Flow path devices

CN122580554APending Publication Date: 2026-08-14KYOCERA CORP
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2025-01-27
Publication Date
2026-08-14

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Abstract

The flow path device includes a flow path portion comprising a first flow path, a plurality of second flow paths, a third flow path, and a fourth flow path. The first flow path extends along a first direction and includes a first portion at an end in the first direction and a second portion at an end opposite to the first portion. The first flow path has a first side surface and a second side surface opposing the first side surface in a second direction orthogonal to the first direction. The plurality of second flow paths are connected to the first flow path by openings in the first side surface between the first and second portions, and are thinner than the first flow path. The third flow path includes a first connecting portion connected to the second portion and extending along the first direction. The fourth flow path includes a second connecting portion connected to the second portion and extending along a third direction at an acute angle relative to the first direction. The second connecting portion has a third side surface on the side of the first connecting portion. The flow path portion has a connecting surface connecting the second side surface and the third side surface. The distance between the third portion where the second side surface and the connecting surface are connected and the fourth portion where the third side surface and the connecting surface are connected is less than or equal to the width of the first flow path.
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Description

[0001] Cross-reference of related applications

[0002] This application asserts priority to Japanese Application No. 2024-11477 (filed on January 30, 2024), the entire publication of which is incorporated herein by reference. Technical Field

[0003] This disclosure relates to flow path devices. Background Technology

[0004] There is a flow path device comprising: a portion (also called a flow path section) of a plurality of branched micro-flow paths for separating a specific type of particle from other types of particles in a liquid containing a variety of particles; and a plurality of holes that are respectively connected to the flow path section and open on their outer surfaces (for example, see Patent Document 1).

[0005] In recent years, there has been an increasing demand for flow path devices to increase the proportion of specific types of particles (e.g., multiple specific types of particles) among the multiple particles contained in the recovered liquid after separation.

[0006] Existing technical documents

[0007] Patent documents

[0008] Patent Document 1: International Publication No. 2023 / 153331 Summary of the Invention

[0009] The problem that the invention aims to solve

[0010] A flow path device is disclosed.

[0011] One embodiment of a flow path device includes a flow path portion. The flow path portion includes a first flow path, a plurality of second flow paths, a third flow path, and a fourth flow path. The first flow path extends along a first direction. The first flow path includes a first portion located at an end in the first direction and a second portion located at an end in the opposite direction to the first portion. The first flow path has a first side surface and a second side surface opposite to the first side surface in a second direction orthogonal to the first direction. The plurality of second flow paths are connected to the first flow path by openings in the first side surface between the first portion and the second portion, and are thinner than the first flow path. The third flow path includes a first connecting portion connected to the second portion. The first connecting portion extends along the first direction. The fourth flow path includes a second connecting portion connected to the second portion. The second connecting portion extends along a third direction at an acute angle relative to the first direction. The second connecting portion has a third side surface located on the side of the first connecting portion. The flow path portion has a connecting surface connecting the second side surface and the third side surface. The distance between the third portion where the second side surface and the connecting surface connect and the fourth portion where the third side surface and the connecting surface connect is less than 1 times the width of the first flow path in the second direction. Attached Figure Description

[0012] Figure 1 This is a top view schematically illustrating an example of the structure of a flow path device.

[0013] Figure 2 This is a front view schematically illustrating an example of the structure of a flow path device.

[0014] Figure 3 This is a top view schematically illustrating an example of the structure of the flow path section and multiple holes in a flow path device.

[0015] Figure 4 It is a top view schematically showing a portion of the flow path section, and it shows the components of... Figure 3 A top view of region IV, which is enclosed by a rectangle with a single dotted line.

[0016] Figure 5 It is shown schematically in Figure 4 A top view of an example of a flow path section in which a first liquid and a second liquid are introduced into a first upstream portion of the main flow path.

[0017] Figure 6 The graph shows the relationship between the size of the interface and the purity of white blood cells in the white blood cell recovery fluid, based on the results of the first case of the experiment.

[0018] Figure 7The graph shows the relationship between the size of the interface and the purity of white blood cells in the white blood cell recovery fluid, based on the results of the second example of the experiment.

[0019] Figure 8 The graph shows the relationship between the size of the interface and the purity of leukocytes in the leukocyte recovery fluid, based on the results of the third example of the experiment.

[0020] Figure 9 The graph shows the relationship between the size of the interface and the purity of leukocytes in the leukocyte recovery fluid, based on the results of the fourth case of the experiment.

[0021] Figure 10 This is a schematic top view showing a portion of the flow path of the flow path device used in the fifth example of the experiment, and it shows the flow path portion and... Figure 3 A top view of an example of the structure of region IV, which is enclosed by a single-dotted line within a rectangle.

[0022] Figure 11 The graph shows the relationship between the size of the interface and the purity of white blood cells in the white blood cell recovery fluid, based on the results of the fifth case of the experiment.

[0023] Figure 12 This is a schematic top view showing a portion of the flow path of the flow path device used in the sixth example of the experiment, and it shows the flow path portion with... Figure 3 A top view of an example of the structure of region IV, which is enclosed by a single-dotted line within a rectangle.

[0024] Figure 13 The graph shows the relationship between the size of the interface and the purity of white blood cells in the white blood cell recovery fluid, based on the results of the sixth case of the experiment.

[0025] Figure 14 This is a schematic top view showing a portion of the flow path, and it shows the connection with... Figure 3 A top view of the area IV, which is enclosed by a single-dotted line of a rectangle, corresponding to other first structural examples of the area.

[0026] Figure 15 This is a schematic top view showing a portion of the flow path, and it shows the connection with... Figure 3 A top view of the area IV, which is enclosed by a single-dotted line within a rectangle, corresponding to other second structural examples of the area. Detailed Implementation

[0027] There is a flow path device comprising: a branched microflow path portion (also called a flow path section) for separating multiple particles of a specific type (also called first particles) from multiple particles of other types (also called second particles) from a liquid containing multiple particles (also called first liquid or liquid being processed), and multiple holes that are respectively connected to the flow path portion and are respectively opened on the outer surface.

[0028] In this flow path device, for example, the flow path portion does not have an opening on its outer surface. The flow path portion includes, for example, a first flow path (also called the main flow path) and a plurality of second flow paths (also called branch flow paths) connected to the main flow path and thinner than the main flow path. The plurality of holes include: a first inlet hole (also called a first inlet hole) and a second inlet hole (also called a second inlet hole) communicating with an upstream portion (also called a first upstream portion) of the main flow path; a discharge hole (also called a first discharge hole) communicating with a downstream portion (also called a first downstream portion) of the main flow path; and a discharge hole (also called a second discharge hole) communicating with the downstream portion (also called a second downstream portion) of each of the plurality of branch flow paths on the opposite side of the main flow path (opposite to the main flow path). The main flow path extends linearly along a first direction. The plurality of branch flow paths each open on a side of the main flow path located in a second direction orthogonal to the first direction between the first upstream portion and the first downstream portion. Furthermore, the flow path portion includes a flow path (also called a third flow path) connecting the first inlet hole to the first upstream portion and a flow path (also called a fourth flow path) connecting the second inlet hole to the first upstream portion. The portion of the fourth flow path that connects to the first upstream portion extends along the second direction and has a side opening in the main flow path located on the side opposite to the second direction. The portion of the third flow path that connects to the first upstream portion extends along the first direction.

[0029] The liquid to be processed is introduced into the main flow path through the first inlet port. Liquid (also called the second liquid or pressing liquid) is introduced into the main flow path through the second inlet port. The pressing liquid can press various particles within the liquid to be processed into multiple branch flow paths in the main flow path. For example, if the diameter of the first particle is larger than the diameter of the second particle, and if the width of each of the multiple branch flow paths is larger than the diameter of the second particle but smaller than the diameter of the first particle, then liquid containing multiple second particles can be introduced from the main flow path into the multiple branch flow paths and discharged from the second outlet port, while liquid containing multiple first particles (also called recovery liquid or separated recovery liquid) is discharged from the first outlet port via the first downstream portion of the main flow path. Thus, the recovery liquid can be recovered via the first outlet port. As a result, liquid containing multiple first particles (recovery liquid) can be separated from the liquid to be processed and recovered from liquid containing multiple second particles. For example, in the case where a blood-containing sample is used in the liquid to be processed, consider a scenario where the first particle is a white blood cell and the second particle is a red blood cell. It should be noted that in the aforementioned flow path device, the function of separating first and second particles of different sizes through multiple branch flow paths, as described later, arises from the relationship between the flow introduced into the branch flow path and the respective centroid positions of the first and second particles. Therefore, the ability to separate the first and second particles is not necessarily determined by the relationship between the width of the branch flow path and the diameters of the first and second particles. For example, in the flow path device, even if the width of the branch flow path is the same as the diameter of the first particle, or even if the width of the branch flow path is larger than the diameter of the first particle, the first particle can still separate from the second particle without being introduced into the branch flow path from the main flow path.

[0030] However, in the aforementioned flow path device, in the first upstream section of the main flow path, the flow of the pressing liquid merges with the flow of the treated liquid in a manner that the direction in which the pressing liquid flows in from the fourth flow path (also known as the second inflow direction) is at a 90-degree angle to the direction in which the treated liquid flows in from the third flow path (also known as the first inflow direction). In this case, in order to increase the recovery rate of the recovered liquid containing a plurality of first particles per unit time, it is considered to increase the flow rate of the treated liquid flowing into the first upstream section of the main flow path from the first inlet orifice via the third flow path.

[0031] However, as the flow rate of the liquid being processed increases, turbulence occurs in the main flow path. Consequently, it becomes difficult to maintain the state in the main flow path where various particles within the liquid being processed are pressed towards multiple branch flow paths. Specifically, in the main flow path, as one approaches the first downstream section, the force (also known as pressing pressure) at which the various particles within the liquid being processed are pressed towards multiple branch flow paths may decrease. As a result, some of the multiple second particles in the liquid being processed can easily flow to the first downstream section. Consequently, the number of second particles mixed into the recovered liquid recovered via the first discharge orifice increases, and the proportion of first particles (e.g., multiple first particles) among the multiple particles contained in the recovered liquid may decrease. For example, in the case where a blood-containing sample is used in the liquid being processed, the proportion of white blood cells (e.g., multiple white blood cells) among all blood cells in the recovered liquid (also known as white blood cell recovery liquid) (also known as white blood cell purity) may decrease. All blood cells include white blood cells and red blood cells.

[0032] Here, for example, with the aim of increasing the proportion of first particles (e.g., multiple first particles) in the multiple particles contained in the recycled liquid, it is considered to reduce the turbulence of the liquid flow in the main flow path. More specifically, for example, it is considered that in the first upstream section of the main flow path, the flow of the pressing liquid and the flow of the treated liquid are merged, with the second inflow direction of the pressing liquid forming an acute angle of less than 90 degrees relative to the first inflow direction of the treated liquid.

[0033] However, even when the second inflow direction is at an acute angle to the first inflow direction, there is room for improvement in increasing the proportion of a specific type of particle (e.g., multiple first particles) among the multiple particles contained in the recovered liquid.

[0034] That is, regarding the flow path device, there is room for improvement in increasing the proportion of a specific type of particle (e.g., multiple first particles) among the multiple particles contained in the recovered liquid.

[0035] Therefore, the inventors of this disclosure have created a technique for flow path devices that can increase the proportion of a specific type of particle (e.g., multiple specific types of particles) among the multiple particles contained in the recovered liquid.

[0036] Various embodiments and examples will be described below with reference to the accompanying drawings. In the drawings, parts having the same or similar structure and function are labeled with the same reference numerals. Repeated descriptions of parts having the same or similar structure and function are omitted in the following description. The drawings are schematic.

[0037] The accompanying drawings include, for convenience, a diagram of a right-handed XYZ coordinate system. In the following description, the +Z direction is used as vertically upward (also simply referred to as upward). Vertically downward is represented by the -Z direction. The direction opposite to the +X direction is also represented by the -X direction. The direction opposite to the +Y direction is also represented by the -Y direction. Additionally, the accompanying drawings include, for convenience, diagrams labeled with arrows representing the first direction D1, the second direction D2, the third direction D3, and the fourth direction D4, respectively.

[0038] In the following description, a "flow path" has a structure for allowing liquid to flow. In this disclosure, when viewing the flow path from above in the -Z direction (a direction orthogonal to both the -Y direction (first direction D1) and the +X direction (second direction D2), the length of the flow path in the direction orthogonal to the direction in which the flow path extends is referred to as the width of the flow path. A relatively small flow path width means a relatively narrow flow path, and a relatively large flow path width means a relatively wide flow path. In this disclosure, unless otherwise specified, the "top view" refers to a view taken from above in the -Z direction.

[0039] <1. An example of a general structure of a flow path device>

[0040] Figure 1 This is a top view schematically showing an example of the structure of the flow path device 1, which is a separation device according to one embodiment. Figure 2 This is a front view schematically illustrating an example of the structure of a flow path device 1 according to one embodiment. As will be described later, the flow path device 1 can function as a device for separating multiple particles of a specific type (also called first particles) Pa11 from a liquid (also called a first liquid) L1 containing multiple types of particles Pa1 to multiple particles of other types (also called second particles) Pa12.

[0041] In one embodiment, the flow path device 1 has, for example, a plate-like shape. The flow path device 1 has, for example, an upper surface 1a as a first surface and a lower surface 1b as a second surface, located opposite to the upper surface 1a. For example, the flow path device 1 has a side surface 1c as a third surface connecting the upper surface 1a and the lower surface 1b. In other words, the outer surface of the flow path device 1 is composed of the upper surface 1a, the lower surface 1b, and the side surface 1c. The upper surface 1a is located on the +Z direction side compared to the lower surface 1b.

[0042] exist Figure 1 and Figure 2In the example, the upper surface 1a faces the +Z direction. In other words, the upper surface 1a is a surface along the XY plane with a normal along the +Z direction. The lower surface 1b faces the -Z direction. In other words, the lower surface 1b is a surface along the XY plane with a normal along the -Z direction. The upper surface 1a and the lower surface 1b are, for example, generally flat and have a rectangular shape.

[0043] The thickness of the flow path device 1 is set to approximately 1 mm to 5 mm. The thickness of the flow path device 1 is its length in the +Z direction. The width of each of the upper surface 1a and lower surface 1b of the flow path device 1 is set to, for example, 10 mm to 50 mm. The width of the upper surface 1a is its length along the +X direction. The width of the lower surface 1b is its length along the +X direction. The length of each of the upper surface 1a and lower surface 1b of the flow path device 1 is set to, for example, 10 mm to 50 mm. The length of the upper surface 1a is its length along the +Y direction. The length of the lower surface 1b is its length along the +Y direction.

[0044] The flow path device 1 includes a flow path portion 2. In one embodiment, the flow path device 1 includes a plurality of holes 3. In another embodiment, the flow path portion 2 is not open on the outer surface of the flow path device 1. The plurality of holes 3 communicate with the flow path portion 2 and are open on the outer surface of the flow path device 1. In this disclosure, "the first part and the second part are connected" means that the first part and the second part are directly connected in a state where a fluid such as a liquid can flow between the first part and the second part, or that the first part is connected to the second part via another part (also called a third part) in a state where a fluid can flow between the first part and the second part. Here, the first part, the second part, and the third part are respectively filled with fluid-flowable portions such as flow paths or holes. For example, the flow path portion 2 is located inside the flow path device 1. From another viewpoint, for example, the flow path portion 2 is not open on the upper surface 1a, the lower surface 1b, and the side surface 1c. Figure 2 The structure of the flow path section 2 is simplified and shown in the figure.

[0045] Figure 3 This is a top view schematically showing an example of the structure of the flow path section 2 and the plurality of holes 3 in the flow path device 1. Figure 3 In the figure, the outer edge of the flow path device 1 is omitted, and the outer edges of the flow path part 2, the first inlet hole 31, the second inlet hole 32, the first outlet hole 33, the second outlet hole 34 and the third outlet hole 35 are depicted with solid lines. Figure 4 This is a top view schematically showing a portion of the flow path section 2. More specifically, Figure 4 It is shown schematically. Figure 3 A top view of region IV, enclosed by a rectangle with a single-dotted line. Figure 4 In the middle, the outer edge of the flow path section 2 is depicted with a solid line.

[0046] The flow path section 2, for example, has a structure in which multiple unopened flow paths are connected to the outer surface of the flow path device 1. The cross-section of each of the multiple flow paths can be, for example, rectangular. The cross-section of a flow path can be a surface formed by imaginarily cutting the flow path along an imaginary plane orthogonal to the direction in which the flow path extends. Figures 1 to 3 As shown, the flow path 2 is located, for example, along the XY plane.

[0047] The flow path section 2 includes a main flow path 21 as a first flow path, multiple branch flow paths 22 as multiple second flow paths, a first inlet flow path 23 as a third flow path, and a second inlet flow path 24 as a fourth flow path.

[0048] The main flow path 21 is a flow path extending along the -Y direction, which is the first direction D1. The main flow path 21 may, for example, extend in a straight line along the -Y direction, which is the first direction D1. The main flow path 21 has a first portion (also called a first downstream portion) 21d and a second portion (also called a first upstream portion) 21u. The first downstream portion 21d is located on the -Y direction side of the main flow path 21, which is the first direction D1. The first upstream portion 21u is located on the opposite side of the main flow path 21, which is the first downstream portion 21d. In other words, the first upstream portion 21u is the portion of the main flow path 21 located at the end opposite to the first downstream portion 21d. Further, the first upstream portion 21u may be the portion of the main flow path 21 located at the end opposite to the first downstream portion 21d. Alternatively, the first upstream portion 21u may be the portion of the main flow path 21 located at the end on the +Y direction side, which is the direction opposite to the first direction D1. In other words, the main path 21 extends from the first upstream portion 21u toward the first downstream portion 21d along the -Y direction, which is the first direction D1. Figure 4 In the example, the first upstream portion 21u is a rectangular portion of the main path 21 that is imaginarily divided by thin double-dotted lines.

[0049] Main road 21 has a first side surface Sw1 and a second side surface Sw2. For example, the first side surface Sw1 is a side surface of main road 21 that is orthogonal to the -Y direction, which is the first direction D1, and is in the +X direction, which is the second direction D2. The second side surface Sw2 is a side surface opposite to the first side surface Sw1 in the +X direction, which is the second direction D2. In other words, the second side surface Sw2 is a side surface of main road 21 that is in the -X direction, which is the fourth direction D4, opposite to the second direction D2. From another perspective, the first side surface Sw1 can be a side surface of main road 21 located on the second direction D2 side, and the second side surface Sw2 can be a side surface of main road 21 located on the fourth direction D4 side.

[0050] Multiple branch flow paths 22 are connected to the main flow path 21 and are thinner than the main flow path 21. Each branch flow path 22 opens on a first side surface Sw1 of the main flow path 21 between a first upstream portion 21u and a first downstream portion 21d. In other words, the multiple branch flow paths 22 open on a first side surface Sw1 between the first downstream portion 21d and the first upstream portion 21u, thereby connecting to the main flow path 21. Furthermore, the main flow path 21 has multiple portions (also called connecting parts) Bc1 to which the multiple branch flow paths 22 are respectively connected. For example, the multiple branch flow paths 22 branch from the main flow path 21 at mutually different positions in the -Y direction, which is the first direction D1. In other words, the multiple connecting parts Bc1 to which the multiple branch flow paths 22 are respectively connected exist at mutually different positions in the -Y direction, which is the first direction D1.

[0051] exist Figures 1 to 3 In the example, multiple branch flow paths 22 extend along the +X direction, which is the second direction D2. From another perspective, the multiple branch flow paths 22 are arranged along the -Y direction, which is the first direction D1. Here, the multiple branch flow paths 22, for example, constitute a group (also called a branch flow path group) 22g of branch flow paths 22. The number of multiple branch flow paths 22 is, for example, set to tens to hundreds. Figures 1 to 3 For convenience, 13 branch flow paths 22 are depicted.

[0052] Multiple branch flow paths 22 each include, for example, a portion opposite to the main flow path 21 (also referred to as a second downstream portion) 22d. Figures 1 to 3 In the example, in each of the plurality of branch flow paths 22, the second downstream portion 22d of the branch flow path 22 is the portion of the branch flow path 22 located at the +X direction side as the second direction D2.

[0053] The first inlet flow path 23 is connected to the first upstream portion 21u of the main flow path 21. The first inlet flow path 23 includes a portion (also called a first connecting portion) Cp1 connected to the first upstream portion 21u. The first connecting portion Cp1 extends along the -Y direction, which is the first direction D1. For example, the first connecting portion Cp1 may extend in a straight line toward the first upstream portion 21u along the -Y direction, which is the first direction D1. In other words, the first inlet flow path 23 is connected to the first upstream portion 21u of the main flow path 21 along the -Y direction, which is the first direction D1. The first inlet flow path 23 is thicker than each of the multiple branch flow paths 22. The width of the first connecting portion Cp1 of the first inlet flow path 23 may be the same as the width of the first upstream portion 21u of the main flow path 21.

[0054] The second inlet flow path 24 is connected to the first upstream portion 21u of the main flow path 21. The second inlet flow path 24 includes a portion (also called the second connecting portion) Cp2 connected to the first upstream portion 21u. For example, the second connecting portion Cp2 opens on the second side Sw2 in the main flow path 21. In other words, for example, the second connecting portion Cp2 opens on the second side Sw2 in the first upstream portion 21u, thereby connecting to the main flow path 21. The second connecting portion Cp2 extends along a third direction D3 at an acute angle relative to the -Y direction, which is the first direction D1. For example, the second connecting portion Cp2 may extend in a straight line towards the first upstream portion 21u along the third direction D3 at an acute angle to the -Y direction, which is the first direction D1. The angle of this acute angle may be set to an angle θ less than 90 degrees. In other words, the angle θ is the angle between the first direction D1 and the third direction D3. Here, for example, the second inlet flow path 24 is connected towards the third direction D3 relative to the first upstream portion 21u of the main flow path 21. From another perspective, the second connecting portion Cp2 is inclined relative to the main flow path 21 in a shape similar to that of the first connecting portion Cp1. In other words, the vector of the third direction D3, which extends from the second connecting portion Cp2 toward the first upstream portion 21u, forms an acute angle θ with the vector of the first direction D1, which extends from the first upstream portion 21u toward the first downstream portion 21d, which is the main flow path 21. The second inlet flow path 24 is thicker than each of the multiple branch flow paths 22. Here, the angle θ can be, for example, greater than 15 degrees and less than 45 degrees. The angle θ can also be 30 degrees. Figure 4 The image shows an example where the angle θ is set to 30 degrees.

[0055] The second inlet flow path 24 has a side surface (also called the third side surface) Sw3 located on the side of the first connecting portion Cp1. More specifically, the second connecting portion Cp2 of the second inlet flow path 24 has a third side surface Sw3 located on the side of the first connecting portion Cp1. Here, the imaginary surface of the third side surface Sw3 along the second connecting portion Cp2 forms an acute angle θ with the imaginary surface of the second side surface Sw2 along the main flow path 21.

[0056] The flow path section 2 has a surface (also called a connecting surface) Cs1 that connects the second side surface Sw2 of the main flow path 21 to the third side surface Sw3 of the second connecting portion Cp2. In other words, the flow path section 2 has a shape where the front end of the corner formed by the first upstream portion 21u of the main flow path 21 and the second connecting portion Cp2 of the second inlet flow path 24 is missing. In other words, the flow path section 2 has a portion (also called an expansion portion) Ac1 in which the flow path is expanded between the first upstream portion 21u of the main flow path 21 and the second connecting portion Cp2 of the second inlet flow path 24. The connecting surface Cs1 can be, for example, a flat rectangular surface.

[0057] exist Figure 4 In the example, the expansion portion Ac1 is an imaginary portion consisting of a thin double-dotted line imaginarily extending from the third side Sw3 along the third direction D3 to the first upstream portion 21u, a thin double-dotted line imaginarily representing the outer edge of the first upstream portion 21u, and a triangular shape enclosed by the connecting surface Cs1. In other words, the expansion portion Ac1 is a portion that expands from a triangular flow path (mainstream flow path 21 and / or second inlet flow path 24) when viewed from above. When viewed from above, the shape of the expansion portion Ac1 can be, for example, an isosceles triangle with the side along the connecting surface Cs1 as its base. In other words, the angle α formed by the third side Sw3 and the connecting surface Cs1 and the angle β formed by the second side Sw2 and the connecting surface Cs1 can be the same or approximately the same. Here, for example, if the angle θ is 30 degrees, then the angles α and β can each be 105 degrees.

[0058] When viewed from above in the flow path section 2, the dimension of the connecting surface Cs1 is set to be less than or equal to the width (also called the first width) W1 of the main flow path 21. The width (first width) W1 of the main flow path 21 is the width of the main flow path 21 in the +X direction, which is the second direction D2. The second side surface Sw2 of the main flow path 21 is connected to the connecting surface Cs1 at the third part P1, and the third side surface Sw3 of the second connecting part Cp2 in the second inlet flow path 24 is connected to the connecting surface Cs1 at the fourth part P2. Here, when viewed from above in the flow path section 2, the distance between the third part P1 where the second side surface Sw2 of the main flow path 21 connects to the connecting surface Cs1 and the fourth part P2 where the third side surface Sw3 of the second connecting part Cp2 connects to the connecting surface Cs1 is the first distance Le1. In this case, the first distance Le1 can be set to less than or equal to 1 times the first width W1. The first distance Le1 can also be more than or equal to 0.1 times and less than 0.5 times the first width W1. When viewed from above, the third part P1 and the fourth part P2 are not limited to point-like parts that are the vertices of the corners, but can also be short line-like parts.

[0059] The plurality of holes 3 include a first inlet hole 31 as a first hole, a second inlet hole 32 as a second hole, a first outlet hole 33 as a third hole, and a second outlet hole 34 as a fourth hole. In one embodiment, for example, the plurality of holes 3 includes a third outlet hole 35 as a fifth hole.

[0060] The first inlet hole 31 communicates with the first upstream portion 21u via the first inlet flow path 23. The first inlet hole 31 can be connected to the first inlet flow path 23. More specifically, the first inlet hole 31 can be connected to the end of the first inlet flow path 23 opposite to the first upstream portion 21u. Alternatively, the first inlet hole 31 communicates with the first upstream portion 21u. The diameter of the first inlet hole 31 is, for example, set to be the same as or greater than the width of the first inlet flow path 23. Figure 1 and Figure 3 In the example, the first inlet flow path 23 is an L-shaped flow path formed by connecting the portion extending from the first inlet hole 31 along the -X direction (fourth direction D4) and the portion extending along the -Y direction (first direction D1) in the order described. In other words, the first inlet flow path 23 extends from the first inlet hole 31 toward the first upstream portion 21u in the order of the -X and -Y directions. Here, the portion between the first inlet hole 31 and the first connecting portion Cp1 in the first inlet flow path 23 is not limited to an L-shaped portion and can have various shapes.

[0061] The second inlet hole 32 communicates with the first upstream portion 21u via the second inlet flow path 24. The second inlet hole 32 can be connected to the second inlet flow path 24. More specifically, the second inlet hole 32 can be connected to the end of the second inlet flow path 24 opposite to the first upstream portion 21u. Alternatively, the second inlet hole 32 communicates with the first upstream portion 21u. The diameter of the second inlet hole 32 is, for example, set to be the same as or greater than the width of the second inlet flow path 24. Figure 1 and Figure 3 In the example, the second inlet flow path 24 is a straight flow path extending from the second inlet hole 32 along the third direction D3. Here, the portion of the second inlet flow path 24 between the second inlet hole 32 and the second connecting portion Cp2 is not limited to a straight portion extending along the third direction D3, and may also have various shapes.

[0062] The first discharge port 33 communicates with the first downstream portion 21d of the main flow path 21. The first discharge port 33 may be connected to the first downstream portion 21d, for example, via a first discharge flow path 25, which serves as a fifth flow path. In other words, the flow path section 2 may include, for example, a first discharge flow path 25 connecting the first discharge port 33 to the first downstream portion 21d. The first discharge flow path 25 is thicker than each of the multiple branch flow paths 22. This first discharge flow path 25 is thicker than the diameter of each of the multiple first particles Pa11, which will be described later. Therefore, the multiple first particles Pa11 that reach the first downstream portion 21d through the portion of the main flow path 21 connected to the multiple branch flow paths 22 can be introduced into the first discharge flow path 25. As a result, in the flow path device 1, liquid containing multiple first particles Pa11 can be discharged from the first discharge port 33 via the first discharge flow path 25. Therefore, in the flow path device 1, liquid containing multiple first particles Pa11 can be recovered as a recovery liquid, for example, from the first downstream portion 21d via the first discharge port 33, etc. The diameter of the first discharge hole 33 can be set to be the same as or greater than the width of the first discharge flow path 25. In one embodiment, the portion of the first discharge flow path 25 connected to the first downstream portion 21d opens into a side opening in the first downstream portion 21d in the +X direction of the second direction D2. This side opening in the first downstream portion 21d in the +X direction of the second direction D2 can be a side located in the first downstream portion 21d in the +X direction of the second direction D2. Figure 1 as well as Figure 3In one example, the first discharge flow path 25 is a U-shaped flow path that is connected to the first downstream portion 21d and extends along the +X direction (second direction D2), along the -Y direction (first direction D1), and along the -X direction (fourth direction D4) in the order described. In other words, the first discharge flow path 25 extends in the order of +X, -Y, and -X directions.

[0063] The second discharge port 34 communicates with the second downstream portion 22d of each of the plurality of branch flow paths 22. The second discharge port 34 may, for example, be connected to the second downstream portion 22d of each of the plurality of branch flow paths 22 via a second discharge flow path 26, which serves as a sixth flow path. In other words, the flow path section 2 may, for example, include a second discharge flow path 26 connecting the second discharge port 34 to the second downstream portion 22d of each of the plurality of branch flow paths 22. More specifically, for example, the plurality of branch flow paths 22 may be connected to the second discharge flow path 26 at different positions in the -Y direction, which is the first direction D1. The second discharge flow path 26 is, for example, wider than each of the plurality of branch flow paths 22 to ensure a sufficient volume to concentrate and guide the liquid flowing from the plurality of branch flow paths 22 to the second discharge port 34. Figure 1 and Figure 3 In the example, the edge of the +X direction end of the second discharge flow path 26 is located near the second discharge hole 34. For example, the diameter of the second discharge hole 34 can be set to be the same as or greater than the width of the flow path of the portion of the second discharge flow path 26 where the end in the -Y direction connects to the second discharge hole 34. Thus, in the flow path device 1, as described later, a liquid containing multiple second particles Pa12 separated by multiple branch flow paths 22 can be discharged from the second discharge hole 34 via the second discharge flow path 26. Figure 1 and Figure 3 In the example, the second discharge flow path 26 is an L-shaped flow path in which multiple second downstream portions 22d of the multiple branch flow paths 22 are connected and connected in the order described, with the thicker portion extending linearly in the -Y direction (which is the first direction D1) and the narrower portion extending linearly in the +Y direction (which is the first direction D1) in a shorter length along the +X direction (which is the second direction D2) in a linear manner. In other words, the second discharge flow path 26 extends in the order of the -Y and +X directions in such a way that it connects to the second discharge hole 34 by converging the outlets of the multiple branch flow paths 22.

[0064] The third discharge port 35 communicates with the first downstream portion 21d of the main flow path 21. The third discharge port 35 may be connected to the first downstream portion 21d, for example, via a third discharge flow path 27, which serves as a seventh flow path. In other words, the flow path section 2 may include, for example, a third discharge flow path 27 connecting the third discharge port 35 to the first downstream portion 21d. The third discharge flow path 27 may be, for example, thicker than each of the multiple branch flow paths 22. Furthermore, the third discharge flow path 27 may be the same width as the main flow path 21, or it may be thicker than the main flow path 21. The diameter of the third discharge port 35 may, for example, be set to be the same as or greater than the width of the third discharge flow path 27. Thus, in the flow path device 1, as described later, most of the second particles Pa12 are separated and removed from the first liquid L1 by the multiple branch flow paths 22, and the remaining liquid, after removing the recovered liquid recovered via the first discharge flow path 25, can be discharged from the third discharge port 35 via the third discharge flow path 27. It should be noted that the remaining liquid may sometimes contain first particles Pa11 and second particles Pa12 that were not removed through separation and recovery. In one embodiment, the portion of the third discharge path 27 connected to the first downstream portion 21d extends along the -Y direction, which is the first direction D1. Figure 1 as well as Figure 3 In one example, the third discharge flow path 27 is a flow path that is connected to the first downstream portion 21d and extends along the -Y direction (first direction D1), along the -X direction (fourth direction D4), along the -Y direction (first direction D1), and along the +X direction (second direction D2) and connected to the third discharge hole 35, in the order described. In other words, the third discharge flow path 27 extends in the order of -Y direction, -X direction, -Y direction, and +X direction.

[0065] In one embodiment, for example, the first inlet hole 31, the second inlet hole 32, the first outlet hole 33, the second outlet hole 34, and the third outlet hole 35 are not open on the upper surface 1a but are open on the lower surface 1b. For example, the first inlet hole 31 has a portion open on the lower surface 1b (also called the first inlet port or first inlet) 1i. The second inlet hole 32 has a portion open on the lower surface 1b (also called the second inlet port or second inlet) 2i. The first outlet hole 33 has a portion open on the lower surface 1b (also called the first outlet port or first outlet) 1o. The second outlet hole 34 has a portion open on the lower surface 1b (also called the second outlet port or second outlet) 2o. The third outlet hole 35 has a portion open on the lower surface 1b (also called the third outlet port or third outlet) 3o.

[0066] As a raw material for flow path device 1 (the material constituting flow path device 1), a resin such as polydimethylsiloxane (PDMS) is used, for example. PDMS, for example, has excellent transferability when resin molding using a mold. Transferability is the property of forming fine irregularities in the resin molded article that correspond to the fine pattern of the mold.

[0067] The flow path device 1 can be manufactured, for example, by joining a plate-shaped portion (also called a first plate-shaped portion) having a fine unevenness on one side corresponding to the pattern of the flow path portion 2 and a plate-shaped portion (also called a second plate-shaped portion) having five through holes corresponding to the first inlet hole 31, the second inlet hole 32, the first outlet hole 33, the second outlet hole 34 and the third outlet hole 35 respectively, in such a way that one side of the second plate-shaped portion covers the fine unevenness of the first plate-shaped portion.

[0068] The first plate-shaped portion, having fine irregularities on one side, can be manufactured, for example, by resin molding. The second plate-shaped portion, having five through holes, can be manufactured, for example, by resin molding, or by forming the five through holes in a flat plate-shaped component formed by resin molding using a punching process. The joining of the first plate-shaped portion and the second plate-shaped portion can be achieved, for example, by surface modification of one side of the first plate-shaped portion and one side of the second plate-shaped portion, and by contact between the one side of the first plate-shaped portion and one side of the second plate-shaped portion, without the use of adhesives. Surface modification can be achieved, for example, by irradiation with oxygen plasma or by irradiation with ultraviolet (UV) light using an excimer lamp. For example, if one side of the first plate-shaped portion and one side of the second plate-shaped portion are made of the same resin, the bonding strength of the one side of the first plate-shaped portion and the one side of the second plate-shaped portion using surface modification can be improved.

[0069] <2. Overview of the functions of flow path devices>

[0070] The function of flow path device 1 will be roughly described below.

[0071] Figure 5 It is a schematic representation in Figure 4 This is a top view of an example of a case in which a first liquid (also called the liquid to be processed) L1 and a liquid different from the first liquid L1 (also called the second liquid or the liquid for pressing) L2 are introduced into the first upstream portion 21u of the main flow path 21 in a part of the flow path 2 shown.

[0072] A first liquid L1 is introduced into the flow path section 2 of the flow path device 1. The first liquid L1 contains a plurality of first particles Pa11 and a plurality of second particles Pa12 as multiple particles Pa1. The plurality of first particles Pa11 are particles that are the objects of separation for a specific type of particle (also called separation object particles). The plurality of second particles Pa12 are particles of other types that are different from the specific type of particle (also called other type particles). In the flow path device 1, a process of separating the plurality of first particles Pa11 and the plurality of second particles Pa12 contained in the first liquid L1 is performed (also called particle separation process). Here, the plurality of particles Pa1 contained in the first liquid L1 may also be three or more types of particles. Hereinafter, the case where the first particle Pa11 and the second particle Pa12 are each one type of particle is illustrated.

[0073] In the flow path device 1, when performing particle separation processing, for example, a first liquid L1 is introduced into the flow path section 2 through the first inlet hole 31, and a second liquid L2 is introduced into the flow path section 2 through the second inlet hole 32. Specific examples and functions of the second liquid L2 will be described later.

[0074] When the first liquid L1 is introduced into the flow path section 2 through the first inlet hole 31, for example, a tube supplying the first liquid L1 (also called the first tube) can be connected to the flow path device 1 from the outside. For this connection of the first tube to the flow path device 1, for example, a cylindrical portion may exist on the lower surface 1b of the flow path device 1, which, when viewed from above, surrounds the first inlet hole 31 around the Z-axis and protrudes in the -Z direction. At one end of the first tube in the longitudinal direction (also called the first end), for example, a connector for connecting to the first inlet hole 31 may be present. At the end of the first tube in the longitudinal direction, different from the first end (also called the second end), a portion (also called the first supply section) for supplying the first liquid L1 to the first inlet hole 31 via the first tube can be connected. The first supply section may, for example, employ a mechanism capable of supplying the first liquid L1 via a pump such as a syringe pump or a plunger pump. Here, the second end of the first tube may, for example, be connected to the first supply section via a three-way valve. In this case, for example, in the flow path device 1, as preparation for the upcoming particle separation process (also known as advance preparation), when the second liquid L2 introduced from the second inlet hole 32 is filled into the flow path section 2, the gas in the flow path section 2 can be discharged from the first inlet hole 31 via the first pipe and the three-way valve by switching the three-way valve, etc.

[0075] When the second liquid L2 is introduced into the flow path section 2 through the second inlet hole 32, for example, a tube (also called a second tube) supplying the second liquid L2 can be connected to the flow path device 1 from the outside of the flow path device 1. For this connection of the second tube to the flow path device 1, for example, a cylindrical portion may be present on the lower surface 1b of the flow path device 1, which, when viewed from above, surrounds the second inlet hole 32 around the Z-axis and protrudes in the -Z direction. At one end of the second tube in the longitudinal direction (also called the third end), for example, a connector for connecting to the second inlet hole 32 may be present. At the end of the second tube in the longitudinal direction different from the third end (also called the fourth end), a portion (also called a second supply section) for supplying the second liquid L2 to the second inlet hole 32 via the second tube can be connected. The second supply section may, for example, employ a mechanism capable of supplying the second liquid L2 by a pump such as an injection pump or a plunger pump.

[0076] For example, the first liquid L1 introduced into the flow path device 1 through the first inlet hole 31 flows into the first upstream portion 21u of the main flow path 21 via the first inlet flow path 23. In other words, the first inlet hole 31 serves as an orifice for introducing the first liquid L1 into the main flow path 21. Additionally, for example, the first inlet flow path 23 serves as a flow path for introducing the first liquid L1 into the first upstream portion 21u of the main flow path 21.

[0077] For example, the second liquid L2 introduced into the flow path device 1 through the second inlet hole 32 flows into the first upstream portion 21u of the main flow path 21 via the second inlet flow path 24. In other words, the second inlet hole 32 serves as an inlet for introducing the second liquid L2 into the main flow path 21. Additionally, for example, the second inlet flow path 24 serves as a flow path for introducing the second liquid L2 into the first upstream portion 21u of the main flow path 21.

[0078] exist Figure 5 The arrow Fp1, depicted by a double-dotted line, indicates the direction in which the second liquid L2 is directed. This direction is along the third direction, D3. Figure 5 In the diagram, arrow Fm1, depicted with a thicker double-dotted line than arrow Fp1, indicates the direction of the main flow (also called the mainstream) of the first liquid L1 flowing from the first inlet flow path 23 into the main flow path 21. This mainstream flows in the direction of the -Y direction, which is the first direction D1. Figure 5 In, with Figure 4 Similarly, a rectangular first upstream portion 21u, imaginarily divided by thin double-dotted lines, is shown in the main road 21.

[0079] exist Figure 5The diagram schematically illustrates the separation of the first particle Pa11 and the second particle Pa12 when the diameter of the first particle Pa11 is larger than the diameter of the second particle Pa12. Specifically, for example, it illustrates a case where the width of each of the plurality of branch flow paths 22 is set to be larger than the diameter of the second particle Pa12 and smaller than the diameter of the first particle Pa11. In each of the plurality of branch flow paths 22, the width of the branch flow path 22 is the length of the branch flow path 22 along the -Y direction, which is the first direction D1. Here, for example, the first liquid L1 may contain multiple particles Pa1, including a plurality of first particles Pa11 with diameters larger than the widths of the plurality of branch flow paths 22 and a plurality of second particles Pa12 with diameters smaller than the widths of the plurality of branch flow paths 22.

[0080] At least the widths of the main flow path 21 and the first inlet flow path 23 are each greater than the diameter of either the first particle Pa11 or the second particle Pa12. Here, the width of the main flow path 21 is its length along the +X direction, which is the second direction D2. The width of the first inlet flow path 23 is its length along the +X direction, which is the second direction D2, near the main flow path 21. The width of the first inlet flow path 23 is its length along the -Y direction, which is the first direction D1, at a position where the first inlet flow path 23 extends along the -X direction, which is the fourth direction D4.

[0081] Multiple second particles Pa12 move in the main flow path 21 in the -Y direction, which is the first direction D1, and are subjected to a pressing force in the +X direction, which is the second direction D2, thereby allowing most of them to be introduced into any of the multiple branch flow paths 22. Most of the multiple second particles Pa12 contained in the first liquid L1 can be discharged to the outside of the flow path device 1 via the second discharge path 26 from the second discharge hole 34 through any of the multiple branch flow paths 22. Here, for example, by adjusting the cross-sectional area and length of each of the multiple branch flow paths 22 connected to the main flow path 21, most of the multiple second particles Pa12 can be introduced from the main flow path 21 into any of the multiple branch flow paths 22 and separated from the multiple first particles Pa11. The multiple second particles Pa12 discharged from the second discharge hole 34 to the outside of the flow path device 1 can, for example, be subjected to specific processing in other devices connected directly to the second discharge hole 34 or via other components such as pipes, or can simply be recycled. Multiple second particles Pa12 discharged from the second discharge port 34 to the outside of the flow path device 1 can also be discarded, for example, directly or via other components such as pipes.

[0082] The multiple first particles Pa11 are hardly introduced into the multiple branch flow paths 22, but move in the -Y direction, which is the first direction D1, within the main flow path 21. Most of the multiple first particles Pa11 are discharged from the first discharge hole 33 to the outside of the flow path device 1 via the main flow path 21 and then via the first discharge flow path 25. Here, the width of the first discharge flow path 25 is greater than the width of the first particles Pa11. Through the same action as introducing most of the multiple second particles Pa12 into any of the multiple branch flow paths 22 in the main flow path 21, the multiple first particles Pa11 reaching the first downstream portion 21d can flow into the first discharge flow path 25 without flowing into the third discharge flow path 27. The multiple first particles Pa11 discharged from the first discharge hole 33 to the outside of the flow path device 1 can be recovered for specific processing, for example, in other devices directly or via other components such as pipes connected to the first discharge hole 33, or simply recovered. In other words, the liquid containing the multiple first particles Pa11 discharged from the first discharge hole 33 to the outside of the flow path device 1 (recovered liquid) is recovered.

[0083] The composition in the first liquid L1, excluding the plurality of second particles Pa12 flowing to any of the plurality of branch flow paths 22 and the plurality of first particles Pa11 flowing to the first discharge flow path 25 (also referred to as the residual composition), flows into the third discharge flow path 27. This residual composition can be discharged from the third discharge port 35 via the third discharge flow path 27. Here, the residual composition discharged from the third discharge port 35 to the outside of the flow path device 1 may, for example, be supplied for specific processing in other devices directly connected to the third discharge port 35 or connected via other components such as pipes, or may simply be recycled. The residual composition discharged from the third discharge port 35 to the outside of the flow path device 1 may, for example, be discarded directly or via other components such as pipes. It should be noted that, as explained above, the residual composition is not necessarily completely free of first particles Pa11 and / or second particles Pa12. The residual composition sometimes contains second particles Pa12 that do not flow to the plurality of branch flow paths 22 and first particles Pa11 that do not flow to the first discharge flow path 25.

[0084] In one embodiment, a flow that introduces a first liquid L1 into multiple branch flow paths 22 (also referred to as an introductory flow) is utilized. The introductory flow facilitates the separation of multiple first particles Pa11 and multiple second particles Pa12 by the main flow path 21 and the multiple branch flow paths 22. Figure 5 In the diagram, the import flow is represented by the shaded region Ar1, which uses a rightward-rising diagonal line. Figure 5The case of the introductory flow represented by region Ar1 is just one example. This introductory flow can vary depending on the relationship between the flow rate and volume of the first liquid L1 introduced into the main flow path 21 from the first introductory flow path 23 and the flow rate and volume of the second liquid L2 introduced into the main flow path 21 from the second introductory flow path 24 in the first upstream portion 21u. By appropriately adjusting region Ar1, multiple first particles Pa11 and multiple second particles Pa12 can be efficiently separated from the first liquid L1. The second liquid L2 presses the first liquid L1 into the multiple branch flow paths 22 from the opposite side of the multiple branch flow paths 22 in the +X direction, which is the second direction D2. In other words, the second liquid L2 can have the effect of pressing the first particles Pa11 and the second particles Pa12, which are multiple particles Pa1, into the first side Sw1 in the +X direction, which is the second direction D2 of the main flow path 21. The second liquid L2 can contribute to the generation of the introductory flow.

[0085] Here, as described above, the main flow path 21 extends along the -Y direction, which is the first direction D1. The first connecting portion Cp1 of the first inlet flow path 23, which connects to the first upstream portion 21u of the main flow path 21, extends along the -Y direction, which is the first direction D1. Multiple branch flow paths 22 are respectively connected to the main flow path 21 between the first upstream portion 21u and the first downstream portion 21d, through openings on the first side surface Sw1 of the main flow path 21. The second inlet flow path 24 is connected to the first upstream portion 21u. Furthermore, the second inlet flow path 24 is connected to the main flow path 21, for example, through an opening on the second side surface Sw2 of the main flow path 21.

[0086] Therefore, by simultaneously introducing a second liquid L2 from the second inlet flow path 24 into the main flow path 21 and a first liquid L1 containing various particles Pa1 from the first inlet flow path 23 into the main flow path 21, a flow of liquid that presses the various particles Pa1 toward the multiple branch flow paths 22 can be generated in the main flow path 21. In other words, for example, by simultaneously supplying the second liquid L2 to the main flow path 21 through the second inlet orifice 32 and the first liquid L1 containing various particles Pa1 to the main flow path 21 through the first inlet orifice 31, a flow of liquid that presses the various particles Pa1 toward the multiple branch flow paths 22 can be generated in the main flow path 21. In other words, for example, when the second liquid L2 is introduced into the first upstream portion 21u from the second inlet hole 32 via the second inlet flow path 24, and the first liquid L1 is introduced into the first upstream portion 21u from the first inlet hole 31 via the first inlet flow path 23, in the main flow path 21, multiple first particles Pa11 and multiple second particles Pa12, which are multiple particles Pa1 contained in the first liquid L1, can flow towards the first downstream portion 21d while being pressed towards the multiple branch flow paths 22. Thus, for example, multiple second particles Pa12, whose diameter is smaller than the width of each of the multiple branch flow paths 22, easily flow into the multiple branch flow paths 22. As a result, for example, the separation of multiple first particles Pa11 with a diameter larger than the width of each of the multiple branch flow paths 22 and multiple second particles Pa12 with a diameter smaller than the width of each of the multiple branch flow paths 22 becomes easier.

[0087] Furthermore, in one embodiment, as described above, the portion of the first discharge flow path 25 connected to the first downstream portion 21d of the main flow path 21 has a side opening in the first downstream portion 21d in the +X direction of the second direction D2. Therefore, for example, through the action of the inlet flow in the main flow path 21, a plurality of first particles Pa11 with diameters larger than the widths of the plurality of branch flow paths 22 can easily flow into the first discharge flow path 25. Thus, for example, the plurality of first particles Pa11 can be easily discharged from the first discharge hole 33 to the outside of the flow path device 1 via the first discharge flow path 25. As a result, for example, the separation of particles of the type with diameters larger than the widths of the plurality of branch flow paths 22 in the first liquid L1—that is, the plurality of first particles Pa11—from the plurality of second particles Pa12 with diameters smaller than the widths of the plurality of branch flow paths 22 becomes easier.

[0088] exist Figure 5In this context, the width of the inflow in the main flow path 21 is represented as the width (also called the second width) Wf1 in the vicinity of the region from the main flow path 21 to the multiple branch flow paths 22. Here, the width of the inflow in the main flow path 21 is the length of the inflow along the +X direction, which is the second direction D2. The second width Wf1 can be set, for example, by adjusting the cross-sectional area and length of the main flow path 21 and the multiple branch flow paths 22, and by adjusting the flow rates of the first liquid L1 and the second liquid L2.

[0089] exist Figure 5 In this example, the second width Wf1 is exemplified as the width in the region Ar1 of the inlet flow that does not contain the centroid positions of the individual first particles Pa11 but contains the centroid positions of the individual second particles Pa12. Here, by making the second width Wf1 such that the centroid positions of the second particles Pa12 are included in the region Ar1 of the inlet flow, a force is effectively applied to the second particles Pa12, causing them to flow into any one of the multiple branch flow paths 22 via the inlet flow. Therefore, the second particles Pa12 can flow into the branch flow path 22, whose width is larger than the diameter of the second particles Pa12. Conversely, since the second width Wf1 is the width in the region Ar1 of the inlet flow that does not contain the centroid positions of the first particles Pa11, the force causing the first particles Pa11 to flow into the multiple branch flow paths 22 via the inlet flow does not sufficiently act on the first particles Pa11. Therefore, for example, even when the width of the branch flow path 22 is slightly larger than the diameter of the first particles Pa11, the first particles Pa11 can flow in the main flow path 21 without flowing into the multiple branch flow paths 22.

[0090] As an example of the first liquid L1, blood or a liquid diluted with physiological saline is used. Blood is a liquid containing various particles Pa1. In this case, an example is used where the first particle Pa11 is leukocytes and the second particle Pa12 is erythrocytes. As an example of a specific treatment for multiple first particles Pa11, the number and concentration of leukocytes are measured. As an example of the remaining composition flowing through the third discharge path 27 and discharged from the flow path device 1 via the third discharge port 35, plasma is used. In this case, as an example of the second liquid L2, physiological saline is used. More specifically, as an example of the second liquid L2, phosphate-buffered saline (PBS) is used. In order for the second liquid L2 to have a function corresponding to the purpose of use of the flow path device 1, the second liquid L2 can also be a liquid in which other components are added to PBS. Other components can be, for example, ethylenediaminetetraacetic acid (EDTA) as the second component, or bovine serum albumin (BSA) as the third component. Here, the main flow path 21 and multiple branch flow paths 22 included in the flow path section 2 function as flow paths for separating particles in the blood. In other words, the flow path section 2 includes a main flow path 21 and multiple branch flow paths 22 for separating particles in the blood.

[0091] The center of gravity of red blood cells is, for example, located 2 to 2.5 micrometers (μm) from the outer edge of the red blood cell. The maximum diameter of red blood cells is, for example, 6 to 8 μm. The center of gravity of white blood cells is, for example, located 5 to 10 μm from the outer edge of the white blood cell. The maximum diameter of white blood cells is, for example, 10 to 20 μm. From the viewpoint of separating red blood cells and white blood cells in the blood, the width of the introduced flow (second width) Wf1 is adopted as a value of 2 to 10 μm.

[0092] The cross-sectional area of ​​the imaginary section along the XZ plane of the main path 21 is set to, for example, 400 square micrometers (μm). 2 Up to 4000μm 2 The length (also called width) of the main path 21 along the +X direction, which is the second direction D2, is set to, for example, 20 μm to 100 μm. The length (also called height) of the main path 21 along the +Z direction is set to, for example, 20 μm to 100 μm. The length of the main path 21 along the -Y direction, which is the first direction D1, is set to, for example, 0.5 mm to 20 mm.

[0093] The cross-sectional area of ​​the imaginary cross section along the YZ plane for each of the multiple branch flow paths 22 is set to, for example, 200 μm. 2 Up to 800μm2 The length (also called width) of each of the multiple branch flow paths 22 along the -Y direction, which is the first direction D1, is set to, for example, 10 μm to 30 μm. The length (also called height) of each of the multiple branch flow paths 22 along the +Z direction is set to, for example, 20 μm to 100 μm. The length of each of the multiple branch flow paths 22 along the +X direction, which is the second direction D2, is set to, for example, 3 mm to 25 mm.

[0094] The flow rate of liquid per unit time in the main flow path 21 is set, for example, to the level of 150 microliters per minute (μL / min) to 480 μL / min. The flow rate of the first liquid L1 introduced into the main flow path 21 from the first inlet port 31 via the first inlet flow path 23 is set, for example, to the level of 90 μL / min to 270 μL / min. The flow rate of the second liquid L2 introduced into the main flow path 21 from the second inlet port 32 via the second inlet flow path 24 is set, for example, to the level of 60 μL / min to 210 μL / min.

[0095] However, as described above, for example, the main flow path 21 extends along the -Y direction, which is the first direction D1. The first connecting portion Cp1 in the first inlet flow path 23, which is connected to the first upstream portion 21u of the main flow path 21, extends along the -Y direction, which is the first direction D1. The second connecting portion Cp2 in the second inlet flow path 24, which is connected to the first upstream portion 21u of the main flow path 21, extends along a third direction D3 at an acute angle relative to the -Y direction, which is the first direction D1.

[0096] By employing this structure, for example, when using flow path device 1 for particle separation processing, such as... Figure 5As shown, in the first upstream section 21u of the main flow path 21, the flow of the second liquid L2 can merge with the flow of the first liquid L1 in a manner that forms an acute angle with the first inflow direction of the first liquid L1 from the second inlet flow path 24 to the first upstream section 21u. The first inflow direction is the direction in which the first liquid L1 flows from the first inlet flow path 23 to the first upstream section 21u along the -Y direction, which is the first direction D1. The second inflow direction is the direction in which the second liquid L2 flows from the second inlet flow path 24 to the first upstream section 21u along the third direction D3. Thus, for example, even if the flow velocity of the first liquid L1 introduced into the main flow path 21 increases, the generation of turbulence in the introduced flow can be reduced in the main flow path 21. As a result, the increase in the proportion of second particles Pa12 (e.g., more than one second particle Pa12) flowing to the first downstream portion 21d in the first liquid L1 can be reduced. Therefore, for example, the increase in the number of second particles Pa12 mixed into the recovered liquid recovered from the first downstream portion 21d via the first discharge port 33, etc., can be reduced. Therefore, the decrease in the proportion of first particles Pa11 (e.g., multiple first particles Pa11) among the multiple particles contained in the recovered liquid can be reduced. Here, for example, if blood or a liquid diluted with physiological saline is used as an example of the first liquid L1, and physiological saline is used as an example of the second liquid L2, the decrease in the proportion of white blood cells (e.g., multiple white blood cells) among all blood cells in the recovered liquid (also called white blood cell purity) can be reduced. All blood cells include white blood cells and red blood cells.

[0097] Furthermore, as described above, for example, the flow path 2 has a connecting surface Cs1 that connects the third side surface Sw3 of the second connecting portion Cp2 to the second side surface Sw2 of the main flow path 21. In other words, the flow path 2 has a shape where the front end of the corner where the first upstream portion 21u of the main flow path 21 and the second connecting portion Cp2 of the second guide flow path 24 form an acute angle is missing. In other words, the flow path 2 has a portion (expansion portion) Ac1 in which the flow path is expanded between the first upstream portion 21u of the main flow path 21 and the second connecting portion Cp2 of the second guide flow path 24. The first distance Le1 is set to be less than or equal to the width (first width) W1 of the main flow path 21. As described above, the first distance Le1 is the distance between the third portion P1 where the second side surface Sw2 of the main flow path 21 connects to the connecting surface Cs1 and the fourth portion P2 where the third side surface Sw3 of the second connecting portion Cp2 connects to the connecting surface Cs1.

[0098] By employing this structure, when using flow path device 1 for particle separation processing, for example, Figure 5 As shown, due to the presence of the expansion portion Ac1, a portion of the flow of the first liquid L1 can temporarily expand from the first upstream portion 21u side of the main flow path 21 towards the second inlet flow path 24, and then be pressed towards the first side Sw1 by the flow of the second liquid L2. In this case, for example, the first liquid L1 flowing along the second side Sw2, which is part of the first liquid L1, and then along the connecting surface Cs1, can be pressed towards the first side Sw1 by the second liquid L2 flowing along the third side Sw3, which is part of the second liquid L2. At the point where the liquids merge in this way, for example, the direction in which the second liquid L2 flowing along the third side Sw3, which is part of the flow of the second liquid L2, presses the first liquid L1 flowing along the connecting surface Cs1 towards the first side Sw1 can be nearly perpendicular to the direction of flow of the first liquid L1 flowing along the connecting surface Cs1. Thus, for example, in the main flow path 21, the generation of turbulence in the inlet flow is reduced, and the force by which the second liquid L2 presses the first liquid L1 towards the multiple branch flow paths 22 can be increased. As a result, in the main flow path 21, the proportion of second particles Pa12 (e.g., more than one second particle Pa12) flowing to the first downstream section 21d in the first liquid L1 can be reduced. Therefore, for example, the number of second particles Pa12 mixed into the recovered liquid recovered from the first downstream section 21d via the first discharge port 33, etc., can be reduced. Therefore, among the multiple particles contained in the recovered liquid, the proportion of first particles Pa11 (e.g., multiple first particles Pa11) of a specific type of particle can be increased. Here, for example, if blood or a liquid diluted with physiological saline is used as an example of the first liquid L1, and physiological saline is used as an example of the second liquid L2, the purity of white blood cells in the white blood cell recovered liquid can be increased. As mentioned above, white blood cell purity is the proportion of white blood cells (e.g., several white blood cells) among all blood cells.

[0099] <3. Relationship between the size of the junctional surface and the purity of white blood cells>

[0100] Here, regarding the case of particle separation processing using the flow path device 1 of the above-described embodiment, various examples of experiments performed will be described, focusing on the relationship between the size of the connecting surface Cs1 and the purity of white blood cells in the white blood cell recovery fluid recovered from the first downstream portion 21d via the first discharge hole 33, etc.

[0101] The following section describes the common conditions (also known as the basic conditions) in all the examples of the experiments conducted, followed by the conditions and results for each example of the experiments conducted.

[0102] <3-1. Basic Conditions for the Experiment>

[0103] <3-1-1. Basic Conditions for Flow Path Devices>

[0104] PDMS is used as the material for the flow path device 1. The first plate-shaped portion and the second plate-shaped portion are joined by means that one side of the second plate-shaped portion covers one side of the first plate-shaped portion in a manner corresponding to the pattern of the flow path portion 2, thereby fabricating the flow path device 1. As the first plate-shaped portion, a plate-shaped portion having fine irregularities on one side corresponding to the pattern of the flow path portion 2 is used. The first plate-shaped portion with fine irregularities on one side is fabricated by resin molding. As the second plate-shaped portion, a plate-shaped portion having five through holes corresponding to the first inlet hole 31, the second inlet hole 32, the first outlet hole 33, the second outlet hole 34, and the third outlet hole 35 is used. The second plate-shaped portion having five through holes is fabricated by resin molding. The joining of the first plate-shaped portion and the second plate-shaped portion is performed without the use of adhesives by surface modification of one side of the first plate-shaped portion and one side of the second plate-shaped portion, and by contact between one side of the first plate-shaped portion and one side of the second plate-shaped portion.

[0105] Each of the multiple flow paths constituting the flow path section 2 has a rectangular cross-section. The cross-section of each flow path is formed by imaginarily cutting the flow path along an imaginary plane orthogonal to the direction of its extension. Regarding the main flow path 21, its width and height are both set to 40 μm. Regarding the multiple branch flow paths 22, each branch flow path 22 has a width of 18 μm and a height of 40 μm. The number of branch flow paths 22 is set to 90. Regarding the first inlet flow path 23, its width and height are both set to 40 μm. Regarding the second inlet flow path 24, its width and height are both set to 40 μm. The connecting surface Cs1 is a flat, rectangular surface. Viewed from above, the shape of the expansion portion Ac1 located between the first upstream portion 21u of the main flow path 21 and the second connecting portion Cp2 of the second inlet flow path 24 is set to be an isosceles triangle with the side along the connecting surface Cs1 as its base. In other words, the angle α between the third side surface Sw3 and the connecting surface Cs1 and the angle β between the second side surface Sw2 and the connecting surface Cs1 are set to be the same.

[0106] <3-1-2. Basic Conditions Regarding the First and Second Liquids>

[0107] As the first liquid L1, a liquid obtained by diluting blood 1.5 times with PBS which is physiological saline is used. The first liquid L1 is supplied to the first introduction flow path 23 from the outside of the flow path device 1 via a tube connected to the first introduction hole 31 and the first introduction hole 31 by an injection pump. The flow rate of the first liquid L1 per unit time introduced into the main flow path 21 from the first introduction hole 31 via the first introduction flow path 23 is adjusted by controlling the operation of the injection pump.

[0108] As the second liquid L2, PBS which is physiological saline is used. The second liquid L2 is supplied to the second introduction flow path 24 from the outside of the flow path device 1 via a tube connected to the second introduction hole 32 and the second introduction hole 32 by an injection pump. The flow rate of the second liquid L2 per unit time introduced into the main flow path 21 from the second introduction hole 32 via the second introduction flow path 24 is adjusted by controlling the operation of the injection pump.

[0109] Before performing the particle separation process using the flow path device 1, as a preliminary preparation, the second liquid L2 is introduced into the flow path portion 2 from the second introduction hole 32, and the flow path portion 2 is filled with the second liquid L2.

[0110] The leukocyte recovery liquid discharged from the first discharge hole 33 to the outside of the flow path device 1 is recovered by a microcentrifuge tube via a member having a resin flow path.

[0111] <3-1-3. Method for calculating the leukocyte purity in the leukocyte recovery liquid>

[0112] The leukocyte purity in the leukocyte recovery liquid is calculated from the concentration of leukocytes (also referred to as leukocyte concentration) and the concentration of all blood cells (also referred to as total blood cell concentration) in the leukocyte recovery liquid measured separately using a measuring device. More specifically, the leukocyte concentration is divided by the total blood cell concentration and multiplied by 100, thereby calculating the leukocyte purity in the leukocyte recovery liquid (unit: percentage (%)). As described above, the leukocyte purity is the proportion of leukocytes (such as multiple leukocytes) among all blood cells.

[0113] As the measuring device, an automatic cell counter LUNA FX-7 (trademark) manufactured by Logos Biosystems is used.

[0114] The measurement of the leukocyte concentration and the total blood cell concentration using the measuring device is performed by sequentially performing a sample preparation process, a sample setting process, and a blood cell concentration measurement process. The sample preparation process is a process for preparing the following sample (also referred to as a specimen). The sample setting process is a process for setting the following specimen in the measuring device. The blood cell concentration measurement process is a process for measuring the following blood cell concentration.

[0115] <<A. Sample preparation process>>

[0116] The white blood cell recovery solution from the microcentrifuge tube was diluted 4-fold with PBS to obtain the diluted white blood cell recovery solution (also known as the diluted recovery solution). The measurement of the white blood cell recovery solution and PBS was performed manually using pipettes, and the mixing of the white blood cell recovery solution and PBS within the microcentrifuge tube was also performed. More specifically, 20 μL of diluted recovery solution was obtained by mixing 15 μL of white blood cell recovery solution and 5 μL of PBS. By diluting the white blood cell recovery solution with this PBS, the concentration of blood cells in the diluted recovery solution was set within a range that the analyzer could stably and accurately measure. The range of blood cell concentrations that the analyzer could stably and accurately measure was per 1 × 10⁻⁶ cells / mL. 5 From 1×10 cells / mL to 1×10 7 cells / mL.

[0117] Next, a sample was prepared by mixing 18 μL of the diluted recovery solution with 2 μL of reagent. The reagent used was a mixture of acridine orange (AO) and propidium iodide (PI). More specifically, the reagent used was Acridine Orange / Propidium Iodide Stain (AO / PI) manufactured by Logos Biosystems. Here, the diluted recovery solution and reagent were manually measured using pipettes, and the diluted recovery solution and reagent were mixed in the microcentrifuge tube. The mixing of the diluted recovery solution and reagent in the microcentrifuge tube was performed by shaking the microcentrifuge tube at room temperature.

[0118] Here, acridine orange (AO) is a dye that penetrates the cell membranes of both living and dead cells, staining all nucleated cells with a green fluorescence (also known as green fluorescence) (or nuclear staining dye). Propidine iodide (PI) is a dye that penetrates into nucleated cells with damaged cell membranes, staining dead cells with a red fluorescence (also known as red fluorescence) (or dead cell staining dye). When multiple cells are stained with both acridine orange (AO) and propidine iodide (PI), living cells with all nuclei emit green fluorescence, while dead cells with all nuclei emit red fluorescence. In other words, after multiple white blood cells are stained with both acridine orange (AO) and propidine iodide (PI), all living white blood cells emit green fluorescence, while all dead white blood cells emit red fluorescence. In contrast, nucleated cells such as human red blood cells, platelets, and fragments (also known as anucleated cells) do not fluoresce due to the action of acridine orange (AO) and propidine iodide (PI).

[0119] <<B. Specimen Setting Procedure>>

[0120] Using a pipette, 10 μL of the specimen obtained in the specimen preparation process is injected into a cell counting slide.

[0121] Then, by inserting the cell counting slide into the slide insertion port provided on the side of LUNA FX-7 (trademark), an automatic cell counter manufactured by Logos Biosystems Co., Ltd. as a measuring instrument, the specimen is set in the measuring instrument.

[0122] <<C. Blood Cell Concentration Measurement Procedure>>

[0123] By operating the measuring instrument in which the specimen is set in the above specimen setting procedure, the white blood cell concentration and the total blood cell concentration of the specimen are sequentially measured in the measuring instrument under the condition of room temperature.

[0124] Regarding the measurement of the white blood cell concentration, in the measuring instrument, when exciting light of a specified wavelength is irradiated onto the specimen in the cell counting slide to cause white blood cells to emit fluorescence, multiple images capturing 8 to 12 regions are obtained. Then, in the measuring instrument, the average value of the white blood cell concentrations obtained by measuring the number of white blood cells for each of the multiple images through image processing is output as the measured value of the white blood cell concentration (unit: cells / mL). The white blood cell concentration is the concentration of white blood cells including both live and dead white blood cells. Here, in the darkroom inside the measuring instrument, when exciting light with a wavelength of 450 nanometers (nm) to 490 nm is irradiated onto the specimen in the cell counting slide and the white blood cells emit green fluorescence with a wavelength of 505 nm to 555 nm, multiple images capturing 8 to 12 regions are obtained. Then, in the measuring instrument, the number of white blood cells is measured for each of the multiple images through image processing. In addition, in the darkroom inside the measuring instrument, when exciting light with a wavelength of 510 nm to 550 nm is irradiated onto the specimen in the cell counting slide and the dead white blood cells emit red fluorescence with a wavelength of 590 nm to 650 nm, multiple images capturing 8 to 12 regions are obtained. Then, in the measuring instrument, the number of dead white blood cells is measured for each of the multiple images through image processing.

[0125] Regarding the measurement of the total blood cell concentration, in the measuring instrument, for the specimen in the cell counting slide, multiple images capturing 8 to 12 regions are obtained under bright field conditions. Then, in the measuring instrument, the average value of the blood cell concentrations obtained by measuring the number of blood cells for each of the multiple images through image processing is output as the measured value of the total blood cell concentration (unit: cells / mL).

[0126] <3-2. The First Example of the Experiment>

[0127] As Figure 4 As shown, in the first example of the experiment, the angle θ between the first direction D1 and the third direction D3 was set to 30 degrees. In other words, the angle θ between the first direction D1 extending along the first connecting portion Cp1 of the first inlet flow path 23 and the third direction D3 extending along the second connecting portion Cp2 of the second inlet flow path 24 was set to 30 degrees.

[0128] In the first example of the experiment, when using the flow path device 1 for particle separation, the flow rate of the first liquid L1 introduced into the main flow path 21 from the first inlet hole 31 via the first inlet flow path 23 was set to 150 μL / min per unit time, and the flow rate of the second liquid L2 introduced into the main flow path 21 from the second inlet hole 32 via the second inlet flow path 24 was set to 120 μL / min per unit time.

[0129] In the first example of the experiment, regarding the size of the connecting surface Cs1, the first distance Le1 was set to six distances: 0 times, 0.5 times, 1 time, 2 times, 3 times, and 5 times the width (first width) W1 of the main flow path 21. As mentioned above, the first distance Le1 is the distance between the third part P1 where the second side Sw2 of the main flow path 21 connects to the connecting surface Cs1, and the fourth part P2 where the third side Sw3 of the second connecting part Cp2 connects to the connecting surface Cs1. In this disclosure, a structure where the first distance Le1 is 0 times the first width W1 refers to a structure in which the second side Sw2 of the main flow path 21 is directly connected to the third side Sw3 of the second connecting part Cp2 without a connecting surface Cs1. In other words, a flow path device (also called the flow path device of the reference example) that directly connects the second side Sw2 of the main flow path 21 to the third side Sw3 of the second connecting part Cp2, based on the flow path device 1, without a connecting surface Cs1, is used as a flow path device with a structure where the first distance Le1 is 0 times the first width W1.

[0130] Furthermore, in the first example of the experiment, particle separation was performed using flow path devices with six different conditions, and the purity of white blood cells in the recovered white blood cell solution was determined. Here, the six conditions for the flow path devices used included a flow path device without a connecting surface Cs1, a flow path device where the first distance Le1 was set to 0.5 times the first width W1, a flow path device where the first distance Le1 was set to 1 times the first width W1, a flow path device where the first distance Le1 was set to 2 times the first width W1, a flow path device where the first distance Le1 was set to 3 times the first width W1, and a flow path device where the first distance Le1 was set to 5 times the first width W1.

[0131] Figure 6 This is a graph showing the relationship between the size of the junction surface Cs1 and the purity of leukocytes in the leukocyte recovery fluid, based on the results of the first example of the experiment. Figure 6 In the diagram, the relationship between the size of the interface Cs1 and the purity of leukocytes in the leukocyte recovery fluid is represented by a plot of multiple blackened circular markers. Figure 6 In the diagram, the horizontal axis represents the dimension of the connecting surface Cs1, showing the ratio of the first distance Le1 relative to the width (first width) W1 of the main flow path 21. In other words, the horizontal axis represents the relative value of the first distance Le1 when the width (first width) W1 of the main flow path 21 is 1. The vertical axis represents the relative value of the white blood cell purity in the white blood cell recovery fluid (also called the relative value of white blood cell purity) when the white blood cell purity in the white blood cell recovery fluid is set to 100, which is the base value for a flow path device without a connecting surface Cs1. The relative value of white blood cell purity is obtained by dividing the white blood cell purity in the white blood cell recovery fluid by the white blood cell purity in the white blood cell recovery fluid calculated for a flow path device without a connecting surface Cs1 (also called the base value of white blood cell purity) and multiplying by 100.

[0132] like Figure 6 As shown, in the first example of the experiment, when the first distance Le1, which is related to the size of the connecting surface Cs1, is 1 times the first width W1 and 0.5 times the first width W1, respectively, the purity of white blood cells in the white blood cell recovery fluid is improved compared to the case where the connecting surface Cs1 is not present.

[0133] Therefore, based on the first example of the experiment, it was confirmed that if a connecting surface Cs1 exists, and the size of the connecting surface Cs1 involves a first distance Le1 that is less than 1 times the width (first width) W1 of the main path 21, then the purity of white blood cells in the white blood cell recovery fluid can be improved compared to the case where the connecting surface Cs1 does not exist.

[0134] In addition, such as Figure 6 As shown, in the first example of the experiment, compared with the case where the first distance Le1 involved in the size of the connecting surface Cs1 is 1 times the first width W1, the purity of white blood cells in the white blood cell recovery fluid is improved when the first distance Le1 involved in the size of the connecting surface Cs1 is 0.5 times the first width W1.

[0135] <3-3. The Second Example of the Experiment>

[0136] like Figure 4 As shown, in the second example of the experiment, the angle θ between the first direction D1 and the third direction D3 was set to 30 degrees, which is the same as the first example of the experiment.

[0137] In the second example of the experiment, when using the flow path device 1 for particle separation, the flow rate of the first liquid L1 introduced into the main flow path 21 from the first inlet 31 via the first inlet flow path 23 was set to 150 μL / min per unit time, and the flow rate of the second liquid L2 introduced into the main flow path 21 from the second inlet 32 ​​via the second inlet flow path 24 was set to 90 μL / min per unit time. That is, in the second example of the experiment, the flow rate of the second liquid L2 introduced into the main flow path 21 from the second inlet 32 ​​via the second inlet flow path 24 was set to 90 μL / min, which is a decrease from 120 μL / min in the first example of the experiment.

[0138] In the second example of the experiment, regarding the dimensions of the connecting surface Cs1, the first distance Le1 was set to four distances: 0 times, 0.5 times, 1 time, and 2 times the width (first width) W1 of the main path 21. As mentioned above, the first distance Le1 is the distance between the third part P1 where the second side Sw2 of the main path 21 connects to the connecting surface Cs1, and the fourth part P2 where the third side Sw3 of the second connecting part Cp2 connects to the connecting surface Cs1.

[0139] Then, in the second example of the experiment, particle separation was performed using flow path devices under four different conditions, and the purity of white blood cells in the white blood cell recovery solution was determined. Here, the four flow path devices used were: a flow path device without a connecting surface Cs1; a flow path device where the first distance Le1 was set to 0.5 times the first width W1; a flow path device where the first distance Le1 was set to 1 times the first width W1; and a flow path device where the first distance Le1 was set to 2 times the first width W1.

[0140] Figure 7 The graph showing the relationship between the size of the junction surface Cs1 and the purity of leukocytes in the leukocyte recovery fluid is based on the results of the second example of the experiment. Figure 7 In, with Figure 6 Similarly, the relationship between the size of the interface Cs1 and the purity of leukocytes in the leukocyte recovery fluid is indicated by several blackened circles. Figure 7 In, with Figure 6 Similarly, the horizontal axis represents the dimension of the connecting surface Cs1, and the ratio of the first distance Le1 to the width (first width) W1 of the main flow path 21 relative to the first width W1. In other words, the horizontal axis represents the relative value of the first distance Le1 when the first width W1 of the main flow path 21 is 1. The vertical axis represents the relative value of the white blood cell purity in the white blood cell recovery fluid when the white blood cell purity in the white blood cell recovery fluid calculated for a flow path device without a connecting surface Cs1 is set to 100 as a reference.

[0141] like Figure 7As shown, in the second example of the experiment, which is the same as the first example of the experiment, when the first distance Le1 involved in the size of the connecting surface Cs1 is 1 times the first width W1 and 0.5 times the first width W1 respectively, the purity of white blood cells in the white blood cell recovery fluid is improved compared with the case where there is no connecting surface Cs1.

[0142] Therefore, based on the second example of the experiment, which is the same as the first example of the experiment mentioned above, there is a connecting surface Cs1. It was confirmed that if the first distance Le1 is less than 1 times the width (first width) W1 of the main path 21, the purity of white blood cells in the white blood cell recovery fluid is improved compared to the case where there is no connecting surface Cs1.

[0143] In addition, such as Figure 7 As shown, in the second example of the experiment, similar to the first example of the experiment, when the first distance Le1 involved in the size of the connecting surface Cs1 is 1 times the first width W1, the purity of white blood cells in the white blood cell recovery fluid is improved when the first distance Le1 involved in the size of the connecting surface Cs1 is 0.5 times the first width W1.

[0144] <3-4. The Third Example of the Experiment>

[0145] like Figure 4 As shown, in the third example of the experiment, the angle θ between the first direction D1 and the third direction D3 was set to 30 degrees, which is the same as the first and second examples of the experiment.

[0146] In the third example of the experiment, when using the flow path device 1 for particle separation, the flow rate of the first liquid L1 introduced into the main flow path 21 from the first inlet 31 via the first inlet flow path 23 was set to 180 μL / min per unit time, and the flow rate of the second liquid L2 introduced into the main flow path 21 from the second inlet 32 ​​via the second inlet flow path 24 was set to 120 μL / min per unit time. That is, in the third example of the experiment, the flow rate of the first liquid L1 introduced into the main flow path 21 from the first inlet 31 via the first inlet flow path 23 was set to 180 μL / min, an increase from 150 μL / min in the first example of the experiment.

[0147] In the third example of the experiment, regarding the dimensions of the connecting surface Cs1, similar to the second example above, the first distance Le1 was set to four distances: 0 times, 0.5 times, 1 time, and 2 times the width (first width) W1 of the main path 21. As mentioned above, the first distance Le1 is the distance between the third part P1 where the second side Sw2 of the main path 21 connects to the connecting surface Cs1, and the fourth part P2 where the third side Sw3 of the second connecting part Cp2 connects to the connecting surface Cs1.

[0148] Then, in the second example of the experiment, particle separation was performed using flow path devices under four different conditions, and the purity of white blood cells in the white blood cell recovery solution was determined. Here, the four flow path devices used were: a flow path device without a connecting surface Cs1; a flow path device where the first distance Le1 was set to 0.5 times the first width W1; a flow path device where the first distance Le1 was set to 1 times the first width W1; and a flow path device where the first distance Le1 was set to 2 times the first width W1.

[0149] Figure 8 The graph showing the relationship between the size of the junction surface Cs1 and the purity of leukocytes in the leukocyte recovery fluid is from the results of the third example of the experiment. Figure 8 In, with Figure 6 and Figure 7 Similarly, the relationship between the size of the interface Cs1 and the purity of leukocytes in the leukocyte recovery fluid is represented by a plot of multiple blackened circular markers. Figure 8 In, with Figure 6 as well as Figure 7 Similarly, the horizontal axis represents the dimension of the connecting surface Cs1, and the ratio of the first distance Le1 to the width (first width) W1 of the main flow path 21 relative to the first width W1. In other words, the horizontal axis represents the relative value of the first distance Le1 when the width (first width) W1 of the main flow path 21 is 1. The vertical axis represents the relative value of the white blood cell purity in the white blood cell recovery fluid when the white blood cell purity in the white blood cell recovery fluid calculated for the flow path device without the connecting surface Cs1 is set to 100 as a reference.

[0150] like Figure 8 As shown, in the third example of the experiment, which is the same as the first and second examples above, when the first distance Le1 related to the size of the connecting surface Cs1 is 1 times the first width W1 and 0.5 times the first width W1 respectively, the purity of white blood cells in the white blood cell recovery fluid is improved compared with the case where there is no connecting surface Cs1.

[0151] Therefore, based on the third example of the experiment, which is the same as the first and second examples of the experiment mentioned above, it was confirmed that if the connecting surface Cs1 exists and the first distance Le1 is less than 1 times the width (first width) W1 of the main path 21, the purity of white blood cells in the white blood cell recovery fluid can be improved compared with the case where the connecting surface Cs1 does not exist.

[0152] In addition, such as Figure 8As shown, in the third example of the experiment, similar to the first and second examples mentioned above, when the first distance Le1 involved in the size of the connecting surface Cs1 is 1 times the first width W1, the purity of white blood cells in the white blood cell recovery fluid is improved when the first distance Le1 involved in the size of the connecting surface Cs1 is 0.5 times the first width W1.

[0153] <3-5. Results of the first to third cases of the experiment>

[0154] like Figures 6 to 8 As shown, in any of the first to third examples of the above experiments, when the first distance Le1 related to the size of the connecting surface Cs1 is 1 times the first width W1 and 0.5 times the first width W1, respectively, the purity of leukocytes in the leukocyte recovery fluid is improved compared to the case where the connecting surface Cs1 is absent. In other words, when using the flow path device 1 for particle separation processing, even if the flow rate of the first liquid L1 introduced from the first inlet hole 31 through the first inlet flow path 23 to the main flow path 21 per unit time and the flow rate of the second liquid L2 introduced from the second inlet hole 32 through the second inlet flow path 24 to the main flow path 21 per unit time are slightly increased or decreased, when the first distance Le1 related to the size of the connecting surface Cs1 is 1 times the first width W1 and 0.5 times the first width W1, respectively, the purity of leukocytes in the leukocyte recovery fluid is improved compared to the case where the connecting surface Cs1 is absent.

[0155] Therefore, it was confirmed that if a connecting surface Cs1 exists, and the first distance Le1 is less than or equal to the width (first width) W1 of the main flow path 21, the purity of leukocytes in the leukocyte recovery fluid can be improved compared to the case where the connecting surface Cs1 does not exist. In other words, it was confirmed that if a connecting surface Cs1 exists, and the first distance Le1 is less than or equal to the width (first width) W1 of the main flow path 21, the proportion of a specific type of particle (e.g., multiple specific types of particles) among the multiple particles contained in the recovery fluid can be increased. As described above, the first distance Le1 is the distance between the third part P1 where the second side surface Sw2 of the main flow path 21 connects to the connecting surface Cs1, and the fourth part P2 where the third side surface Sw3 of the second connecting part Cp2 connects to the connecting surface Cs1.

[0156] <3-6. The Fourth Experiment>

[0157] like Figure 4 As shown, in the fourth example of the experiment, the angle θ between the first direction D1 and the third direction D3 was set to 30 degrees, which is the same as the first example of the experiment.

[0158] In the fourth example of the experiment, similar to the first example above, when using the flow path device 1 for particle separation, the flow rate of the first liquid L1 introduced into the main flow path 21 from the first inlet hole 31 via the first inlet flow path 23 was set to 150 μL / min per unit time, and the flow rate of the second liquid L2 introduced into the main flow path 21 from the second inlet hole 32 via the second inlet flow path 24 was set to 120 μL / min per unit time.

[0159] In the fourth example of the experiment, regarding the dimensions of the connecting surface Cs1, the first distance Le1 was set to six times the width (first width) W1 of the main path 21: 0, 0.1, 0.2, 0.3, 0.4, and 0.5 times. As mentioned above, the first distance Le1 is the distance between the third part P1 where the second side Sw2 of the main path 21 connects to the connecting surface Cs1, and the fourth part P2 where the third side Sw3 of the second connecting part Cp2 connects to the connecting surface Cs1.

[0160] Furthermore, in the fourth example of the experiment, particle separation was performed using each of the six flow path devices, and the purity of white blood cells in the white blood cell recovery solution was determined. Here, the six flow path devices used were: a flow path device without a connecting surface Cs1; a flow path device where the first distance Le1 was set to 0.1 times the first width W1; a flow path device where the first distance Le1 was set to 0.2 times the first width W1; a flow path device where the first distance Le1 was set to 0.3 times the first width W1; a flow path device where the first distance Le1 was set to 0.4 times the first width W1; and a flow path device where the first distance Le1 was set to 0.5 times the first width W1.

[0161] Figure 9 The graph showing the relationship between the size of the junction surface Cs1 and the purity of leukocytes in the leukocyte recovery fluid is based on the results of the fourth example of the experiment. Figure 9 In, with Figures 6 to 8 Similarly, the relationship between the size of the interface Cs1 and the purity of leukocytes in the leukocyte recovery fluid is represented by a plot of multiple blackened circular markers. Figure 9 In, with Figures 6 to 8 Similarly, the horizontal axis represents the dimension of the connecting surface Cs1, and the ratio of the first distance Le1 to the width (first width) W1 of the main flow path 21 relative to the first width W1. In other words, the horizontal axis represents the relative value of the first distance Le1 when the width (first width) W1 of the main flow path 21 is 1. The vertical axis represents the relative value of the white blood cell purity in the white blood cell recovery fluid when the white blood cell purity in the white blood cell recovery fluid calculated for the flow path device without the connecting surface Cs1 is set to 100 as a reference.

[0162] like Figure 9 As shown, in the fourth example of the experiment, when the first distance Le1 involved in the size of the connecting surface Cs1 was 0.1 times, 0.2 times, 0.3 times, 0.4 times and 0.5 times the first width W1, the purity of white blood cells in the white blood cell recovery fluid was steadily increased compared with the case where the connecting surface Cs1 was not present.

[0163] Therefore, based on the fourth example of the experiment, it was confirmed that if a connecting surface Cs1 exists and the first distance Le1 is more than 0.1 times and less than 0.5 times the width (first width) W1 of the main path 21, the purity of white blood cells in the white blood cell recovery fluid can be stably improved compared with the case where there is no connecting surface Cs1.

[0164] In addition, such as Figure 9 As shown, in the fourth example of the experiment, the highest leukocyte purity in the leukocyte recovery fluid was achieved when the first distance Le1, related to the size of the connecting surface Cs1, was 0.4 times the first width W1, ranging from 0.1 to 0.5 times. From another perspective, as the first distance Le1 related to the size of the connecting surface Cs1 increases from 0.1 to 0.4 times the first width W1, there is a tendency for the leukocyte purity in the leukocyte recovery fluid to increase; conversely, when the first distance Le1 related to the size of the connecting surface Cs1 increases from 0.4 to 0.5 times, there is a tendency for the leukocyte purity in the leukocyte recovery fluid to decrease. In the fourth example of this experiment, when the first distance Le1 related to the size of the connecting surface Cs1 was 0.4 times the first width W1, the leukocyte purity in the leukocyte recovery fluid reached its maximum value, approximately 88%.

[0165] <3-7. The Fifth Experiment>

[0166] Figure 10 This is a top view schematically showing a portion of the flow path section 2 of the flow path device 1 used in the fifth example of the experiment. More specifically, Figure 10 This schematically illustrates the flow path section 2 of the flow path device 1 used in the fifth example of the experiment, and the flow path device 1 used in the fifth example of the experiment. Figure 3 A top view of the region IV corresponding to the rectangle enclosed by a single-dotted line. Figure 10 In, with Figure 3 and Figure 4 Similarly, the outer edge of the flow path section 2 is depicted with a solid line.

[0167] like Figure 10As shown, in the fifth example of the experiment, the angle θ between the first direction D1 and the third direction D3 was set to 15 degrees. In other words, the angle θ between the first direction D1 extending along the first connecting portion Cp1 of the first inlet flow path 23 and the third direction D3 extending along the second connecting portion Cp2 of the second inlet flow path 24 was set to 15 degrees. That is, in the fifth example of the experiment, the angle θ was set to 15 degrees, which is a reduction from the 30 degrees in the fourth example of the experiment described above.

[0168] In the fifth experiment, similar to the fourth experiment above, when using the flow path device 1 for particle separation, the flow rate of the first liquid L1 introduced into the main flow path 21 from the first inlet hole 31 via the first inlet flow path 23 was set to 150 μL / min per unit time, and the flow rate of the second liquid L2 introduced into the main flow path 21 from the second inlet hole 32 via the second inlet flow path 24 was set to 120 μL / min per unit time.

[0169] In the fifth experiment, regarding the dimensions of the connecting surface Cs1, similar to the fourth experiment above, the first distance Le1 was set to six times the width (first width) W1 of the main path 21: 0, 0.1, 0.2, 0.3, 0.4, and 0.5 times. As mentioned above, the first distance Le1 is the distance between the third part P1 where the second side Sw2 of the main path 21 connects to the connecting surface Cs1, and the fourth part P2 where the third side Sw3 of the second connecting part Cp2 connects to the connecting surface Cs1.

[0170] Furthermore, in the fifth experiment, similar to the fourth experiment described above, particle separation was performed using each of the six flow path devices, and the purity of white blood cells in the white blood cell recovery solution was determined. Here, the six flow path devices used were: a flow path device without a connecting surface Cs1; a flow path device where the first distance Le1 was set to 0.1 times the first width W1; a flow path device where the first distance Le1 was set to 0.2 times the first width W1; a flow path device where the first distance Le1 was set to 0.3 times the first width W1; a flow path device where the first distance Le1 was set to 0.4 times the first width W1; and a flow path device where the first distance Le1 was set to 0.5 times the first width W1.

[0171] Figure 11 The graph showing the relationship between the size of the junction surface Cs1 and the purity of leukocytes in the leukocyte recovery fluid is from the fifth case of the experiment. Figure 11 In, with Figure 9 Similarly, the relationship between the size of the interface Cs1 and the purity of leukocytes in the leukocyte recovery fluid is represented by a plot of multiple blackened circular markers. Figure 11 In, with Figure 9Similarly, the horizontal axis represents the dimension of the connecting surface Cs1, and the ratio of the first distance Le1 to the width (first width) W1 of the main flow path 21 relative to the first width W1. In other words, the horizontal axis represents the relative value of the first distance Le1 when the width (first width) W1 of the main flow path 21 is 1. The vertical axis represents the relative value of the white blood cell purity in the white blood cell recovery fluid when the white blood cell purity in the white blood cell recovery fluid calculated for the flow path device without the connecting surface Cs1 is set to 100 as a reference.

[0172] like Figure 11 As shown, in the fifth example of the experiment, similar to the fourth example above, when the first distance Le1 related to the size of the connecting surface Cs1 was 0.1 times, 0.2 times, 0.3 times, 0.4 times and 0.5 times the first width W1, the purity of white blood cells in the white blood cell recovery fluid was steadily increased compared with the case where the connecting surface Cs1 was not present.

[0173] Therefore, based on the fifth example of the experiment, which is the same as the fourth example of the experiment above, it was confirmed that if there is a connecting surface Cs1 and the first distance Le1 is more than 0.1 times and less than 0.5 times the width (first width) W1 of the main path 21, the purity of white blood cells in the white blood cell recovery fluid can be stably improved compared with the case where there is no connecting surface Cs1.

[0174] In addition, such as Figure 11 As shown, in the fifth example of the experiment, similar to the fourth example, the highest leukocyte purity in the leukocyte recovery fluid was achieved when the first distance Le1 related to the size of the connecting surface Cs1 was 0.4 times the first width W1, ranging from 0.1 to 0.5 times. From another perspective, as the first distance Le1 related to the size of the connecting surface Cs1 increases from 0.1 to 0.4 times the first width W1, there is a tendency for the leukocyte purity in the leukocyte recovery fluid to increase; conversely, when the first distance Le1 related to the size of the connecting surface Cs1 increases from 0.4 to 0.5 times, there is a tendency for the leukocyte purity to decrease. In the fifth example of this experiment, when the first distance Le1 related to the size of the connecting surface Cs1 was 0.4 times the first width W1, the leukocyte purity in the leukocyte recovery fluid reached its maximum value, approximately 69%.

[0175] <3-8. The Sixth Experiment>

[0176] Figure 12 This is a top view schematically showing a portion of the flow path section 2 of the flow path device 1 used in the sixth example of the experiment. More specifically, Figure 12 This schematically illustrates the flow path section 2 of the flow path device 1 used in the sixth example of the experiment, and the flow path device 1 used in the sixth example of the experiment. Figure 3A top view of the region IV corresponding to the rectangle enclosed by a single-dotted line. Figure 12 In, with Figure 3 , Figure 4 as well as Figure 10 Similarly, the outer edge of the flow path section 2 is depicted with a solid line.

[0177] like Figure 12 As shown, in the sixth example of the experiment, the angle θ between the first direction D1 and the third direction D3 was set to 45 degrees. In other words, the angle θ between the first direction D1 extending along the first connecting portion Cp1 of the first inlet flow path 23 and the third direction D3 extending along the second connecting portion Cp2 of the second inlet flow path 24 was set to 45 degrees. That is, in the sixth example of the experiment, the angle θ was set to 45 degrees, an increase from 30 degrees in the fourth example of the experiment described above.

[0178] In the sixth experiment, similar to the fourth and fifth experiments above, when using the flow path device 1 for particle separation, the flow rate of the first liquid L1 introduced from the first inlet hole 31 through the first inlet flow path 23 into the main flow path 21 per unit time was set to 150 μL / min, and the flow rate of the second liquid L2 introduced from the second inlet hole 32 through the second inlet flow path 24 into the main flow path 21 per unit time was set to 120 μL / min.

[0179] In the sixth experiment, regarding the dimensions of the connecting surface Cs1, similar to the fourth and fifth experiments above, the first distance Le1 was set to 0, 0.1, 0.2, 0.3, 0.4, and 0.5 times the width (first width) W1 of the main path 21. As mentioned above, the first distance Le1 is the distance between the third part P1 where the second side Sw2 of the main path 21 connects to the connecting surface Cs1, and the fourth part P2 where the third side Sw3 of the second connecting part Cp2 connects to the connecting surface Cs1.

[0180] Furthermore, in the sixth example of the above experiment, similar to the fourth and fifth examples, particle separation was performed using each of the six flow path devices, and the purity of white blood cells in the white blood cell recovery solution was determined. Here, the six flow path devices used were: a flow path device without a connecting surface Cs1; a flow path device where the first distance Le1 was set to 0.1 times the first width W1; a flow path device where the first distance Le1 was set to 0.2 times the first width W1; a flow path device where the first distance Le1 was set to 0.3 times the first width W1; a flow path device where the first distance Le1 was set to 0.4 times the first width W1; and a flow path device where the first distance Le1 was set to 0.5 times the first width W1.

[0181] Figure 13 The graph showing the relationship between the size of the junction surface Cs1 and the purity of leukocytes in the leukocyte recovery fluid is from the results of the sixth case of the experiment. Figure 13 In, with Figure 9 and Figure 11 Similarly, the relationship between the size of the interface Cs1 and the purity of leukocytes in the leukocyte recovery fluid is represented by a plot of multiple blackened circular markers. Figure 13 In, with Figure 9 as well as Figure 11 Similarly, the horizontal axis represents the dimension of the connecting surface Cs1, and the ratio of the first distance Le1 to the width (first width) W1 of the main flow path 21 relative to the first width W1. In other words, the horizontal axis represents the relative value of the first distance Le1 when the width (first width) W1 of the main flow path 21 is 1. The vertical axis represents the relative value of the white blood cell purity in the white blood cell recovery fluid when the white blood cell purity in the white blood cell recovery fluid calculated for the flow path device without the connecting surface Cs1 is set to 100 as a reference.

[0182] like Figure 13 As shown, in the sixth example of the experiment, similar to the fourth and fifth examples above, when the first distance Le1 related to the size of the connecting surface Cs1 was 0.1 times, 0.2 times, 0.3 times, 0.4 times, and 0.5 times the first width W1, the purity of white blood cells in the white blood cell recovery fluid was steadily increased compared to the case where the connecting surface Cs1 was not present.

[0183] Therefore, based on the sixth case of the experiment, similar to the fourth and fifth cases mentioned above, it was confirmed that if a connecting surface Cs1 exists and the first distance Le1 is more than 0.1 times and less than 0.5 times the width (first width) W1 of the main path 21, the purity of white blood cells in the white blood cell recovery fluid can be stably improved compared to the case where there is no connecting surface Cs1.

[0184] In addition, such as Figure 13As shown, in the sixth example of the experiment, similar to the fourth and fifth examples mentioned above, the highest leukocyte purity in the leukocyte recovery fluid was achieved when the first distance Le1 related to the size of the connecting surface Cs1 was 0.4 times the first width W1, ranging from 0.1 to 0.5 times. From another perspective, as the first distance Le1 related to the size of the connecting surface Cs1 increases from 0.1 to 0.4 times the first width W1, there is a tendency for the leukocyte purity in the leukocyte recovery fluid to increase; conversely, when the first distance Le1 related to the size of the connecting surface Cs1 increases from 0.4 to 0.5 times, there is a tendency for the leukocyte purity in the leukocyte recovery fluid to decrease. In the sixth example of this experiment, when the first distance Le1 related to the size of the connecting surface Cs1 was 0.4 times the first width W1, the leukocyte purity in the leukocyte recovery fluid reached its maximum value, approximately 75%.

[0185] <3-9. Results of Experiments 4 through 6>

[0186] like Figure 9 , Figure 11 and Figure 13 As shown, in any of the fourth to sixth examples of the above experiments, when the first distance Le1 related to the size of the connecting surface Cs1 is 0.1 times, 0.2 times, 0.3 times, 0.4 times, and 0.5 times the first width W1, respectively, the purity of leukocytes in the leukocyte recovery fluid is consistently increased compared to the case where the connecting surface Cs1 is absent. In other words, even if the angle θ between the first direction D1 and the third direction D3 increases or decreases between 15 degrees and 45 degrees, when the first distance Le1 related to the size of the connecting surface Cs1 is 0.1 times, 0.2 times, 0.3 times, 0.4 times, and 0.5 times the first width W1, respectively, the purity of leukocytes in the leukocyte recovery fluid is consistently increased compared to the case where the connecting surface Cs1 is absent.

[0187] Therefore, it was confirmed that if a connecting surface Cs1 exists, and the first distance Le1 is more than 0.1 times and less than 0.5 times the width (first width) W1 of the main flow path 21, the purity of white blood cells in the white blood cell recovery fluid can be stably improved compared to the case where the connecting surface Cs1 does not exist. In other words, it was confirmed that if a connecting surface Cs1 exists, and the first distance Le1 is more than 0.1 times and less than 0.5 times the width (first width) W1 of the main flow path 21, the proportion of specific types of particles (e.g., multiple specific types of particles) among the multiple particles contained in the recovery fluid can be increased. As mentioned above, the first distance Le1 is the distance between the third part P1 where the second side surface Sw2 of the main flow path 21 connects to the connecting surface Cs1, and the fourth part P2 where the third side surface Sw3 of the second connecting part Cp2 connects to the connecting surface Cs1.

[0188] Furthermore, from another perspective, it has been confirmed that if a connecting surface Cs1 exists, and the angle θ between the first direction D1 extending along the first connecting portion Cp1 of the first inlet flow path 23 and the third direction D3 extending along the second connecting portion Cp2 of the second inlet flow path 24 is 15 degrees or more and 45 degrees or less, then the purity of white blood cells in the white blood cell recovery fluid can be stably improved compared to the case where the connecting surface Cs1 does not exist. In other words, it has been confirmed that if a connecting surface Cs1 exists, and the angle θ between the first direction D1 extending along the first connecting portion Cp1 of the first inlet flow path 23 and the third direction D3 extending along the second connecting portion Cp2 of the second inlet flow path 24 is 15 degrees or more and 45 degrees or less, then the proportion of a specific type of particle (e.g., multiple specific types of particles) among the multiple particles contained in the recovery fluid can be stably improved.

[0189] Furthermore, as described above, the maximum purity of leukocytes in the leukocyte recovery fluid obtained in the fourth example of the above experiment with an angle θ of 30 degrees was approximately 88%. In contrast, the maximum purity of leukocytes in the leukocyte recovery fluid obtained in the fifth example of the above experiment with an angle θ of 15 degrees was approximately 69%, and the maximum purity of leukocytes in the leukocyte recovery fluid obtained in the sixth example of the above experiment with an angle θ of 45 degrees was approximately 75%. Therefore, it was confirmed that if a connecting surface Cs1 exists, and the angle θ between the first direction D1 extending along the direction of the first connecting portion Cp1 of the first inlet flow path 23 and the direction of the main flow path 21, and the third direction D3 extending along the direction of the second connecting portion Cp2 of the second inlet flow path 24 is 30 degrees, then the purity of leukocytes in the leukocyte recovery fluid can be further improved compared to the case where the connecting surface Cs1 does not exist. In other words, it was confirmed that if a connecting surface Cs1 exists, and the angle θ between the first direction D1 extending along the direction of the first connecting portion Cp1 of the first inlet flow path 23 and the direction of the main flow path 21 and the third direction D3 extending along the direction of the second connecting portion Cp2 of the second inlet flow path 24 is 30 degrees, then the proportion of a specific type of particle (e.g., multiple specific types of particles) among the multiple particles contained in the recovered liquid can be further increased.

[0190] <4. Summary of Implementation Methods>

[0191] In one embodiment of the flow path device 1, the main flow path 21 extends along a first direction D1 and has a first upstream portion 21u and a first downstream portion 21d. A plurality of branch flow paths 22, thinner than the main flow path 21, are connected to the main flow path 21 through openings in a first side surface Sw1 between the first downstream portion 21d and the first upstream portion 21u. A first connecting portion Cp1 in the first inlet flow path 23, connected to the first upstream portion 21u, extends along the first direction D1. A second connecting portion Cp2 in the second inlet flow path 24, connected to the first upstream portion 21u, extends along a third direction D3. The first direction D1 and the third direction D3 form an acute angle. The flow path section 2 has a connecting surface Cs1 that connects the second side surface Sw2 of the main flow path 21 to the third side surface Sw3 of the second connecting portion Cp2 located on the side of the first connecting portion Cp1. The distance (first distance) Le1 between the third part P1, which connects the second side Sw2 of the main road 21 to the connecting surface Cs1, and the fourth part P2, which connects the third side Sw3 of the second connecting part Cp2 to the connecting surface Cs1, is set to less than 1 times the width (first width) W1 of the main road 21.

[0192] According to this structure, in the flow path device 1, when a first liquid L1 is introduced from the first inlet flow path 23 into the first upstream portion 21u of the main flow path 21 and a second liquid L2 is introduced from the second inlet flow path 24 into the first upstream portion 21u of the main flow path 21 for particle separation processing, for example, in the main flow path 21, the generation of turbulence in the inlet flow is reduced, and the force by which the second liquid L2 presses the first liquid L1 toward the multiple branch flow paths 22 can be increased. As a result, the proportion of the multiple second particles Pa12 in the first liquid L1 that flow to the first downstream portion 21d (e.g., more than one second particle Pa12) can be reduced. Therefore, for example, the number of second particles Pa12 mixed into the recovered liquid recovered from the first downstream portion 21d via the first discharge hole 33, etc., can be reduced. Therefore, the proportion of first particles Pa11 (e.g., multiple first particles Pa11) that are a specific type of particle among the multiple particles contained in the recovered liquid can be increased. Here, for example, as a first liquid L1, blood or a liquid made by diluting blood with saline is used; as a second liquid L2, when saline is used, the purity of white blood cells, which is the proportion of white blood cells (e.g., multiple white blood cells) in all the blood cells in the white blood cell recovery fluid, which is the recovery fluid, can be improved.

[0193] <5. Other Implementation Methods>

[0194] This disclosure is not limited to the one embodiment described above, and various changes and improvements can be made without departing from the spirit of this disclosure.

[0195] In one embodiment described above, the connecting surface Cs1 is, for example, a flat surface, but is not limited thereto. For example, the connecting surface Cs1 may be a slightly curved surface or a surface with slight irregularities. Here, for example, the portion of the connecting surface Cs1 that connects to the second side surface Sw2 of the main flow path 21 may form a sharp corner with the second side surface Sw2, or it may form a non-sharp corner with the second side surface Sw2. For example, the portion of the second connecting portion Cp2 of the connecting surface Cs1 that connects to the third side surface Sw3 may form a sharp corner with the third side surface Sw3, or it may form a non-sharp corner with the third side surface Sw3.

[0196] In the above embodiment, when viewed from above, the shape of the expansion portion Ac1 is an isosceles triangle with the side along the connecting surface Cs1 as its base, but it is not limited to this. For example, when viewed from above, the shape of the expansion portion Ac1 may be a right triangle with the side along the connecting surface Cs1 as its adjacent side, or it may be a shape along other triangles.

[0197] In other words, in the above embodiment, the angle α formed by the third side Sw3 and the connecting surface Cs1, and the angle β formed by the second side Sw2 and the connecting surface Cs1, are not necessarily the same or approximately the same. For example, angles α and β can also be different.

[0198] Figure 14 and Figure 15 These are schematic top views showing a portion of the flow path section 2. More specifically, Figure 14 It is an illustrative representation of... Figure 3 A top view of the area IV, which is enclosed by a single-dotted line of a rectangle, corresponding to other first structural examples of the area. Figure 15 It is an illustrative representation of... Figure 3 A top view of another second structural example corresponding to region IV, which is enclosed by a rectangle with a single-dotted dashed line. Figure 14 and Figure 15 In the middle, the outer edges of the flow path section 2 are depicted with solid lines. Figure 14 and Figure 15 In the figures, when particle separation is performed using the flow path device 1, in the upstream part of the part where the flow of the first liquid L1 and the flow of the second liquid L2 merge, an example of the direction in which the first liquid L1 is directed is schematically shown by an arrow drawn with a thick double-dotted line, and an example of the direction in which the second liquid L2 is directed is schematically shown by an arrow drawn with a double-dotted line.

[0199] For example, such as Figure 14As shown, angle β can also be greater than angle α. For example, angle β can be an obtuse angle, and angle α can be an acute angle. In this case, when using the flow path device 1 for particle separation processing, for example, the first liquid L1 flowing along the second side Sw2, which is part of the first liquid L1, and then along the connecting surface Cs1, can be pressed by the second liquid L2 flowing along the third side Sw3, which is part of the second liquid L2, towards the first side Sw1. At the point where liquids merge in this way, for example, the direction in which the second liquid L2 flowing along the third side Sw3, which is part of the flow of the second liquid L2, presses the first liquid L1 flowing along the connecting surface Cs1 towards the first side Sw1 can be nearly perpendicular to the direction of flow of the first liquid L1 flowing along the connecting surface Cs1. Thus, for example, in the main flow path 21, the generation of turbulence in the inlet flow is reduced, and the force by which the second liquid L2 presses the first liquid L1 towards the multiple branch flow paths 22 can be increased. As a result, the proportion of second particles Pa12 (e.g., more than one second particle Pa12) flowing to the first downstream portion 21d in the first liquid L1 can be reduced. Therefore, for example, the number of second particles Pa12 mixed into the recovered liquid recovered from the first downstream portion 21d via the first discharge port 33, etc., can be reduced. Therefore, the proportion of first particles Pa11 (e.g., multiple first particles Pa11) as a specific type of particle among the multiple particles contained in the recovered liquid can be increased. Here, for example, as an example of the first liquid L1, blood or a liquid diluted with physiological saline is used; as an example of the second liquid L2, when physiological saline is used, the white blood cell purity, representing the proportion of white blood cells (e.g., multiple white blood cells) among all blood cells in the white blood cell recovered liquid, can be increased. Here, for example, when the angle α is close to 90 degrees, the direction in which the second liquid L2, which flows along the third side Sw3 as part of the flow of the second liquid L2, presses the first liquid L1, which flows along the connecting surface Cs1, toward the first side Sw1 can be closer to perpendicular to the direction in which the first liquid L1 flows along the connecting surface Cs1.

[0200] For example, such as Figure 15As shown, angle α can also be greater than angle β. For example, angle α can be an obtuse angle, and angle β can be an acute angle. In this case, when using the flow path device 1 for particle separation processing, for example, the first liquid L1 flowing along the second side Sw2, which is part of the first liquid L1, can be pressed towards the first side Sw1 by the second liquid L2 flowing along the third side Sw3, which is part of the second liquid L2, and then along the connecting surface Cs1. At the point where liquids merge in this way, for example, the direction in which the second liquid L2, which flows along the third side Sw3, which is part of the flow of the second liquid L2, presses the first liquid L1 flowing along the second side Sw2 towards the first side Sw1 can be nearly perpendicular to the direction of flow of the first liquid L1 flowing along the second side Sw2. Thus, for example, in the main flow path 21, the generation of turbulence in the inlet flow is reduced, and the force by which the second liquid L2 presses the first liquid L1 towards the multiple branch flow paths 22 can be increased. As a result, the proportion of second particles Pa12 (e.g., more than one second particle Pa12) flowing to the first downstream portion 21d in the first liquid L1 can be reduced. Therefore, for example, the number of second particles Pa12 mixed into the recovered liquid recovered from the first downstream portion 21d via the first discharge port 33, etc., can be reduced. Therefore, the proportion of first particles Pa11 (e.g., multiple first particles Pa11) as a specific type of particle among the multiple particles contained in the recovered liquid can be increased. Here, for example, as an example of the first liquid L1, blood or a liquid diluted with physiological saline is used; as an example of the second liquid L2, when physiological saline is used, the white blood cell purity, representing the proportion of white blood cells (e.g., multiple white blood cells) among all blood cells in the white blood cell recovered liquid, can be increased. Here, for example, when the angle β is close to 90 degrees, the direction in which the second liquid L2 flows along the third side Sw3, which is part of the flow of the second liquid L2, presses the first liquid L1, which flows along the second side Sw2, toward the first side Sw1, is closer to the direction of the flow of the first liquid L1, which flows along the second side Sw2, to be more perpendicular to the direction of the flow of the first liquid L1, which flows along the second side Sw2.

[0201] Furthermore, the inventors confirmed that when angle θ is fixed at 30 degrees and angles α and β are each set to 105 degrees, angle α is set to 60 degrees and angle β is set to 150 degrees, and angle α is set to 150 degrees and angle β is set to 60 degrees, the occurrence of turbulence in the inflow of the main flow path 21 is reduced to the same extent. Therefore, for example, when angle θ is 30 degrees and the total of angles α and β is 210 degrees, angles α and β can also be 60 degrees or more and 150 degrees or less, respectively.

[0202] In one embodiment described above, for example, the first inlet hole 31, the second inlet hole 32, the first outlet hole 33, the second outlet hole 34, and the third outlet hole 35 are each open on the lower surface 1b, but are not limited thereto. For example, at least one of the first inlet hole 31, the second inlet hole 32, the first outlet hole 33, the second outlet hole 34, and the third outlet hole 35 may not be open on the lower surface 1b and may be open on the upper surface 1a. In other words, for example, the first inlet hole 31, the second inlet hole 32, the first outlet hole 33, the second outlet hole 34, and the third outlet hole 35 may be open on either the upper surface 1a or the lower surface 1b.

[0203] In one embodiment described above, the flow path device 1 may have, for example, a set of first inlet holes 31 and first inlet flow paths 23 as inlet portions for the first liquid L1, but is not limited thereto. For example, the flow path device 1 may also have two or more sets of first inlet holes 31 and first inlet flow paths 23 as inlet portions for the first liquid L1. Furthermore, in one embodiment described above, the flow path device 1 may have, for example, a set of second inlet holes 32 and second inlet flow paths 24 as inlet portions for the second liquid L2, but is not limited thereto. For example, the flow path device 1 may also have two or more sets of second inlet holes 32 and second inlet flow paths 24 as inlet portions for the second liquid L2. Here, the inlet portions for the first liquid L1 and the inlet portions for the second liquid L2 can be connected to the main flow path 21 in an appropriate relationship, within a range where the proportion of first particles Pa11 (e.g., multiple first particles Pa11) of a specific type of particle among the multiple particles contained in the recovered liquid can be increased when using the flow path device 1 for particle separation processing.

[0204] In one embodiment described above, for example, when the second liquid L2 is introduced into the flow path device 1 from the second inlet 2i, a liquid suction section for drawing the second liquid L2 from the main flow path 21 via multiple branch flow paths 22 and the second discharge hole 34 may also be connected to the second discharge hole 34. In this case, for example, a tubular member for connecting the liquid suction section to the second discharge hole 34 may be connected to the flow path device 1 from the outside. Here, connecting the liquid suction section to the second discharge hole 34 via the tubular member means that fluid can flow between the liquid suction section and the second discharge hole 34 via the tubular member. To connect this tubular member to the flow path device 1, for example, a cylindrical portion may be present on the lower surface 1b of the flow path device 1, which, when viewed from above, is arranged to surround the second discharge hole 34 about the Z-axis and protrudes in the -Z direction.

[0205] In one embodiment described above, for example, the flow path portion 2 and the plurality of holes 3 in the flow path device 1 may not include the third discharge flow path 27 as the seventh flow path and the third discharge hole 35 as the fifth hole. In this case, for example, the first discharge flow path 25 as the fifth flow path may extend along the -Y direction, which is the first direction D1, in the same way as the main flow path 21. For example, the main flow path 21 may also include the first discharge flow path 25 as the fifth flow path. Here, the first discharge hole 33 may also be directly connected to the first downstream portion 21d of the main flow path 21. In addition, for example, the recovered liquid may be recovered from the first downstream portion 21d through various paths.

[0206] In one embodiment described above, for example, the widths of the first inlet flow path 23, the second inlet flow path 24, the first outlet flow path 25, the second outlet flow path 26, and the third outlet flow path 27 may be constant or variable from upstream to downstream. For example, the first inlet flow path 23 may also have a portion where its width continuously or gradually decreases as it approaches the main flow path 21 from the first inlet hole 31. In other words, for example, the first inlet flow path 23 may also have a portion where its width continuously or gradually decreases as it approaches the main flow path 21. For example, the second inlet flow path 24 may also have a portion where its width continuously or gradually decreases as it approaches the main flow path 21 from the second inlet hole 32. In other words, for example, the second inlet flow path 24 may also have a portion where its width continuously or gradually decreases as it approaches the main flow path 21. For example, the first outlet flow path 25 may also have a portion where its width continuously or gradually increases as it approaches the first outlet hole 33 from the main flow path 21. In other words, for example, the first discharge path 25 may also have a portion whose width continuously or gradually increases as it moves away from the main flow path 21. Similarly, the third discharge path 27 may also have a portion whose width continuously or gradually increases as it approaches the third discharge port 35 from the main flow path 21.

[0207] In one embodiment described above, for example, the first liquid L1 may be a liquid containing various particles Pa1 other than blood. In this case, the second liquid L2 can be, for example, various liquids corresponding to the first liquid L1. Various liquids can be, for example, water.

[0208] As described above, the flow path devices have been described in detail, but the above description is illustrative in all respects and this disclosure is not limited thereto. Furthermore, the various examples described above can be combined as long as they do not contradict each other. Moreover, numerous other examples not illustrated can be conceived without departing from the scope of this disclosure.

[0209] This disclosure includes the following.

[0210] In one embodiment, (1) the flow path device includes: a flow path portion that is not open on its outer surface; and a plurality of holes that communicate with the flow path portion and are open on the outer surface, the flow path portion including a first flow path, a plurality of second flow paths, a third flow path, and a fourth flow path, the first flow path extending linearly along a first direction, the first flow path including a first downstream portion located on the side of the first direction and a first upstream portion located on the side opposite to the first downstream portion, the first flow path having a first side surface in a second direction orthogonal to the first direction and a second side surface in a fourth direction opposite to the second direction, the plurality of second flow paths being connected to the first flow path and being thinner than the first flow path, the plurality of second flow paths being located between the first upstream portion and the first downstream portion of the first flow path and opening on the first side surface, the plurality of second flow paths each including a second downstream portion on the side opposite to the first flow path, the third flow path including a first connecting portion connected to the first upstream portion, the first connecting portion facing towards The fourth flow path extends linearly towards the first upstream portion along the first direction. It includes a second connecting portion connected to the first upstream portion, which opens on a second side. The second connecting portion extends linearly towards the first upstream portion along a third direction at an acute angle to the first direction. The second connecting portion has a third side located on the side of the first connecting portion. The plurality of holes include a first hole, a second hole, a third hole, and a fourth hole. The first hole communicates with the first upstream portion via the third flow path, the second hole communicates with the first upstream portion via the fourth flow path, the third hole communicates with the first downstream portion, and the fourth hole communicates with the second downstream portion of each of the plurality of second flow paths. The flow path portion has a connecting surface connecting the second side and the third side. The distance between the third portion connecting the second side and the connecting surface and the fourth portion connecting the third side and the connecting surface is less than one time the width of the first flow path in the second direction.

[0211] (2) In the flow path device of (1) above, the angle between the first direction and the third direction may be more than 15 degrees and less than 45 degrees.

[0212] (3) In the flow path device of (2) above, the angle between the first direction and the third direction can also be 30 degrees.

[0213] (4) In the flow path device of (2) or (3) above, the distance between the third part and the fourth part may be more than 0.1 times and less than 0.5 times the width of the first flow path in the second direction.

[0214] Explanation of reference numerals in the attached figures:

[0215] 1. Flow path devices

[0216] 2 Flow path section

[0217] 21 Mainstream Road

[0218] 21d First downstream section

[0219] 21u First upstream section

[0220] 22 Branch Flow Paths

[0221] 22d Second downstream section

[0222] 23 First Import Flow Path

[0223] 24 Second Inlet Flow Path

[0224] 3 holes

[0225] 31 First inlet hole

[0226] 32 Second Inlet Hole

[0227] 33 First discharge hole

[0228] 34 Second discharge hole

[0229] 35 Third outlet hole

[0230] Cp1 First connection part

[0231] Cp2 Second connection part

[0232] Cs1 Connection Surface

[0233] D1 First Direction

[0234] D2 Second Direction

[0235] D3 third direction

[0236] D4 Fourth Direction

[0237] L1 First Liquid

[0238] L2 Second Liquid

[0239] Le1 First Distance

[0240] Part 3, Page 1

[0241] P2 Part 4

[0242] Pa1 Multiple particles

[0243] Pa11 First Particle

[0244] Pa12 Second Particle

[0245] Sw1 First Side View

[0246] Sw2 Second Side

[0247] Sw3 Third Side

[0248] W1 is the first width.

Claims

1. A flow path device, wherein, The flow path device includes a flow path section. The flow path section includes a first flow path, multiple second flow paths, a third flow path, and a fourth flow path. The first flow path extends along the first direction. The first flow path includes a first portion located at the end in the first direction and a second portion located at the end in the opposite direction to the first portion. The first flow path has a first side surface and a second side surface opposite the first side surface in a second direction orthogonal to the first direction. The plurality of second flow paths are respectively connected to the first flow path by openings on the first side between the first portion and the second portion, and are thinner than the first flow path. The third flow path includes a first connection portion connected to the second portion. The first connecting portion extends along the first direction. The fourth flow path includes a second connection portion connected to the second portion. The second connecting portion extends along a third direction at an acute angle relative to the first direction. The second connecting portion has a third side located on the same side as the first connecting portion. The flow path section has a connecting surface that connects the second side and the third side. The distance between the third portion where the second side and the connecting surface are connected and the fourth portion where the third side and the connecting surface are connected is less than 1 times the width of the first flow path in the second direction.

2. The flow path device according to claim 1, wherein, The angle between the first direction and the third direction is greater than 15 degrees and less than 45 degrees.

3. The flow path device according to claim 2, wherein, The angle between the first direction and the third direction is 30 degrees.

4. The flow path device according to claim 2 or 3, wherein, The distance between the third part and the fourth part is more than 0.1 times and less than 0.5 times the width of the first flow path in the second direction.

Citation Information

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