Channel structure, channel structure unit, and lipid particle production method

Abstract

To provide a channel structure which enables high mixing efficiency and uniform mixing to be achieved.SOLUTION: This channel structure comprises: a first channel group including one or more channels; a second channel group including two or more channels and connected to the first channel group through a branch; a third channel group including one or more channels and connected to the second channel group through a merging part; the branch; and the merging part. The branch includes a first channel group side branch opening and a second channel group side branch opening. The merging part includes a second channel group side merging opening and a third channel group side merging opening. When the first channel group includes N channels while the second channel group includes M channels, and M is equal to or larger than N, a sum total of an opening area of the second channel group side branch opening is equal to or less than an M / N multiple of that of the first channel group side branch opening, and at least one opening area of the second channel group side merging openings is equal to or less than at least one opening area of the third channel group side merging openings.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present embodiment relates to a flow path structure, a flow path structure unit, and a method for manufacturing lipid particles.

Background Art

[0002] There are methods that use flow paths for mixing, stirring, and diluting various liquids. At this time, the mixing efficiency can be improved by generating vortices in the flow path. However, if a flow in the opposite direction to the main flow direction of the flow in the flow path occurs, it may conversely cause a decrease in the mixing efficiency and the uniformity after mixing.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0004] The problem to be solved by the present invention is to provide a flow path structure, a flow path structure unit, and a method for manufacturing lipid particles that achieve uniform mixing with high mixing efficiency.

Means for Solving the Problems

[0005] The flow path structure of the embodiment includes a first flow path group, a second flow path group, a third flow path group, a branch portion, and a confluence portion. The first flow path group includes one or more flow paths. The second flow path group is connected to the first flow path group via the branch portion and includes two or more flow paths. The third flow path group is connected to the second flow path group via the confluence portion and includes one or more flow paths. The branch portion includes a first flow path group side branch opening that connects to an end of the flow path included in the first flow path group close to the second flow path group, and a second flow path group side branch opening that connects to an end of the flow path included in the second flow path group close to the first flow path group. The confluence portion includes a second flow path group side confluence opening that connects to an end of the second flow path group close to the third flow path group, and a third flow path group side confluence opening that connects to an end of the third flow path group close to the second flow path group. Further, when the first flow path group includes N flow paths, the second flow path group includes M flow paths, and M is equal to or greater than N, the total opening area of the second flow path group side branch openings is M / N times or less the total opening area of the first flow path group side branch openings, and at least one opening area of the second flow path group side confluence openings is equal to or less than at least one opening area of the third flow path group side confluence openings.

Brief Description of the Drawings

[0006]

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Embodiments for Carrying Out the Invention

[0007] Hereinafter, embodiments will be described with reference to the accompanying drawings. In each embodiment, substantially the same components may be denoted by the same reference numerals, and the description thereof may be partially omitted. The drawings are schematic, and the relationship between the thickness and the planar dimensions of each part, the ratio of the thicknesses of each part, etc. may be different from the actual ones.

[0008] When a fluid flows through the flow path structure, the direction of the main flow in the flow path is as indicated by the arrow in FIG. 1 and will be described as being substantially along the pipe axis direction. That is, it will be described that the fluid flows from the first flow path through the second flow path or the third flow path and into the fourth flow path.

[0009] Also, in this specification, the "fluid" is not limited to a liquid and may be a gas.

[0010] Also, in this specification, the "flow path" refers to a space within the flow path structure through which a fluid can flow. The flow path has openings on the upstream side and the downstream side of the fluid, respectively. The flow path has a base material such as resin, glass, ceramics, or metal as its wall surface, and the top surface or the bottom surface of the flow path is sealed by the base material of the flow path structure.

[0011] (First Embodiment) FIG. 1 is a schematic diagram showing an example of a flow path structure 100 according to the first embodiment. In the present embodiment, the flow path structure 100 includes a first flow path 1, a second flow path 2, a third flow path 3, a fourth flow path 4, a branch portion 5, and a confluence portion 6. The second flow path 2 is connected to the first flow path 1 via the branch portion 5, the third flow path 3 is connected to the first flow path 1 via the branch portion 5, and the fourth flow path 4 is connected to the second flow path 2 and the third flow path 3 via the confluence portion 6. That is, the downstream end of the first flow path 1, the upstream end of the second flow path 2, and the upstream end of the third flow path 3 are connected to the branch portion 5, and the downstream end of the second flow path 2, the downstream end of the third flow path 3, and the upstream end of the fourth flow path 4 are connected to the confluence portion 6. Here, when the end of the flow path is "connected" to the branch portion 5 or the confluence portion 6, it means that the opening of the end of the flow path and the opening of the branch portion 5 or the confluence portion 6 are liquid-tightly connected so as to communicate with each other's internal space and form a continuous space. Further, the material of the flow path structure 100 is not particularly limited, and for example, a resin such as cycloolefin polymer (COP) may be used.

[0012] In this specification, unless otherwise specified, in FIG. 1, the flow path wall surface located closest to the front of the paper surface is referred to as the top surface, the flow path wall surface facing the top surface and located deeper in the paper surface than the top surface is referred to as the bottom surface, and the flow path wall surface intersecting the top surface and the bottom surface is referred to as the flow path side surface. Further, the dimension of the flow path perpendicular to the tube axis direction and parallel to the paper surface in FIG. 1 is described as the flow path width. The flow path depth is based on the plane including the top surface unless otherwise specified. In FIG. 1, the depth of the flow path is indicated by a hatched pattern. The darker the color of the hatched pattern, the relatively shallower it is compared to the white portion. However, the density of the color of the hatched pattern is only a guide, and the depth and density do not necessarily correspond. On the other hand, in this specification, unless otherwise specified, the dimension perpendicular to the tube axis direction and parallel to the paper surface in FIG. 1 is described as the flow path width.

[0013] The channel widths and channel depths of the first channel 1, the second channel 2, the third channel 3, and the fourth channel 4 are appropriately determined in consideration of various conditions such as the type and flow velocity of the fluid supplied to the channel structure 100. For example, there is a Reynolds number Re as a numerical value considering the shape of the channel structure 100, the type of fluid, and the flow velocity. The Reynolds number Re is a dimensionless numerical value defined by the following formula (1) using ρ [kg / m 3 : density of the fluid, V [m / s]: velocity of the fluid, L [m]: representative length, μ [Pa·s]: viscosity of the fluid.

[0014] Re = ρVL / μ…(1) In calculating the Reynolds number of the channel according to this embodiment, the hydraulic diameter d H is used as the representative length L. The hydraulic diameter d H is defined by the following formula (2) where A is the cross-sectional area of the channel and P is the perimeter of the channel cross-section.

[0015] d H = 4A / P…(2) The representative length L when obtaining the Reynolds number of the fluid flowing in the channel is often the hydraulic diameter d H , but the channel depth, the channel width, or their average value, etc. may also be used as the representative length.

[0016] In order to generate and sustain a swirling flow, the Reynolds number calculated from the above formula (1) is preferably 10 or more in the channel structure 100. Also, in order to generate a uniform swirling flow and avoid the generation of turbulent flow in the channel, the Reynolds number is preferably less than 2300 in the channel structure 100. In particular, when the channel width of the first channel 1 is the "reference width" and the channel depth is the "reference depth", it is preferable that the Reynolds number in the section having at least one of the reference width or the reference depth in the channel is 10 or more. Also, in the third branch opening 53 and the second confluence opening 62 where the area of the channel cross-section perpendicular to the tube axis direction in the channel is the smallest in the figure, it is preferable that the Reynolds number is less than 2300. In addition, in order to further promote the generation of a uniform swirling flow and further prevent the generation of turbulent flow in the channel, it is more preferable that the Reynolds number is approximately 50 or more and 1000 or less in the entire channel structure 100.

[0017] Hereinafter, each part of the flow path structure 100 in this embodiment will be described in detail.

[0018] The first flow path 1 shown in FIG. 1 has a constant flow path width and flow path depth. For example, a case where both the reference flow path width and the reference flow path depth are 0.3 mm will be described as an example. At this time, it is preferable that the average flow velocity of the fluid in the first flow path 1 is about 0.1 m / s or more. Assuming that the fluid is close to water and the representative length is the hydraulic diameter, the Reynolds number at around room temperature is around 30. When a pump is used as a device for introducing the fluid into the flow path structure 100 according to this embodiment, it is preferable to use a pump that does not cause pulsation. As such a pump, one with a liquid feeding rate of about 1 mL / sec can be easily obtained. Considering this situation, the reference flow path width and the reference flow path depth are preferably approximately 3 mm or less.

[0019] The branch portion 5 shown in FIG. 1 is a portion that connects the first flow path 1, the second flow path 2, and the third flow path 3. The branch portion 5 is connected to the downstream end of the first flow path 1, the upstream end of the second flow path 2, and the upstream end of the third flow path 3. The branch portion 5 includes a first branch opening 51 that connects to the end of the first flow path 1 close to the second flow path 2 and the third flow path 3 (downstream end), a second branch opening 52 that connects to the end of the second flow path 2 close to the first flow path 1 (upstream end), and a third branch opening 53 that connects to the end of the third flow path 3 close to the first flow path 1 (upstream end). The first branch opening 51 is the end of the first flow path, the end of the branch portion, and the boundary between the first flow path and the branch portion 5. The second branch opening 52 is the end of the second flow path, the end of the branch portion, and the boundary between the second flow path and the branch portion. The third branch opening 53 is the end of the third flow path, the end of the branch portion, and the boundary between the third flow path and the branch portion. In the present embodiment, an example is shown in which the flow path width changes across the first branch opening 51, and the second branch opening 52 and the third branch opening 53 are adjacent to each other. As shown in this example, the cross-sections of the second flow path 2 with the second branch opening 52 as an end and the third flow path 3 with the third branch opening 3 as an end do not overlap. In this example, inside the branch portion 5, from the branch portion 5 side toward the first flow path 1, the cross-sectional area of the flow path decreases. The location where this decrease stops is defined as the first branch opening 51. Similarly, inside the branch portion 5, the location where the decrease in the cross-sectional area from the branch portion 5 side toward the second flow path 2 stops is defined as the second branch opening 52, and the location where the decrease in the cross-sectional area from the branch portion 5 side toward the third flow path 3 stops is defined as the third branch opening 53. Also, the plane including the first branch opening 51 is defined such that it is perpendicular to the tube axis direction in the first flow path 1 to define the first branch opening 51. Similarly, the plane including the second branch opening 52 is perpendicular to the tube axis direction in the second flow path 2, and the plane including the third branch opening 53 is perpendicular to the tube axis direction in the third flow path 3. That is, the branch portion 5 corresponds to the region 5 shown shaded in FIG. 2. Since these openings are set for convenience in defining the region of the branch portion 5, the joint of the base material of the actual flow path structure 100 does not necessarily coincide with the opening defined in this specification. Here, if the area of the region defined as the opening is defined as the opening area, the opening area of at least one of the second branch opening 52 or the third branch opening 53 is less than or equal to the opening area of the first branch opening 51.In the present embodiment, a state where at least the third branch opening 53 has an opening area equal to or less than that of the first branch opening 51 is taken as an example.

[0020] FIG. 3 shows a perspective view of the flow path structure 100. In FIG. 3, the opening area S53 of the third branch opening 53 is equal to or less than the opening area S51 of the first branch opening 51. S53 is smaller than S51 and the opening area S52 of the second branch opening 52. Also, it is preferable that S51≈S52 + S53. Specifically, it is preferable that the sum of the opening areas of the second branch opening 52 and the third branch opening 53 is less than twice the opening area of the first branch opening 51. More preferably, the sum of the opening areas of the second branch opening 52 and the third branch opening 53 is 1.0 times or more and 2.0 times or less with respect to the opening area of the first branch opening 51, still more preferably 1.0 times or more and 1.9 times or less, and still more preferably 1.0 times or more and 1.5 times or less. Thus, in the branch portion 5, by reducing the opening area of at least one of the second branch opening 52 or the third branch opening 53 and bringing the opening area of the upstream branch opening (the first branch opening 51) closer to the sum of the opening areas of the downstream branch openings (the second branch opening 52 and the third branch opening 53), it is possible to suppress the generation of vortices accompanied by backflow in one or more regions of the branch portion 5, the second flow path, and the third flow path. Generally, in a flow path where the cross-sectional area of the flow path increases, the flow velocity decreases according to the law of conservation of flow rate, and the pressure increases accordingly by Bernoulli's law. Therefore, in a portion where the increase in the flow path cross-section is large, an adverse pressure gradient occurs where the pressure downstream is higher than that upstream, and vortices accompanied by backflow may occur. A vortex accompanied by backflow is, for example, a vortex generated when the flow near the wall surface with a low flow velocity peels off from the wall surface when the adverse pressure gradient becomes large. On the other hand, if the increase in the flow path cross-sectional area is small, the adverse pressure gradient and the vortices accompanied by backflow can be suppressed. Therefore, by bringing the opening area of the upstream branch opening closer to the sum of the opening areas of the downstream branch openings, it becomes possible to suppress the generation of vortices accompanied by backflow in the branch portion.

[0021] As shown in FIGS. 1 to 3, the confluence portion 6 includes a second confluence opening 62 that connects to an end portion (downstream end portion) of the second flow path 2 close to the fourth flow path 4, a third confluence opening 63 that connects to an end portion (downstream end portion) of the third flow path 3 close to the fourth flow path 4, and a fourth confluence opening 64 that connects to an end portion (upstream end portion) of the fourth flow path 4 close to the second flow path 2 and the third flow path 3. The second confluence opening 62 is an end portion of the second flow path, an end portion of the confluence portion, and a boundary between the second flow path and the confluence portion. The third confluence opening 63 is an end portion of the third flow path, an end portion of the confluence portion, and a boundary between the third flow path and the confluence portion. The fourth confluence opening 64 is an end portion of the fourth flow path, an end portion of the confluence portion, and a boundary between the fourth flow path and the confluence portion. In the present embodiment, the second confluence opening 62 and the third confluence opening 63 are adjacent to each other, and an example is shown in which the flow path width changes with the fourth confluence opening 64 interposed therebetween. As shown in this example, the cross sections of the second flow path 2 having the second confluence opening 62 as an end portion and the third flow path 3 having the third branch opening 3 as an end portion do not overlap. In this example, inside the confluence portion 6, from the confluence portion 6 side toward the fourth flow path 4, the cross-sectional area of the flow path decreases. The location where this decrease stops is defined as the fourth confluence opening 64. Similarly, inside the confluence portion 6, the location where the decrease in the cross-sectional area from the confluence portion 6 side toward the second flow path 2 stops is defined as the second confluence opening 62, and the location where the decrease in the cross-sectional area from the confluence portion 6 side toward the third flow path 3 stops is defined as the third confluence opening 63. Also, the plane including the second confluence opening 62 is defined with the second confluence opening 62 being perpendicular to the tube axis direction in the second flow path 2. Similarly, the plane including the third confluence opening 63 is perpendicular to the tube axis direction in the third flow path 3, and the plane including the fourth confluence opening 64 is perpendicular to the tube axis direction in the fourth flow path 4. That is, the confluence portion 6 corresponds to the region 6 shown hatched in FIG. 2. Since these openings are set for convenience in defining the region of the confluence portion 6, the joint of the base material of the actual flow path structure 100 does not have to coincide with the openings defined in this specification.

[0022] The opening area of at least one of the second confluence opening 62 or the third confluence opening 63 is less than or equal to the opening area of the fourth confluence opening 64. In the present embodiment, the opening area S62 of the second confluence opening 62 is less than or equal to the opening area S64 of the fourth confluence opening 64. S62 is smaller than S64 and the opening area S63 of the third confluence opening 63. Also, in the vicinity of the second confluence opening 62, the channel depth of the second channel 2 is shallower than the channel depths of the third channel 3 and the fourth channel 4. Further, the normal direction of the second confluence opening 62 is different from the axial directions of the third channel 3 and the fourth channel 4. With this structure, the fluid flowing into the confluence portion 6 from the second channel 2 collides with at least a part of the wall surface of the confluence portion 6, the wall surface of the third channel 3, and the wall surface of the fourth channel 4, so that the fluid flowing into the confluence portion 6 from the second channel 2 has a velocity component substantially perpendicular to the wall surface with which it collides and a velocity component in the channel depth direction, generating a vortex. Further, by merging with the fluid supplied from the third channel 3, a swirling flow (swirl) 13 is formed in which the rotation axis is parallel to the axial direction of the fourth channel. Thus, in the confluence portion 6, by making the end of at least one of the upstream channels shallower and creating a difference between the normal direction of the end face of the shallower channel and the axial direction of the downstream channel, it is possible to generate a swirling flow.

[0023] Fig. 4 shows a cross-sectional view of the confluence portion 6 perpendicular to the second confluence opening 62. The cross-sectional shape of the confluence portion 6 is preferably a square with the same width and depth as shown in Fig. 4(a). However, it is not necessary to precisely make it a square, and a substantially square shape with one side slightly longer may be sufficient. Also, if possible, a shape in which the two corners at the bottom of the cross-section are curved surfaces, an R shape, as shown in Fig. 4(b) is also preferable, or a curved surface shape, an R shape, with a radius equal to half the distance of the side of the square at the bottom of the cross-section as shown in Fig. 4(c) may be used. With such a cross-sectional shape, the transverse vortex becomes closer to a perfect circle and the transverse vortex is maintained for a longer time. As a result, the fluid can be well mixed and agitated. Such a cross-sectional shape is not limited to the confluence portion 6 only, and such a cross-sectional shape may be used throughout the channel. In this embodiment, since the channel width is constant, the opening area depends on the channel depth. Here, FIG. 5 shows a schematic diagram of a cross section along the pipe axis direction of the second channel 2 and the third channel 3. As shown in FIG. 5, it is preferable that the channel depth d6 at the second confluence opening 62 is less than 1 / 2 of the channel depth d4 at the fourth confluence opening 64. Further, it is more preferable that d6 / d4 is 1 / 3 or less. By setting the value of d6 / d4 in this way, the velocity at which the fluid flows from the second channel 2 into the confluence portion 6 in accordance with the law of conservation of flow rate increases, and a stronger swirling flow is more likely to occur. Although a shallower channel depth d6 can obtain a flow velocity capable of generating a stronger swirling flow, if it is made too shallow, there is a possibility of excessive pressure loss. Also, in the event of the presence of foreign matter, there is a risk of blockage. Therefore, through experiments or simulations, the channel depth d6 is designed to be shallower. For example, while changing d6 / d4 to smaller values such as 1 / 1, 1 / 2, 1 / 3..., among the set conditions where experimental results show that desired indicators such as the degree of mixing, the degree of dilution, the quality of the product (particle size distribution, inclusion concentration), the machining accuracy of the channel, the pressure loss, or the robustness against foreign matter are appropriate, the condition with the shallowest channel depth d6 may be set. As described above, an example of continuously changing the cross-sectional areas of the second channel 2 and the third channel 3 by changing the channel depth has been explained. Instead of changing the channel depth, at least a part of the channel width may be continuously changed to continuously change the cross-sectional areas of the second channel 2 and the third channel 3.

[0024] The third flow path 3 in the present embodiment has substantially symmetry with respect to the second flow path 2. For example, in the second flow path 2, the opening area S62 of the second confluence opening 62 is smaller than the opening area S52 of the second branch opening 52, and the cross-sectional area of the second flow path 2 decreases from upstream to downstream. In contrast, in the third flow path 3, the opening area S63 of the third confluence opening 63 is larger than the opening area S53 of the third branch opening 53, and the cross-sectional area of the third flow path 3 increases from upstream to downstream. Further, the value obtained by dividing S62 by S52 is preferably 0.5 times or more and 2.0 times or less of the value obtained by dividing S53 by S63, and more preferably 0.8 times or more and 1.2 times or less. It is most preferable that the value obtained by dividing S62 by S52 is equal to the value obtained by dividing S53 by S63.

[0025] In the flow path structure 100 according to the present embodiment, it is preferable that S52 is 0.5 times or more and 2.0 times or less of S63, and / or S53 is 0.5 times or more and 2.0 times or less of S62. It is more preferable that S52 is 0.8 times or more and 1.2 times or less of S63, and / or S53 is 0.8 times or more and 1.2 times or less of S62. It is most preferable that S52 is equal to S63, and / or S53 is equal to S62. In the present embodiment, S53 is equal to S62, and S63 is equal to S52.

[0026] In this way, by making the structures of the respective ends of the second flow path 2 and the third flow path 3 symmetrical, it becomes possible to approximate the flow rates of the fluids flowing through the second flow path and the third flow path 3. The greater the flow rate difference between the second flow path 2 and the third flow path 3, the more difficult rapid mixing becomes, and there is a possibility that it becomes difficult to adjust the pressure in the flow path with the smaller flow rate. Therefore, from the viewpoint of the robustness of the product, it is preferable to split the flow into approximately the same amount.

[0027] Note that since the accuracy of die casting or cutting, which is a preferable method for manufacturing the present flow path structure 100, is generally 5 μm, considering the working accuracy of the flow path, it is desirable that the flow path depth d6 is 10 μm or more.

[0028] In order to generate a uniform swirling flow and avoid the generation of turbulent flow and cavitation in the flow path, it is advisable to avoid making the flow path depth d6 excessively shallow and the opening area of the second confluence opening 62 excessively small. In order to avoid the generation of turbulent flow, it is preferable to set the opening area such that the Reynolds number is less than 2300. Further, from the viewpoints of suppressing cavitation and avoiding clogging due to bubbles or the like in the flow path, the flow path width and the flow path depth of the first to third branch openings (51, 52, 53) and the second to fourth confluence openings (62, 63, 64) are preferably 5 μm or more.

[0029] At least a part of the second flow path 2 and the third flow path 3 has a structure in which the shape of the cross section perpendicular to the pipe axis direction of the flow path continuously changes. For example, in the present embodiment, the shape of the cross section perpendicular to the pipe axis direction of the second flow path 2 continuously changes from the second branch opening 52 toward the second confluence opening 62, and the shape of the cross section perpendicular to the pipe axis direction of the third flow path 3 continuously changes from the third branch opening 53 toward the third confluence opening 63. Here, "continuously changing" means that the shape of the flow path changes smoothly and the shape of the cross section does not involve a sudden change. It is preferable that the area of the flow path cross section continuously changes from the upstream side to the downstream side in the second flow path 2 and the third flow path 3, the shape of the flow path changes smoothly, and the cross-sectional area does not involve a sudden change. In addition, according to the present embodiment, since the flow path width is constant, at least a part of the second flow path 2 has a structure in which the flow path depth continuously changes. Here, "continuously changing" means that the shape of the flow path changes smoothly and the flow path depth does not involve a sudden change. Generally, at a location where the area of the flow path cross section rapidly expands, a vortex accompanied by a backflow formed by a fluid that cannot follow the main flow may occur on the downstream side thereof, and at a location where the area rapidly contracts, a vortex accompanied by a backflow may occur on the upstream side thereof. Therefore, by designing so that the area of the flow path cross section does not involve a sudden change from the upstream side to the downstream side in the second flow path 2 and the third flow path 3, the generation of vortices accompanied by backflows in the second flow path and the third flow path 3 can be suppressed. The second flow path 2 and the third flow path 3 shown in FIG. 5 have a continuously changing flow path depth and a sloped bottom surface. Let the angle formed by the bottom surface and the top surface in the second flow path 2 be the expansion angle θs2, and the angle formed by the bottom surface and the top surface in the third flow path 3 be the expansion angle θs3. θs2 and θs3 are not limited, but for example, it is preferable that they be 10° or less. More generally, in a section of an arbitrary distance W in the flow path, when the hydraulic diameter of the upstream end in the section is d H1 , the hydraulic diameter of the downstream end is d H2 , and the expansion angle is θs, it is desirable that θs be 10° or less while W, d H1 , d H2 satisfy the following relational expression (3).

[0030] d H2 = d H1 + 2×W×tan(θs / 2)…(3) Thus, in a flow path with an increase or decrease in cross-sectional area, by restricting the upper limit value of the divergence angle, it is possible to suppress the generation of vortices accompanied by backflow due to the adverse pressure gradient.

[0031] FIG. 6 is a schematic diagram showing an example of the flow path structure 100 according to the first embodiment. The angle θ5 formed between the axial direction of the flow in the second flow path 2 and the axial direction of the first flow path 1 changes from the upstream side to the downstream side in the second flow path 2. Similarly, the angle θ6 formed between the axial direction of the third flow path 3 and the axial direction of the first flow path 1 changes from the upstream side to the downstream side in the third flow path 3. Generally, when the direction of the main flow changes abruptly, vortices accompanied by backflow may be generated by the fluid that cannot follow the main flow. Therefore, by designing such that the axial direction (i.e., the normal direction of the cross-section) continuously changes from the upstream side to the downstream side in the second flow path 2 and the third flow path 3, it is possible to suppress the generation of vortices accompanied by backflow in the second flow path 2 and the third flow path 3.

[0032] In FIG. 6, let the angle formed between the axial direction in the first flow path 1 and the plane including the second branch opening 52 be θ1, the angle formed between the axial direction in the first flow path 1 and the plane including the third branch opening 53 be θ2, the angle formed between the plane including the second branch opening 52 and the axial direction in the fourth flow path 4 be θ3, and the angle formed between the plane including the third branch opening 53 and the axial direction in the fourth flow path 4 be θ4. In the flow path structure 100, it is preferable that the magnitudes of θ1 and θ4, and θ2 and θ3 are the same, respectively. That is, it is preferable that the upstream end of the second flow path 2 and the downstream end of the third flow path 3, and the upstream end of the third flow path 3 and the downstream end of the second flow path 2 are symmetric with respect to the center point 20 which is the midpoint of the branch portion 5 and the confluence portion 6. The magnitudes of θ1 to θ4 are not particularly limited, but for example, it is desirable that each is greater than 0° and less than 90°. Further, it is more preferable that each of the magnitudes of θ1 to θ4 is 0° or more and 70° or less.

[0033] Including the flow paths in the middle other than the respective end portions of the second flow path 2 and the third flow path 3, it is preferable that the second flow path 2 and the third flow path 3 have an approximately point-symmetrical shape with the midpoint between the branch portion 5 and the confluence portion 6 as the center point 20. The center point 20 is the midpoint of the line segment connecting the intersection on the branch portion 5 side of the extension lines of the respective pipe axes of the second flow path 2 and the third flow path 3 and the intersection on the confluence portion 6 side, as viewed from a cross-section parallel to the plane of FIG. 1. By making the shapes of the respective flow paths from the branch portion 5 to the confluence portion 6 similar, it is possible to make the flow rates of the fluids flowing through the second flow path 2 and the third flow path 3 closer to being equal.

[0034] The example in which the pipe axis direction, the angle formed by the bottom surface and the top surface, and the cross-sectional area of the flow path change uniformly throughout the second flow path 2 has been described above. By changing uniformly throughout the second flow path 2 and the third flow path 3 in this way and increasing the region where the pipe axis direction and the cross-sectional area change, the change rates of the pipe axis direction, the angle formed by the bottom surface and the top surface, and the cross-sectional area of the flow path can be suppressed. Therefore, from the viewpoint of suppressing vortices accompanied by backflow in the second flow path 2 and the third flow path 3, it is preferable to change uniformly throughout the second flow path 2 and the third flow path 3. However, the pipe axis direction, the angle formed by the bottom surface and the top surface, and the cross-sectional area of the flow path do not necessarily need to change throughout the second flow path 2 and the third flow path 3.

[0035] The flow path width of the fourth flow path 4 in the present embodiment is constant. The upstream end portion of the fourth flow path 4 and the confluence portion 6 are connected via the fourth confluence opening 64. The downstream opening of the fourth flow path 4 may be connected to a flow path structure other than the flow path structure 100.

[0036] In the fourth flow path 4, a swirling flow 13 is formed (Fig. 3). The axis of rotation of the swirling flow 13 is substantially parallel to the main axis of the fourth flow path 4. From the upstream side to the downstream side of the fourth flow path 4, since the swirling flow 13 persists over a long distance compared to a transverse vortex, the mixing of the fluid flowing into the fourth flow path 4 via the third flow path 3 and the fluid flowing into the fourth flow path 4 via the second flow path 2 is promoted and stirred. Further, unlike a transverse vortex, the swirling flow 13 does not include a flow in the direction opposite to the axial direction of the pipe within the fourth flow path 4. Thereby, the difference in the degree of mixing between the substances caught by the reverse flow and those not is eliminated, and a more uniform mixing can be realized.

[0037] By using such a flow path structure 100 for fluid mixing, it is possible to effectively mix the fluid by the swirling flow generated within the flow path. For example, when a solvent is mixed with and stirred into a solution, the solution will be diluted compared to before mixing. At this time, by effectively mixing and stirring the fluids with each other, dilution can be made more uniform.

[0038] In the present embodiment, the case where both the reference flow path width and the reference flow path depth are 0.3 mm has been described as an example, but the dimensions of the flow path do not have to be on such an order. The opening area of the flow path included in the flow path structure 100 is 100 mm 2 Although it is preferably the following, from the viewpoints of reducing pressure loss, suppressing cavitation, and avoiding clogging due to air bubbles or the like in the flow path, the flow path width and the flow path depth are preferably 5 μm or more.

[0039] In the present embodiment, from the viewpoint of ensuring the strength of the mold for mass-producing the flow path, when the flow path depth is L and the flow path width is W, the ratio L / W of these is preferably 1 or less.

[0040] Note that the side surface of the flow path of the flow path structure 100 shown in FIG. 1 consists of a plane parallel to the normal of the plane of FIG. 1. Although it is not always necessary for the side surface of the flow path to be parallel to the normal of the plane of FIG. 1, by designing the side surface of the flow path to be parallel to the normal of the plane of FIG. 1, it becomes possible to easily create the flow path with only one-directional processing perpendicular to the paper surface. Further, the top surface of the flow path structure 100 is included in a single plane from the top surface of the first flow path 1 to the top surfaces of the second flow path 2, the third flow path 3, and the fourth flow path 4. By designing the top surface to be included in a single plane, as shown in FIG. 7, it becomes possible to use a single flat plate-like member 70 as the member for the top surface of the flow path structure 100. As a result, it becomes possible to manufacture the flow path structure 100 by simply sealing a single flat plate over the flow path with the side surfaces and the bottom surface processed, so that the manufacturing cost becomes lower and the flow path structure 100 can be manufactured with higher precision. However, it is not always necessary for the top surface to be included in a single plane.

[0041] FIG. 8 is a perspective view of the flow path structure 100 and a view showing some of the vortices other than the swirling flow 13 that can occur at the confluence portion 6 and the branching portion 5. The cross section rapidly decreases upstream and downstream of the third branch opening 53. Therefore, at the corner provided immediately below (in the depth direction) of the third branch opening 53, a vortex 11 can be generated by the fluid that cannot follow the mainstream due to the rapid decrease in the cross section. When the second flow path 2 does not exist, the vortex 11 becomes a vortex with a reverse flow. However, since the rotation axis of the vortex 11 is substantially parallel to the normal direction of the second branch opening 52, the vortex 11 is pushed toward the second flow path 2 and becomes a swirling flow. On the other hand, the cross-sectional area rapidly increases upstream and downstream of the second confluence opening 62. Therefore, at the corner provided immediately below (in the depth direction) of the second confluence opening 62, a vortex 12 can be generated by the fluid that cannot follow the mainstream due to the rapid increase in the cross-sectional area. When the third flow path 3 does not exist, the vortex 12 becomes a vortex with a reverse flow. However, since the rotation axis of the vortex 12 is substantially parallel to the normal direction of the third confluence opening 63, the vortex 12 is pushed by the flow flowing out from the third flow path 3 and becomes a swirling flow. By converting these vortices with reverse flows into swirling flows, a more uniform mixing can be realized.

[0042] (First Modification Example) FIG. 9 is an example of a schematic view of the flow path structure 100 in this modification example. Thus, at a location where the second branch opening 52 and the third branch opening 53 are adjacent, the second flow path 2 and the third flow path 3 may be smoothly connected. Similarly, at a location where the second confluence opening 62 and the third confluence opening 63 are adjacent, the second flow path 2 and the third flow path 3 may be smoothly connected.

[0043] (Second Modification Example) In the first embodiment, an example in which the axial direction of the flow path, the angle formed by the bottom surface and the top surface, and the cross-sectional area of the flow path uniformly change in the entire range from the branch portion 5 to the confluence portion 6 of the flow path structure 100 in the entire region of the second flow path 2 or the third flow path 3 has been described. However, the region where the axial direction of the flow path, the angle formed by the bottom surface and the top surface, and the cross-sectional area of the flow path change does not have to be the entire region. Also, in the second flow path 2 and the third flow path 3, the rate of change of the axial direction of the flow path, the angle formed by the bottom surface and the top surface, or the cross-sectional area of the flow path does not have to be constant. In this modification example, the flow path structure 100 having a region where the angle formed by the bottom surface and the top surface does not change in the second flow path 2 and the third flow path 3 will be described. FIG. 10 is a schematic cross-sectional view along the axial direction of the flow path structure 100 in this modification example. In FIG. 10, the flow path depth in the region of the second flow path 2 close to the branch portion 5 is constant, and the flow path depth in the region of the third flow path 3 close to the confluence portion 6 is constant. By configuring the second flow path 2 and the third flow path 3 in such a structure, the region with a large flow path cross-sectional area can be lengthened, and the pressure loss in the second flow path 2 and the third flow path 3 can be reduced. In this embodiment, it is particularly preferable that the region where the flow path depth changes and the region where it does not change are smoothly connected.

[0044] (Third Modification Example) FIG. 11 is a schematic cross-sectional view along the pipe axis direction of the flow path structure 100 in this modified example. In the flow path structure 100 of this modified example, the top surfaces of the first flow path 1, the second flow path 2, and the fourth flow path 4 are included in a single plane. Let this plane be plane α. On the other hand, the bottom surfaces of the first flow path 1, the third flow path 3, and the fourth flow path 4 are included in a single plane different from plane α. Let the plane including the bottom surfaces of the first flow path 1, the third flow path 3, and the fourth flow path 4 be plane β. By designing such that the top surfaces of the first flow path 1, the second flow path 2, and the fourth flow path 4 are included in a single plane α, it becomes possible to use a single flat plate-shaped member for the top surface member. Similarly, by designing such that the plane including the bottom surfaces of the first flow path 1, the third flow path 3, and the fourth flow path 4 is included in a single plane β, it becomes possible to use a single flat plate-shaped member for the bottom surface member. As a result, it becomes possible to fabricate the flow path structure 100 simply by sandwiching and sealing the processed flow paths between the side surface and the bottom surface, or between the side surface and the top surface with two flat plates. Therefore, for example, compared with the case of fabricating the flow path structure by creating the flow paths divided by the plane γ shown in the figure and abutting those flow paths against each other, misalignment between the flow paths that may occur in the joining of fine flow paths is eliminated, and the flow path structure 100 can be fabricated with higher precision.

[0045] (Fourth Modified Example) FIG. 12 is a schematic diagram showing an example of the flow path structure 100 in this modified example. In at least a part of the first flow path 1, the shape of the cross section perpendicular to the tube axis direction in the first flow path 1 continuously changes as it approaches the first branch opening 51. If the region far from the branch portion 5 in the first flow path 1 is defined as region 1a, and the region between region 1a and the branch portion 5 is defined as region 1b, the cross-sectional area of region 1b increases from region 1a toward the branch portion 5. In this way, by expanding the opening area S51 of the first branch opening 51, the sum of the cross-sectional areas of the flows flowing into the branch portion 5 and the sum of the cross-sectional areas of the flows flowing out from the branch portion 5 can be made closer, and it becomes possible to suppress the generation of vortices accompanied by a sudden increase in the cross-sectional area at the branch portion 5. However, if the expansion angle θ8 of region 1b is made too large, vortices accompanied by backflow may occur in region 1b, so θ8 is preferably 10° or less. However, this value does not limit the shape of the flow path structure 1.

[0046] Also, although not shown, when another flow path structure 100 is further provided and used on the downstream side of the flow path structure, the fourth flow path 4 in the figure is connected to the branch portion 5 of another flow path structure. At this time, if the region far from the confluence portion 6 in the figure in the fourth flow path 4 is defined as region 4b, and the region between region 4b and the confluence portion 6 in the figure is defined as region 4a, the cross-sectional area of region 4b increases from region 4a toward the branch portion 5 of another flow path structure. The expansion angle θ9 of region 4b is preferably 10° or less, similar to θ8, but θ8 and θ9 do not necessarily have to be the same value.

[0047] (Fifth Modified Example) FIG. 13 is a schematic diagram showing an example of the flow path structure 100 in this modified example. In this modified example, similar to the fourth modified example, the cross-sectional area of region 1b increases from region 1a toward the branch portion 5. However, among the flow paths connected to the downstream side of the branch portion 5, the cross-sectional area of region 1b increases while being biased toward the flow path with the largest opening area at the boundary with the branch portion 5, which is different from the fourth modified example. In this modified example, among the flow paths connected to the downstream side of the branch portion 5, since the opening area of the second branch opening 52, which is the boundary between the second flow path 2 and the branch portion 5, is the largest, the cross-sectional area of region 1b increases while being biased toward the second flow path 2. Near the boundary between the branch portion 5 and the flow path with the largest opening area downstream thereof, the flow is more likely to separate and reverse flow is likely to occur. Therefore, as shown in this modified example, by increasing the cross-sectional area of the upstream flow path with respect to the branch portion 5 while being biased toward the flow path with the largest opening area downstream of the branch portion 5, it is possible to suppress the separated flow accompanied by reverse flow. Similarly, also in the fourth flow path 4, the cross-sectional area of region 4b increases while being biased to one side. Although not shown, the same structure as the branch portion 5 is connected to the downstream of the fourth flow path 4, and further downstream thereof, flow paths having the same structure as the second flow path 2 and the third flow path 3 are arranged and connected in the same positional relationship as the second flow path 2 and the third flow path 3 shown in the figure.

[0048] (Sixth Modified Example) FIG. 14 is a schematic diagram showing an example of the flow path structure 100 in this modified example. The cross-sections of the first flow path 1 and the fourth flow path 4 are larger than the cross-sections of the second flow path 2 and the third flow path 3. By designing the flow paths upstream of the branch portion 5 to be larger in this way, it is possible to make the sum of the cross-sectional areas at the upstream end with respect to the branch pipe closer to the sum of the cross-sectional areas at the downstream end, and it becomes possible to suppress the vortices accompanied by reverse flow due to a sharp increase in the cross-sectional area.

[0049] (Seventh Modified Example) FIG. 15 is a schematic diagram showing an example of the flow path structure 100 in this modified example. In this modified example, a plane obtained by extending the downstream end portion of the side surface of the third flow path 3 closer to the second flow path 2 is defined as plane δ. The second confluence opening 62, which is the boundary between the second flow path 2 and the confluence portion 6, is included in plane δ.

[0050] The confluence part 6 according to this embodiment does not necessarily have a substantially line-symmetric shape with the axial direction of the first flow path 1 as the axis. For example, in FIG. 15, the side surface between the second confluence opening 62 and the fourth confluence opening 64 is a plane, while the side surface between the third confluence opening 63 and the fourth confluence opening 64 partly includes a curved surface. The side surface between the second confluence opening 62 and the fourth confluence opening 64 is an extension of the fourth flow path 4 toward the first flow path 1 side, and the angle θ formed by this side surface and the plane δ decreases, for example, as compared with the case of FIG. 1.

[0051] With such a configuration, the collision of the flow flowing out from the third flow path 3 against the side surface of the confluence part 6 can be alleviated, and the generation of vortices accompanied by backflow can be suppressed.

[0052] (Second Embodiment) FIGS. 16 to 18 are respectively a schematic view of the flow path structure 100a in this embodiment as viewed from the top surface side, a schematic cross-sectional view along the pipe axis direction of the second flow path 2 and the third flow path 3 of the flow path structure 100a, and a perspective view of the flow path structure 100a. At the location where the branch part 5 is connected to the second flow path 2 and the third flow path 3, the flow path depths of the second flow path 2 and the third flow path 3 are the same as the depth of the first flow path 1. However, the flow path width of the second flow path 2 is narrower than the flow path width of the first flow path 1. In the first embodiment, the flow path depth of the second flow path 2 was made shallower to approximate the sum of the cross-sectional areas of the flow flowing into the branch part 5 and the cross-sectional area flowing out from the branch part 5. However, in this embodiment, by narrowing the flow path width, the sum of the cross-sectional areas of the flow flowing into the branch part 5 and the cross-sectional area flowing out from the branch part 5 is approximated, and the generation of vortices accompanied by backflow is suppressed.

[0053] (First Variation) FIG. 19 is an example of a schematic view of the flow path structure 100a in this variation. At the location where the confluence part 6 is connected to the second flow path 2 and the third flow path 3, the flow path depth of the third flow path 3 is the same as the depth of the fourth flow path 4. However, the flow path width of the third flow path 3 is narrower than the flow path width of the fourth flow path 4. In the second embodiment, the flow path width of the third flow path 3 was the same as the flow path width of the fourth flow path 4. However, in this embodiment, by narrowing the flow path width, the velocity of the fluid flowing from the second flow path 2 into the confluence part 6 increases, and a stronger swirling flow is more likely to occur.

[0054] (Third Embodiment) In the first and second embodiments, an example has been described in which one first flow path 1 is provided upstream of the branch portion 5, two flow paths, i.e., a second flow path 2 and a third flow path 3, are provided downstream of the branch portion 5, and one fourth flow path 4 is provided downstream of the confluence portion 6. However, the number of flow paths is not limited to this. Fig. 20 shows a schematic diagram of a flow path structure 100b having N flow paths (where 1 ≤ N) upstream of the branch portion 5b, M flow paths (where 2 ≤ M) downstream of the branch portion 5b, M flow paths upstream of the confluence portion 6b, and O flow paths (where 1 ≤ O) downstream of the confluence portion 6b. In the present embodiment, the N flow paths upstream of the branch portion 5b are collectively referred to as a first flow path group 10, the M flow paths downstream of the branch portion 5b and upstream of the confluence portion 6b are collectively referred to as a second flow path group 20, and the O flow paths downstream of the confluence portion 6b are collectively referred to as a third flow path group 30. The flow path structure 100b includes a first flow path group 10 including one or more flow paths, a second flow path group 20 including two or more flow paths and connected to the first flow path group 10 via the branch portion 5b, and a third flow path group 30 including one or more flow paths and connected to the second flow path group via the confluence portion 6b. The branch portion 5b includes a first flow path group side branch opening 51b connected to an end of the flow path included in the first flow path group 10 close to the second flow path group 20, and a second flow path group side branch opening 52b connected to an end of the flow path included in the second flow path group 20 close to the first flow path group 10. The confluence portion 6b includes a second flow path group side confluence opening 62b connected to an end of the second flow path group 20 close to the third flow path group 30, and a third flow path group side confluence opening 63b connected to an end of the third flow path group 30 close to the second flow path group 20. Here, since the second flow path group side branch opening 51b is the boundary between each flow path included in the first flow path group 10 and the branch portion 5b, the number of the first flow path group side branch openings 51b is the same as the number of flow paths (N) included in the first flow path group 10. Similarly, since the second flow path group side branch opening 52b is the boundary between each flow path included in the second flow path group 20 and the branch portion 5b, the number of the second flow path group side branch openings 52b is the same as the number of flow paths (M) included in the second flow path group 20. Further, when M is equal to or greater than N, regarding the total opening area ΣSi of the first flow path group side branch openings 51b and the total opening area ΣSj of the second flow path group side branch openings 52b, it is preferable that ΣSj is 1.0 times or more and M / N times or less with respect to ΣSi, and more preferably 0.75 × M / N times or less. Further, it is desirable that the relationship ΣSj ≒ ΣSi is satisfied.By ensuring that the total opening area of the first flow path group side branch openings 51b does not exceed the total opening area of the second flow path group side branch openings 52b in this way, it is possible to suppress the vortices accompanied by reverse flow generated by a sudden change in cross-sectional area.

[0055] When ΣSj / ΣSi is greater than 1, although it is possible to suppress the vortices accompanied by reverse flow as it approaches 1, excessive pressure loss may occur in the pipe with a narrowed cross-sectional area in an attempt to approach 1. Also, in the event of the presence of foreign matter, there is a risk of blockage. Therefore, through experiments or simulations, ΣSi and ΣSj are brought closer, for example, ΣSj / ΣSi is changed to smaller values such as 1.0×(M / N), 0.9×(M / N), 0.8×(M / N)···, and among the set conditions where experimental results show that desired indicators such as the degree of suppression of vortices accompanied by reverse flow, the degree of mixing, the degree of dilution, the quality of the product (particle size distribution, inclusion concentration), the machining accuracy of the flow path, the pressure loss, or the robustness against foreign matter are appropriate, the condition where ΣSj / ΣSi is closest to 1 should be set.

[0056] Note that at least one opening area of the second flow path group side branch openings 52b is less than or equal to at least one opening area of the first flow path group side branch openings 51b.

[0057] Since the second flow path group side confluence opening 62b is the boundary between each flow path included in the second flow path group 20 and the confluence part 6b, the number of second flow path group side confluence openings 62b is the same as the number (M) of the flow paths included in the second flow path group 20. Similarly, since the third flow path group side confluence opening 63b is the boundary between each flow path included in the third flow path group 30 and the confluence part 6b, the number of third flow path group side confluence openings 63b is the same as the number (O) of the flow paths included in the third flow path group 30. Regarding the j-th opening area Sj' of the second flow path group side confluence opening 62b and the k-th opening area Sk of the third flow path group side confluence opening 63b, it is sufficient that at least one of Sj' is smaller than at least one of Sk.

[0058] The flow paths included in the second flow path group 20 are flow paths that connect the branch portion 5b and the confluence portion 6b. In at least one flow path included in the second flow path group 20, the opening area of the second flow path group side confluence opening 62b is smaller than the opening area of the second flow path group side branch opening 52b, and the cross-sectional area of the flow path decreases from upstream to downstream.

[0059] Note that at least a part of the flow paths included in the second flow path group 20 has a structure in which the shape of the cross section perpendicular to the tube axis direction of the flow path continuously changes. For example, it may be a structure in which the flow path depth continuously changes, or it may be a structure in which the flow path width continuously changes.

[0060] It is preferable that the top surfaces of the flow paths included in the first flow path group 10, the second flow path group 20, and the third flow path group 30 are included in a single plane. By designing so that the top surface is included in a single plane, as shown in FIG. 7, it becomes possible to use a single flat plate member as the member for the top surface of the flow path structure 100b. As a result, it becomes possible to manufacture the flow path structure 100b by simply sealing a single flat plate over the flow paths with the side surfaces and the bottom surface processed, so that the manufacturing cost becomes lower and the flow path structure 100b can be manufactured with higher precision. Alternatively, at least a part of the top surfaces of the flow paths included in the first flow path group 10, the second flow path group 20, and the third flow path group 30 is included in a single plane (first plane), and among the bottom surfaces of the flow paths included in the first flow path group 10, the second flow path group 20, and the third flow path group 30, the bottom surface facing the top surface not included in the first plane may be included in a single plane (second plane) different from the first plane.

[0061] Note that, among the flow paths included in the second flow path group 20, it is preferable that the opening area of at least one flow path is smaller than the opening area of the second flow path group side branch opening 52b, and among the flow paths included in the second flow path group 20, it is preferable that the opening area of at least another flow path is larger than the opening area of the second flow path group side branch opening 52b. That is, it is preferable that the second flow path group 20 includes a flow path whose cross-sectional area expands from upstream to downstream and a flow path whose cross-sectional area contracts from upstream to downstream. As an example, a structure in which the cross-sectional area of the j-th flow path included in the second flow path group 20 expands from upstream to downstream and the cross-sectional area of the (M−j + 1)-th flow path included in the second flow path group 20 contracts from upstream to downstream is also preferable.

[0062] Note that the flow path width and flow path depth of the flow paths included in the flow path structure 100b are preferably 5 μm or more. At least, the flow path width and flow path depth may be 5 μm or more at the location where the flow path cross-sectional area is the smallest. That is, the flow path width and flow path depth of the second flow path group side confluence opening 62b are preferably 5 μm or more. Further, the depth of the flow paths included in the flow path structure 100b is preferably equal to or less than the width of the flow paths. Further, the opening area of the flow paths included in the flow path structure 100b is preferably 2 100 mm or less.

[0063] Note that the second flow path group 20 preferably has an approximately point-symmetrical shape with the midpoint between the branch portion 5b and the confluence portion 6b as the center point. As an example, the value obtained by dividing the opening area of the opening in the second flow path group side confluence opening 62b that connects to the j-th flow path included in the second flow path group 20 by the opening area of the opening in the second flow path group side branch opening 52b that connects to the j-th flow path included in the second flow path group 20 is 0.5 times or more and 2.0 times or less, more preferably 0.8 times or more and 1.2 times or less, of the value obtained by dividing the opening area of the opening in the second flow path group side branch opening 52b that connects to the (M−j + 1)-th flow path included in the second flow path group 20 by the opening area of the opening in the second flow path group side confluence opening 62b that connects to the (M−j + 1)-th flow path included in the second flow path group 20. Note that it is most preferable that this value is 1.0 times.

[0064] Note that, in the flow path structure 100b according to the present embodiment, the opening area of the opening that connects to the j-th flow path included in the second flow path group 20 among the second flow path group side branch openings 52b is 0.5 times or more and 2.0 times or less the opening area of the opening that connects to the (M−j + 1)-th flow path included in the second flow path group 20 among the second flow path group side confluence openings 62b, or / and, the opening area of the opening that connects to the (M−j + 1)-th flow path included in the second flow path group 20 among the second flow path group side branch openings 52b is preferably 0.5 times or more and 2.0 times or less the opening area of the opening that connects to the j-th flow path included in the second flow path group 20 among the second flow path group side confluence openings 62b. These values are more preferably 0.8 times or more and 1.2 times or less, and most preferably 1.0 times.

[0065] Note that the flow path structure 100b may also have a structure in which the shape of the cross section perpendicular to the tube axis direction of the flow path continuously changes as it approaches the first branch portion 5b in at least a part of the flow paths included in the first flow path group 10 or the flow paths included in the third flow path group 30, like the flow path structure 100 shown in FIG. 12.

[0066] Note that a plurality of flow path structures 100b may be used and implemented as a fluid structure unit.

[0067] Note that the flow path structure 100b may further include a configuration such as an inlet portion 80 capable of allowing two or more types of fluids to flow into at least one flow path included in the first flow path group 10.

[0068] (Fourth Embodiment) Figure 21 is an example of a schematic diagram when a plurality of flow channel structures are used in combination. In the present embodiment, a structure including flow channel structures 110 and 120 having the same shape as the flow channel structure 100 is defined as a flow channel structure unit 300. Further, in FIG. 21, an inlet portion 80 capable of allowing two types of fluids to flow into the first flow channel 1 is provided on the upstream side of the flow channel structure 100. By connecting a plurality of flow channel structures in this way, a repetitive swirling flow can be generated, and more rapid mixing of different types of liquids can be achieved. Although not shown, the inlet portion 80 may have a structure with three or more branches and be capable of allowing three or more types of fluids to flow in.

[0069] Note that the number of flow channel structures included in the flow channel structure unit 300 shown in the figure is three, but the number of flow channels may be one or two, and further, four or more may be possible.

[0070] Also, although the figure shows a state where a plurality of flow channel structures are connected in series, the connection method of the flow channel structures is not limited to this, and may include a structure connected in parallel via a branch portion 5 or the like.

[0071] In addition, since the inlet portion 80 in the figure has two inlets, two types of fluids can flow in, but the number of inlets and the number of types of liquids are not limited to this. The inlet portion 80 may have three or more inlets and be capable of allowing three or more types of liquids to flow in.

[0072] (Fourth Embodiment) In the present embodiment, a manufacturing method of the flow channel structure (hereinafter, collectively referred to as "flow channel structure 100") described in the first to third embodiments will be described below with reference to FIG. 22. As shown in FIG. 22(a), the flow channel structure 100 includes, for example, a substrate 102 in which a groove 101 functioning as a flow channel is formed, and a plate-shaped lid portion 103 joined to the substrate 102 so as to cover the top surface of the groove 101.

[0073] The material of the substrate 102 may be appropriately selected from resins such as acrylic, polyethylene, polypropylene, and polycarbonate, glass, ceramics, or metals according to the application. For example, if the flow path structure 100 is for medical use, cycloolefin polymer (COP) or the like is also a preferable example. If it is to be reused many times, ceramics such as glass and quartz are preferable due to their stability. If adjustment of temperature or the like is to be achieved, a metal with a corrosion-resistant treatment on its surface may be used. The groove 101 can be formed, for example, by press working or cutting using a mold. At the location corresponding to the shallow part, the groove 101 may be formed or cut shallower than other parts.

[0074] As the material of the lid portion 103, for example, the same materials as those described for the substrate 102 can be used. The lid portion 103 can be, for example, plate-shaped. Alternatively, as shown in FIG. 22(b), a thin film-like lid portion 104 may be used.

[0075] The film-like lid portion 104 can also be provided with sensor terminals 105 for monitoring the state of the fluid. Alternatively, various functions or characteristics such as high thermal conductivity or a function (not shown) of performing a specific treatment on a specific substance can be imparted to the film-like lid portion 104.

[0076] When there is a concern that the film-like lid portion 104 may bulge due to internal pressure, as shown in FIG. 22(c), the bulging may be suppressed by pressing the pressing plate 106 from above the film-like lid portion 104. The pressing plate 106 may be provided with a heat medium flow path 107 for heat exchange disposed therein, or electrical terminals (not shown) having a sensor function.

[0077] The flow path structure 100 can be manufactured by such a simple procedure as forming the groove 101 in the substrate 102 and joining the lid portion 103 or the film-like lid portion 104. Therefore, for example, since it is not necessary to form grooves in both the substrate 102 and the lid portion 103 and to perform precise alignment therebetween, the mass productivity is very high.

[0078] Furthermore, the depth of the groove 101 at the location where the channel depth becomes small is made the same as that of other portions, and a film-like lid portion 104 whose thickness varies depending on the position is attached to the corresponding location to form a channel whose channel depth changes. That is, the channel formed in this way has a varying channel depth due to the thickness of the top surface varying depending on the position. Even in such a structure, highly uniform mixing can be achieved, similar to the structure in which the shape of the bottom surface varies depending on the position.

[0079] (Fifth Embodiment) In this embodiment, a fluid stirring method is provided. The fluid stirring method includes flowing a fluid to be stirred through the flow channel structure 100 of the embodiment. According to the fluid stirring method, by using the flow channel structure 100 of the embodiment, the fluid can be more mixed and stirred.

[0080] When using the flow channel structure 100 of the first to fourth embodiments, this method includes flowing the fluid so that it passes through the first flow channel 1 and then through the second flow channel 2 or the third flow channel 3 and flows through the fourth flow channel 4. Also, in this method, the fluid flowing in the channel may be two or more different types of fluids, and according to the flow channel structure 100 of the above first to fourth embodiments, these fluids can be mixed and stirred.

[0081] (Sixth Embodiment) In this embodiment, a method for manufacturing lipid particles 200 encapsulating a drug 202 using the flow channel structure 100 of the embodiment will be described.

[0082] First, the lipid particles 200 produced by this method will be described. As shown in FIG. 23, the lipid particles 200 are composed of a lipid membrane formed by arranging lipid molecules and are substantially spherical and hollow. A drug 202 is encapsulated in the lumen 201 of the lipid particles 200. The lipid particles 200 can be used, for example, to deliver the drug 202 into cells.

[0083] FIG. 24 is a flowchart showing an example of a method for producing lipid particles 200. The method for producing lipid particles 200 includes a step of condensing a drug 202 (in the case of a nucleic acid) (condensing step S1), using the flow channel structure 100 of the embodiment, from one of the inlets located upstream of the first flow channel 1 (the first inlet), flowing a first solution containing a lipid, which is a material of the lipid particles 200, into an organic solvent, flowing a second solution containing the drug 202 into an aqueous solvent from another inlet (the second inlet) located upstream of the first flow channel 1 to mix the first solution and the second solution to obtain a mixed solution (mixing step S2), a step of forming particles of the lipid by reducing the concentration of the organic solvent in the mixed solution to generate lipid particles 200 encapsulating the drug 202 (particle formation step S3), and a step of concentrating the lipid particle 200 solution (concentrating step S4). This production method can be carried out using, for example, the flow channel structure shown in FIG. 25. (a) of FIG. 25 shows an agglomeration flow channel structure 301 having a configuration for performing the condensing step S1, (b) shows the flow channel structure 302 of the embodiment for performing the mixing step S2, (c) shows a particle formation flow channel structure 303 having a configuration for performing the particle formation step S3, and (d) shows a concentration flow channel structure 304 having a configuration for performing the concentrating step S4.

[0084] Hereinafter, an example of the procedure of this production method will be described.

[0085] First, a first solution and a second solution are prepared. The first solution contains a lipid in an organic solvent. The lipid is a lipid that constitutes the lipid particles 200. The second solution contains the drug 202 in an aqueous solvent.

[0086] · Condensing step S1 The drug 202 is, for example, a nucleic acid although not limited thereto. The nucleic acid drug 202 is, for example, a nucleic acid containing DNA, RNA, and / or other nucleotides, such as mRNA of a specific gene, DNA encoding a gene, DNA containing a gene expression cassette containing a gene and other sequences such as a promoter for expressing the gene, a vector, and the like. When the drug 202 is a nucleic acid, first, an agglomeration step S1 of agglomerating the nucleic acid (drug 202) may be performed.

[0087] Nucleic acid condensation is performed, for example, using a nucleic acid condensation peptide. The nucleic acid condensation peptide can reduce the particle size of the lipid particle 200 by condensing the nucleic acid into a smaller size, and can encapsulate more nucleic acid within the lipid particle 200. As a result, the amount of nucleic acid remaining outside the lipid particle 200 that can cause aggregation of the lipid particle 200 can be reduced.

[0088] Preferred nucleic acid condensation peptides are, for example, peptides containing 45% or more of cationic amino acids in total. More preferred nucleic acid condensation peptides have RRRRRR (the first amino acid sequence) at one end and the sequence RQRQR (the second amino acid sequence) at the other end. Between the first amino acid sequence and the second amino acid sequence, there are included 0 or more intermediate sequences consisting of RRRRRR or RQRQR. Also, among the first amino acid sequence, the second amino acid sequence, and the intermediate sequence, two or more neutral amino acids are included between two adjacent sequences. The neutral amino acid is, for example, G or Y. The other end may have RRRRRR (the first amino acid sequence) instead of the second amino acid sequence.

[0089] The above nucleic acid condensation peptide preferably has the following amino acid sequence: RQRQRYYRQRQRGGRRRRRR (SEQ ID NO: 1) RQRQRGGRRRRRR (SEQ ID NO: 2) RRRRRRYYRQRQRGGRRRRRR (SEQ ID NO: 3).

[0090] Furthermore, a nucleic acid condensation peptide having the following amino acid sequence can also be used in combination with any of the above nucleic acid condensation peptides. This peptide can further condense the nucleic acid condensate condensed by the above nucleic acid condensation peptide.

[0091] GNQSSNFGPMKGGNFGGRSSGPYGGGGQYFAKPRNQGGY (M9) (SEQ ID NO: 4) As shown in Fig. 25(a), the aggregating channel structure 301 for performing the aggregating step S1 is, for example, a Y-shaped channel. An aggregating agent inlet 312 is provided, for example, at the upstream end of one of the branched channels 311 of the Y-shape, and an aggregating agent containing a nucleic acid condensing peptide is flowed therethrough. A chemical agent inlet 314 is provided at the upstream end of the other channel 313, and a solution containing a nucleic acid (chemical agent 202) in an aqueous solvent is flowed therethrough. The aqueous solvent is, for example, water, saline such as physiological saline, an aqueous glycine solution, or a buffer solution. As a result, the condensing agent and the solution containing the chemical agent 202 are mixed in the channel 315 where the channels 311 and 313 merge. By mixing, a second solution containing the condensed chemical agent 202 is obtained.

[0092] The condensing step S1 does not necessarily need to be performed using a channel, and it is sufficient to mix and stir an aggregating agent and a solution containing a nucleic acid (chemical agent 202) in an aqueous solvent.

[0093] Since the above effects are achieved, when the chemical agent 202 is a nucleic acid, it is preferable to perform the condensing step S1. However, when the chemical agent 202 is not a nucleic acid, or when it is a nucleic acid but does not need to be condensed, etc., it is not necessary to perform the condensing step S1.

[0094] · Mixing step S2 Next, the first solution and the second solution are mixed. The second solution may be the one prepared as described above when the chemical agent 202 is a nucleic acid. Or when using a nucleic acid that does not condense or a chemical agent 202 that is not a nucleic acid, the second solution can be prepared by mixing the chemical agent 202 with any of the above aqueous solvents selected according to the type. The chemical agent 202 that is not a nucleic acid contains, for example, a protein, a peptide, an amino acid, another organic compound, or an inorganic compound as an active ingredient. The chemical agent 202 may be, for example, a therapeutic agent or a diagnostic agent for a disease. However, the chemical agent 202 is not limited to these, and any substance may be used as long as it can be encapsulated in the lipid particles 200.

[0095] The medicament 202 may further contain reagents such as, for example, a pH adjuster, an osmotic pressure adjuster, and / or a medicament activator, etc., as necessary. The pH adjuster is, for example, an organic acid such as citric acid and its salts, etc. The osmotic pressure adjuster is sugar or an amino acid, etc. The medicament activator is, for example, a reagent that assists the activity of the active ingredient. These may be added after the condensation step S1 is performed.

[0096] The medicament 202 may be a single substance or may contain a plurality of substances. The concentration of the medicament 202 in the second solution is preferably, for example, 0.01% to 1.0% (by weight).

[0097] The first solution can be produced by mixing a lipid and an organic solvent. The lipid may be, for example, a lipid that is a main component of a biological membrane. Also, the lipid may be artificially synthesized. The lipid may contain, for example, a phospholipid or a sphingolipid, for example, a base lipid such as diacylphosphatidylcholine, diacylphosphatidylethanolamine, ceramide, sphingomyelin, dihydrosphingomyelin, cephalin, or cerebroside, or a combination thereof, etc.

[0098] For example, as the base lipid, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), 1,2-stearoyl-sn-glycero-3-phosphoethanolamine (DSPE), 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC), 1,2-di-O-octadecyl-3-trimethylammonium propane (DOTMA), 1,2-dioleoyl-3-dimethylammonium propane (DODAP), 1,2-dimyristoyl-3-dimethylammonium propane (14:0 DAP), 1,2-dipalmitoyl-3-dimethylammonium propane (16:0 DAP), 1,2-distearoyl-3-dimethylammonium propane (18:0 DAP), N-(4-carboxybenzyl)-N,N-dimethyl-2,3-bis(oleoyloxy)propane (DOBAQ), 1,2-dioleoyl-3-trimethylammonium propane (DOTAP), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC), 1,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPS), or cholesterol, Or it is preferable to use any combination thereof, etc. In particular, it is preferable to use DOTAP and / or DOPE.

[0099] The lipid preferably further contains a first lipid compound and / or a second lipid compound that are biodegradable lipids. The first lipid compound can be represented by the formula Q-CHR2.

[0100] (In the formula, Q is a nitrogen-containing aliphatic group that contains two or more tertiary nitrogens and does not contain oxygen, R is each independently a C 12 ~C 24 aliphatic group, At least one R contains a linking group LR selected from the group consisting of -C(=O)-O-, -O-C(=O)-, -O-C(=O)-O-, -S-C(=O)-, -C(=O)-S-, -C(=O)-NH-, and -NHC(=O)- in its main chain or side chain).

[0101] The first lipid compound is a lipid having a structure represented by, for example, the following formula.

Chemical formula

[0102]

Chemical formula

[0103]

Chem.

[0104]

Chem.

[0105] In particular, it is preferable to use the lipid compound of formula (1-01) and / or the lipid compound of formula (1-02).

[0106] The second lipid compound can be represented by the formula P-[X-W-Y-W’-Z]2 and can be represented by the following formula.

[0107] (In the formula, P is an alkyleneoxy containing one or more ether bonds in the main chain, X is each independently a divalent linking group containing a tertiary amine structure, W is each independently C1-C6 alkylene, Y is each independently a divalent linking group selected from the group consisting of a single bond, an ether bond, a carboxylic acid ester bond, a thiocarboxylic acid ester bond, a thioester bond, an amide bond, a carbamate bond, and a urea bond, W’ is each independently a single bond or C1-C6 alkylene, Z is each independently a fat-soluble vitamin residue, a sterol residue, or a C 12 ~C 22 aliphatic hydrocarbon group).

[0108] The second lipid compound is a lipid having a structure represented by, for example, the following formula.

[0109]

Chem.

[0110]

Chem.

[0111]

Chem.

[0112] In particular, it is preferable to use the compound of formula (2-01).

[0113] When the first lipid compound and the second lipid compound are included, it is possible to increase the encapsulation amount of the drug 202 in the lipid particles 200 and enhance the introduction efficiency of the drug 202 into cells. Also, cell death of the introduced cells can be reduced.

[0114] The base lipid is preferably contained in an amount of 30% to about 80% (molar ratio) based on the total lipid material. Alternatively, it may be composed almost entirely of the base lipid. The first and second lipid compounds are preferably contained in an amount of about 20% to about 70% (molar ratio) based on the total lipid material.

[0115] The lipid preferably also contains a lipid that prevents aggregation of the lipid particles 200. For example, the lipid that prevents aggregation preferably further contains a PEG-modified lipid, such as polyethylene glycol (PEG) dimyristoyl glycerol (DMG-PEG), a polyamide oligomer derived from an omega-amino (oligoethylene glycol) alkanoic acid monomer (U.S. Patent No. 6,320,017), or monosialoganglioside. Such a lipid is preferably contained in an amount of about 1% to about 10% (molar ratio) based on the total lipid material of the lipid particles 200.

[0116] The lipid may further contain a lipid that is relatively less toxic for adjusting toxicity; a lipid having a functional group for binding a ligand to the lipid particles 200; a lipid for suppressing leakage of inclusions such as cholesterol, for example, cholesterol. In particular, it is preferable to include cholesterol.

[0117] For example, the lipid particles 200 preferably contain a compound of formula (1-01) or formula (1-02) and / or a compound of formula (2-01), DOPE and / or DOTAP, cholesterol, and DMG-PEG.

[0118] The type and composition of the lipid are appropriately selected in consideration of the acid dissociation constant (pKa) of the target lipid particles 200, the size of the lipid particles 200, the type of inclusion, or the stability in the cells to be introduced. For example, in order to make the lipid constituting the lipid particles 200 have a desired composition, the composition of the lipid contained in the first solution may be set to the same ratio.

[0119] The organic solvent of the first solution is, for example, ethanol, methanol, isopropyl alcohol, ether, chloroform, benzene, or acetone. The concentration of the lipid in the organic solvent is preferably, for example, 0.1% to 0.5% (by weight).

[0120] The mixing of the first solution and the second solution is performed using the flow channel structure 302 of the embodiment as shown in FIG. 25(b). Here, as in the third embodiment, the flow channel structures 110 and 120 having the same shape as the flow channel structure 100 are connected in series as the flow channel structure 302, and these are shown as the flow channel structure unit 300, but the flow channel structure 302 is not limited thereto.

[0121] When performing the aggregation step S1, the downstream end of the flow path 315 of the aggregation flow path structure 301 is connected to one end of the inlet portion 80 of the flow path structure 302 of the embodiment, and the second solution is supplied therefrom. When the condensation step S1 is not performed, a second solution inlet (not shown) is provided at one upstream end of the inlet portion 80, and the second solution is supplied therefrom. The other upstream end of the inlet portion 80 is provided with, for example, a first solution inlet 321 at its upstream end, and the first solution is supplied therefrom. As a result, the first solution and the second solution are mixed to obtain a mixed solution. When the flow path structure unit 300 is provided, the mixed solution is further mixed and stirred there. For example, when the condensation step S1 is not performed, the first solution may be flowed through one upstream end of the inlet portion 80, and the second solution may be flowed through the first solution inlet 321.

[0122] · Particle formation step S3 Next, in the particle formation step S3, the concentration of the organic solvent in the mixed solution is decreased. For example, it is preferable to relatively decrease the organic solvent concentration by adding a large amount of an aqueous solution to the mixed solution. For example, an aqueous solution three times the amount of the mixed solution is added to the mixed solution. As the aqueous solution, the same one as the aqueous solvent used for the first solution can be used. By decreasing the organic solvent concentration, the lipid can be particleized, and lipid particles 200 encapsulating the drug 202 can be generated. As a result, a lipid particle solution containing the lipid particles 200 is obtained.

[0123] As shown in FIG. 25(c), the particle formation flow path structure 303 for performing the particle formation step S3 is, for example, a Y-shaped flow path. The upstream end of one of the branched Y-shaped flow paths 331 is connected to, for example, the most downstream end of the flow path structure 302 (the fourth flow path 4 in this example), and the mixed solution is supplied therefrom. The upstream end of the other flow path 332 is provided with, for example, an aqueous solution inlet 333, and the aqueous solution is flowed through there. As a result, the aqueous solution is mixed with the mixed solution in the flow path 334 where the flow path 331 and the flow path 332 merge. As a result, the lipid is particleized, lipid particles 200 encapsulating the drug 202 are generated, and a lipid particle solution containing the lipid particles 200 is obtained.

[0124] The particle formation step S3 does not necessarily need to be performed using a flow path. For example, an aqueous solution may be added to the mixed solution collected in a container.

[0125] In this way, the lipid particles 200 can be produced.

[0126] · Concentration step S4 The method for producing lipid particles according to the embodiment may further include concentrating the lipid particle solution as necessary (concentration step S4). Concentration is performed, for example, by removing a part of the solvent and / or the remaining lipid and drug 202 from the lipid particle solution. Concentration can be performed, for example, by ultrafiltration. For ultrafiltration, it is preferable to use, for example, an ultrafiltration filter with a pore size of 2 nm to 100 nm. For example, Amicon (registered trademark) Ultra-15 (Merck) or the like can be used as the filter. By performing the concentration step S4, a lipid particle solution with high purity and concentration can be obtained. The concentration of the lipid particles 200 in the lipid particle solution after concentration is 1×10 13 particles / mL to 5×10 13 particles / mL is preferably about. However, the concentration step S4 is not necessarily required.

[0127] As shown in Fig. 25(d), the concentration channel structure 304 for performing the concentration step S4 includes a channel 341 and a filter 342 provided on the wall surface of the channel 341. The upstream end of the channel 341 is connected to, for example, the channel 334 of the particle formation channel structure 303.

[0128] The filter 342 is provided, for example, in place of a part of the wall surface of the channel 341. Any of the ultrafiltration filters described above can be used as the filter 342.

[0129] By flowing the lipid particle solution through the channel 341, the remaining materials and excess solvent etc. pass through the filter 342 and are discharged outside the channel 341, and the lipid particles 200 remain in the channel 341 and flow downstream, thereby concentrating the lipid particle solution. The downstream end of the channel 341 may be provided with a discharge port 343 for collecting the concentrated lipid particle solution, or may be connected to a tank for collecting the lipid particle solution.

[0130] The concentration step S4 does not necessarily have to be performed using a flow path. For example, the lipid particle solution collected in a container may be filtered through a filter.

[0131] In addition, the method for producing lipid particles according to the embodiment may further perform a treatment for improving the quality of the lipid particles 200 as necessary. Improving the quality may include, for example, preventing leakage of the drug 202 from the lipid particles 200, increasing the encapsulation amount of the drug 202 in the lipid particles 200, increasing the ratio (encapsulation rate) of the lipid particles 200 encapsulating the drug 202, reducing and preventing aggregation of the lipid particles 200 with each other, and / or reducing the variation in the size of the lipid particles 200. For example, a treatment of cooling the lipid particle solution may be performed. Such a treatment may also be performed using a flow path.

[0132] Each of the above-described flow paths is, for example, a micro flow path. The flow of the fluid in the flow path, the injection of the fluid into the flow path, the extraction of the fluid from the tank, and / or the accommodation of the lipid particle solution in the container, etc. can be performed by, for example, a pump or an extrusion mechanism configured and controlled so that these operations are automatically performed.

[0133] The method for producing lipid particles according to the embodiment does not necessarily have to perform the condensation step S1 and the concentration step S4 as described above, and may include at least the mixing step S2 and the particle formation step S3.

[0134] According to the method for producing lipid particles of the embodiment, since the mixing step S2 is performed using the flow path structure of the embodiment, the first solution and the second solution can be uniformly and well mixed and stirred, and it is possible to produce higher-quality lipid particles 200. For example, effects such as an increase in the encapsulation amount of the drug 202, a reduction in the average particle diameter of the lipid particles 200, and an increase in the ratio of the lipid particles 200 encapsulating the drug 202 can be obtained.

[0135] In addition, for the production of the lipid particles described in this specification, the flow path structure 100b shown in the third embodiment may be used.

[0136] The embodiments of the present invention have been described above. However, these embodiments are presented as examples and are not intended to limit the scope of the invention. These novel embodiments can be implemented in various other forms, and various omissions, replacements, and changes can be made without departing from the gist of the invention. These embodiments are included in the scope and gist of the invention, and are included in the invention described in the claims and the equivalent scope thereof.

[0137] In addition, in this specification, although the axial direction of the flow path structure and the direction of the main flow have been described as being as indicated by the arrows in FIG. 1, the axial direction of the flow path structure and the direction of the main flow are not limited thereto.

[0138] Also, the "axial axis" described in this specification may be, for example, the central axis of the flow path. However, this definition does not narrowly limit the interpretation of the "axial axis", and should be appropriately interpreted without impairing the gist of the invention described in the embodiments.

[0139] In addition, the embodiments and modification examples described in this specification can be arbitrarily combined.

[0140] Furthermore, the present disclosure includes examples according to the following supplementary notes.

[0141] [Supplementary Note 1] a first flow path group including one or more flow paths; a second flow path group connected to the first flow path group via a branch portion and including two or more flow paths; a third flow path group connected to the second flow path group via a confluence portion and including one or more flow paths; a first flow path group side branch opening connected to an end of the flow path included in the first flow path group close to the second flow path group, and a second flow path group side branch opening connected to an end of the flow path included in the second flow path group close to the first flow path group, the branch portion including the same; a second flow path group side confluence opening connected to an end of the second flow path group close to the third flow path group, and a third flow path group side confluence opening connected to an end of the third flow path group close to the second flow path group, the confluence portion including the same; comprising The first flow path group includes N flow paths, The second flow path group includes M flow paths, When M is equal to or greater than N, The total opening area of the branch openings on the second flow path group side is equal to or less than M / N times the total opening area of the branch openings on the first flow path group side, At least one opening area of the confluence openings on the second flow path group side is equal to or less than at least one opening area of the confluence openings on the third flow path group side. Flow path structure.

[0142] [Appendix 2] At least one opening area of the branch openings on the second flow path group side is equal to or less than at least one opening area of the branch openings on the first flow path group side, The flow path structure according to Appendix 1.

[0143] [Appendix 3] At least a part of the flow paths included in the second flow path group has a structure in which the shape of the cross section perpendicular to the tube axis direction of the flow path continuously changes, The flow path structure according to Appendix 1 or 2.

[0144] [Appendix 4] At least a part of the flow paths included in the second flow path group has a structure in which the flow path depth continuously changes, The flow path structure according to any one of Appendices 1 to 3.

[0145] [Appendix 5] At least a part of the flow paths included in the second flow path group has a structure in which the flow path width continuously changes, The flow path structure according to any one of Appendices 1 to 4.

[0146] [Appendix 6] The top surfaces of the flow paths included in the first flow path group, the second flow path group, and the third flow path group are included in a single plane, The flow path structure according to any one of Appendices 1 to 5.

[0147] [Appendix 7] At least a part of the top surfaces of the flow paths included in the first flow path group, the second flow path group, and the third flow path group is included in the first plane. Among the bottom surfaces of the flow paths included in the first flow path group, the second flow path group, and the third flow path group, the bottom surface facing the top surface that is not included in at least the first plane is included in a second plane different from the first plane. The flow path structure according to any one of Appendices 1 to 6.

[0148] [Appendix 8] At least one of the flow paths included in the second flow path group is such that the opening area of the confluence opening on the second flow path group side is smaller than the opening area of the branch opening on the second flow path group side. The flow path structure according to any one of Appendices 1 to 7.

[0149] [Appendix 9] At least one of the flow paths included in the second flow path group is such that the opening area of the confluence opening on the second flow path group side is larger than the opening area of the branch opening on the second flow path group side. The flow path structure according to any one of Appendices 1 to 8.

[0150] [Appendix 10] The flow path width and the flow path depth of the confluence opening on the second flow path group side are 5 μm or more. The flow path structure according to any one of Appendices 1 to 9.

[0151] [Appendix 11] The second flow path group has an approximately point-symmetrical shape with the midpoint between the branch portion and the confluence portion as the center point. The flow path structure according to any one of Appendices 1 to 10.

[0152] [Appendix 12] The depth of the flow path included in the flow path structure is less than or equal to the width of the flow path. The flow path structure according to any one of Appendices 1 to 11.

[0153] [Appendix 13] The opening area of the flow path included in the flow path structure is 100 mm2 The following The flow path structure according to any one of Appendices 1 to 12.

[0154] [Appendix 14] Further comprising an inlet portion capable of allowing two or more types of fluids to flow into at least one flow path included in the first flow path group. The flow path structure according to any one of Appendices 1 to 13.

[0155] [Appendix 15] At least a part of the flow path included in the first flow path group or the flow path included in the third flow path group has a structure in which the shape of a cross section perpendicular to the tube axis direction of the flow path continuously changes as it approaches the first branch portion. The flow path structure according to any one of Appendices 1 to 16.

[0156] [Appendix 16] The first flow path, A second flow path connected to the first flow path via a branch portion, A third flow path connected to the first flow path via the branch portion, A fourth flow path connected to the second flow path and the third flow path via a confluence portion, The branch portion including a first branch opening connected to an end portion of the first flow path close to the second flow path and the third flow path, a second branch opening connected to an end portion of the second flow path close to the first flow path, and a third branch opening connected to an end portion of the third flow path close to the first flow path, The confluence portion including a second confluence opening connected to an end portion of the second flow path close to the fourth flow path, a third confluence opening connected to an end portion of the third flow path close to the fourth flow path, and a fourth confluence opening connected to an end portion of the fourth flow path close to the second flow path and the third flow path, Comprising The total opening area of the second branch opening and the third branch opening is not more than twice the opening area of the first branch opening. The opening area of at least one of the second confluence opening or the third confluence opening is not more than the opening area of the fourth confluence opening. The flow path structure.

[0157] [Appendix 17] A fluid structure unit comprising a plurality of flow path structures described in any one of Appendices 1 to 16.

[0158] [Appendix 18] A method for producing lipid particles encapsulating a drug using the flow path structure described in any one of Appendices 1 to 16, flowing a first solution containing the material lipid of the lipid particles into an organic solvent from a first inlet located upstream of the first flow path group, flowing a second solution containing the drug into an aqueous solvent from a second inlet located upstream of the first flow path group, mixing the first solution and the second solution to obtain a mixed solution; a step of forming particles of the lipid by reducing the concentration of the organic solvent in the mixed solution to generate the lipid particles encapsulating the drug; A method for producing lipid particles, comprising the above steps.

Explanation of Reference Numerals

[0159] 1... first flow path, 1a, 1b... regions, 2... second flow path, 3... third flow path, 4... fourth flow path, 4a, 4b... regions, 5... branch portion, 6... confluence portion, 10... first flow path group, 20... second flow path group, 30... third flow path group, 51... first branch opening, 52... second branch opening, 53... third branch opening, 62... second confluence opening, 63... third confluence opening, 64... fourth confluence opening, 70... flat member, 80... inlet portion, 100, 110a, 110, 120... flow path structures, 101... groove, 102... substrate, 103... lid portion, 104... film-like lid portion, 105... sensor terminal, 106... pressing plate, 107... heat medium flow path, 200... lipid particles, 201... inner cavity, 202... drug, 300... fluid structure unit, 301... flow path structure for aggregation, 302... flow path structure, 303... flow path structure for particle formation, 304... flow path structure for concentration, 311... flow path, 312... aggregating agent inlet, 313... flow path, 314... drug inlet, 315... flow path, 321... first solution inlet, 331... flow path, 332... flow path, 333... aqueous solution inlet, 334... flow path, 341... flow path, 342... filter, 343... discharge port

Claims

1. A first flow path group including one or more flow paths, a second flow path group connected to the first flow path group via a branch portion and including two or more flow paths, a third flow path group connected to the second flow path group via a confluence portion and including one or more flow paths, a first flow path group side branch opening connected to an end portion of the flow path included in the first flow path group close to the second flow path group, and a second flow path group side branch opening connected to an end portion of the flow path included in the second flow path group close to the first flow path group, the branch portion including the same, a second flow path group side confluence opening connected to an end portion of the second flow path group close to the third flow path group, and a third flow path group side confluence opening connected to an end portion of the third flow path group close to the second flow path group, the confluence portion including the same, comprising, the first flow path group includes N flow paths, the second flow path group includes M flow paths, when M is equal to or greater than N, the total opening area of the second flow path group side branch openings is equal to or less than M / N times the total opening area of the first flow path group side branch openings, at least one opening area of the second flow path group side confluence openings is equal to or less than at least one opening area of the third flow path group side confluence openings, a flow path structure.

2. At least one opening area of the second flow path group side branch openings is equal to or less than at least one opening area of the first flow path group side branch openings, The flow path structure according to claim 1.

3. At least a part of the flow paths included in the second flow path group has a structure in which the shape of the cross section perpendicular to the pipe axis direction of the flow path continuously changes, The flow path structure according to claim 1.

4. At least a part of the flow paths included in the second flow path group has a structure in which the flow path depth continuously changes, The flow path structure according to claim 3.

5. At least a part of the flow paths included in the second flow path group has a structure in which the flow path width continuously changes, The flow path structure according to claim 3.

6. The top surfaces of the flow paths included in the first flow path group, the second flow path group, and the third flow path group are included in a single plane, The flow path structure according to claim 1.

7. At least a part of the top surfaces of the flow paths included in the first flow path group, the second flow path group, and the third flow path group is included in a first plane, Among the bottom surfaces of the flow paths included in the first flow path group, the second flow path group, and the third flow path group, at least the bottom surface facing the top surface not included in the first plane is included in a second plane different from the first plane, The flow path structure according to claim 1.

8. Among the flow paths included in the second flow path group, at least one has an opening area of the second flow path group side confluence opening smaller than the opening area of the second flow path group side branch opening. The flow path structure according to claim 1.

9. Among the flow paths included in the second flow path group, at least one has an opening area of the second flow path group side confluence opening larger than the opening area of the second flow path group side branch opening. The flow path structure according to claim 8.

10. The flow path width and flow path depth of the second flow path group side confluence opening are 5 μm or more. The flow path structure according to claim 1.

11. The second flow path group has an approximately point-symmetrical shape with the midpoint between the branch portion and the confluence portion as the center point. The flow path structure according to claim 1.

12. The depth of the flow path included in the flow path structure is equal to or less than the width of the flow path. The flow path structure according to claim 1.

13. The opening area of the flow path included in the flow path structure is 100 mm ２ or less, The flow path structure according to claim 1.

14. The flow path structure further includes an inlet portion capable of introducing two or more types of fluids into at least one flow path included in the first flow path group. The flow path structure according to claim 1.

15. At least a part of the flow paths included in the first flow path group or the flow paths included in the third flow path group has a structure in which the shape of the cross section perpendicular to the tube axis direction of the flow path continuously changes as it approaches the first branch portion. The flow path structure according to claim 1.

16. A first flow path, A second flow path connected to the first flow path via a branch portion, A third flow path connected to the first flow path via the branch portion, A fourth flow path connected to the second flow path and the third flow path via a confluence portion, A branch portion including a first branch opening connecting to an end of the first flow path near the second flow path and the third flow path, a second branch opening connecting to an end of the second flow path near the first flow path, and a third branch opening connecting to an end of the third flow path near the first flow path, A confluence portion including a second confluence opening connecting to an end of the second flow path near the fourth flow path, a third confluence opening connecting to an end of the third flow path near the fourth flow path, and a fourth confluence opening connecting to an end of the fourth flow path near the second flow path and the third flow path, Comprising The sum of the opening areas of the second branch opening and the third branch opening is 2 times or less the opening area of the first branch opening. The opening area of at least one of the second confluence opening or the third confluence opening is equal to or less than the opening area of the fourth confluence opening, the flow path structure.

17. A fluid structure unit comprising a plurality of the flow path structures according to Claim 1.

18. A method for producing lipid particles encapsulating a drug using the flow path structure according to any one of Claims 1 to 16, wherein a first solution containing the material lipid of the lipid particles is flowed from a first inlet located upstream of the first flow path group into an organic solvent, and a second solution containing the drug is flowed from a second inlet located upstream of the first flow path group into an aqueous solvent to mix the first solution and the second solution to obtain a mixed solution; and a step of forming the lipid particles encapsulating the drug by reducing the concentration of the organic solvent in the mixed solution. A method for producing lipid particles, comprising the above steps.

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