in Figure 8. Figure 11 is a plan view of a fluid mixing device according to Comparative Example 3. Figure 12 is a partially enlarged view of the fluid mixing device shown in Figure 11. Figure 13 is a photograph showing the flow state of the first and second fluids flowing through the mixing channel under predetermined conditions in the fluid mixing device shown in Figure 11. Figure 14 is a particle size distribution graph showing the volume distribution of the particle size of the product.

[0028] Embodiments of the present invention will be described below with reference to the drawings. Note that the illustrations are for illustrative purposes only to aid in understanding the present invention, and the appearance, dimensions, etc., may differ from those of the actual product. Furthermore, the present invention is not limited to the following embodiments.

[0029] First Embodiment (Fluid Mixing Device) First, a fluid mixing device according to one embodiment of the present invention will be described. The fluid mixing device 1 according to this embodiment, shown in Figure 1, is a device for mixing fluids. As shown in Figure 1, the fluid mixing device 1 has a base tip 2a with a groove 9 formed therein and a cover tip 2b that covers the base tip 2a. Clamping plates 4a and 4b are fixed to the fluid mixing device 1 by a plurality of screws 8a and a plurality of nuts 8b. Tubes 7a to 7c are fixed to the clamping plate 4a via connectors 70a to 70c. Details of these components will be described below.

[0030] In Figures 1 and 2, the X-axis is parallel to the longitudinal direction of the base chip 2a, the Y-axis is parallel to the short-axis direction of the base chip 2a, and the Z-axis is perpendicular to the X and Y axes. The X, Y, and Z axes are orthogonal to each other. Hereafter, the positive direction of the Z-axis will be referred to as upward, and the negative direction of the Z-axis will be referred to as downward.

[0031] The base chip 2a is composed of a flattened plate and has a groove 9. The groove 9 is formed on one main surface (upper surface) of the base chip 2a. The base chip 2a is made of any material suitable for the fluid flow through the groove 9. The material that makes up the base chip 2a is not particularly limited, but may include plastics (cycloolefin polymer, polypropylene, polydimethylsiloxane, polycarbonate, polyethylene terephthalate, acrylic resin, etc.), glass, silicon, ceramics, metals, etc.

[0032] The cover chip 2b is made of a plate similar to the base chip 2a and is placed on top of the base chip 2a so as to cover the surface of the base chip 2a where the groove 9 is formed. By stacking the cover chip 2b on the base chip 2a, a flow path is formed between the base chip 2a and the cover chip 2b along the groove 9. As a result, the fluid can flow inside the groove 9 without leaking out of the groove 9.

[0033] The cover tip 2b is made of the same material as the base tip 2a, but it may be made of a different material. Through holes 3a and 3b are formed at regular intervals along the Y axis at one end of the cover tip 2b in the X-axis direction. A through hole 3c is formed at the other end of the cover tip 2b in the X-axis direction.

[0034] The clamping plates 4a and 4b are each composed of flattened plates and clamp the base tip 2a and cover tip 2b from above and below. As a result, the base tip 2a and cover tip 2b are fixed (pressed) from above and below by the clamping plates 4a and 4b. The materials that make up the clamping plates 4a and 4b are not particularly limited, but include plastics (cycloolefin polymer, polypropylene, polydimethylsiloxane, polycarbonate, polyethylene terephthalate, acrylic resin, etc.), glass, silicon, ceramics, metals, etc.

[0035] Through holes 5a and 5b are formed at regular intervals along the Y axis at one end of the clamping plate 4a in the X-axis direction. A through hole 5c is formed at the other end of the clamping plate 4a in the X-axis direction.

[0036] Connectors 70a and 70b, attached to one end of tubes 7a and 7b, are fitted into the through holes 5a and 5b of the clamping plate 4a. At least a portion of the connectors 70a and 70b passes through the through holes 5a and 5b and fits into the through holes 3a and 3b of the cover tip 2b. A connector 70c, attached to one end of tube 7c, is fitted into the through hole 5c of the clamping plate 4a. At least a portion of the connector 70c passes through the through hole 5c and fits into the through hole 3c of the cover tip 2b.

[0037] Tubes 7a to 7c are made of plastic such as polytetrafluoroethylene, although this is not particularly limited. Connectors 70a to 70c are made of plastic, although this is not particularly limited. The length of tubes 7a to 7c is not particularly limited, but is between 0.1 and 2.0 m. The inner diameter of tubes 7a to 7c is not particularly limited, but is between 0.1 and 1.5 mm. The length and inner diameter of each tube may be the same or different.

[0038] Furthermore, if the fluid can be directly introduced into the fluid mixing device 1 without using tubes 7a, 7b and connectors 70a, 70b, then tubes 7a, 7b and connectors 70a, 70b may be omitted. Also, if the fluid can be directly discharged from the fluid mixing device 1 without using tube 7c and connector 70c, then tubes 7c and connector 70c may be omitted. In addition, if the fluid can be introduced into the fluid mixing device 1 and discharged from the fluid mixing device 1, then clamping plates 4a and 4b may be omitted.

[0039] Three screw holes 6 are formed at regular intervals along the X-axis at one end of the clamping plate 4a in the Y-axis direction. Three screw holes 6 are formed at regular intervals along the X-axis at the other end of the clamping plate 4a in the Y-axis direction. Similarly, three screw holes 6 are formed at regular intervals along the X-axis at one end of the clamping plate 4b in the Y-axis direction. Three screw holes 6 are formed at regular intervals along the X-axis at the other end of the clamping plate 4b in the Y-axis direction.

[0040] With the clamping plates 4a and 4b sandwiching the base tip 2a and cover tip 2b from above and below, the clamping plates 4a and 4b are fixed by six screws 8a and six nuts 8b. The screws 8a pass through the screw holes 6 formed in the clamping plate 4a and also pass through the screw holes 6 formed in the clamping plate 4b. The nuts 8b are screwed onto the screws 8a on the lower surface of the clamping plate 4b. The means for fixing the clamping plates 4a and 4b are not limited to screws 8a and nuts 8b, and other fixing means such as hardening with synthetic resin may also be used.

[0041] As shown in FIG. 2, at least the groove portion 9 has two fluid introduction channels (the first fluid introduction channel 10a and the second fluid introduction channel 10b) and a mixing channel 20. The central axis C0 (see FIG. 3A) of the mixing channel 20 is formed along the X-axis. The depth of the groove portion 9 is not particularly limited, but is 0.05 to 0.5 mm, or 0.1 to 0.3 mm. In the present embodiment, the mixing channel 20 has a rectangular cross-sectional channel.

[0042] The end portions 40a and 40b are formed at regular intervals along the Y-axis at one end of the base chip 2a in the X-axis direction. The end portion 40c is formed at the other end of the base chip 2a in the X-axis direction.

[0043] As shown in FIG. 1, the end portions 40a to 40c are located directly below the through holes 3a to 3c. The through holes 5a to 5c formed in the clamping plate 4a, the through holes 3a to 3c formed in the cover chip 2b, and the end portions 40a to 40c formed in the base chip 2a communicate with each other. Therefore, the first fluid flowing through the tube 7a flows into the first fluid introduction channel 10a (FIG. 2) through the end portion 40a. The second fluid flowing through the tube 7b flows into the second fluid introduction channel 10b (FIG. 2) through the end portion 40b. Further, the fluid flowing through the fluid discharge channel 30 (FIG. 2) flows out into the tube 7c through the end portion 40c.

[0044] As shown in FIG. 2, in the groove portion 9 of the fluid mixing device 1, the first fluid introduction channel 10a and the second fluid introduction channel 10b communicate with the mixing channel 20 at their respective downstream ends. The groove portion 9 has, in addition to the first fluid introduction channel 10a, the second fluid introduction channel 10b, and the mixing channel 20, expansion channels 12a, 12b, a fluid discharge channel 30, and end portions 40a to 40c, but the configuration of the groove portion 9 is not limited thereto. The expansion channels 12a, 12b, the fluid discharge channel 30, and the end portions 40a to 40c can be appropriately modified or omitted as long as the fluid can be made to flow into the first fluid introduction channel 10a and the second fluid introduction channel 10b and flow out from the mixing channel 20.

[0045] FIG. 3A is an enlarged view of the periphery of the communication ports 11a and 11b with respect to the mixing channel 20 of the first fluid introduction channel 10a and the second fluid introduction channel 10b of FIG. 2. As shown in FIG. 3A, the first fluid introduction channel 10a and the second fluid introduction channel 10b each extend linearly along the X-axis. The central axis C1 of the first fluid introduction channel 10a and the central axis C2 of the second fluid introduction channel 10b are arranged substantially parallel to each other. Note that the angle of the central axis C1 of the first fluid introduction channel 10a with respect to the X-axis direction and the angle of the central axis C2 of the second fluid introduction channel 10b with respect to the X-axis direction are not limited to this.

[0046] For example, as shown in FIG. 3B, the first fluid introduction channel 10a may extend toward the communication port 11a at an angle θ1 of 30 degrees or less (including 0 degrees) with respect to the extending direction (X-axis direction) of the mixing channel 20. Further, the second fluid introduction channel 10b may extend toward the communication port 11b at an angle θ2 of 30 degrees or less (including 0 degrees) with respect to the extending direction (X-axis direction) of the mixing channel 20. Note that FIG. 3A can be said to be an example in the case where the angles θ1 and θ2 in FIG. 3B are 0 degrees. Thus, if the angles θ1 and θ2 are 30 degrees or less, they are included in the present embodiment and exhibit the same operational effects. Note that these angles θ1 and θ2 are absolute values, and the case where the first fluid introduction channel 10a and the second fluid introduction channel 10b are inclined 30 degrees or less in the direction opposite to that shown in FIG. 3B is also included in the present embodiment.

[0047] The length (channel length) of each of the first fluid introduction channel 10a and the second fluid introduction channel 10b is not particularly limited. The lengths of the first fluid introduction channel 10a and the second fluid introduction channel 10b may be, for example, 1.0 to 30.0 mm. The lengths of each of the first fluid introduction channel 10a and the second fluid introduction channel 10b may be equal or different.

[0048] As shown in Figure 3A, the width W1 of the first fluid introduction channel 10a and the width W2 of the second fluid introduction channel 10b are not particularly limited and may be equal in width or different in width. The width W1 of the first fluid introduction channel 10a is not particularly limited, but is 0.05 to 1 mm or 0.07 to 0.5 mm. The width W2 of the second fluid introduction channel 10b is not particularly limited, but is 0.07 to 2 mm or 0.1 to 1.0 mm. In this embodiment, the width W2 of the second fluid introduction channel 10b is designed to be larger than the width W1 of the first fluid introduction channel 10a, but is not limited to this.

[0049] As shown in Figure 3A, the width W0 of the mixing channel 20 is greater than the width W1 of the first fluid introduction channel 10a and the width W2 of the second fluid introduction channel 10b. The width W0 of the mixing channel 20 is not particularly limited, but is 0.2 to 3 mm or 0.5 to 1.5 mm. The length of the mixing channel 20 is not particularly limited, but is 2 to 100 mm or 5 to 20 mm. The depth of the mixing channel 20 is not particularly limited, but is 0.05 to 0.5 mm or 0.1 to 0.3 mm. The cross-sectional area of ​​the mixing channel 20 is, for example, 0.05 to 1 mm². 2 It can be done this way.

[0050] As shown in Figure 3A, the communication port 11a of the first fluid introduction channel 10a to the mixing channel 20 and the communication port 11b of the second fluid introduction channel 10b to the mixing channel 20 are separated in the Y-axis direction. In this embodiment, the distance between the communication ports 11a and 11b can be expressed by the center-to-center distance D1 between the communication ports 11a and 11b. The center-to-center distance D1 may be the distance between the central axis C1 of the first fluid introduction channel 10a at the communication port 11a and the central axis C2 of the second fluid introduction channel 10b at the communication port 11b. It is preferable that the center-to-center distance D1 is 0.5 times or more the width W0 of the mixing channel 20. Note that the communication ports 11a and 11b may be separated in the Z-axis direction.

[0051] Furthermore, the center-to-center distance D1 is greater than the larger of the two widths W1 and W2 of the first fluid introduction channel 10a and the second fluid introduction channel 10b (W2 in this embodiment). The ratio D1 / W2 of the center-to-center distance D1 to the width W2 is not particularly limited, but for example, 1 < D1 / W2 ≤ 7.

[0052] The ratio W0 / h of the width W0 of the mixing channel 20 to the depth h along the Z-axis of the mixing channel 20 is not particularly limited, but is preferably 1 or more, 2 or more, or 3 to 7. However, this numerical range applies when the first fluid introduction channel 10a and the second fluid introduction channel 10b are arranged along the Y-axis, and when the first fluid introduction channel 10a and the second fluid introduction channel 10b are arranged along the Z-axis upstream of the mixing channel 20, it is preferable that the ratio of h / W0 is within this range. In this embodiment, it is preferable that the Z-axis substantially coincides with the direction of gravity, but the X-axis, Y-axis, or other intermediate axes may substantially coincide with the direction of gravity.

[0053] The first fluid introduction channel 10a is connected to an expansion channel 12a on its upstream side. The upstream end of the expansion channel 12a is connected to the terminal portion 40a. The expansion channel 12a extends linearly along the Y-axis from the terminal portion 40a, and its downstream end is connected to the upstream end of the first fluid introduction channel 10a at approximately a right angle. The width of the expansion channel 12a is greater than the width of the first fluid introduction channel 10a. The cross-sectional area of ​​the expansion channel 12a is greater than the cross-sectional area of ​​the first fluid introduction channel 10a.

[0054] The second fluid introduction channel 10b is connected to an expansion channel 12b on its upstream side. The upstream end of the expansion channel 12b is connected to the terminal portion 40b. Most of the expansion channel 12b extends linearly along the X-axis from the terminal portion 40b and is connected to the upstream end of the second fluid introduction channel 10b at a predetermined inclination angle. This inclination angle is not particularly limited. The width of the expansion channel 12b is greater than the width of the second fluid introduction channel 10b. The cross-sectional area of ​​the expansion channel 12b is greater than the cross-sectional area of ​​the second fluid introduction channel 10b.

[0055] The mixing channel 20 is connected to a fluid outlet channel 30 on its downstream side. The fluid outlet channel 30 is smoothly connected to the downstream end of the mixing channel 20 and extends mostly along the Y-axis. The downstream end of the fluid outlet channel 30 is connected to the terminal portion 40c. The width of the fluid outlet channel 30 may be the same as or different from the width of the mixing channel 20. The cross-sectional area of ​​the fluid outlet channel 30 may be the same as or different from the cross-sectional area of ​​the mixing channel 20.

[0056] Note that the above dimensional relationships are for one embodiment, and may differ from the above numerical range when industrially produced. However, as described later, when the first fluid is introduced into the mixing channel 20 through the first fluid introduction channel 10a and the second fluid is introduced into the mixing channel 20 through the second fluid introduction channel 10b, it is important that the configuration is such that the first fluid flowing near the side wall 21a on the side of the mixing channel 20 on the first fluid introduction channel 10a side moves away from the side wall 21a and approaches the side wall 21b on the side of the mixing channel 20 on the side of the second fluid introduction channel 10b.

[0057] In the fluid mixing device 1 of this embodiment, the shape of the cross-sectional shape of the channel of the groove 9 (expansion channels 12a, 12b, first fluid introduction channel 10a, second fluid introduction channel 10b, mixing channel 20, and fluid outlet channel 30) is rectangular (partially square), but is not limited to this. For example, the cross-sectional shape of the channel of the groove 9 may be a quadrilateral other than a rectangle, a polygon with triangles or more sides, a circle, an ellipse, or any other shape.

[0058] The fluid mixing device 1 of this embodiment has two fluid introduction channels (a first fluid introduction channel 10a and a second fluid introduction channel 10b) and a mixing channel 20 that communicates with the downstream ends of each fluid introduction channel. Since such a fluid mixing device 1 only requires two fluid introduction channels for introducing fluid into the mixing channel 20, it can have a simple structure.

[0059] As described above, in the fluid mixing device 1 of this embodiment, as shown in Figures 3A and 3B, the first fluid introduction channel 10a extends toward the communication port 11a at an angle θ1 of 30 degrees or less with respect to the extending direction (X-axis direction) of the mixing channel 20. The second fluid introduction channel 10b extends toward the communication port 11b at an angle θ2 of 30 degrees or less with respect to the extending direction (X-axis direction) of the mixing channel 20. Therefore, the first fluid introduction channel 10a, the second fluid introduction channel 10b, and the mixing channel 20 can be housed in a narrow space with a limited width, enabling fluid mixing in a narrow space with a limited width. Furthermore, by appropriately modifying or omitting the expansion channels 12a, 12b, the fluid outlet channel 30, and the end portions 40a to 40c, it is possible to house part or all of the fluid mixing device 1 in a narrow space with a limited width.

[0060] Furthermore, the angle θ1 of the first fluid introduction channel 10a with respect to the mixing channel 20 and the angle θ2 of the second fluid introduction channel 10b with respect to the mixing channel 20, as shown in Figure 3B, are preferably 15 degrees or less, more preferably 10 degrees or less, even more preferably 5 degrees or less, and even more preferably substantially 0 degrees (including 3 degrees or less). This makes it possible to narrow the width of the fluid confluence section consisting of the first fluid introduction channel 10a, the second fluid introduction channel 10b, and the mixing channel 20, making it possible to mix fluids in spaces with limited width, such as catheters, capillaries, nozzles, injection needles, needles, tubes, pipes, hoses, etc. Moreover, such fluid mixing devices can be easily used in parallel in spaces with limited width.

[0061] From a similar viewpoint, as shown in Figure 3B, each fluid introduction channel may extend toward the communication ports 11a and 11b such that the angle θ3 between the central axis C1 of the first fluid introduction channel 10a and the central axis C2 of the second fluid introduction channel 10b is 60 degrees or less. With this configuration, the first fluid introduction channel 10a, the second fluid introduction channel 10b, and the mixing channel 20 can be housed in a narrow space with a limited width.

[0062] In particular, as shown in Figure 3A, by making the angle θ3 between the central axis C1 of the first fluid introduction channel 10a and the central axis C2 of the second fluid introduction channel 10b substantially 0 degrees (each fluid introduction channel is approximately parallel), the fluids can be mixed in a space that is substantially the same width as the mixing channel 20.

[0063] In conventional fluid mixing devices with two fluid introduction channels, such as T-shaped or V-shaped micromixers, it was common knowledge among those skilled in the art that the angle θ3 between the central axis C1 of the first fluid introduction channel 10a and the central axis C2 of the second fluid introduction channel 10b must be 180 degrees or more in order to cause the fluids to collide with each other, otherwise the fluids cannot be sufficiently mixed. In contrast, the fluid mixing device 1 of this embodiment overturns this conventional wisdom by enabling sufficient mixing even when the angle θ3 between the central axes C1 and C2 is 60 degrees or less (including cases where they are substantially parallel).

[0064] In this embodiment, an expanded flow channel 12a with a larger flow channel cross-sectional area than the first fluid introduction channel 10a may be connected to the upstream side of the first fluid introduction channel 10a. Similarly, an expanded flow channel 12b with a larger flow channel cross-sectional area than the second fluid introduction channel 10b may be connected to the upstream side of the second fluid introduction channel 10b. This configuration prevents clogging of the fluid flowing through the first fluid introduction channel 10a and the second fluid introduction channel 10b, and allows the fluid to be introduced into the mixing channel at a desired flow velocity through the fluid introduction channels.

[0065] As described above, the communication ports 11a and 11b shown in Figure 3A are separated in the Y-axis direction, and it is preferable that the distance between the communication ports 11a and 11b (center-to-center distance D1) is 0.5 times or more the width W0 of the mixing channel 20. With the communication ports separated in this way, when the first fluid is introduced into the mixing channel 20 through the first fluid introduction channel 10a and the second fluid is introduced into the mixing channel 20 through the second fluid introduction channel 10b, the first fluid flowing near the side wall 21a on the side of the mixing channel 20 on the first fluid introduction channel 10a side moves away from the side wall 21a and approaches the side wall 21b on the side of the mixing channel 20 on the side of the second fluid introduction channel 10b, thereby efficiently mixing the first fluid and the second fluid. Conventionally, it is thought that the first fluid and the second fluid form separate flows and mix at their boundary. The fluid flowing near the side walls 21a and 21b of the mixing channel 20 is far from the boundary and therefore unlikely to mix. However, in the present invention, the first fluid flowing near the side wall 21a on the side of the first fluid introduction channel 10a of the mixing channel 20 moves away from the side wall 21a and approaches the side wall 21b on the side of the second fluid introduction channel 10b of the mixing channel 20, making it easier for the first fluid and the second fluid to mix.

[0066] The fluid mixing device 1 of this embodiment can rapidly and uniformly mix a first fluid introduced into the mixing channel 20 from a first fluid introduction channel 10a and a second fluid introduced into the mixing channel 20 from a second fluid introduction channel 10b within the mixing channel 20. Therefore, as described later, such a fluid mixing device 1 is suitably used as a fluid mixing method according to the present invention. Furthermore, as described later, the fluid mixing device 1 of this embodiment can easily produce desired nanoparticles based on the material contained in the first or second fluid. Therefore, such a fluid mixing device 1 is suitably used as a method for producing nanoparticles.

[0067] Furthermore, the fluid mixing device 1 according to this embodiment can be used in fields such as chemical synthesis to rapidly mix materials and reaction initiators to produce a uniform reaction in reactors, etc. The fluid mixing device 1 according to this embodiment can also be used in devices that mix two fluids inside a nozzle, such as a spray, injector, or dispenser. Moreover, the fluid mixing device 1 according to this embodiment can also be used in devices that rapidly and uniformly mix fuel and an oxidizer (for example, gasoline and air, hydrogen and oxygen, etc.) and send it to a combustion chamber.

[0068] (Method for mixing fluids) Next, a method for mixing fluids according to one embodiment of the present invention will be described. The method for mixing fluids according to this embodiment can be carried out using a fluid mixing device 1, but is not limited thereto. The first fluid and the second fluid to be mixed may be liquids such as organic solvents or aqueous solvents, but the fluids may also be gases.

[0069] The fluid mixing method according to this embodiment includes, as shown in Figures 1 and 2, a step of introducing a first fluid into a mixing channel 20 through a first fluid introduction channel 10a, and a step of introducing a second fluid into the mixing channel 20 through a second fluid introduction channel 10b. In the fluid mixing method of this embodiment, these steps are for mixing the flow of the first fluid and the flow of the second fluid inside the mixing channel 20, and the order of these steps is not particularly limited. For example, the first fluid may be introduced into the mixing channel 20 through the first fluid introduction channel 10a, and the second fluid may be introduced into the mixing channel 20 through the second fluid introduction channel 10b.

[0070] First, as shown in Figures 1 and 2, the first fluid is introduced into the fluid mixing device 1 through tube 7a, for example, by a syringe pump. The second fluid is also introduced into the fluid mixing device 1 through tube 7b, for example, by a syringe pump. The first fluid flows into the expansion channel 12a through end 40a, and then into the first fluid introduction channel 10a. The second fluid flows into the expansion channel 12b through end 40b, and then into the second fluid introduction channel 10b.

[0071] Furthermore, the first fluid is introduced into the mixing channel 20 through the first fluid introduction channel 10a. The second fluid is also introduced into the mixing channel 20 through the second fluid introduction channel 10b. By introducing the first and second fluids into the mixing channel 20 in this manner, the Reynolds number in the mixing channel 20 is made to be above a predetermined value.

[0072] The first fluid and the second fluid are mixed in the mixing channel 20. The mixed fluid, which is the mixture of the first and second fluids in the mixing channel 20, flows from the mixing channel 20 into the fluid discharge channel 30 and is discharged into the tube 7c through the end portion 40c. The mixed fluid is discharged from the tube 7c. As shown in Figure 4, the mixed fluid discharged from the tube 7c may be stored in a container such as a test tube.

[0073] In the fluid mixing method of this embodiment, it is believed that the first fluid and the second fluid are mixed inside the mixing channel 20 by the fluid flow described below. As shown in Figure 5A, the first fluid flowing near the side wall 21a on the first fluid introduction channel 10a side of the mixing channel 20 moves away from the side wall 21a and approaches the side wall 21b on the second fluid introduction channel 10b side of the mixing channel 20. As a result, a first boundary 60 is generated as the boundary between the flow containing a large amount of the first fluid and the flow containing a small amount of the first fluid. In addition, a second boundary 70 is formed between the second fluid introduced into the mixing channel 20 through the second fluid introduction channel 10b and the flow containing a large amount of the first fluid.

[0074] Conventionally, it is thought that the first fluid and the second fluid form separate flows and mix at their boundary. The fluid flowing near the side wall 21a of the mixing channel 20 is far from the boundary and therefore unlikely to mix. However, in the present invention, the first fluid flowing near the side wall 21a on the first fluid introduction channel 10a side of the mixing channel 20 moves away from the side wall 21a and approaches the side wall 21b on the second fluid introduction channel 10b side of the mixing channel 20, making it easier for the first fluid and the second fluid to mix.

[0075] In addition, the second boundary 70 disappears (becomes unclear or disturbed) midway through the mixing channel 20. This indicates that uniform mixing was promoted both inside and outside the second boundary 70, and that the mixing efficiency of the first and second fluids was high. The direction in which the disappearance of the second boundary 70 progresses (the direction of extension of the second boundary 70) is nearly parallel to the direction of extension of the mixing channel 20.

[0076] When both the first and second fluids are liquids, air bubbles may be introduced into the mixing channel 20. Even if air bubbles are introduced into the mixing channel 20, if the first fluid flowing near the side wall 21a on the first fluid introduction channel 10a side of the mixing channel 20 moves away from the side wall 21a and approaches the side wall 21b on the second fluid introduction channel 10b side of the mixing channel 20, the same effect as when no air bubbles are present in the mixing channel 20 (making it easier for the first and second fluids to mix) can be obtained.

[0077] Furthermore, if the first fluid flowing near the side wall 21a on the first fluid introduction channel 10a side of the mixing channel 20 moves away from the vicinity of the side wall 21a and approaches the side wall 21b on the second fluid introduction channel 10b side of the mixing channel 20, the fluid conditions inside the mixing channel 20 may be set as appropriate. For example, by appropriately setting the ratio of the flow rate of the first fluid introduced from the first fluid introduction channel 10a to the flow rate of the second fluid introduced from the second fluid introduction channel 10b, the flow rate of the fluid flowing inside the mixing channel 20, the Reynolds number inside the mixing channel 20, etc., it is possible to make the first fluid flowing near the side wall 21a on the first fluid introduction channel 10a side of the mixing channel 20 move away from the vicinity of the side wall 21a and approach the side wall 21b on the second fluid introduction channel 10b side of the mixing channel 20.

[0078] The Reynolds number Re in the mixing channel 20 is calculated based on the following formula (1) for a rectangular cross-section channel, where ρ is the fluid density, U is the average fluid velocity, μ is the fluid viscosity, w is the channel width of the mixing channel 20, h is the channel depth of the mixing channel 20, and Q is the flow rate.

[0079]

[0080] In Figure 5A, the predetermined Reynolds number is 500 as an example, but it is not particularly limited as long as it is possible to cause the flow of the first fluid in the mixing channel 20 to move away from the vicinity of the side wall 21a and approach the side wall 21b on the second fluid introduction channel 10b side of the mixing channel 20, in the manner shown in Figure 5A. Depending on the fluid conditions inside the mixing channel 20, the flow state of the first and second fluids inside the mixing channel 20 may differ.

[0081] Figure 5B is a conceptual diagram showing an example of the flow state of the first and second fluids flowing through the mixing channel 20 in the fluid mixing device shown in Figure 2, at the same temperature as in Figure 5A, but with a larger total flow rate of fluid flowing inside the mixing channel 20 and a higher Reynolds number in the mixing channel 20. In Figure 5B, the predetermined value of the Reynolds number is 650 as an example, but it is not particularly limited as long as it is possible to cause the flow of the first fluid in the mixing channel 20 to move away from the vicinity of the side wall 21a and approach the side wall 21b on the second fluid introduction channel 10b side of the mixing channel 20, as shown in Figure 5B.

[0082] As shown in Figure 5B, the first fluid flowing near the side wall 21a on the first fluid introduction channel 10a side of the mixing channel 20 moves away from the side wall 21a and approaches the side wall 21b on the second fluid introduction channel 10b side of the mixing channel 20. As a result, a first boundary 60 is created as the boundary between the flow containing a large amount of the first fluid and the flow containing a small amount of the first fluid. In addition, a second boundary 70 is formed between the second fluid introduced into the mixing channel 20 through the second fluid introduction channel 10b and the flow containing a large amount of the first fluid.

[0083] Conventionally, it is thought that the first fluid and the second fluid form separate flows and mix at their boundary. The fluid flowing near the side wall 21a of the mixing channel 20 is far from the boundary and therefore unlikely to mix. However, in the present invention, the first fluid flowing near the side wall 21a on the first fluid introduction channel 10a side of the mixing channel 20 moves away from the side wall 21a and approaches the side wall 21b on the second fluid introduction channel 10b side of the mixing channel 20, making it easier for the first fluid and the second fluid to mix.

[0084] Furthermore, in Figure 5B, the second boundary 70 disappears midway through the mixing channel 20. In Figure 5B, the second boundary 70 disappears further upstream than in Figure 5A. This indicates that more uniform mixing is promoted both inside and outside the second boundary 70 than in the case of Figure 5A, and that the mixing efficiency of the first and second fluids is further improved.

[0085] Figure 5C is a conceptual diagram showing an example of the flow state of the first and second fluids flowing through the mixing channel 20 in the fluid mixing device shown in Figure 2, when the total flow rate of the fluid flowing inside the mixing channel 20 is greater than in Figure 5B, at the same temperature as in Figures 5A and 5B, and the Reynolds number in the mixing channel 20 is set higher. In Figure 5C, the predetermined value of the Reynolds number is 1700 as an example, but it is not particularly limited as long as it is possible to cause the flow of the first fluid in the mixing channel 20 to move away from the vicinity of the side wall 21a and approach the side wall 21b on the second fluid introduction channel 10b side of the mixing channel 20, as shown in the manner of Figure 5C.

[0086] As shown in Figure 5C, the first fluid flowing near the side wall 21a on the first fluid introduction channel 10a side of the mixing channel 20 moves away from the side wall 21a and approaches the side wall 21b on the second fluid introduction channel 10b side of the mixing channel 20. As a result, a first boundary 60 is created as the boundary between the flow containing a large amount of the first fluid and the flow containing a small amount of the first fluid. In addition, a second boundary 70 is formed between the second fluid introduced into the mixing channel 20 through the second fluid introduction channel 10b and the flow containing a large amount of the first fluid.

[0087] Conventionally, it is thought that the first fluid and the second fluid form separate flows and mix at their boundary. The fluid flowing near the side wall 21a of the mixing channel 20 is far from the boundary and therefore unlikely to mix. However, in the present invention, the first fluid flowing near the side wall 21a on the first fluid introduction channel 10a side of the mixing channel 20 moves away from the side wall 21a and approaches the side wall 21b on the second fluid introduction channel 10b side of the mixing channel 20, making it easier for the first fluid and the second fluid to mix.

[0088] Furthermore, in Figure 5C, the second boundary 70 disappears midway through the mixing channel 20. In Figure 5C, the second boundary 70 disappears further upstream than in Figures 5A and 5B. This indicates that more uniform mixing is promoted both inside and outside the second boundary 70 than in Figures 5A and 5B, and that the mixing efficiency of the first and second fluids is further improved.

[0089] In addition, even in the cases of Figures 5B and 5C, if both the first and second fluids are liquids, air bubbles may be introduced into the mixing channel 20. Even if air bubbles are introduced into the mixing channel 20, if the first fluid flowing near the side wall 21a on the first fluid introduction channel 10a side of the mixing channel 20 moves away from the side wall 21a and approaches the side wall 21b on the second fluid introduction channel 10b side of the mixing channel 20, the same effect as when no air bubbles are present in the mixing channel 20 (making it easier for the first and second fluids to mix) can be obtained.

[0090] Thus, in the fluid mixing method according to this embodiment, the first fluid flowing near the side wall 21a on the first fluid introduction channel 10a side of the mixing channel 20 moves away from the side wall 21a and approaches the side wall 21b on the second fluid introduction channel 10b side of the mixing channel 20, thereby rapidly and uniformly mixing the first fluid and the second fluid.

[0091] Figures 5A to 5C show examples of the flow states of the first and second fluids flowing through the mixing channel 20. However, if the first fluid flowing near the side wall 21a on the first fluid introduction channel 10a side of the mixing channel 20 moves away from the side wall 21a and approaches the side wall 21b on the second fluid introduction channel 10b side of the mixing channel 20, then the flow state may differ from that shown in Figures 5A to 5C.

[0092] Furthermore, by introducing the first and second fluids into the mixing channel 20 such that the Reynolds number in the mixing channel 20 is equal to or greater than a predetermined value, the second boundary 70 disappears at an earlier stage (closer to the communication ports 11a and 11b), thereby improving the mixing efficiency of the first and second fluids.

[0093] In the fluid mixing method of this embodiment, the flow rates of the first fluid and the second fluid introduced into the mixing channel 20 are not particularly limited. It is preferable to pass the first fluid and the second fluid through each fluid introduction channel such that the flow rate of the second fluid in the second fluid introduction channel 10b is greater than the flow rate of the first fluid in the first fluid introduction channel 10a.

[0094] Preferably, the flow rate of the second fluid introduced into the mixing channel 20 is, for example, 2 times or more, 3 times or more, 5 times or more, 8 times or more, or 10 times or more. By passing the first fluid and the second fluid through their respective fluid introduction channels in this way, the first fluid flowing near the side wall 21a on the first fluid introduction channel 10a side of the mixing channel 20 can be moved away from the side wall 21a and closer to the side wall 21b on the second fluid introduction channel 10b side of the mixing channel 20.

[0095] The fluid mixing method according to this embodiment can be applied when mixing fluids in a space with a limited width, such as a catheter, capillary, nozzle, injection needle, needle, tube, pipe, or hose.

[0096] (Method for Manufacturing Nanoparticles) Next, a method for manufacturing nanoparticles according to one embodiment of the present invention will be described. The method for manufacturing nanoparticles according to this embodiment is a method for manufacturing nanoparticles such as lipid nanoparticles, polymer nanoparticles, inorganic nanoparticles, and metal nanoparticles. The method for manufacturing nanoparticles according to this embodiment can be carried out using a fluid mixing device 1, but is not limited thereto.

[0097] The nanoparticle manufacturing method according to this embodiment involves mixing a first fluid and a second fluid inside a flow channel to produce nanoparticles. In addition to the fluid mixing method described above, this method can be carried out by mixing the first fluid and the second fluid under specific conditions. The following description of the nanoparticle manufacturing method according to this embodiment will mainly focus on the differences from the fluid mixing method described above, with common details with the fluid mixing method described above omitted as appropriate.

[0098] In the nanoparticle manufacturing method according to this embodiment, as shown in Figure 4, the fluid mixing device 1 may be immersed in a constant temperature water bath with the tubes 7a to 7c attached. This allows the temperature of the fluid mixing device 1, the tubes 7a to 7c, and the fluid flowing inside them to be adjusted to below room temperature, above room temperature (for example, 10°C or higher, 15°C or higher, 20°C or higher), 45°C or higher, or 55°C or higher. The means for adjusting the temperature of the fluid mixing device 1, the tubes 7a to 7c, and the fluid flowing inside them are not limited to a constant temperature water bath, but may be other means.

[0099] As shown in Figures 1 and 2, the method for producing nanoparticles in this embodiment includes the steps of introducing a first fluid into a mixing channel 20 through a first fluid introduction channel 10a and introducing a second fluid into the mixing channel 20 through a second fluid introduction channel 10b.

[0100] The first fluid contains at least one material. This material may be dissolved in the first fluid. For example, nanoparticles can be generated by rapidly mixing a material dissolved in the first fluid with a second fluid, which is a poor solvent for that material. Examples of materials included in the first fluid include lipids, lipids modified with polyethylene glycol, biodegradable synthetic polymers, polymers, inorganic substances, and metals. Examples of lipids include phospholipids, cholesterol, fatty acids, glycerolipids, sphingolipids, sterol lipids, prenolic lipids, and saccharolipids, as well as functional lipids such as cationic lipids and pH-responsive lipids.

[0101] Examples of phospholipids include phosphatidylglycerol, phosphatidylserine, phosphatidylcholine, and phosphatidylethanolamine, with phosphatidylcholine being preferred. Examples of phosphatidylcholine include dimyristoylphosphatidylcholine (DMPC), dipalmitoylphosphatidylcholine (DPPC), distearoylphosphatidylcholine (DSPC), diarachidoylphosphatidylcholine (DAPC), hydrogenated soybean phosphatidylcholine (HSPC), egg phosphatidylcholine (EPC), 1-palmitoyl-2-oleoylphosphatidylcholine (POPC), and dioleoylphosphatidylcholine (DOPC). These lipids are soluble in suitable solvents such as methanol, ethanol, and chloroform. Examples of biodegradable synthetic polymers include glycolic acid lactate copolymer (PLGA), polylactic acid, polyglycolic acid, and polydioxanone.

[0102] The second fluid is an aqueous solvent. The second fluid may contain at least one water-soluble material. Examples of water-soluble materials include proteins, peptides, and lipids modified with polyethylene glycol. Preferably, the second fluid contains at least one of proteins and peptides. The aqueous solvent may contain a solvent that allows lipid nanoparticles to be stably dispersed. The aqueous solvent may contain, for example, water, as well as physiologically or pharmaceutically acceptable additives such as buffers and salts. The aqueous solvent may be a buffer such as a phosphate buffer, citrate buffer, phosphate-buffered saline (PBS), or HEPES buffer. The aqueous solvent may also contain an alcohol. Examples of alcohols include ethanol, t-butanol, 1-propanol, 2-propanol, and 2-butoxyethanol.

[0103] Examples of proteins include apolipoproteins and their genetically modified forms. Examples of apolipoproteins include at least one selected from the group consisting of apolipoproteins A to E, such as apolipoprotein AI (apoA-I), apolipoprotein A-II (apoA-II), apolipoprotein C (apoC), apolipoprotein E (apoE), and their genetically modified forms. Of these, apolipoprotein AI (apoA-I) and its genetically modified form apoA-I are preferred.

[0104] A genetically modified apolipoprotein refers to a variant or analogue (i.e., a functional equivalent) that has a function equivalent to that of an apolipoprotein (e.g., lipid-binding function). Examples of genetically modified apolipoproteins include partial fragments of apolipoproteins and apolipoproteins formed by combining them. An example of a genetically modified apolipoprotein AI is apoA-I, which lacks 43 amino acids at the N-terminus. Examples of peptides include apoA-I partial peptides and apoA-I mimic peptides.

[0105] The nanoparticle manufacturing method according to this embodiment includes, as shown in Figures 1 and 2, a step of introducing a first fluid into a mixing channel 20 through a first fluid introduction channel 10a, and a step of introducing a second fluid into the mixing channel 20 through a second fluid introduction channel 10b. In the nanoparticle manufacturing method of this embodiment, these steps are for mixing the flow of the first fluid and the flow of the second fluid inside the mixing channel 20, and the order of these steps is not particularly limited. For example, the first fluid may be introduced into the mixing channel 20 through the first fluid introduction channel 10a, and the second fluid may be introduced into the mixing channel 20 through the second fluid introduction channel 10b.

[0106] In the nanoparticle manufacturing method according to this embodiment, similar to the fluid mixing method described above, first, as shown in Figures 1 and 2, a first fluid is introduced into the fluid mixing device 1 through tube 7a, for example, by a syringe pump. A second fluid is also introduced into the fluid mixing device 1 through tube 7b, for example, by a syringe pump. The first fluid flows into the expansion channel 12a through the end portion 40a, and then into the first fluid introduction channel 10a. The second fluid flows into the expansion channel 12b through the end portion 40b, and then into the second fluid introduction channel 10b.

[0107] Furthermore, the first fluid is introduced into the mixing channel 20 through the first fluid introduction channel 10a. The second fluid is also introduced into the mixing channel 20 through the second fluid introduction channel 10b. By introducing the first and second fluids into the mixing channel 20 in this manner, the Reynolds number in the mixing channel 20 is made to be above a predetermined value.

[0108] Furthermore, the first fluid and the second fluid are mixed in the mixing channel 20. The mixed fluid, which is the mixture of the first and second fluids in the mixing channel 20, flows from the mixing channel 20 into the fluid discharge channel 30 and is discharged into the tube 7c through the end portion 40c. The mixed fluid is discharged from the tube 7c. As shown in Figure 4, the mixed fluid discharged from the tube 7c may be stored in a container such as a test tube.

[0109] In the nanoparticle manufacturing method of this embodiment, similar to the fluid mixing method described above, for example, the ratio of the flow rate of the first fluid introduced from the first fluid introduction channel 10a to the flow rate of the second fluid introduced from the second fluid introduction channel 10b, and the Reynolds number inside the mixing channel 20 are set as appropriate. As a result, as illustrated in Figures 5A to 5C, the first fluid flowing near the side wall 21a on the first fluid introduction channel 10a side of the mixing channel 20 moves away from the side wall 21a and approaches the side wall 21b on the second fluid introduction channel 10b side of the mixing channel 20, making it easier for the first fluid and the second fluid to mix.

[0110] Figures 5A to 5C show examples of the flow states of the first and second fluids flowing through the mixing channel 20. However, if the first fluid flowing near the side wall 21a on the first fluid introduction channel 10a side of the mixing channel 20 moves away from the side wall 21a and approaches the side wall 21b on the second fluid introduction channel 10b side of the mixing channel 20, then the flow state may differ from that shown in Figures 5A to 5C.

[0111] In addition, in the nanoparticle manufacturing method of this embodiment, as with the fluid mixing method described above, bubbles may be introduced into the mixing channel 20. Even if bubbles are introduced into the mixing channel 20, if the first fluid flowing near the side wall 21a on the first fluid introduction channel 10a side of the mixing channel 20 moves away from the side wall 21a and approaches the side wall 21b on the second fluid introduction channel 10b side of the mixing channel 20, the same effect as when no bubbles are present in the mixing channel 20 (the first fluid and the second fluid become easier to mix) can be obtained.

[0112] Thus, in the nanoparticle manufacturing method according to this embodiment, the first fluid flowing near the side wall 21a on the first fluid introduction channel 10a side of the mixing channel 20 moves away from the side wall 21a and approaches the side wall 21b on the second fluid introduction channel 10b side of the mixing channel 20, making it easier for the first fluid and the second fluid to mix. This promotes rapid and uniform mixing of the first fluid, in which at least one material is dissolved, and the second fluid, making it possible to easily manufacture the desired nanoparticles.

[0113] Furthermore, in the nanoparticle manufacturing method of this embodiment, if the first fluid and the second fluid are introduced into the mixing channel 20 such that the Reynolds number in the mixing channel 20 is equal to or greater than a predetermined value, the second boundary 70 disappears at an earlier stage (closer to the communication ports 11a and 11b), thereby improving the mixing efficiency of the first fluid and the second fluid. As a result, desired nanoparticles can be easily manufactured. The fluid conditions in the mixing channel 20 for manufacturing nanoparticles may vary depending on the particle size and composition of the nanoparticles, but the predetermined value of the Reynolds number in the mixing channel 20 is not particularly limited, however, as an example, it is preferably 500 or more, and from the viewpoint of pressure resistance of the fluid mixing device 1 and connectors 70a to 70c, it is preferably 6000 or less, more preferably 4000 or less, or 2400 or less.

[0114] In the nanoparticle manufacturing method of this embodiment, it is preferable to pass the first fluid and the second fluid through each fluid introduction channel such that the flow rate of the second fluid in the second fluid introduction channel 10b is greater than the flow rate of the first fluid in the first fluid introduction channel 10a. By passing the first fluid and the second fluid through each fluid introduction channel in this way, the first fluid flowing near the side wall 21a on the first fluid introduction channel 10a side of the mixing channel 20 can be moved away from the vicinity of the side wall 21a and closer to the side wall 21b on the second fluid introduction channel 10b side of the mixing channel 20.

[0115] Furthermore, as illustrated in Figures 5A to 5C, the direction in which the second boundary 70 disappears (the direction of extension of the second boundary 70) is nearly parallel to the direction of extension of the mixing channel 20, and the portion of the second boundary 70 that disappears is less likely to come into contact with the side walls 21a and 21b of the mixing channel 20. Therefore, when nanoparticles are generated by mixing the first fluid and the second fluid, the products that may be generated in the portion of the second boundary 70 that disappears are less affected by the side walls 21a and 21b of the mixing channel 20.

[0116] The nanoparticle manufacturing method of this embodiment produces nanoparticles of varying particle sizes depending on the mixing conditions of the first and second fluids. For example, it is suitable for producing nanoparticles with a particle size of 30 to 200 nm, and can also produce very small nanoparticles smaller than 30 nm, as well as very small nanoparticles of about 8 to 15 nm.

[0117] Therefore, the nanoparticle manufacturing method of this embodiment can be used to produce various nanoparticles (rHDL, liposomes, lipid nanoparticles, polymer nanoparticles, polymer-lipid hybrids, etc.) that can be used as carriers in drug delivery systems, pharmaceuticals, cosmetics, or quasi-drugs.

[0118] Second Embodiment The fluid mixing device according to this embodiment differs from the first embodiment in the configuration of the groove portion of the base chip, but the other configurations are common, and as long as there is no contradiction, it can achieve the same effects as the fluid mixing device 1 of the first embodiment. Furthermore, the fluid mixing method according to this embodiment can be carried out using the fluid mixing device of this embodiment. Furthermore, the nanoparticle manufacturing method according to this embodiment can be carried out using the fluid mixing device of this embodiment. In the following description, parts common to the first embodiment will be omitted from description as much as possible, and the same reference numerals as in the first embodiment will be used to the extent necessary. The parts that are omitted from description are described in the first embodiment.

[0119] As shown in Figure 8, the fluid mixing device 1_1 according to this embodiment has a base tip 2a1 in which a groove 9_1 is formed. The groove 9_1 has a first fluid introduction channel 10a, a second fluid introduction channel 10b, and a mixing channel 20. The central axis C0 (see Figure 9) of the mixing channel 20 is formed along the X axis.

[0120] As shown in Figure 8, in the groove 9_1, the first fluid introduction channel 10a and the second fluid introduction channel 10b are in communication with the mixing channel 20 at their respective downstream ends. In addition to the first fluid introduction channel 10a, the second fluid introduction channel 10b and the mixing channel 20, the groove 9_1 also has expansion channels 12a and 12b1, a fluid outlet channel 30 and end sections 40a to 40c. In this embodiment, the first fluid introduction channel 10a and the second fluid introduction channel 10b are mirror-symmetric to each other across the XZ plane, but the length, width, depth, etc. of the first fluid introduction channel 10a and the second fluid introduction channel 10b may be partially different. The expansion channels 12a and 12b1 are mirror-symmetric to each other across the XZ plane, but the length, width, depth, etc. of the expansion channels 12a and 12b1 may be partially different.

[0121] Figure 9 is an enlarged view of the area around the communication ports 11a and 11b of the first fluid introduction channel 10a and the second fluid introduction channel 10b to the mixing channel 20 in Figure 8. As shown in Figure 9, the first fluid introduction channel 10a and the second fluid introduction channel 10b each extend linearly along the X-axis. The central axis C1 of the first fluid introduction channel 10a and the central axis C2 of the second fluid introduction channel 10b are arranged substantially parallel to each other. However, the angle of the central axis C1 of the first fluid introduction channel 10a with respect to the X-axis direction and the angle of the central axis C2 of the second fluid introduction channel 10b with respect to the X-axis direction are not limited to these.

[0122] Similar to the first embodiment, the first fluid introduction channel 10a may extend toward the communication port 11a at an angle θ1 (see Figure 3B) of 30 degrees or less (including 0 degrees) with respect to the extending direction (X-axis direction) of the mixing channel 20. The second fluid introduction channel 10b may also extend toward the communication port 11b at an angle θ2 (see Figure 3B) of 30 degrees or less (including 0 degrees) with respect to the extending direction (X-axis direction) of the mixing channel 20. In this embodiment as well, if angles θ1 and θ2 are 30 degrees or less, it is included in this embodiment and achieves the same effects.

[0123] The lengths (channel lengths) of the first fluid introduction channel 10a and the second fluid introduction channel 10b are not particularly limited. In this embodiment, the first fluid introduction channel 10a and the second fluid introduction channel 10b are each formed to be of equal length.

[0124] The first fluid introduction channel 10a is connected to an expansion channel 12a on its upstream side. The upstream end of the expansion channel 12a is connected to the end portion 40a. The expansion channel 12a extends linearly along the Y-axis from the end portion 40a, and its downstream end is connected to the upstream end of the first fluid introduction channel 10a at approximately a right angle. The length of the expansion channel 12a is not particularly limited, but is approximately the same as the length of the first fluid introduction channel 10a. The length of the expansion channel 12a may be longer or shorter than the length of the first fluid introduction channel 10a. The width of the expansion channel 12a is greater than the width of the first fluid introduction channel 10a. The cross-sectional area of ​​the expansion channel 12a is greater than the cross-sectional area of ​​the first fluid introduction channel 10a.

[0125] The second fluid introduction channel 10b is connected to an expansion channel 12b1 on its upstream side. The upstream end of the expansion channel 12b1 is connected to the end portion 40b. The expansion channel 12b1 extends linearly along the Y-axis from the end portion 40b, and its downstream end is connected to the upstream end of the second fluid introduction channel 10b at approximately a right angle. The length of the expansion channel 12b1 is not particularly limited, but is approximately equal to the length of the second fluid introduction channel 10b. The length of the expansion channel 12b1 may be longer or shorter than the length of the second fluid introduction channel 10b. The width of the expansion channel 12b1 is greater than the width of the second fluid introduction channel 10b. The cross-sectional area of ​​the expansion channel 12b1 is greater than the cross-sectional area of ​​the second fluid introduction channel 10b.

[0126] The mixing channel 20 is connected to a fluid outlet channel 30 on its downstream side. The fluid outlet channel 30 is smoothly connected to the downstream end of the mixing channel 20 and extends mostly along the Y-axis. The downstream end of the fluid outlet channel 30 is connected to the terminal portion 40c.

[0127] As shown in Figure 8, in the base chip 2a1 of this embodiment, the first fluid introduction channel 10a extends toward the communication port 11a at an angle θ1 of 30 degrees or less with respect to the direction of extension of the mixing channel 20 (X-axis direction). The second fluid introduction channel 10b extends toward the communication port 11b at an angle θ2 of 30 degrees or less with respect to the direction of extension of the mixing channel 20 (X-axis direction). In the fluid mixing device 1_1 of this embodiment having the base chip 2a1, the first fluid introduction channel 10a, the second fluid introduction channel 10b, and the mixing channel 20 can be housed in a narrow space with a limited width, enabling fluid mixing in a narrow space with a limited width.

[0128] The fluid mixing device 1_1 of this embodiment can rapidly and uniformly mix a first fluid introduced into the mixing channel 20 from a first fluid introduction channel 10a and a second fluid introduced into the mixing channel 20 from a second fluid introduction channel 10b within the mixing channel 20. Therefore, the fluid mixing device 1_1 of this embodiment is suitably used as the fluid mixing method according to the present invention as described above.

[0129] The fluid mixing device 1_1 of this embodiment can easily produce desired nanoparticles based on the materials contained in the first or second fluid as described above. Therefore, the fluid mixing device 1_1 of this embodiment is suitably used as a method for producing nanoparticles.

[0130] It should be noted that the present invention is not limited to the embodiments described above, and can be modified in various ways within the scope of the present invention. For example, the following modifications are possible.

[0131] As shown in Figure 2, in the fluid mixing device 1, one fluid outlet channel 30 is connected downstream of the mixing channel 20, but two or more fluid outlet channels may be connected.

[0132] Furthermore, as shown in Figure 2, in the fluid mixing device 1, the groove 9 had an expansion channel 12a upstream of the first fluid introduction channel 10a, but the expansion channel 12a may be omitted. In this case, the length of the first fluid introduction channel 10a may be extended as needed. The same applies to the second fluid introduction channel 10b.

[0133] Furthermore, the groove 9 only needs to have at least a first fluid introduction channel 10a, a second fluid outlet channel 10b, and a mixing channel 20, and does not need to have a fluid outlet channel 30 and end portions 40a to 40c.

[0134] If the expansion channels 12a, 12b and the end portions 40a, 40b are omitted from the groove portion 9, the first fluid and the second fluid may be introduced directly or indirectly (through a tube, etc.) into the first fluid introduction channel 10a and the second fluid introduction channel 10b. In this case as well, the effects described in the above embodiment can be obtained.

[0135] If the fluid outlet channel 30 and the end portion 40c are omitted from the groove portion 9, the mixed fluid of the first fluid and the second fluid may be discharged directly or indirectly (through a tube, etc.) from the downstream side of the mixing channel 20. In this case as well, the effects described in the above embodiment can be obtained.

[0136] The present invention will be described below based on more detailed examples, but the present invention is not limited to these examples.

[0137] Example 1 A fluid mixing experiment was conducted using the fluid mixing device 1 shown in Figures 1 and 2. In fabricating the fluid mixing device 1 shown in Figures 1 and 2, a base chip 2a was made by cutting a plate of cycloolefin polymer. The depth of the groove 9 was set to 0.20 mm. The width W0 of the mixing channel 20 was set to 0.65 mm and the length to 14.0 mm. The first fluid introduction channel 10a and the second fluid introduction channel 10b were formed parallel to each other as shown in Figure 3A. The width W1 of the first fluid introduction channel 10a was set to 0.1 mm and the length in the X-axis direction was set to 27.5 mm. The width W2 of the second fluid introduction channel 10b was set to 0.2 mm and the length in the X-axis direction was set to 5.0 mm. The distance D1 between the centers of the communication port 11a of the first fluid introduction channel 10a and the communication port 11b of the second fluid introduction channel 10b was set to 0.5 mm. The distance between the central axis C1 of the first fluid introduction channel 10a and the central axis C0 of the mixing channel 20 was set to 0.275 mm, and the distance between the central axis C2 of the second fluid introduction channel 10b and the central axis C0 of the mixing channel 20 was set to 0.225 mm.

[0138] A cover chip 2b was fabricated by cutting a cycloolefin polymer plate. The base chip 2a and the cover chip 2b were then joined together. In this manner, the fluid mixing device 1 shown in Figures 1 and 2 was fabricated.

[0139] As shown in Figure 1, connectors 70a to 70c were attached to the through holes 3a to 3c of the cover chip 2b, and the fluid mixing device 1 was fixed by clamping plates 4a and 4b from above and below. In addition, tubes 7a to 7c were connected to the connectors 70a to 70c.

[0140] For tubes 7a and 7b, polytetrafluoroethylene tubing with an inner diameter of 0.5 mm and a length of 45 cm was used. For tube 7c, polytetrafluoroethylene tubing with an inner diameter of 1.0 mm and a length of 25 cm was used. Tubes 7a and 7b were then connected to syringe pumps (Chemyx Fusion 6000X and Chemyx Fusion 200).

[0141] As shown in Figures 1 and 2, using the fabricated fluid mixing device 1, the first fluid was introduced into the mixing channel 20 via the first fluid introduction channel 10a through tube 7a, and the second fluid was introduced into the mixing channel 20 via the second fluid introduction channel 10b through tube 7b, thereby mixing the first and second fluids. Ethanol was used as the first fluid, and pure water was used as the second fluid. The fluid discharged from the mixing channel 20 through tube 7c was collected in a container.

[0142] When introducing the first and second fluids into the fluid mixing device 1, the flow rate ratio of the second fluid to the first fluid was set to 10:1, the temperature of the mixing channel 20 was set to approximately 25°C (room temperature), and the total flow rate of the first and second fluids (flow rate of fluids flowing through the mixing channel 20) was set to 16.5 mL / min. The Reynolds number in the mixing channel 20 was 529.

[0143] However, the Reynolds number Re in the mixing channel 20 was calculated based on the aforementioned formula (1). In formula (1), w was set to 0.65 mm and h to 0.2 mm. For ρ and μ, values ​​(literature values ​​or calculated values ​​based on literature values) were used when ethanol (first fluid) and pure water (second fluid) were completely mixed.

[0144] Under the above conditions, the flow state of the fluid through the mixing channel 20 was observed. The mixing channel 20 was observed and photographed using an inverted phase-contrast microscope (Olympus CKX41) equipped with a digital video camera (Sony HDR-PJ630). The results are shown in Figure 6A.

[0145] As shown in Figure 6A, the first fluid flowing near the side wall 21a on the first fluid introduction channel 10a side of the mixing channel 20 moved away from the side wall 21a and approached the side wall 21b on the second fluid introduction channel 10b side of the mixing channel 20. As a result, a first boundary 60 was created as the boundary between the flow containing a large amount of the first fluid and the flow containing a small amount of the first fluid. Furthermore, a second boundary 70 between the second fluid introduced into the mixing channel 20 through the second fluid introduction channel 10b and the flow containing a large amount of the first fluid disappeared midway through the mixing channel 20. This result demonstrates that rapid and uniform mixing of the first fluid and the second fluid can be achieved.

[0146] As shown in Figure 6A, the direction in which the second boundary 70 disappeared (the direction of extension of the second boundary 70) was nearly parallel to the direction of extension of the mixing channel 20. This result indicates that when nanoparticles are generated by mixing the first fluid and the second fluid, the portion where the second boundary 70 disappears is less likely to come into contact with the side walls 21a and 21b of the mixing channel 20, and the products that may be generated in the portion where the second boundary 70 disappears are less affected by the side walls 21a and 21b of the mixing channel 20. Note that in Figures 6A and later, in order to prevent the drawings from becoming cluttered, the symbols indicating the first fluid introduction channel 10a, the second fluid introduction channel 10b, and the mixing channel 20, as well as the XYZ coordinate axes, have been omitted.

[0147] Example 2 A fluid mixing experiment was conducted using the same fluid mixing device 1 as in Example 1. The total flow rate of the first and second fluids was set to 22.0 mL / min. All other experimental conditions were the same as in Example 1. The Reynolds number in the mixing channel 20 was 705. The results are shown in Figure 6B.

[0148] As shown in Figure 6B, the first fluid flowing near the side wall 21a on the first fluid introduction channel 10a side of the mixing channel 20 moved away from the side wall 21a and approached the side wall 21b on the second fluid introduction channel 10b side of the mixing channel 20. As a result, a first boundary 60 was created as the boundary between the flow containing a large amount of the first fluid and the flow containing a small amount of the first fluid. Furthermore, the position where the second boundary 70 between the second fluid introduced into the mixing channel 20 through the second fluid introduction channel 10b and the flow containing a large amount of the first fluid disappears shifted further upstream in the mixing channel 20 than in Example 1. This result indicates that the mixing of the first and second fluids proceeds at an earlier stage (further upstream in the mixing channel 20). As shown in Figure 6B, the direction in which the disappearance of the second boundary 70 progresses (the extension direction of the second boundary 70) was nearly parallel to the extension direction of the mixing channel 20. These results indicate that when nanoparticles are generated by mixing the first fluid and the second fluid, the portion where the second boundary 70 disappears is less likely to come into contact with the side walls 21a and 21b of the mixing channel 20, and the products that may be generated in the portion where the second boundary 70 disappears are less affected by the side walls 21a and 21b of the mixing channel 20.

[0149] Example 3 A fluid mixing experiment was conducted using the same fluid mixing device 1 as in Example 1. The total flow rate of the first and second fluids was set to 55.0 mL / min. All other experimental conditions were the same as in Example 1. The Reynolds number in the mixing channel 20 was 1763. The results are shown in Figure 6C.

[0150] As shown in Figure 6C, the first fluid flowing near the side wall 21a on the first fluid introduction channel 10a side of the mixing channel 20 moved away from the side wall 21a and approached the side wall 21b on the second fluid introduction channel 10b side of the mixing channel 20. As a result, a first boundary 60 was created as the boundary between the flow containing a large amount of the first fluid and the flow containing a small amount of the first fluid. Furthermore, the position where the second boundary 70 between the second fluid introduced into the mixing channel 20 through the second fluid introduction channel 10b and the flow containing a large amount of the first fluid disappears shifted further upstream in the mixing channel 20 than in Example 2. This result indicates that the mixing of the first and second fluids proceeds at an earlier stage (further upstream in the mixing channel 20). As shown in Figure 6C, the direction in which the disappearance of the second boundary 70 progresses (the extension direction of the second boundary 70) was nearly parallel to the extension direction of the mixing channel 20. These results indicate that when nanoparticles are generated by mixing the first fluid and the second fluid, the portion where the second boundary 70 disappears is less likely to come into contact with the side walls 21a and 21b of the mixing channel 20, and the products that may be generated in the portion where the second boundary 70 disappears are less affected by the side walls 21a and 21b of the mixing channel 20.

[0151] The results from these Examples 1 to 3 demonstrate that rapid and uniform mixing of the first fluid and the second fluid can be achieved when the Reynolds number in the mixing channel 20 is 529 or higher. Furthermore, it was demonstrated that rapid and uniform mixing of the first fluid and the second fluid can be achieved when the total flow rate of the first and second fluids is 16.5 mL / min or higher.

[0152] Furthermore, these results indicate that the higher the Reynolds number in the mixing channel 20, the easier it is for the first fluid and the second fluid to mix at an earlier stage (further upstream in the mixing channel 20), thereby improving the mixing efficiency of the first and second fluids. Additionally, the greater the total flow rate of the fluids flowing through the mixing channel 20, the easier it is for the first and second fluids to mix at an earlier stage (further upstream in the mixing channel 20), thereby improving the mixing efficiency of the first and second fluids.

[0153] Example 4 A fluid mixing experiment was conducted using the fluid mixing device 1_1 shown in Figure 8. First, the base chip 2a1 shown in Figure 8 was fabricated using the same material and processing method as the fluid mixing device 1 in Example 1. The depth of the groove 9_1 was the same as that of the fluid mixing device 1 in Example 1. The width W0 of the mixing channel 20 was 0.75 mm and the length was 37.375 mm. The width W1 of the first fluid introduction channel 10a was 0.2 mm and the length in the X-axis direction was 4.125 mm. The width W2 of the second fluid introduction channel 10b was 0.2 mm and the length in the X-axis direction was 4.125 mm. The distance D1 between the centers of the communication port 11a of the first fluid introduction channel 10a and the communication port 11b of the second fluid introduction channel 10b was 0.55 mm. The distance between the central axis C1 of the first fluid introduction channel 10a and the central axis C0 of the mixing channel 20 was 0.275 mm, and the distance between the central axis C2 of the second fluid introduction channel 10b and the central axis C0 of the mixing channel 20 was also 0.275 mm.

[0154] The fluid mixing device 1_1 used in this embodiment was fabricated by using the same components as those in the fluid mixing device 1 of Example 1, except for the base chip 2a1, and assembling them in the same manner.

[0155] The fabricated fluid mixing device 1_1 was used to conduct experiments under the same experimental conditions as in Example 3. The total flow rate of the first and second fluids was set to 55.0 mL / min. The Reynolds number in the mixing channel 20 was 1577. The results are shown in Figure 10.

[0156] As shown in Figure 10, the same results as in Example 3 were obtained in this embodiment. The first fluid flowing near the side wall 21a on the first fluid introduction channel 10a side of the mixing channel 20 moved away from the side wall 21a and approached the side wall 21b on the second fluid introduction channel 10b side of the mixing channel 20. As a result, a first boundary 60 was created as the boundary between the flow containing a large amount of the first fluid and the flow containing a small amount of the first fluid. In addition, a second boundary 70 between the second fluid introduced into the mixing channel 20 through the second fluid introduction channel 10b and the flow containing a large amount of the first fluid disappeared midway through the mixing channel 20. From these results, it was shown that rapid and uniform mixing of the first fluid and the second fluid can be achieved even with a fluid mixing device 1_1 having a base chip 2a1.

[0157] As shown in Figure 10, the direction in which the second boundary 70 disappears (the direction of extension of the second boundary 70) was nearly parallel to the direction of extension of the mixing channel 20. This result indicates that when nanoparticles are generated by mixing the first fluid and the second fluid, the portion where the second boundary 70 disappears is less likely to come into contact with the side walls 21a and 21b of the mixing channel 20, and the products that may be generated in the portion where the second boundary 70 disappears are less affected by the side walls 21a and 21b of the mixing channel 20.

[0158] Comparative Example 1 A fluid mixing experiment was conducted using the same fluid mixing device 1 as in Example 1. The total flow rate of the first and second fluids was set to 5.5 mL / min. All other experimental conditions were the same as in Example 1. The Reynolds number in the mixing channel 20 was 176. The results are shown in Figure 7A. As shown in Figure 7A, the first fluid flowing near the side wall 21a on the first fluid introduction channel 10a side of the mixing channel 20 did not leave the vicinity of the side wall 21a.

[0159] Comparative Example 2 A fluid mixing experiment was conducted using the same fluid mixing device 1 as in Example 1. The total flow rate of the first and second fluids was set to 11.0 mL / min. All other experimental conditions were the same as in Example 1. The Reynolds number in the mixing channel 20 was 353. The results are shown in Figure 7B. As shown in Figure 7B, the first fluid flowing near the side wall 21a on the first fluid introduction channel 10a side of the mixing channel 20 did not leave the vicinity of the side wall 21a.

[0160] The results from these comparative examples 1 and 2 show that, at least when the Reynolds number in the mixing channel 20 is 353 or less, the mixing efficiency of the first and second fluids may not be sufficient, making it difficult to achieve rapid and uniform mixing of the first and second fluids. Furthermore, it was shown that when the total flow rate of the first and second fluids is 11.0 mL / min or less, the mixing efficiency of the first and second fluids may not be sufficient, making it difficult to achieve rapid and uniform mixing of the first and second fluids.

[0161] Comparative Example 3 A fluid mixing experiment was conducted using the fluid mixing device 101 shown in Figure 11. First, the base chip 102a shown in Figure 11 was fabricated using the same material and processing method as the fluid mixing device 1_1 of Example 4. As shown in Figure 11, the groove 109 has a first fluid introduction channel 110a, a second fluid introduction channel 110b, and a mixing channel 20. The central axis C0 of the mixing channel 20 (see Figure 12) is formed along the X axis. As shown in Figure 12, the first fluid introduction channel 110a was extended linearly along the Y axis toward the communication port 111a at an angle of 90 degrees with respect to the extension direction (X axis direction) of the central axis C0 of the mixing channel 20 and connected to the mixing channel 20. The second fluid introduction channel 110b was extended linearly along the Y axis toward the communication port 111b at an angle of 90 degrees with respect to the extension direction (X axis direction) of the central axis C0 of the mixing channel 20 and connected to the mixing channel 20. The first fluid introduction channel 110a and the second fluid introduction channel 110b are formed such that the central axis C1 of the first fluid introduction channel 110a and the central axis C2 of the second fluid introduction channel 110b are aligned in a straight line with respect to each other.

[0162] An expansion channel 112a was formed linearly along the X-axis from the end portion 40a, and the downstream end of the expansion channel 112a was connected to the upstream end of the first fluid introduction channel 110a at approximately a right angle. An expansion channel 112b was formed linearly along the X-axis from the end portion 40b, and the downstream end of the expansion channel 112b was connected to the upstream end of the second fluid introduction channel 110b at approximately a right angle.

[0163] The fluid outlet channel 30 was smoothly connected to the downstream end of the mixing channel 20 and was formed to extend mostly along the Y-axis. The downstream end of the fluid outlet channel 30 was connected to the terminal portion 40c.

[0164] The depth of the groove 109 of the base chip 102a was the same as that of the fluid mixing device in Example 4. The width W0 and length of the mixing channel 20 were the same as those in Example 4. The width W1 of the first fluid introduction channel 110a was the same as that of the first fluid introduction channel 10a in Example 4, and the length in the Y-axis direction was 4.125 mm, the same as the length in the X-axis direction of the first fluid introduction channel 10a in Example 4. The width W2 of the second fluid introduction channel 110b was the same as that of the second fluid introduction channel 10b in Example 4, and the length in the Y-axis direction was 4.125 mm, the same as the length in the X-axis direction of the second fluid introduction channel 10b in Example 4.

[0165] The fluid mixing device 101 used in this comparative example was fabricated by using the same components as those used in the fluid mixing device 1_1 of Example 4, except for the base chip 102a, and assembling them in the same manner.

[0166] The fabricated fluid mixing device 101 was used to conduct experiments under the same experimental conditions as in Example 4. The total flow rate of the first and second fluids was set to 55.0 mL / min. The results are shown in Figure 13.

[0167] As shown in Figure 13, the boundary between the first fluid introduced from the first fluid introduction channel 110a and the second fluid introduced from the second fluid introduction channel 110b disappeared near the communication port 111a. Here, in the direction in which the disappearance of the boundary between the first and second fluids progressed, there was a channel side wall including the side wall 21a of the mixing channel 20, either at or near the communication port 111a. Since the portion where the boundary between the first and second fluids disappears is likely to come into contact with the channel side wall including the side wall 21a of the mixing channel 20 near the communication port 111a, it was shown that products that may be generated in the portion where the boundary between the first and second fluids disappears are susceptible to the influence of the channel side wall including the side wall 21a of the mixing channel 20 near the communication port 111a.

[0168] Example 5: Nanoparticle manufacturing experiments were conducted using the fluid mixing device 1 shown in Figures 1 and 2. In this example, the same fluid mixing device used in Example 1 was used as the fluid mixing device 1.

[0169] Using a fluid mixing device 1, the first fluid was introduced into the mixing channel 20 via the first fluid introduction channel 10a through tube 7a, and the second fluid was introduced into the mixing channel 20 via the second fluid introduction channel 10b through tube 7b, thereby mixing the first and second fluids. The first fluid used was ethanol containing 2.5 mg / mL of distearoyl phosphatidylcholine (DSPC) and 1.2 mg / mL of cholesterol. The second fluid used was PBS (Phosphate-buffered saline). The flow rate of the first fluid was 5 mL / min, the flow rate of the second fluid was 45 mL / min, and the total flow rate of the first and second fluids was 50 mL / min. The fluid discharged from the mixing channel 20 through tube 7c was collected in a container.

[0170] The particle size was evaluated using a particle size distribution analyzer (Zetasizer Nano ZS, DLS method) on the recovered fluid as a sample. The volume distribution of particle size for the sample is shown in Figure 14. The Z-mean particle size of the product in the fluid was 36.3 nm, and the polydispersity index (PDI) was 0.044. These results demonstrate that lipid nanoparticles consisting of DSPC and cholesterol can be produced using the fabricated fluid mixing device 1.

[0171] 1…Fluid mixing device 2a, 2a1…Base chip 2b…Cover chip 3a-3c…Through hole 4a, 4b…Clamping plate 5a-5c…Through hole 6…Screw hole 7a-7c…Tube 70a-70c…Connector 8a…Screw 8b…Nut 9, 9_1…Groove 10a…First fluid introduction channel 10b…Second fluid introduction channel 11a, 11b…Communication port 12a, 12b, 12b1…Expansion channel 20…Mixing channel 21a, 21b…Side wall 30…Fluid discharge channel 40a-40c…End section 60…First boundary 70…Second boundary 101…Fluid mixing device 102a…Base chip 109…Groove 110a…First fluid introduction channel 110b…Second fluid introduction channel 111a, 111b...Communication port 112a, 112b...Expansion channel

Claims

1. A fluid mixing device having two fluid introduction channels and a mixing channel communicating with the downstream end of each of the fluid introduction channels, wherein the respective communication ports of the fluid introduction channels to the mixing channels are spaced apart in a direction perpendicular to the extending direction of the mixing channels, and at least one of the fluid introduction channels extends toward the communication port at an angle of 30 degrees or less with respect to the extending direction of the mixing channel.

2. The fluid mixing device according to claim 1, wherein each of the fluid introduction channels extends toward the communication port such that the angle between the central axis of one fluid introduction channel and the central axis of the other fluid introduction channel is 60 degrees or less.

3. The fluid mixing device according to claim 1 or 2, wherein an expanded channel having a larger cross-sectional area than the fluid introduction channel is connected to the upstream side of the fluid introduction channel.

4. The fluid mixing device according to any one of claims 1 to 3, wherein the distance between each of the aforementioned communication ports is 0.5 times or more the width of the mixing channel.

5. A method for mixing fluids using the fluid mixing device described in any one of claims 1 to 4.

6. A fluid mixing method comprising the steps of introducing a first fluid into a mixing channel through one of two fluid introduction channels, and introducing a second fluid into the mixing channel through the other fluid introduction channel, wherein the first fluid, which flows near the side wall of the mixing channel on the side of the one fluid introduction channel, moves away from the side wall and approaches the side wall of the mixing channel on the side of the other fluid introduction channel, thereby mixing the first fluid and the second fluid.

7. The fluid mixing method according to claim 6, wherein the first fluid and the second fluid are introduced into the mixing channel such that the Reynolds number in the mixing channel is equal to or greater than a predetermined value.

8. The fluid mixing method according to claim 7, wherein the predetermined value of the Reynolds number in the mixing channel is 529 or more and 1765 or less.

9. A method for mixing fluids according to any one of claims 6 to 8, wherein the first fluid is passed through one fluid introduction channel and the second fluid is passed through the other fluid introduction channel such that the flow rate of the second fluid in the other fluid introduction channel is greater than the flow rate of the first fluid in the one fluid introduction channel.

10. A method for producing nanoparticles using a fluid mixing device according to any one of claims 1 to 4.

11. A method for producing nanoparticles, comprising the steps of: introducing a first fluid containing at least one material into a mixing channel through one of two fluid introduction channels; and introducing a second fluid into the mixing channel through the other fluid introduction channel, wherein the first fluid flowing near the side wall on the side of the mixing channel on the side of the one fluid introduction channel leaves the vicinity of the side wall and approaches the side wall on the side of the mixing channel on the side of the other fluid introduction channel.

12. The method for producing nanoparticles according to claim 11, wherein the first fluid and the second fluid are introduced into the mixing channel such that the Reynolds number in the mixing channel is equal to or greater than a predetermined value.

13. The method for producing nanoparticles according to claim 12, wherein the predetermined value of the Reynolds number in the mixing channel is 529 or more and 1765 or less.

14. A method for producing nanoparticles according to any one of claims 11 to 13, wherein the first fluid is passed through one fluid introduction channel and the second fluid through the other fluid introduction channel such that the flow rate of the second fluid in the other fluid introduction channel is greater than the flow rate of the first fluid in the one fluid introduction channel.

15. The method for producing nanoparticles according to any one of claims 11 to 14, wherein the material contains lipids.

16. The method for producing nanoparticles according to any one of claims 11 to 15, wherein the second fluid comprises at least one water-soluble material.

17. The method for producing nanoparticles according to claim 16, wherein the water-soluble material comprises at least one of a protein and a peptide.

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