Flow Channel Devices
The flow path device optimizes particle separation by using an angled flow design and expanded connection surfaces to enhance the recovery efficiency and purity of specific particles like white blood cells, addressing turbulence-induced inefficiencies in existing technologies.
Patent Information
- Application Number
- JP2025543715
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- Priority Date
- 2024-01-30
- Filing Date
- 2025-01-27
- Publication Date
- 2025-10-27
- Estimated Expiration
- 2045-01-27
AI Technical Summary
Existing flow path devices face challenges in efficiently increasing the proportion of specific particles, such as white blood cells, in the recovery liquid by maintaining the separation efficiency despite high flow velocities that cause turbulence and reduce particle recovery purity.
The flow path device incorporates a design with a main flow path and branch flow paths, where the flow of a pressing liquid forms an acute angle with the main flow path's inflow, and includes expanded connection surfaces to minimize turbulence, ensuring efficient separation and recovery of specific particles.
This design enhances the recovery efficiency of specific particles by reducing turbulence, maintaining high purity levels even at increased flow velocities, thereby improving the recovery amount per unit time.
Smart Images

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Abstract
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority from Japanese Application No. 2024-11477 (filed January 30, 2024), the entire disclosure of which is incorporated herein by reference. [Technical Field]
[0002] The present disclosure relates to a fluid path device. [Background technology]
[0003] There is a flow path device that includes a portion (also referred to as a flow path portion) with a plurality of branched fine flow paths for separating a specific type of particle from other types of particles in a liquid containing multiple types of particles, and a plurality of holes that are each connected to this flow path portion and each open on the outer surface (see, for example, the description in Patent Document 1).
[0004] In recent years, there has been an increasing demand for flow channel devices to increase the proportion of specific types of particles (for example, multiple specific types of particles) among multiple particles contained in a recovered liquid after separation. [Prior art documents] [Patent documents]
[0005] [Patent Document 1] International Publication No. 2023 / 153331 Summary of the Invention [Problem to be solved by the invention]
[0006] A flow path device is disclosed.
[0007] One embodiment of a flow path device includes a flow path section. The flow path section 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 from the first portion. The first flow path has a first side surface and a second side surface facing the first side surface in a second direction perpendicular to the first direction. Each of the plurality of second flow paths is connected to the first flow path by opening at the first side surface between the first portion and the second portion, and is narrower 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 forming an acute angle with the first direction. The second connection portion has a third side surface located on the side of the first connection portion. The flow path portion has a connection surface connecting the second side surface and the third side surface. The distance between a third portion where the second side surface and the connection surface are connected and a fourth portion where the third side surface and the connection surface are connected is equal to or less than one time the width of the first flow path in the second direction. [Brief explanation of the drawings]
[0008] [Figure 1] FIG. 1 is a plan view schematically showing an example of the configuration of a flow channel device. [Figure 2] FIG. 2 is a front view schematically showing an example of the configuration of a flow channel device. [Figure 3] FIG. 3 is a plan view schematically showing an example of the configuration of a flow channel portion and a plurality of holes in a flow channel device. [Figure 4] FIG. 4 is a plan view schematically showing a part of the flow path portion, and is a plan view showing an area IV surrounded by a rectangular dashed line in FIG. [Figure 5] FIG. 5 is a plan view schematically illustrating an example of a state in which the first liquid and the second liquid are introduced into a first upstream portion of the main flow path in a part of the flow path section shown in FIG. [Figure 6] FIG. 6 is a graph showing the relationship between the size of the connection surface and the purity of white blood cells in the white blood cell collection fluid, based on the results of the first example of the experiment. [Figure 7] FIG. 7 is a graph showing the relationship between the size of the connection surface and the purity of white blood cells in the white blood cell collection fluid, based on the results of the second example of the experiment. [Figure 8] FIG. 8 is a graph showing the relationship between the size of the connection surface and the purity of white blood cells in the white blood cell collection fluid, based on the results of the third example of the experiment. [Figure 9] FIG. 9 is a graph showing the relationship between the size of the connection surface and the purity of white blood cells in the white blood cell collection fluid, based on the results of the fourth example of the experiment. [Figure 10] FIG. 10 is a plan view schematically showing a portion of the flow path section of the flow path device used in the fifth example of the experiment, and is a plan view showing an example of the configuration of a region of the flow path section corresponding to region IV surrounded by the rectangular dashed line in FIG. 3. [Figure 11] FIG. 11 is a graph showing the relationship between the size of the connection surface and the purity of white blood cells in the white blood cell collection fluid, based on the results of the fifth example of the experiment. [Figure 12] FIG. 12 is a plan view showing a schematic view of a portion of the flow path section of the flow path device used in the sixth example of the experiment, and is a plan view showing an example of the configuration of a region of the flow path section corresponding to region IV surrounded by the rectangular dashed line in FIG. 3. [Figure 13] FIG. 13 is a graph showing the relationship between the size of the connection surface and the purity of white blood cells in the white blood cell collection fluid, based on the results of the sixth example of the experiment. [Figure 14] FIG. 14 is a plan view schematically showing a part of the flow path portion, and is a plan view showing another first configuration example of a region corresponding to region IV surrounded by a rectangular dashed line in FIG. [Figure 15] FIG. 15 is a plan view schematically showing a part of the flow path portion, and is a plan view showing another second configuration example of a region corresponding to region IV surrounded by a rectangular dashed line in FIG. DETAILED DESCRIPTION OF THE INVENTION
[0009] There is a flow path device that includes a portion (also referred to as a flow path portion) with branched fine flow paths, and a plurality of holes that each communicate with this flow path portion and are each open on the outer surface, for separating a plurality of particles of a specific type (also referred to as a first particle) from a plurality of particles of another type (also referred to as a second particle) from a liquid (also referred to as a first liquid or a liquid to be treated) that contains a plurality of types of particles.
[0010] In this flow path device, for example, the flow path section does not open on the outer surface. The flow path section includes, for example, a first flow path (also referred to as a main flow path) and multiple second flow paths (also referred to as branch flow paths) that are each connected to the main flow path and narrower than the main flow path. The multiple holes include a first inlet hole (also referred to as a first inlet hole) and a second inlet hole (also referred to as a second inlet hole), each of which leads to an upstream portion (also referred to as a first upstream portion) of the main flow path, a discharge hole (also referred to as a first discharge hole) that leads to a downstream portion (also referred to as a first downstream portion) of the main flow path, and a discharge hole (also referred to as a second discharge hole) that leads to a downstream portion (also referred to as a second downstream portion) of each of the multiple branch flow paths on the opposite side from the main flow path. The main flow path extends linearly along the first direction. Each of the multiple branch flow paths opens, between the first upstream portion and the first downstream portion of the main flow path, on a side surface of the main flow path that is located on the side of the main flow path in a second direction that is perpendicular to the first direction. The flow path section further includes a flow path (also referred to as a third flow path) connecting the first introduction hole and the first upstream portion, and a flow path (also referred to as a fourth flow path) connecting the second introduction hole and the first upstream portion. The fourth flow path has a portion connected to the first upstream portion extending along the second direction and opening at a side surface of the main flow path located on the opposite side from the second direction. The third flow path has a portion connected to the first upstream portion extending in the first direction.
[0011] The first inlet hole introduces the liquid to be treated toward the main flow path. The second inlet hole introduces a liquid (also referred to as the second liquid or the pressing liquid) toward the main flow path. The pressing liquid can press multiple types of particles in the liquid to be treated toward the multiple branch flow paths in the main flow path. Here, for example, if the diameter of the first particles is larger than the diameter of the second particles, and the widths of the multiple branch flow paths are larger than the diameter of the second particles but smaller than the diameter of the first particles, the liquid containing the multiple second particles can be introduced from the main flow path into the multiple branch flow paths and discharged from the second discharge hole, and the liquid containing the multiple first particles (also referred to as the recovered liquid or the recovered liquid after separation) can be discharged from the first discharge hole via the first downstream section of the main flow path. This allows the recovered liquid to be recovered via the first discharge hole. As a result, the liquid containing the multiple first particles (the recovered liquid) can be separated from the liquid containing the multiple second particles and recovered from the liquid to be treated. For example, when a blood-containing sample is used as the liquid to be treated, the first particle may be a white blood cell and the second particle may be a red blood cell. In the above-described flow path device, the function of separating the first particle and the second particle, which are different in size, using the multiple branch flow paths is achieved by the relationship between the flow introduced into the branch flow paths and the respective center-of-gravity positions of the first particle and the second particle, as described below. Therefore, whether the first particle and the second particle can be separated does not necessarily depend on the relationship between the width of the branch flow path and the diameter of the first particle and the diameter of the second particle. For example, in a flow path device, even if the width of the branch flow path is approximately 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 be separated from the second particle without being introduced from the main flow path into the branch flow path.
[0012] In the above-described flow path device, the flow of the forcing liquid merges with the flow of the liquid to be treated in a first upstream portion of the main flow path such that the direction in which the liquid to be treated flows in from the third flow path (also referred to as the first inflow direction) and the direction in which the pressing liquid flows in from the fourth flow path (also referred to as the second inflow direction) form an angle of 90 degrees. In this case, in order to improve the recovery amount per unit time of the recovery liquid containing the plurality of first particles, it is conceivable to increase the flow velocity of the liquid to be treated flowing from the first inlet through the third flow path into the first upstream portion of the main flow path.
[0013] However, when the flow velocity of the liquid to be treated increases, turbulence occurs in the flow of the liquid in the main channel. This makes it difficult to maintain a state in the main channel where multiple types of particles in the liquid to be treated are pressed toward the multiple branch channels by the pressing liquid. In particular, in the main channel, the force with which the multiple types of particles in the liquid to be treated are pressed toward the multiple branch channels by the pressing liquid (also referred to as pressing force) may decrease as the liquid approaches the first downstream section of the main channel. This may make it easier for some of the multiple second particles in the liquid to flow to the first downstream section. As a result, the number of second particles mixed into the recovery liquid recovered through the first discharge hole may increase, and the proportion of first particles (e.g., multiple first particles) among the multiple particles contained in the recovery liquid may decrease. For example, when a sample containing blood is used as the liquid to be treated, the proportion (also referred to as white blood cell purity) of white blood cells (e.g., multiple white blood cells) among all blood cells in the recovery liquid (also referred to as white blood cell recovery liquid) may decrease. All blood cells include white blood cells and red blood cells.
[0014] Here, for example, it is conceivable to reduce turbulence in the flow of liquid in the main flow path in order to increase the proportion of first particles (e.g., a plurality of first particles) among a plurality of particles contained in the recovery liquid. More specifically, for example, it is conceivable to merge the flow of the pressing liquid with the flow of the liquid to be treated in a form in which the second inflow direction of the pressing liquid forms an acute angle of less than 90 degrees with the first inflow direction of the liquid to be treated in a first upstream portion of the main flow path.
[0015] However, even when the second inflow direction forms an acute angle with respect to the first inflow direction, there is room for improvement in terms of increasing the proportion of particles of a specific type (e.g., a plurality of first particles) among the plurality of particles contained in the recovery liquid.
[0016] That is, there is room for improvement in the flow path device in terms of increasing the proportion of particles of a particular type (for example, a plurality of first particles) among a plurality of particles contained in the collected liquid.
[0017] Therefore, the inventors of the present disclosure have created a technology for a flow path device that can increase the proportion of particles of a specific type (e.g., particles of multiple specific types) among multiple particles contained in a recovery liquid.
[0018] In this regard, various embodiments and examples will be described below with reference to the drawings. In the drawings, parts having the same or similar configurations and functions are designated by the same reference numerals. Duplicate descriptions of parts having the same or similar configurations and functions will be omitted in the following description. The drawings are schematic.
[0019] The drawings include diagrams in which a right-handed XYZ coordinate system is indicated for convenience. In the following description, the +Z direction is used as the vertically upward direction (also simply referred to as the upward direction). The vertically downward direction is also expressed as the -Z direction. The direction opposite to the +X direction is also expressed as the -X direction. The direction opposite to the +Y direction is also expressed as the -Y direction. The drawings also include diagrams in which arrows indicating each of the first direction D1, second direction D2, third direction D3, and fourth direction D4 are indicated for convenience.
[0020] In the following description, a "channel" has a structure through which a liquid flows. In the present disclosure, when a channel is viewed in a plan view in the -Z direction, which is a direction perpendicular to both the -Y direction as the first direction D1 and the +X direction as the second direction D2, the length of the channel in the direction perpendicular to the direction in which the channel extends is referred to as the width of the channel. A relatively small width of the channel means that the channel is relatively narrow, and a relatively large width of the channel means that the channel is relatively wide. In the present disclosure, "when viewed in a plan view" means when the channel is viewed in the -Z direction, unless otherwise specified.
[0021] <1. An example of a schematic configuration of a flow channel device> Fig. 1 is a plan view schematically showing an example of the configuration of a flow channel device 1 as a separation device according to an embodiment. Fig. 2 is a front view schematically showing an example of the configuration of the flow channel device 1 according to an embodiment. As will be described later, the flow channel device 1 can function as a device for separating a plurality of particles of a specific type (also referred to as first particles) Pa11 from a plurality of particles of another type (also referred to as second particles) Pa12 from a liquid (also referred to as a first liquid) L1 containing a plurality of types of particles Pa1.
[0022] 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 opposite to the upper surface 1a. The flow path device 1 has, for example, 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 closer to the +Z direction than the lower surface 1b.
[0023] In the examples of Figures 1 and 2, the upper surface 1a faces the +Z direction. In other words, the upper surface 1a is a surface along the XY plane and has a normal line 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 and has a normal line along the -Z direction. Each of the upper surface 1a and the lower surface 1b is, for example, approximately flat and has a rectangular shape.
[0024] The thickness of the flow path device 1 is set to, for example, about 1 millimeter (mm) to 5 mm. The thickness of the flow path device 1 is the length of the flow path device 1 in the +Z direction. The widths of the upper surface 1a and the lower surface 1b of the flow path device 1 are set to, for example, about 10 mm to 50 mm. The width of the upper surface 1a is the length of the upper surface 1a in the +X direction. The width of the lower surface 1b is the length of the lower surface 1b in the +X direction. The lengths of the upper surface 1a and the lower surface 1b of the flow path device 1 are set to, for example, about 10 mm to 50 mm. The length of the upper surface 1a is the length of the upper surface 1a in the +Y direction. The length of the lower surface 1b is the length of the lower surface 1b in the +Y direction.
[0025] The flow path device 1 includes a flow path section 2. In one embodiment, the flow path device 1 includes a plurality of holes 3. In one embodiment, the flow path section 2 does not open on the outer surface of the flow path device 1. Each of the plurality of holes 3 communicates with the flow path section 2 and opens on the outer surface of the flow path device 1. In the present disclosure, the expression "a first portion communicates with a second portion" means a configuration in which the first portion is directly connected to the second portion such that a fluid, such as a liquid, can flow between the first and second portions, or a configuration in which the first portion is connected to the second portion via another portion (also referred to as a third portion) such that a fluid can flow between the first and second portions. Here, the first portion, second portion, and third portion each refer to a portion through which a fluid can flow, such as a flow path or a hole. For example, the flow path section 2 is located inside the flow path device 1. From another perspective, for example, the flow path section 2 does not open on any of the upper surface 1a, the lower surface 1b, or the side surface 1c. In FIG. 2, the configuration of the flow path section 2 is shown in a simplified form.
[0026] FIG. 3 is a plan view schematically showing an example of the configuration of the flow path section 2 and the plurality of holes 3 in the flow path device 1. In FIG. 3, the outer edge of the flow path device 1 is omitted, and the outer edges of the flow path section 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 by solid lines. FIG. 4 is a plan view schematically showing a part of the flow path section 2. More specifically, FIG. 4 is a plan view schematically showing region IV surrounded by a dashed line in the rectangle of FIG. 3. In FIG. 4, the outer edge of the flow path section 2 is depicted by solid lines.
[0027] The flow path section 2 has a configuration in which, for example, a plurality of flow paths that are not open on the outer surface of the flow path device 1 are connected together. The cross section of each of the plurality of flow paths may be, for example, rectangular. The cross section of a flow path may be a surface formed by virtually cutting the flow path along a virtual plane that is perpendicular to the direction in which the flow path extends. As shown in FIGS. 1 to 3, the flow path section 2 is located, for example, along the XY plane.
[0028] The flow path section 2 includes a main flow path 21 as a first flow path, a plurality of branch flow paths 22 as a plurality of second flow paths, a first introduction flow path 23 as a third flow path, and a second introduction flow path 24 as a fourth flow path.
[0029] The main flow path 21 is a flow path extending along the −Y direction as the first direction D1. For example, the main flow path 21 may extend linearly along the −Y direction as the first direction D1. The main flow path 21 has a first portion (also referred to as a first downstream portion) 21d and a second portion (also referred to as a first upstream portion) 21u. The first downstream portion 21d is located on the −Y direction side of the main flow path 21 as the first direction D1. The first downstream portion 21d may be a portion located at an end of the main flow path 21 on the −Y direction side as the first direction D1. The first upstream portion 21u is located on the opposite side of the main flow path 21 from the first downstream portion 21d. In other words, the first upstream portion 21u is a portion located at an end of the main flow path 21 on the opposite side from the first downstream portion 21d. In other words, the first upstream portion 21u may be a portion of the main flow path 21 located at an end opposite to the first downstream portion 21d. From another perspective, the first upstream portion 21u may be a portion of the main flow path 21 located at an end on the +Y direction side, which is the direction opposite to the first direction D1, of the main flow path 21. In other words, the main flow 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. In the example of FIG. 4, the first upstream portion 21u is a rectangular portion of the main flow path 21 that is virtually separated by a thin two-dot chain line.
[0030] The main flow path 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 the main flow path 21 facing the +X direction as a second direction D2 that is perpendicular to the −Y direction as a first direction D1. The second side surface Sw2 is a side surface facing the first side surface Sw1 in the +X direction as the second direction D2. In other words, the second side surface Sw2 is a side surface of the main flow path 21 facing the −X direction as a fourth direction D4 that is opposite to the second direction D2. From another perspective, the first side surface Sw1 may be a side surface of the main flow path 21 located on the second direction D2 side, and the second side surface Sw2 may be a side surface of the main flow path 21 located on the fourth direction D4 side.
[0031] Each of the branch flow paths 22 is connected to the main flow path 21 and is narrower than the main flow path 21. Each of the branch flow paths 22 opens at a first side surface Sw1 of the main flow path 21 between a first upstream portion 21u and a first downstream portion 21d of the main flow path 21. In other words, each of the branch flow paths 22 connects to the main flow path 21 by opening at the first side surface Sw1 between the first downstream portion 21d and the first upstream portion 21u. In other words, the main flow path 21 has multiple portions (also referred to as connection portions) Bc1 to which the branch flow paths 22 are connected. For example, each of the branch flow paths 22 branches off from the main flow path 21 at different positions in the −Y direction as the first direction D1. In other words, the connection portions Bc1 to which the branch flow paths 22 are connected are located at different positions in the −Y direction as the first direction D1.
[0032] In the examples of FIGS. 1 to 3, each of the branch flow paths 22 extends along the +X direction, which is the second direction D2. From another perspective, the branch flow paths 22 are arranged side by side along the -Y direction, which is the first direction D1. Here, the branch flow paths 22, for example, form a group 22g of branch flow paths 22 (also referred to as a branch flow path group). The number of the branch flow paths 22 is set to, for example, several tens to several hundreds. For convenience, 13 branch flow paths 22 are depicted in FIGS. 1 to 3.
[0033] Each of the plurality of branch flow paths 22 includes, for example, a portion (also referred to as a second downstream portion) 22d on the opposite side to the main flow path 21. In the examples of Figures 1 to 3, in each of the plurality of branch flow paths 22, the second downstream portion 22d of the branch flow path 22 is a portion located at the end of the branch flow path 22 on the +X direction side as the second direction D2.
[0034] 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 Cp1 (also referred to as a first connection portion) connected to the first upstream portion 21u. The first connection portion Cp1 extends along the −Y direction as the first direction D1. For example, the first connection portion Cp1 may extend linearly along the −Y direction as the first direction D1 toward the first upstream portion 21u. In other words, the first inlet flow path 23 is connected to the first upstream portion 21u of the main flow path 21 in the −Y direction as the first direction D1. The first inlet flow path 23 is wider than each of the multiple branch flow paths 22. The width of the first connection 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.
[0035] The second inlet flow channel 24 is connected to the first upstream portion 21u of the main flow channel 21. The second inlet flow channel 24 includes a portion Cp2 (also referred to as a second connection portion) connected to the first upstream portion 21u. For example, the second connection portion Cp2 opens at the second side surface Sw2 of the main flow channel 21. In other words, the second connection portion Cp2 is connected to the main flow channel 21 by opening at the second side surface Sw2 of the first upstream portion 21u. The second connection portion Cp2 extends along a third direction D3 that forms an acute angle with the −Y direction as the first direction D1. For example, the second connection portion Cp2 may extend linearly toward the first upstream portion 21u along the third direction D3 that forms an acute angle with the −Y direction as the first direction D1. The acute angle θ may be set to an angle θ that is 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 to the first upstream portion 21u of the main flow path 21 in the third direction D3. From another perspective, the second connection portion Cp2 is inclined relative to the main flow path 21 so as to approach the first connection portion Cp1. In other words, an acute angle θ is formed between a vector along the third direction D3, which is the direction in which the second connection portion Cp2 extends toward the first upstream portion 21u, and a vector along the first direction D1, which is the direction in which the main flow path 21 extends from the first upstream portion 21u toward the first downstream portion 21d. The second inlet flow path 24 is wider than each of the multiple branch flow paths 22. Here, the angle θ may be, for example, greater than or equal to 15 degrees and less than or equal to 45 degrees. The angle θ may be 30 degrees. FIG. 4 shows an example in which the angle θ is set to 30 degrees.
[0036] The second inlet flow path 24 has a side surface (also referred to as a third side surface) Sw3 located on the side of the first connection portion Cp1. More specifically, the second connection portion Cp2 of the second inlet flow path 24 has the third side surface Sw3 located on the side of the first connection portion Cp1. Here, an imaginary plane along the third side surface Sw3 of the second connection portion Cp2 and an imaginary plane along the second side surface Sw2 of the main flow path 21 form an acute angle θ.
[0037] The flow path section 2 has a surface (also referred to as a connection surface) Cs1 that connects the second side surface Sw2 of the main flow path 21 and the third side surface Sw3 of the second connection portion Cp2. In other words, the flow path section 2 has a shape in which the tip of the acute angle formed between the first upstream portion 21u of the main flow path 21 and the second connection portion Cp2 of the second inlet flow path 24 is chipped. In yet other words, the flow path section 2 has a portion (also referred to as an expanded portion) Ac1 between the first upstream portion 21u of the main flow path 21 and the second connection portion Cp2 of the second inlet flow path 24 in a shape in which the flow path is expanded. The connection surface Cs1 may be, for example, a rectangular flat surface.
[0038] In the example of FIG. 4 , the extended portion Ac1 is a virtual triangular portion surrounded by a thin two-dot chain line extending virtually from the third side surface Sw3 to the first upstream portion 21u along the third direction D3, a thin two-dot chain line representing the outer edge of the first upstream portion 21u, and the connecting surface Cs1. In other words, the extended portion Ac1 is a triangular portion in plan view where the flow path (the main flow path 21 and / or the second inlet flow path 24) is extended. In plan view, the shape of the extended portion Ac1 may be, for example, an isosceles triangle along an isosceles triangle whose base is the side along the connecting surface Cs1. 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 may be the same or substantially the same. Here, for example, if the angle θ is 30 degrees, the angles α and β may each be 105 degrees.
[0039] When the flow path section 2 is viewed in a plan view, the size of the connection surface Cs1 is set to be equal to or smaller than the width (also referred to as 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 and the connection surface Cs1 are connected at a third portion P1, and the third side surface Sw3 of the second connection portion Cp2 of the second introduction flow path 24 and the connection surface Cs1 are connected at a fourth portion P2. Here, when the flow path section 2 is viewed in a plan view, the distance between the third portion P1, where the second side surface Sw2 of the main flow path 21 and the connection surface Cs1 are connected, and the fourth portion P2, where the third side surface Sw3 of the second connection portion Cp2 and the connection surface Cs1 are connected, is set to be a first distance Le1. In this case, the first distance Le1 may be set to be equal to or smaller than the first width W1. The first distance Le1 may be 0.1 to 0.5 times the first width W1. Each of the third portion P1 and the fourth portion P2 is not limited to a point-like portion as the apex of a corner when viewed in a plane, but may be a linear portion having a short length.
[0040] The plurality of holes 3 includes 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.
[0041] The first inlet hole 31 communicates with the first upstream portion 21u via the first inlet flow path 23. The first inlet hole 31 may be connected to the first inlet flow path 23. More specifically, the first inlet hole 31 may be connected to the end of the first inlet flow path 23 opposite the first upstream portion 21u. From another perspective, the first inlet hole 31 communicates with the first upstream portion 21u. The diameter of the first inlet hole 31 is set, for example, to be equal to or greater than the width of the first inlet flow path 23. In the example of FIGS. 1 and 3 , the first inlet flow path 23 is an L-shaped flow path in which a portion extending from the first inlet hole 31 along the −X direction (fourth direction D4) and a portion extending along the −Y direction (first direction D1) are connected in this order. In other words, the first inlet flow path 23 extends from the first inlet hole 31 toward the first upstream portion 21u in the −X direction and then the −Y direction. Here, the portion of the first introduction flow path 23 between the first introduction hole 31 and the first connection portion Cp1 is not limited to an L-shaped portion, and may have various shapes.
[0042] The second inlet hole 32 communicates with the first upstream portion 21u via the second inlet flow path 24. The second inlet hole 32 may be connected to the second inlet flow path 24. More specifically, the second inlet hole 32 may be connected to an end of the second inlet flow path 24 opposite the first upstream portion 21u. From another perspective, the second inlet hole 32 communicates with the first upstream portion 21u. The diameter of the second inlet hole 32 is set, for example, to be equal to or greater than the width of the second inlet flow path 24. In the examples of FIGS. 1 and 3 , the second inlet flow path 24 is a linear 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 connection portion Cp2 is not limited to a linear portion extending along the third direction D3 and may have various shapes.
[0043] The first discharge hole 33 communicates with the first downstream portion 21d of the main flow path 21. The first discharge hole 33 may be connected to the first downstream portion 21d via, for example, a first discharge flow path 25 serving 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 hole 33 and the first downstream portion 21d. The first discharge flow path 25 is wider than each of the branch flow paths 22. The first discharge flow path 25 is wider than each of the first particles Pa11 described below. This allows the first particles Pa11, which have passed through a portion of the main flow path 21 where the branch flow paths 22 are connected and reached the first downstream portion 21d, to be introduced into the first discharge flow path 25. As a result, in the flow path device 1, a liquid containing the first particles Pa11 can be discharged from the first discharge hole 33 via the first discharge flow path 25. Therefore, in the flow path device 1, a liquid containing a plurality of first particles Pa11 can be recovered as a recovered liquid from the first downstream portion 21d via, for example, the first discharge holes 33. The diameter of the first discharge holes 33 may 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 that is connected to the first downstream portion 21d opens at a side surface of the first downstream portion 21d in the +X direction as the second direction D2. The side surface of the first downstream portion 21d in the +X direction as the second direction D2 may be a side surface of the first downstream portion 21d that is located on the +X direction side as the second direction D2. 1 and 3, the first discharge flow path 25 is a U-shaped flow path in which a portion connected to the first downstream portion 21d and extending along the +X direction (second direction D2), a portion extending along the -Y direction (first direction D1), and a portion extending along the -X direction (fourth direction D4) are connected in this order. In other words, the first discharge flow path 25 extends in the +X direction, -Y direction, and -X direction in this order.
[0044] The second discharge hole 34 communicates with the second downstream portion 22d of each of the branch flow paths 22. The second discharge hole 34 may be connected to the second downstream portion 22d of each of the branch flow paths 22 via, for example, a second discharge flow path 26 serving as a sixth flow path. In other words, the flow path section 2 may include, for example, a second discharge flow path 26 connecting the second discharge hole 34 to the second downstream portion 22d of each of the branch flow paths 22. More specifically, for example, each of the branch flow paths 22 may be connected to the second discharge flow path 26 at different positions in the −Y direction (the first direction D1). The second discharge flow path 26 is wider than each of the branch flow paths 22, for example, to ensure a sufficient volume for collectively directing the liquid flowing in from the branch flow paths 22 to the second discharge hole 34. In the example of FIGS. 1 and 3 , the edge of the second discharge flow path 26 in the +X direction is located near the second discharge hole 34. For example, the diameter of the second discharge hole 34 may be set to be equal to or greater than the width of the second discharge flow path 26 at the end in the -Y direction connected to the second discharge hole 34. This allows the flow path device 1 to discharge a liquid containing a plurality of second particles Pa12 separated by the plurality of branch flow paths 22, as described below, from the second discharge hole 34 via the second discharge flow path 26. In the example of FIGS. 1 and 3 , the second discharge flow path 26 is an L-shaped flow path to which the plurality of second downstream portions 22d of the plurality of branch flow paths 22 are connected, and which extends linearly along the -Y direction as the first direction D1. The second discharge flow path 26 has a wide portion in the +X direction as the second direction D2 and a narrow portion in the +Y direction as the first direction D1, which are connected in this order. In other words, the second discharge flow path 26 extends in the -Y direction and then the +X direction, such that the outlets of the plurality of branch flow paths 22 are collected and connected to the second discharge hole 34.
[0045] The third discharge hole 35 communicates with the first downstream portion 21d of the main flow path 21. The third discharge hole 35 may be connected to the first downstream portion 21d, for example, via a third discharge flow path 27 serving 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 hole 35 and the first downstream portion 21d. The third discharge flow path 27 may be wider than each of the multiple branch flow paths 22. The third discharge flow path 27 may have the same width as the main flow path 21 or may be wider than the main flow path 21. The diameter of the third discharge hole 35 may be set to be, for example, the same as or greater than the width of the third discharge flow path 27. As a result, in the flow path device 1, as described below, 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 removal of the recovered liquid recovered via the first discharge flow path 25 and the like, can be discharged from the third discharge hole 35 via the third discharge flow path 27. Note that this remaining liquid may include the first particles Pa11 and the second particles Pa12 that were not removed by the separation and recovery. In one embodiment, the portion of the third discharge flow path 27 that is connected to the first downstream portion 21d extends along the −Y direction as the first direction D1. In the example of FIGS. 1 and 3 , the third discharge flow path 27 is a flow path in which a portion that is connected to the first downstream portion 21d and extends along the −Y direction as the first direction D1, a portion that extends along the −X direction as the fourth direction D4, a portion that extends along the −Y direction as the first direction D1, and a portion that extends along the +X direction as the second direction D2 and is connected to the third discharge hole 35 are connected in this order. In other words, the third discharge flow path 27 extends in the order of the -Y direction, the -X direction, the -Y direction, and the +X direction.
[0046] In one embodiment, for example, the first inlet 31, the second inlet 32, the first outlet 33, the second outlet 34, and the third outlet 35 do not open to the upper surface 1a but open to the lower surface 1b. For example, the first inlet 31 has a portion 1i (also referred to as a first inlet or a first inlet) that opens to the lower surface 1b. The second inlet 32 has a portion 2i (also referred to as a second inlet or a second inlet) that opens to the lower surface 1b. The first outlet 33 has a portion 1o (also referred to as a first outlet or a first outlet) that opens to the lower surface 1b. The second outlet 34 has a portion 2o (also referred to as a second outlet or a second outlet) that opens to the lower surface 1b. The third outlet 35 has a portion 3o (also referred to as a third outlet or a third outlet) that opens to the lower surface 1b.
[0047] The material of the flow channel device 1 (the material constituting the flow channel device 1) is, for example, a resin such as polydimethylsiloxane (PDMS). PDMS has excellent transferability, for example, when resin molding is performed using a mold. Transferability is a property that allows fine irregularities corresponding to the fine pattern of the mold to be formed in the resin molded product.
[0048] The flow path device 1 can be manufactured, for example, by joining a plate-shaped portion (also referred to as the first plate-shaped portion) having fine irregularities on one side corresponding to the pattern of the flow path section 2 with a plate-shaped portion (also referred to as the 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, in such a manner that one side of the second plate-shaped portion covers the fine irregularities of the first plate-shaped portion.
[0049] The first plate-shaped portion having fine irregularities on one side can be produced, for example, by resin molding. The second plate-shaped portion having five through-holes can be produced, for example, by resin molding, or by forming five through-holes in a flat plate-shaped member formed by resin molding using a punching process or the like. The bonding between the first plate-shaped portion and the second plate-shaped portion can be achieved without adhesive, for example, by surface-modifying one side of the first plate-shaped portion and one side of the second plate-shaped portion, and by contacting one side of the first plate-shaped portion with one side of the second plate-shaped portion. The surface modification can be achieved, for example, by irradiation with oxygen plasma or 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 type of resin, the strength of the bond between one side of the first plate-shaped portion and one side of the second plate-shaped portion, which has been surface-modified, can be improved.
[0050] <2. Example of general function of flow path device> The function of the flow path device 1 is broadly described below.
[0051] Figure 5 is a plan view schematically showing an example of how a first liquid (also called the liquid to be treated) L1, which is the target of treatment, and a liquid (also called the second liquid or the liquid for pressing) L2, which is different from the first liquid L1, are introduced into the first upstream portion 21u of the main flow path 21 in a part of the flow path section 2 shown in Figure 4.
[0052] 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 types of particles Pa1. Each of the multiple first particles Pa11 is a particle to be separated as a specific type of particle (also referred to as separation target particle). Each of the multiple second particles Pa12 is a particle of a different type (also referred to as other type of particle) different from the specific type of particle. In the flow path device 1, a process (also referred to as particle separation process) is performed on the multiple types of particles Pa1 contained in the first liquid L1 to separate the multiple first particles Pa11 from the multiple second particles Pa12. Here, the multiple types of particles Pa1 contained in the first liquid L1 may be three or more types of particles. In the following, a case will be exemplified in which each of the first particles Pa11 and the second particles Pa12 is a single type of particle.
[0053] In the flow path device 1, when a particle separation process is performed, for example, a first liquid L1 is introduced into the flow path section 2 through the first introduction hole 31, and a second liquid L2 is introduced into the flow path section 2 through the second introduction hole 32. Specific examples and functions of the second liquid L2 will be described later.
[0054] When the first liquid L1 is introduced into the flow path section 2 through the first inlet hole 31, for example, a tube (also referred to as a first tube) for supplying the first liquid L1 may be connected to the flow path device 1 from outside the flow path device 1. To connect this first tube to the flow path device 1, for example, a cylindrical portion may be present on the underside 1b of the flow path device 1, surrounding the first inlet hole 31 around the Z axis in a plan view and protruding in the −Z direction. One longitudinal end (also referred to as a first end) of the first tube may have, for example, a connector for connecting to the first inlet hole 31. A longitudinal end (also referred to as a second end) of the first tube different from the first end may be connected to a portion (also referred to as a first supply unit) for supplying the first liquid L1 to the first inlet hole 31 via the first tube. The first supply unit may be, for example, a mechanism capable of supplying the first liquid L1 using a pump such as a syringe pump or a plunger pump. Here, a first supply unit may be connected to the second end of the first tube via, for example, a three-way valve, etc. In this case, for example, in the flow path device 1, as a preparation immediately before a particle separation process (also referred to as advance preparation), when the second liquid L2 introduced from the second inlet hole 32 fills the flow path unit 2, gas or the like within the flow path unit 2 may be discharged from the first inlet hole 31 via the first tube and the three-way valve, etc., by switching the three-way valve, etc.
[0055] When the second liquid L2 is introduced into the flow path section 2 through the second inlet hole 32, for example, a tube (also referred to as a second tube) for supplying the second liquid L2 may be connected to the flow path device 1 from outside the flow path device 1. To connect this 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, surrounding the second inlet hole 32 around the Z axis in a plan view and protruding in the −Z direction. One longitudinal end (also referred to as a third end) of the second tube may have, for example, a connector for connecting to the second inlet hole 32. A longitudinal end (also referred to as a fourth end) of the second tube different from the third end may be connected to a portion (also referred to as a second supply unit) for supplying the second liquid L2 to the second inlet hole 32 via the second tube. The second supply unit may be, for example, a mechanism capable of supplying the second liquid L2 using a pump such as a syringe pump or a plunger pump.
[0056] For example, the first liquid L1 introduced into the flow path device 1 from the first introduction hole 31 flows into the first upstream portion 21u of the main flow path 21 via the first introduction flow path 23. In other words, the first introduction hole 31 serves as a hole for introducing the first liquid L1 into the main flow path 21. Furthermore, for example, the first introduction 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.
[0057] For example, the second liquid L2 introduced into the flow path device 1 from the second introduction hole 32 flows into the first upstream portion 21u of the main flow path 21 via the second introduction flow path 24. In other words, the second introduction hole 32 serves as a hole for introducing the second liquid L2 into the main flow path 21. Furthermore, for example, the second introduction 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.
[0058] In FIG. 5, arrow Fp1 drawn with a two-dot chain line indicates the direction in which the second liquid L2 flows. This direction is along the third direction D3. In FIG. 5, arrow Fm1 drawn with a two-dot chain line thicker than arrow Fp1 indicates the direction in which the main flow (also referred to as the mainstream) of the first liquid L1 flowing from the first introduction channel 23 through the main channel 21 flows. The direction in which this mainstream flows is along the −Y direction as the first direction D1. As in FIG. 4, FIG. 5 shows a rectangular first upstream portion 21u of the main channel 21 that is virtually separated by a thin two-dot chain line.
[0059] 5 schematically illustrates how the first particles Pa11 and the second particles Pa12 are separated from each other when the diameter of the first particles Pa11 is larger than the diameter of the second particles Pa12. Specifically, for example, a case is illustrated in which the width of each of the plurality of branch channels 22 is set to be larger than the diameter of the second particles Pa12 and smaller than the diameter of the first particles Pa11. In each of the plurality of branch channels 22, the width of the branch channel 22 is the length of the branch channel 22 along the −Y direction, which is the first direction D1. Here, for example, the first liquid L1 may contain multiple types of particles Pa1, including a plurality of first particles Pa11 each having a diameter larger than the width of each of the plurality of branch channels 22, and a plurality of second particles Pa12 each having a diameter smaller than the width of each of the plurality of branch channels 22.
[0060] At least the width of each of the main flow channel 21 and the first inlet flow channel 23 is larger than the diameter of either the first particle Pa11 or the second particle Pa12. Here, the width of the main flow channel 21 is the length of the main flow channel 21 along the +X direction as the second direction D2. The width of the first inlet flow channel 23 is the length of the first inlet flow channel 23 along the +X direction as the second direction D2 in the vicinity of the main flow channel 21. The width of the first inlet flow channel 23 is the length of the first inlet flow channel 23 along the -Y direction in the first direction D1 at a position where the first inlet flow channel 23 extends along the -X direction as the fourth direction D4.
[0061] The second particles Pa12 move in the main flow path 21 in the −Y direction as a first direction D1 while receiving a force pressing them in the +X direction as a second direction D2, and thus most of the second particles Pa12 can be introduced into one of the branch flow paths 22. Most of the second particles Pa12 contained in the first liquid L1 can pass through one of the branch flow paths 22 and then pass through the second discharge flow path 26 and be discharged from the second discharge hole 34 to the outside of the flow path device 1. Here, for example, by adjusting the cross-sectional area and length of each of the branch flow paths 22 connected to the main flow path 21, most of the second particles Pa12 can be introduced from the main flow path 21 to one of the branch flow paths 22 and separated from the first particles Pa11. The second particles Pa12 discharged from the second discharge hole 34 to the outside of the flow path device 1 may be subjected to a specific process or simply collected, for example, in another device connected to the second discharge hole 34 directly or via another member such as a pipe. The plurality of second particles Pa12 discharged from the second discharge hole 34 to the outside of the flow path device 1 may be discarded, for example, directly or via another member such as a pipe.
[0062] The plurality of first particles Pa11 move in the −Y direction as the first direction D1 within the main channel 21 without being introduced into the plurality of branch channels 22. Most of the plurality of first particles Pa11 pass through the main channel 21 and then pass through the first discharge channel 25 and are discharged from the first discharge hole 33 to the outside of the flow channel device 1. Here, the width of the first discharge channel 25 is larger than that of the first particles Pa11. Due to the same effect as when most of the plurality of second particles Pa12 are introduced into one of the plurality of branch channels 22 in the main channel 21, the plurality of first particles Pa11 that have reached the first downstream portion 21d may flow into the first discharge channel 25 rather than the third discharge channel 27. The plurality of first particles Pa11 discharged from the first discharge hole 33 to the outside of the flow channel device 1 may be collected, for example, in another device connected to the first discharge hole 33 directly or via another member such as a pipe, and subjected to a specific process or simply collected. In other words, the liquid (recovered liquid) containing the plurality of first particles Pa11 discharged from the first discharge hole 33 to the outside of the flow path device 1 is recovered.
[0063] The composition of the first liquid L1 excluding the plurality of second particles Pa12 flowing into any of the plurality of branch flow paths 22 and the plurality of first particles Pa11 flowing into the first discharge flow path 25 (also referred to as the remaining composition) flows into the third discharge flow path 27. This remaining composition can be discharged from the third discharge hole 35 via the third discharge flow path 27. Here, the remaining composition discharged from the third discharge hole 35 to the outside of the flow path device 1 may be subjected to a specific process in another device connected to the third discharge hole 35 directly or via another member such as a pipe, or may simply be collected. The remaining composition discharged from the third discharge hole 35 to the outside of the flow path device 1 may be discarded, for example, directly or via another member such as a pipe. Note that, as is clear from the above description, this remaining composition is not necessarily completely free of the first particles Pa11 and / or the second particles Pa12. The remaining composition may include second particles Pa12 that did not flow into the plurality of branch channels 22 and first particles Pa11 that did not flow into the first discharge channel 25.
[0064] In one embodiment, a flow (also referred to as an introduction flow) that introduces the first liquid L1 into the multiple branch channels 22 is used. The introduction flow can contribute to separation of the multiple first particles Pa11 and the multiple second particles Pa12 by the main channel 21 and the multiple branch channels 22. The introduction flow is indicated by a hatched region Ar1 in FIG. 5 using diagonal lines slanting upward to the right. The state of the introduction flow indicated by the region Ar1 in FIG. 5 is merely an example. The state of this introduction flow can change depending on the relationship between the flow velocity and flow rate of the first liquid L1 introduced from the first introduction channel 23 to the main channel 21 and the flow velocity and flow rate of the second liquid L2 introduced from the second introduction channel 24 to the first upstream portion 21u of the main channel 21, etc. By appropriately adjusting the region Ar1, the multiple first particles Pa11 and the multiple second particles Pa12 are efficiently separated from the first liquid L1. The second liquid L2 presses the first liquid L1 toward the branch channels 22 in the +X direction as the second direction D2 from the side opposite to the branch channels 22. In other words, the second liquid L2 may have the role of pressing the first particles Pa11 and the second particles Pa12, which are the multiple types of particles Pa1, against the first side surface Sw1 of the main channel 21 in the +X direction as the second direction D2 of the main channel 21. The second liquid L2 can contribute to the generation of an introduction flow.
[0065] Here, as described above, the main flow path 21 extends along the −Y direction as the first direction D1. The first connection portion Cp1 of 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 as the first direction D1. Each of the multiple branch flow paths 22 is connected to the main flow path 21 by opening at a first side surface Sw1 of the main flow path 21 between the first upstream portion 21u and the first downstream portion 21d of the main flow path 21. The second inlet flow path 24 is connected to the first upstream portion 21u. The second inlet flow path 24 is connected to the main flow path 21 by opening at a second side surface Sw2 of the main flow path 21, for example.
[0066] For this reason, by introducing the first liquid L1 containing multiple types of particles Pa1 into the main channel 21 from the first inlet channel 23 while the second liquid L2 is being introduced into the main channel 21 from the second inlet channel 24, a liquid flow can be generated in the main channel 21 that presses the multiple types of particles Pa1 toward the multiple branch channels 22. In other words, for example, by supplying the first liquid L1 containing multiple types of particles Pa1 to the main channel 21 through the first inlet hole 31 while supplying the second liquid L2 to the main channel 21 through the second inlet hole 32, a liquid flow can be generated in the main channel 21 that presses the multiple types of particles Pa1 toward the multiple branch channels 22. 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, the plurality of first particles Pa11 and the plurality of second particles Pa12 as the plurality of types of particles Pa1 contained in the first liquid L1 can flow toward the first downstream portion 21d while being pressed toward the plurality of branch flow paths 22. This makes it easier for, for example, the plurality of second particles Pa12, of the plurality of first particles Pa11 and the plurality of second particles Pa12 as the plurality of types of particles Pa1, to flow into the plurality of branch flow paths 22. As a result, for example, among the multiple first particles Pa11 and multiple second particles Pa12 as multiple types of particles Pa1 in the first liquid L1, it becomes easy to separate the multiple first particles Pa11 having a diameter larger than the width of each of the multiple branch flow paths 22 and the multiple second particles Pa12 having a diameter smaller than the width of each of the multiple branch flow paths 22.
[0067] Furthermore, in one embodiment, as described above, the portion of the first discharge flow path 25 that connects to the first downstream portion 21d of the main flow path 21 opens on a side surface of the first downstream portion 21d in the +X direction, which is the second direction D2. Therefore, for example, due to the action of the introduction flow in the main flow path 21, the multiple first particles Pa11 that have a diameter larger than the width of each of the multiple branch flow paths 22 tend to flow into the first discharge flow path 25. This allows, for example, the multiple first particles Pa11 to 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, of the multiple types of particles Pa1 in the first liquid L1, the multiple first particles Pa11 that are species of particles that have a diameter larger than the width of each of the multiple branch flow paths 22 and the multiple second particles Pa12 that have a diameter smaller than the width of each of the multiple branch flow paths 22 are easily separated.
[0068] 5, the width of the introduction flow in the main channel 21 is shown as width Wf1 (also referred to as second width) near the region where the main channel 21 branches into the multiple branch flow channels 22. Here, the width of the introduction flow in the main channel 21 is the length of the introduction flow along the +X direction as the second direction D2. The second width Wf1 can be set, for example, by adjusting the cross-sectional areas and lengths of the main channel 21 and the multiple branch flow channels 22 and adjusting the flow rates of the first liquid L1 and the second liquid L2.
[0069] In FIG. 5, the second width Wf1 is illustrated as a width in which the center of gravity of each of the plurality of first particles Pa11 is not included in the region Ar1 of the inlet flow, but the center of gravity of each of the plurality of second particles Pa12 is included. Here, because the second width Wf1 is a width in which the center of gravity of the second particles Pa12 is included in the region Ar1 of the inlet flow, the force of the inlet flow effectively acts on the second particles Pa12, urging the second particles Pa12 into one of the plurality of branch channels 22. Therefore, the second particles Pa12 can flow into a branch channel 22 whose width is larger than the diameter of the second particles Pa12. In contrast, because the second width Wf1 is a width in which the center of gravity of the first particles Pa11 is not included in the region Ar1 of the inlet flow, the force of the inlet flow does not sufficiently act on the first particles Pa11, urging the first particles Pa11 into the plurality of branch channels 22. Therefore, for example, even if the width of the branch flow paths 22 is somewhat larger than the diameter of the first particles Pa11, the first particles Pa11 can flow through the main flow path 21 without flowing into the multiple branch flow paths 22.
[0070] An example of the first liquid L1 is blood or a liquid obtained by diluting blood with physiological saline. Blood is a liquid containing multiple types of particles Pa1. In this case, an example is adopted in which the first particles Pa11 are white blood cells and the second particles Pa12 are red blood cells. An example of the specific processing of the multiple first particles Pa11 is measuring the number and concentration of white blood cells. An example of the residual composition that flows through the third discharge flow path 27 and is discharged from the flow path device 1 via the third discharge hole 35 is plasma. In this case, physiological saline is used as an example of the second liquid L2. More specifically, phosphate-buffered saline (PBS) is used as an example of the second liquid L2. In order to impart functions to the second liquid L2 according to the intended use of the flow path device 1, a liquid obtained by adding other components to PBS may be used as the second liquid L2. As the other component, for example, ethylenediaminetetraacetic acid (EDTA) may be applied as a second component, and bovine serum albumin (BSA) may be applied as a third component. Here, the main channel 21 and the multiple branch channels 22 included in the channel section 2 function as channels for separating particles in the blood. In other words, the channel section 2 includes the main channel 21 and the multiple branch channels 22 for separating particles in the blood.
[0071] The center of gravity of a red blood cell is, for example, about 2 micrometers (μm) to 2.5 μm from the outer edge of the red blood cell. The maximum diameter of a red blood cell is, for example, about 6 μm to 8 μm. The center of gravity of a white blood cell is, for example, about 5 μm to 10 μm from the outer edge of the white blood cell. The maximum diameter of a white blood cell is, for example, about 10 μm to 20 μm. From the viewpoint of separating red blood cells and white blood cells in the blood, a value of about 2 μm to 10 μm is adopted for the width (second width) Wf1 of the introduced flow.
[0072] The cross-sectional area of the virtual cross section of the main flow channel 21 along the XZ plane is, for example, 400 square micrometers (μm 2 ) to 4000 μm 2The length (also referred to as width) of the main flow path 21 along the +X direction as the second direction D2 is set to, for example, about 20 μm to 100 μm. The length (also referred to as height) of the main flow path 21 along the +Z direction is set to, for example, about 20 μm to 100 μm. The length (also referred to as height) of the main flow path 21 along the −Y direction as the first direction D1 is set to, for example, about 0.5 mm to 20 mm.
[0073] The cross-sectional area of the imaginary cross section of each of the branch channels 22 along the YZ plane is, for example, 200 μm 2 to 800 μm 2 The length (also referred to as width) of each of the plurality of branch flow paths 22 along the −Y direction as the first direction D1 is set to, for example, about 10 μm to 30 μm. The length (also referred to as height) of each of the plurality of branch flow paths 22 along the +Z direction as the second direction D2 is set to, for example, about 20 μm to 100 μm. The length (also referred to as height) of each of the plurality of branch flow paths 22 along the +X direction as the second direction D2 is set to, for example, about 3 mm to 25 mm.
[0074] The flow rate of the liquid per unit time in the main channel 21 is set, for example, to about 150 microliters per minute (μL / min) to 480 μL / min. The flow rate per unit time of the first liquid L1 introduced into the main channel 21 from the first introduction hole 31 via the first introduction channel 23 is set, for example, to about 90 μL / min to 270 μL / min. The flow rate per unit time of the second liquid L2 introduced into the main channel 21 from the second introduction hole 32 via the second introduction channel 24 is set, for example, to about 60 μL / min to 210 μL / min.
[0075] As described above, for example, the main flow path 21 extends along the −Y direction as the first direction D1. The first connection portion Cp1 of 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 as the first direction D1. The second connection portion Cp2 of the second inlet flow path 24, which is connected to the first upstream portion 21u of the main flow path 21, extends along the third direction D3, which forms an acute angle with the −Y direction as the first direction D1.
[0076] 5, when a particle separation process is performed using the flow channel device 1, the flow of the second liquid L2 can merge with the flow of the first liquid L1 in a manner such that a second inflow direction of the second liquid L2 from the second inflow channel 24 to the first upstream section 21u of the main flow channel 21 forms an acute angle with a first inflow direction of the first liquid L1 from the first inflow channel 23 to the first upstream section 21u. The first inflow direction is the direction in which the first liquid L1 flows from the first inflow channel 23 to the first upstream section 21u of the main flow channel 21 along the −Y direction as a first direction D1. The second inflow direction is the direction in which the second liquid L2 flows from the second inflow channel 24 to the first upstream section 21u of the main flow channel 21 along a third direction D3. This can reduce the occurrence of turbulence in the introduced flow in the main flow channel 21, even if the flow rate of the first liquid L1 introduced into the main flow channel 21 increases. As a result, it can reduce an increase in the proportion of second particles Pa12 (e.g., one or more second particles Pa12) among the plurality of second particles Pa12 in the first liquid L1 that flow to the first downstream portion 21d. Therefore, it can reduce an increase in the number of second particles Pa12 that are mixed into the recovered liquid that is recovered from the first downstream portion 21d via the first discharge hole 33 or the like. Therefore, it can reduce a decrease in the proportion of first particles Pa11 (e.g., a plurality of first particles Pa11) among the plurality of particles contained in the recovered liquid. Here, for example, when blood or a liquid obtained by diluting blood 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, a decrease in the proportion of white blood cells (e.g., multiple white blood cells) among all blood cells in the recovery liquid (also referred to as white blood cell recovery liquid) (also referred to as white blood cell purity) can be reduced. All blood cells include white blood cells and red blood cells.
[0077] As described above, for example, the flow path section 2 has a connection surface Cs1 connecting the third side surface Sw3 of the second connection portion Cp2 and the second side surface Sw2 of the main flow path 21. In other words, the flow path section 2 has a shape in which the tip of the acute angle formed between the first upstream portion 21u of the main flow path 21 and the second connection portion Cp2 of the second inlet flow path 24 is chipped. In further other words, the flow path section 2 has a portion (expanded portion) Ac1 in which the flow path is expanded between the first upstream portion 21u of the main flow path 21 and the second connection portion Cp2 of the second inlet flow path 24. The first distance Le1 is set to be equal to or less than 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 is connected to the connection surface Cs1, and the fourth portion P2 where the third side surface Sw3 of the second connection portion Cp2 is connected to the connection surface Cs1.
[0078] 5, for example, due to the presence of the expansion portion Ac1, a portion of the flow of the first liquid L1 may expand from the first upstream portion 21u of the main flow path 21 toward the second inlet flow path 24, and then be pushed toward the first side surface Sw1 by the flow of the second liquid L2. In this case, for example, the first liquid L1 that flows along the second side surface Sw2 (which is part of the first liquid L1) and then along the connection surface Cs1 may be pushed toward the first side surface Sw1 by the second liquid L2 that flows along the third side surface Sw3 (which is part of the second liquid L2). In this configuration, at a location where the liquids converge, for example, the direction in which the second liquid L2 that flows along the third side surface Sw3 (which is part of the flow of the second liquid L2) pushes the first liquid L1 that flows along the connection surface Cs1 toward the first side surface Sw1 may approach a perpendicular direction to the flow direction of the first liquid L1 that flows along the connection surface Cs1. This can increase the force with which the second liquid L2 presses the first liquid L1 toward the branch flow paths 22, while reducing turbulence in the introduced flow in the main flow path 21. As a result, the proportion of the second particles Pa12 (e.g., one or more second particles Pa12) in the first liquid L1 that flow to the first downstream portion 21d among the second particles Pa12 in the first liquid L1 can be reduced in the main flow path 21. This can reduce the number of second particles Pa12 mixed into the recovery liquid recovered from the first downstream portion 21d via the first discharge holes 33, for example. This can increase 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 recovery liquid. Here, for example, when blood or a liquid in which blood is diluted with physiological saline is used as the first liquid L1 and physiological saline is used as the second liquid L2, the white blood cell purity in the white blood cell recovery liquid can be improved. White blood cell purity, as described above, is the percentage of white blood cells (e.g., white blood cells) among all blood cells.
[0079] 3. Relationship between connection surface size and leukocyte purity Here, various examples of experiments conducted to examine the relationship between the size of the connection 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., when particle separation processing is performed using the flow path device 1 according to the embodiment described above will be described.
[0080] Below, the conditions common to all examples of the experiments carried out (also referred to as basic conditions) are explained, and then the conditions and results of each example of the experiments carried out are explained.
[0081] <3-1. Basic conditions for the experiment> <3-1-1. Basic conditions for flow path devices> PDMS was used as the material for the flow channel device 1. The flow channel device 1 was fabricated by bonding a first plate-like portion and a second plate-like portion together in such a manner that one side of the second plate-like portion covered a fine concave-convex pattern corresponding to the pattern of the flow channel section 2 on one side of the first plate-like portion. A plate-like portion having a fine concave-convex pattern corresponding to the pattern of the flow channel section 2 on one side was used as the first plate-like portion. The first plate-like portion having a fine concave-convex pattern on one side was fabricated by resin molding. A plate-like 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 was used as the second plate-like portion. The second plate-like portion having five through holes was fabricated by resin molding. The joining of the first plate-shaped portion and the second plate-shaped portion was carried out without the use of adhesive 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.
[0082] Each of the multiple flow paths constituting the flow path section 2 had a rectangular cross section. The cross section of the flow path was a surface formed by virtually cutting the flow path along a virtual plane perpendicular to the direction in which the flow path extended. Regarding the main flow path 21, the width of the main flow path 21 was set to 40 μm, and the height of the main flow path 21 was set to 40 μm. Regarding the multiple branch flow paths 22, the width of each of the multiple branch flow paths 22 was set to 18 μm, and the height of each of the multiple branch flow paths 22 was set to 40 μm. The number of the multiple branch flow paths 22 was set to 90. Regarding the first inlet flow path 23, the width of the first inlet flow path 23 was set to 40 μm, and the height of the first inlet flow path 23 was set to 40 μm. Regarding the second inlet flow path 24, the width of the second inlet flow path 24 was set to 40 μm, and the height of the second inlet flow path 24 was set to 40 μm. The connection surface Cs1 was set to a rectangular flat surface. When the flow path section 2 is viewed in plan, the shape of the extension portion Ac1 located between the first upstream portion 21u of the main flow path 21 and the second connection portion Cp2 of the second inlet flow path 24 is set to be an isosceles triangle along an isosceles triangle having a base along the side along the connection surface Cs1. In other words, the angle α formed between the third side surface Sw3 and the connection surface Cs1 and the angle β formed between the second side surface Sw2 and the connection surface Cs1 are set to be the same.
[0083] <3-1-2. Basic conditions for the first and second liquids> The first liquid L1 was a liquid obtained by diluting blood 1.5 times with PBS as physiological saline. The first liquid L1 was supplied to the first inlet flow channel 23 by a syringe pump from the outside of the flow channel device 1 via a tube connected to the first inlet hole 31 and the first inlet hole 31. The flow rate of the first liquid L1 per unit time introduced from the first inlet hole 31 through the first inlet flow channel 23 into the main flow channel 21 was adjusted by controlling the operation of the syringe pump.
[0084] PBS, which serves as physiological saline, was used as the second liquid L2. The second liquid L2 was supplied to the second inlet flow channel 24 by a syringe pump via a tube connected to the second inlet hole 32 from the outside of the flow channel device 1 and the second inlet hole 32. The flow rate per unit time of the second liquid L2 introduced into the main flow channel 21 from the second inlet hole 32 via the second inlet flow channel 24 was adjusted by controlling the operation of the syringe pump.
[0085] Immediately before the flow path device 1 was used to perform the particle separation process, as a preliminary preparation, the second liquid L2 was introduced into the flow path section 2 through the second introduction hole 32, and the flow path section 2 was filled with the second liquid L2.
[0086] The white blood cell collection solution discharged from the first discharge hole 33 to the outside of the flow path device 1 was collected in an Eppendorf tube via a resin member having a flow path.
[0087] <3-1-3. How to determine the leukocyte purity in leukocyte recovery fluid> The white blood cell purity in the white blood cell collection fluid was calculated from the white blood cell concentration (also referred to as white blood cell concentration) and the concentration of all blood cells (also referred to as total blood cell concentration) in the white blood cell collection fluid, each measured using a measuring device. More specifically, the white blood cell concentration was divided by the total blood cell concentration, and the result was multiplied by 100 to calculate the white blood cell purity (unit: percentage (%)) in the white blood cell collection fluid. As described above, white blood cell purity is the proportion of white blood cells (e.g., multiple white blood cells) among all blood cells.
[0088] The measuring device used was LUNA FX-7 (trademark), an automated cell counter manufactured by Logos Biosystems.
[0089] The measurement of each of the white blood cell concentration and the whole blood cell concentration using the measuring instrument was executed by sequentially performing a sample preparation step, a sample setting step, and a blood cell concentration measurement step. The sample preparation step is a step in which the following sample (also referred to as a specimen) is prepared. The sample setting step is a step in which the following sample is set in the measuring instrument. The blood cell concentration measurement step is a step in which the concentration of the following blood cells is measured.
[0090] <<A. Sample Preparation Step>> The white blood cell recovery solution collected in an Eppendorf tube was diluted 4-fold with PBS to obtain a diluted white blood cell recovery solution (also referred to as a diluted recovery solution). Here, manually, the measurement using a pipette for each of the white blood cell recovery solution and PBS and the mixing of the white blood cell recovery solution and PBS in the Eppendorf tube were performed. More specifically, by mixing 15 μL of the white blood cell recovery solution and 5 μL of PBS, 20 μL of the diluted recovery solution was obtained. By diluting the white blood cell recovery solution using this PBS, the concentration of blood cells in the diluted recovery solution was set within the range of the concentration of blood cells in which the measuring instrument can perform stable and highly accurate measurement. The range of the concentration of blood cells in which the measuring instrument can perform stable and highly accurate measurement was from 1×10 5 cells per milliliter (cells / mL) to 1×10 7 cells / mL.
[0091] Next, a sample was prepared by mixing 18 μL of the recovered diluted solution and 2 μL of the reagent. As the reagent, a reagent in which acridine orange (AO) and propidium iodide (PI) were mixed was used. More specifically, as the reagent, an acridine orange / propidium iodide stain (AO / PI) manufactured by Logos Biosystems was used. Here, manually, the metering using each pipette of the recovered diluted solution and the reagent, and the mixing of the recovered diluted solution and the reagent in the Eppendorf tube were performed. The mixing of the recovered diluted solution and the reagent in the Eppendorf tube was carried out by shaking the Eppendorf tube at room temperature.
[0092] Here, acridine orange (AO) is a dye (also referred to as a nuclear staining dye) that penetrates the cell membranes of both living and dead cells, stains all nucleated cells, and emits green fluorescence (also referred to as green fluorescence). Propidium iodide (PI) is a dye (also referred to as a dead cell staining dye) that penetrates nucleated cells with damaged cell membranes, stains dead cells, and emits red fluorescence (also referred to as red fluorescence). When multiple cells are stained with both acridine orange (AO) and propidium iodide (PI), living cells with all nuclei among the multiple cells emit green fluorescence, and dead cells with all nuclei among the multiple cells emit red fluorescence. In other words, when multiple white blood cells are stained with both acridine orange (AO) and propidium iodide (PI), all living white blood cells among the multiple white blood cells emit green fluorescence, and all dead white blood cells among the multiple white blood cells emit red fluorescence. In contrast, cells without nuclei (also referred to as anucleated cells) such as human red blood cells, platelets, and fragments do not emit fluorescence by the action of acridine orange (AO) and propidium iodide (PI).
[0093] <<B. Sample Setting Step>> 10 μL of the sample obtained in the sample preparation process was pipetted and injected into a cell counting slide.
[0094] Subsequently, the cell counting slide was inserted into the slide insertion port provided on the side of LUNA FX-7 (trademark), an automatic cell counter manufactured by Logos Biosystems, as the measuring instrument, thereby setting the sample in the measuring instrument.
[0095] <<C. Blood Cell Concentration Measurement Process>> By operating the measuring instrument in which the sample was set in the above sample setting process, the measurement of the white blood cell concentration and the measurement of the total blood cell concentration of the sample were sequentially performed in the measuring instrument under room temperature conditions.
[0096] Regarding the measurement of the white blood cell concentration, when the sample in the cell counting slide was irradiated with excitation light of a predetermined wavelength in the measuring instrument and the white blood cells were emitting fluorescence, a plurality of images capturing regions from 8 to 12 locations were acquired. Then, in the measuring instrument, the average value of the white blood cell concentration obtained by measuring the number of white blood cells by image processing for each of these plurality of images was output as the measured value of the white blood cell concentration (unit: cells / mL). The white blood cell concentration was the concentration of white blood cells including both living and dead white blood cells. Here, in the dark room inside the measuring instrument, when the sample in the cell counting slide was irradiated with excitation light having a wavelength from 450 nanometers (nm) to 490 nm and the white blood cells were emitting green fluorescence having a wavelength from 505 nm to 555 nm, a plurality of images capturing regions from 8 to 12 locations were acquired. Then, in the measuring instrument, the number of white blood cells was measured by image processing for each of these plurality of images. Also, in the dark room inside the measuring instrument, when the sample in the cell counting slide was irradiated with excitation light having a wavelength from 510 nm to 550 nm and the dead white blood cells were emitting red fluorescence having a wavelength from 590 nm to 650 nm, a plurality of images capturing regions from 8 to 12 locations were acquired. Then, in the measuring instrument, the number of dead white blood cells was measured by image processing for each of these plurality of images.
[0097] For the measurement of total blood cell concentration, the instrument captured multiple images of 8 to 12 regions of the sample in the cell count slide under bright field conditions. The instrument then processed the images to count the number of blood cells, and the average of the blood cell concentrations was output as the total blood cell concentration measurement (unit: cells / mL).
[0098] <3-2. First example of experiment> 4, in the first example of the experiment, the angle θ formed between the first direction D1 and the third direction D3 was set to 30 degrees. In other words, the angle θ formed between the first direction D1 along the direction in which the first connection portion Cp1 of the first inlet flow path 23 and the main flow path 21 extend, and the third direction D3 along the direction in which the second connection portion Cp2 of the second inlet flow path 24 extends was set to 30 degrees.
[0099] In the first example of the experiment, when the flow path device 1 was used to perform particle separation processing, the flow rate per unit time 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 was set to 150 μL / min, and the flow rate per unit time 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 was set to 120 μL / min.
[0100] In a first example experiment, the size of the connection surface Cs1 was determined by setting the first distance Le1 to six distances: 0, 0.5, 1, 2, 3, and 5 times 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 and the connection surface Cs1 are connected, and the fourth portion P2 where the third side surface Sw3 of the second connection portion Cp2 and the connection surface Cs1 are connected. In the present disclosure, a configuration in which the first distance Le1 is 0 times the first width W1 means a configuration in which the connection surface Cs1 does not exist and the second side surface Sw2 of the main flow path 21 and the third side surface Sw3 of the second connection portion Cp2 are directly connected. In other words, a flow path device (also referred to as a flow path device according to a reference example) based on the flow path device 1, in which the second side surface Sw2 of the main flow path 21 and the third side surface Sw3 of the second connection portion Cp2 are directly connected without providing a connection surface Cs1, was adopted as a flow path device having a configuration in which the first distance Le1 is 0 times the first width W1.
[0101] In a first example experiment, six different flow path devices were used to perform particle separation and determine the purity of white blood cells in a white blood cell recovery fluid. The six different flow path devices used were a flow path device without a connection surface Cs1, a flow path device in which the first distance Le1 was set to 0.5 times the first width W1, a flow path device in which the first distance Le1 was set to 1 time the first width W1, a flow path device in which the first distance Le1 was set to 2 times the first width W1, a flow path device in which the first distance Le1 was set to 3 times the first width W1, and a flow path device in which the first distance Le1 was set to 5 times the first width W1.
[0102] FIG. 6 is a graph showing the relationship between the size of the connection surface Cs1 and the white blood cell purity in the white blood cell collection fluid, based on the results of the first example experiment. In FIG. 6, the relationship between the size of the connection surface Cs1 and the white blood cell purity in the white blood cell collection fluid is plotted using a plurality of filled circles. In FIG. 6, the horizontal axis represents the ratio of the first distance Le1 to the first width W1, where the width (first width) W1 of the main flow path 21 is used as the reference, as the size of the connection surface Cs1. 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 used as the reference value of 1. The vertical axis represents the relative value of the white blood cell purity in the white blood cell collection fluid (also referred to as the relative value of the white blood cell purity) when the white blood cell purity in the white blood cell collection fluid determined for a flow path device without the connection surface Cs1 is used as the reference value of 100. The relative value of white blood cell purity is the value 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 obtained for a flow path device that does not have connection surface Cs1 (also called the reference value of white blood cell purity), and multiplying the result by 100.
[0103] As shown in Figure 6, in the first example of the experiment, when the first distance Le1 related to the size of the connection surface Cs1 was 1 time the first width W1 and 0.5 times the first width W1, the purity of white blood cells in the white blood cell recovery fluid was improved compared to when the connection surface Cs1 was not present.
[0104] Therefore, according to the first example of the experiment, it was confirmed that if the connection surface Cs1 exists and the first distance Le1 related to the size of the connection surface Cs1 is less than or equal to 1 time 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 improved compared to when the connection surface Cs1 does not exist.
[0105] Furthermore, as shown in Figure 6, in the first example of the experiment, the purity of white blood cells in the white blood cell recovery fluid was improved when the first distance Le1 related to the size of the connection surface Cs1 was 0.5 times the first width W1 compared to when the first distance Le1 related to the size of the connection surface Cs1 was 1 time the first width W1.
[0106] <3-3. Second example of experiment> As shown in FIG. 4, 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, as in the first example of the experiment.
[0107] In the second example of the experiment, when the flow path device 1 was used to perform a particle separation process, the flow rate per unit time 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 was set to 150 μL / min, and the flow rate per unit time 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 was set to 90 μL / min. That is, in the second example of the experiment, the flow rate per unit time 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 was set to 90 μL / min, which was reduced from 120 μL / min in the first example of the experiment.
[0108] In the second example experiment, the size of the connection surface Cs1 was determined by setting the first distance Le1 to four distances: 0, 0.5, 1, and 2 times 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 and the connection surface Cs1 are connected, and the fourth portion P2 where the third side surface Sw3 of the second connection portion Cp2 and the connection surface Cs1 are connected.
[0109] In a second example of the experiment, the particle separation process was performed and the white blood cell purity in the white blood cell recovery fluid was determined using four different flow path devices. The four different flow path devices used were a flow path device without the connection surface Cs1, a flow path device in which the first distance Le1 was set to 0.5 times the first width W1, a flow path device in which the first distance Le1 was set to 1 time the first width W1, and a flow path device in which the first distance Le1 was set to 2 times the first width W1.
[0110] FIG. 7 is a graph showing the relationship between the size of the connection surface Cs1 and the white blood cell purity in the white blood cell collection solution, based on the results of the second example experiment. In FIG. 7, as in FIG. 6, the relationship between the size of the connection surface Cs1 and the white blood cell purity in the white blood cell collection solution is plotted using a plurality of filled circles. In FIG. 7, as in FIG. 6, the horizontal axis shows the ratio of the first distance Le1 to the first width W1, where the width (first width) W1 of the main flow path 21 is used as the reference, as the size of the connection surface Cs1. In other words, the horizontal axis shows the relative value of the first distance Le1 when the first width W1 of the main flow path 21 is used as the reference value of 1. The vertical axis shows the relative value of the white blood cell purity in the white blood cell collection solution (relative value of white blood cell purity) when the white blood cell purity in the white blood cell collection solution determined for a flow path device without the connection surface Cs1 is used as the reference value of 100.
[0111] As shown in Figure 7, in the second example of the experiment, as in the first example of the experiment above, when the first distance Le1 related to the size of the connection surface Cs1 was 1 time the first width W1 and 0.5 times the first width W1, the white blood cell purity in the white blood cell recovery fluid was improved compared to when the connection surface Cs1 was not present.
[0112] Therefore, according to the second example of the experiment, as in the first example of the experiment described above, it was confirmed that if the connection surface Cs1 is present and the first distance Le1 is less than or equal to 1 time 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 improved compared to when the connection surface Cs1 is not present.
[0113] Furthermore, as shown in Figure 7, in the second example of the experiment, as in the first example of the experiment described above, the purity of white blood cells in the white blood cell recovery fluid was improved when the first distance Le1 related to the size of the connection surface Cs1 was 0.5 times the first width W1 compared to when the first distance Le1 related to the size of the connection surface Cs1 was 1 time the first width W1.
[0114] <3-4. Third Experimental Example> As shown in Figure 4, in the third example of the experiment, as in the first and second examples of the experiment above, the angle θ between the first direction D1 and the third direction D3 was set to 30 degrees.
[0115] In the third example of the experiment, when the flow path device 1 was used to perform a particle separation process, the flow rate per unit time of the first liquid L1 introduced from the first inlet hole 31 into the main flow path 21 via the first inlet flow path 23 was set to 180 μL / min, and the flow rate per unit time of the second liquid L2 introduced from the second inlet hole 32 into the main flow path 21 via the second inlet flow path 24 was set to 120 μL / min. That is, in the third example of the experiment, the flow rate per unit time of the first liquid L1 introduced from the first inlet hole 31 into the main flow path 21 via the first inlet flow path 23 was set to 180 μL / min, which was increased from 150 μL / min in the first example of the experiment.
[0116] In the third example of the experiment, as in the second example of the experiment, the size of the connection surface Cs1 was set to four distances: 0, 0.5, 1, and 2 times 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 and the connection surface Cs1 are connected, and the fourth portion P2 where the third side surface Sw3 of the second connection portion Cp2 and the connection surface Cs1 are connected.
[0117] In a second example of the experiment, the particle separation process was performed and the white blood cell purity in the white blood cell recovery fluid was determined using four different flow path devices. The four different flow path devices used were a flow path device without the connection surface Cs1, a flow path device in which the first distance Le1 was set to 0.5 times the first width W1, a flow path device in which the first distance Le1 was set to 1 time the first width W1, and a flow path device in which the first distance Le1 was set to 2 times the first width W1.
[0118] FIG. 8 is a graph showing the relationship between the size of the connection surface Cs1 and the white blood cell purity in the white blood cell collection fluid, based on the results of the third example experiment. In FIG. 8, as in FIGS. 6 and 7, the relationship between the size of the connection surface Cs1 and the white blood cell purity in the white blood cell collection fluid is plotted using a plurality of filled circles. In FIG. 8, as in FIGS. 6 and 7, the horizontal axis shows the ratio of the first distance Le1 to the first width W1, where the width (first width) W1 of the main flow path 21 is used as the reference, as the size of the connection surface Cs1. In other words, the horizontal axis shows the relative value of the first distance Le1 when the width (first width) W1 of the main flow path 21 is used as the reference value of 1. The vertical axis shows the relative value of the white blood cell purity in the white blood cell collection fluid (relative value of white blood cell purity) when the white blood cell purity in the white blood cell collection fluid determined for a flow path device without the connection surface Cs1 is used as the reference value of 100.
[0119] As shown in Figure 8, in the third example of the experiment, as in the first and second examples of the experiment above, when the first distance Le1 related to the size of the connection surface Cs1 was 1 time the first width W1 and 0.5 times the first width W1, respectively, the white blood cell purity in the white blood cell recovery fluid was improved compared to when the connection surface Cs1 was not present.
[0120] Therefore, according to the third example of the experiment, as in the first and second examples of the experiment described above, it was confirmed that if the connection surface Cs1 is present and the first distance Le1 is less than or equal to 1 time 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 improved compared to when the connection surface Cs1 is not present.
[0121] Furthermore, as shown in Figure 8, in the third example of the experiment, as in the first and second examples of the experiment described above, the purity of white blood cells in the white blood cell recovery fluid was improved when the first distance Le1 related to the size of the connection surface Cs1 was 0.5 times the first width W1 compared to when the first distance Le1 related to the size of the connection surface Cs1 was 1 time the first width W1.
[0122] <3-5. Results of Experiments 1 to 3> 6 to 8 , in all of the first to third examples of the above experiments, when the first distance Le1 related to the size of the connection surface Cs1 was 1 time the first width W1 and 0.5 times the first width W1, the white blood cell purity in the white blood cell collection solution was improved compared to when the connection surface Cs1 was not present. In other words, when the flow path device 1 was used to perform a particle separation process, even if the flow rate per unit time of the first liquid L1 introduced from the first inlet hole 31 into the main flow path 21 via the first inlet flow path 23 and the flow rate per unit time of the second liquid L2 introduced from the second inlet hole 32 into the main flow path 21 via the second inlet flow path 24 were slightly increased or decreased, the white blood cell purity in the white blood cell collection solution was improved compared to when the connection surface Cs1 was not present when the first distance Le1 related to the size of the connection surface Cs1 was 1 time the first width W1 and 0.5 times the first width W1.
[0123] Therefore, it was confirmed that when the connection surface Cs1 is present and the first distance Le1 is equal to or less than the width (first width) W1 of the main channel 21, the purity of white blood cells in the white blood cell collection fluid can be improved compared to when the connection surface Cs1 is not present. In other words, it was confirmed that when the connection surface Cs1 is present and the first distance Le1 is equal to or less than the width (first width) W1 of the main channel 21, the proportion of specific types of particles (e.g., multiple specific types of particles) among multiple particles contained in the collection fluid can be improved. As described above, the first distance Le1 is the distance between the third portion P1 where the second side surface Sw2 of the main channel 21 and the connection surface Cs1 are connected, and the fourth portion P2 where the third side surface Sw3 of the second connection portion Cp2 and the connection surface Cs1 are connected.
[0124] <3-6. Fourth Experimental Example> As shown in FIG. 4, 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, as in the first example of the experiment.
[0125] In the fourth example of the experiment, as in the first example of the experiment above, when the flow path device 1 was used to perform particle separation processing, the flow rate per unit time 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 was set to 150 μL / min, and the flow rate per unit time 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 was set to 120 μL / min.
[0126] In a fourth example experiment, the size of the connection surface Cs1 was set to six distances, namely, 0, 0.1, 0.2, 0.3, 0.4, and 0.5 times 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 and the connection surface Cs1 are connected, and the fourth portion P2 where the third side surface Sw3 of the second connection portion Cp2 and the connection surface Cs1 are connected.
[0127] In a fourth example experiment, six different flow path devices were used to perform particle separation and determine the purity of white blood cells in a white blood cell recovery fluid. The six different flow path devices used were: a flow path device without a connection surface Cs1, a flow path device in which the first distance Le1 was set to 0.1 times the first width W1, a flow path device in which the first distance Le1 was set to 0.2 times the first width W1, a flow path device in which the first distance Le1 was set to 0.3 times the first width W1, a flow path device in which the first distance Le1 was set to 0.4 times the first width W1, and a flow path device in which the first distance Le1 was set to 0.5 times the first width W1.
[0128] FIG. 9 is a graph showing the relationship between the size of the connection surface Cs1 and the white blood cell purity in the white blood cell collection solution, based on the results of the fourth example experiment. In FIG. 9, as in FIGS. 6 to 8, the relationship between the size of the connection surface Cs1 and the white blood cell purity in the white blood cell collection solution is plotted using a plurality of filled circles. In FIG. 9, as in FIGS. 6 to 8, the horizontal axis shows the ratio of the first distance Le1 to the first width W1, where the width (first width) W1 of the main flow path 21 is used as the reference, as the size of the connection surface Cs1. In other words, the horizontal axis shows the relative value of the first distance Le1 when the width (first width) W1 of the main flow path 21 is used as the reference value of 1. The vertical axis shows the relative value of the white blood cell purity in the white blood cell collection solution (relative value of white blood cell purity) when the white blood cell purity in the white blood cell collection solution determined for a flow path device without the connection surface Cs1 is used as the reference value of 100.
[0129] As shown in Figure 9, in the fourth example of the experiment, when the first distance Le1 related to the size of the connection surface Cs1 was 0.1 times, 0.2 times, 0.3 times, 0.4 times, and 0.5 times the first width W1, the white blood cell purity in the white blood cell recovery fluid was stably improved compared to when the connection surface Cs1 was not present.
[0130] Therefore, according to the fourth example of the experiment, it was confirmed that if the connection surface Cs1 exists and the first distance Le1 is 0.1 times or more and 0.5 times or less 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 when the connection surface Cs1 does not exist.
[0131] 9 , in the fourth example of the experiment, the white blood cell purity in the white blood cell collection solution was highest when the first distance Le1 related to the size of the connection surface Cs1 was 0.4 times the first width W1, which was between 0.1 and 0.5 times the first width W1. From another perspective, the white blood cell purity in the white blood cell collection solution tended to improve as the first distance Le1 related to the size of the connection surface Cs1 increased from 0.1 to 0.4 times the first width W1, and the white blood cell purity in the white blood cell collection solution tended to decrease as the first distance Le1 related to the size of the connection surface Cs1 increased from 0.4 to 0.5 times the first width W1. In the fourth example of the experiment, the white blood cell purity in the white blood cell collection solution was at its maximum value of approximately 88% when the first distance Le1 related to the size of the connection surface Cs1 was 0.4 times the first width W1.
[0132] <3-7. Fifth Experimental Example> Fig. 10 is a plan view schematically showing a part of the flow channel section 2 of the flow channel device 1 used in the fifth example of the experiment. More specifically, Fig. 10 is a plan view schematically showing a region of the flow channel section 2 of the flow channel device 1 used in the fifth example of the experiment, the region corresponding to region IV surrounded by the rectangular dashed line in Fig. 3. In Fig. 10, as in Figs. 3 and 4, the outer edge of the flow channel section 2 is drawn with a solid line.
[0133] 10 , in the fifth example 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, which is along the direction in which the first connection portion Cp1 of the first inlet flow path 23 and the main flow path 21 extend, and the third direction D3, which is along the direction in which the second connection portion Cp2 of the second inlet flow path 24 extends, was set to 15 degrees. That is, in the fifth example experiment, the angle θ was set to 15 degrees, which was reduced from 30 degrees in the fourth example experiment.
[0134] In the fifth example of the experiment, as in the fourth example of the experiment described above, when the flow path device 1 was used to perform particle separation processing, the flow rate per unit time of the first liquid L1 introduced from the first introduction hole 31 through the first introduction flow path 23 into the main flow path 21 was set to 150 μL / min, and the flow rate per unit time of the second liquid L2 introduced from the second introduction hole 32 through the second introduction flow path 24 into the main flow path 21 was set to 120 μL / min.
[0135] In the fifth example of the experiment, as in the fourth example of the experiment, the size of the connection surface Cs1 was set to six distances, namely, 0, 0.1, 0.2, 0.3, 0.4, and 0.5 times 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 and the connection surface Cs1 are connected, and the fourth portion P2 where the third side surface Sw3 of the second connection portion Cp2 and the connection surface Cs1 are connected.
[0136] In the fifth example of the experiment, as in the fourth example of the experiment, six different flow path devices were used to perform particle separation and determine the purity of white blood cells in the white blood cell recovery fluid. The six different flow path devices used were: a flow path device without the connection surface Cs1, a flow path device in which the first distance Le1 was set to 0.1 times the first width W1, a flow path device in which the first distance Le1 was set to 0.2 times the first width W1, a flow path device in which the first distance Le1 was set to 0.3 times the first width W1, a flow path device in which the first distance Le1 was set to 0.4 times the first width W1, and a flow path device in which the first distance Le1 was set to 0.5 times the first width W1.
[0137] FIG. 11 is a graph showing the relationship between the size of the connection surface Cs1 and the white blood cell purity in the white blood cell collection solution, based on the results of the fifth example experiment. In FIG. 11, as in FIG. 9, the relationship between the size of the connection surface Cs1 and the white blood cell purity in the white blood cell collection solution is plotted using a plurality of filled circles. In FIG. 11, as in FIG. 9, the horizontal axis shows the ratio of the first distance Le1 to the first width W1, where the width (first width) W1 of the main flow path 21 is used as the reference, as the size of the connection surface Cs1. In other words, the horizontal axis shows the relative value of the first distance Le1 when the width (first width) W1 of the main flow path 21 is used as the reference value of 1. The vertical axis shows the relative value of the white blood cell purity in the white blood cell collection solution (relative value of white blood cell purity) when the white blood cell purity in the white blood cell collection solution determined for a flow path device without the connection surface Cs1 is used as the reference value of 100.
[0138] As shown in Figure 11, in the fifth example of the experiment, as in the fourth example of the experiment described above, when the first distance Le1 related to the size of the connection surface Cs1 was 0.1 times, 0.2 times, 0.3 times, 0.4 times, and 0.5 times the first width W1, the white blood cell purity in the white blood cell recovery fluid was stably improved compared to when the connection surface Cs1 was not present.
[0139] Therefore, according to the fifth example of the experiment, as in the fourth example of the experiment described above, it was confirmed that if the connection surface Cs1 is present and the first distance Le1 is 0.1 times or more and 0.5 times or less the width (first width) W1 of the main flow path 21, the white blood cell purity in the white blood cell recovery fluid can be stably improved compared to when the connection surface Cs1 is not present.
[0140] 11 , in the fifth example of the experiment, as in the fourth example of the experiment described above, the white blood cell purity in the white blood cell collection solution was highest when the first distance Le1 related to the size of the connection surface Cs1 was 0.4 times the first width W1, which was between 0.1 and 0.5 times the first width W1. From another perspective, the white blood cell purity in the white blood cell collection solution tended to improve as the first distance Le1 related to the size of the connection surface Cs1 increased from 0.1 to 0.4 times the first width W1, while the white blood cell purity tended to decrease as the first distance Le1 related to the size of the connection surface Cs1 increased from 0.4 to 0.5 times. In the fifth example of the experiment, the white blood cell purity in the white blood cell collection solution was at its maximum value of approximately 69% when the first distance Le1 related to the size of the connection surface Cs1 was 0.4 times the first width W1.
[0141] <3-8. Sixth Experimental Example> Fig. 12 is a plan view schematically showing a part of the flow channel section 2 of the flow channel device 1 used in the sixth example of the experiment. More specifically, Fig. 12 is a plan view schematically showing a region of the flow channel section 2 of the flow channel device 1 used in the sixth example of the experiment, the region corresponding to region IV surrounded by the rectangular dashed line in Fig. 3. In Fig. 12, the outer edge of the flow channel section 2 is drawn with a solid line, as in Figs. 3, 4, and 10.
[0142] 12, in the sixth example 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, which is along the direction in which the first connection portion Cp1 of the first inlet flow path 23 and the main flow path 21 extend, and the third direction D3, which is along the direction in which the second connection portion Cp2 of the second inlet flow path 24 extends, was set to 45 degrees. That is, in the sixth example experiment, the angle θ was set to 45 degrees, which is increased from 30 degrees in the fourth example experiment.
[0143] In the sixth example of the experiment, as in the fourth and fifth examples of the experiment described above, when the flow path device 1 was used to perform particle separation processing, the flow rate per unit time 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 was set to 150 μL / min, and the flow rate per unit time 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 was set to 120 μL / min.
[0144] In the sixth experimental example, as in the fourth and fifth experimental examples described above, the size of the connection surface Cs1 was set to six distances, namely, 0, 0.1, 0.2, 0.3, 0.4, and 0.5 times 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 and the connection surface Cs1 are connected, and the fourth portion P2 where the third side surface Sw3 of the second connection portion Cp2 and the connection surface Cs1 are connected.
[0145] In the sixth example of the experiment, similarly to the fourth and fifth examples of the experiment, six conditions of flow path devices were used to perform a particle separation process and determine the white blood cell purity in the white blood cell recovery fluid. Here, the six conditions of the flow path devices used were a flow path device without the connection surface Cs1, a flow path device in which the first distance Le1 was set to 0.1 times the first width W1, a flow path device in which the first distance Le1 was set to 0.2 times the first width W1, a flow path device in which the first distance Le1 was set to 0.3 times the first width W1, a flow path device in which the first distance Le1 was set to 0.4 times the first width W1, and a flow path device in which the first distance Le1 was set to 0.5 times the first width W1.
[0146] FIG. 13 is a graph showing the relationship between the size of the connection surface Cs1 and the white blood cell purity in the white blood cell collection solution, based on the results of the sixth example experiment. In FIG. 13, as in FIGS. 9 and 11, the relationship between the size of the connection surface Cs1 and the white blood cell purity in the white blood cell collection solution is plotted using a plurality of filled circles. In FIG. 13, as in FIGS. 9 and 11, the horizontal axis shows the ratio of the first distance Le1 to the first width W1, where the width (first width) W1 of the main flow path 21 is used as the reference, as the size of the connection surface Cs1. In other words, the horizontal axis shows the relative value of the first distance Le1 when the width (first width) W1 of the main flow path 21 is used as the reference value of 1. The vertical axis shows the relative value of the white blood cell purity in the white blood cell collection solution (relative value of white blood cell purity) when the white blood cell purity in the white blood cell collection solution determined for a flow path device without the connection surface Cs1 is used as the reference value of 100.
[0147] As shown in Figure 13, in the sixth example of the experiment, as in the fourth and fifth examples of the experiment described above, when the first distance Le1 related to the size of the connection surface Cs1 was 0.1 times, 0.2 times, 0.3 times, 0.4 times, and 0.5 times the first width W1, the white blood cell purity in the white blood cell recovery fluid was stably improved compared to when the connection surface Cs1 was not present.
[0148] Therefore, according to the sixth example of the experiment, as in the fourth and fifth examples of the experiment described above, it was confirmed that if the connection surface Cs1 is present and the first distance Le1 is 0.1 times or more and 0.5 times or less the width (first width) W1 of the main flow path 21, the white blood cell purity in the white blood cell recovery fluid can be stably improved compared to when the connection surface Cs1 is not present.
[0149] 13 , in the sixth example of the experiment, similar to the fourth and fifth examples of the experiment, the white blood cell purity in the white blood cell collection solution was highest when the first distance Le1 related to the size of the connection surface Cs1 was 0.4 times the first width W1, which was between 0.1 and 0.5 times the first width W1. From another perspective, the white blood cell purity in the white blood cell collection solution tended to improve as the first distance Le1 related to the size of the connection surface Cs1 increased from 0.1 to 0.4 times the first width W1, whereas the white blood cell purity in the white blood cell collection solution tended to decrease as the first distance Le1 related to the size of the connection surface Cs1 increased from 0.4 to 0.5 times. In the sixth example of the experiment, the white blood cell purity in the white blood cell collection solution was at its maximum value of approximately 75% when the first distance Le1 related to the size of the connection surface Cs1 was 0.4 times the first width W1.
[0150] <3-9. Results of Experiments 4 to 6> 9, 11, and 13, in all of the fourth to sixth experimental examples described above, when the first distance Le1 related to the size of the connection surface Cs1 was 0.1, 0.2, 0.3, 0.4, or 0.5 times the first width W1, the white blood cell purity in the white blood cell collection solution was stably improved compared to when the connection surface Cs1 was not present. In other words, even when the angle θ formed between the first direction D1 and the third direction D3 was increased or decreased between 15 degrees and 45 degrees, when the first distance Le1 related to the size of the connection surface Cs1 was 0.1, 0.2, 0.3, 0.4, or 0.5 times the first width W1, the white blood cell purity in the white blood cell collection solution was stably improved compared to when the connection surface Cs1 was not present.
[0151] Therefore, it was confirmed that when the connection surface Cs1 is present and the first distance Le1 is 0.1 to 0.5 times the width (first width) W1 of the main flow channel 21, the purity of white blood cells in the white blood cell collection fluid can be stably improved compared to when the connection surface Cs1 is not present. In other words, it was confirmed that when the connection surface Cs1 is present and the first distance Le1 is 0.1 to 0.5 times the width (first width) W1 of the main flow channel 21, the proportion of specific types of particles (e.g., multiple specific types of particles) among the multiple particles contained in the collection fluid can be improved. 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 channel 21 and the connection surface Cs1 are connected, and the fourth portion P2 where the third side surface Sw3 of the second connection portion Cp2 and the connection surface Cs1 are connected.
[0152] From another perspective, it was confirmed that when the connection surface Cs1 is present and the angle θ formed between the first direction D1 along the extension direction of the first connection portion Cp1 of the first introduction flow channel 23 and the main flow channel 21 and the third direction D3 along the extension direction of the second connection portion Cp2 of the second introduction flow channel 24 is 15 degrees or more and 45 degrees or less, the purity of white blood cells in the white blood cell collection solution can be stably improved compared to when the connection surface Cs1 is not present. In other words, it was confirmed that when the connection surface Cs1 is present and the angle θ formed between the first direction D1 along the extension direction of the first connection portion Cp1 of the first introduction flow channel 23 and the main flow channel 21 and the third direction D3 along the extension direction of the second connection portion Cp2 of the second introduction flow channel 24 is 15 degrees or more and 45 degrees or less, the proportion of a specific type of particle (e.g., multiple specific type of particle) among multiple particles contained in the collection solution can be stably improved.
[0153] Furthermore, as described above, the maximum white blood cell purity in the white blood cell collection solution obtained in the fourth example of the above experiment, in which the angle θ was 30 degrees, was approximately 88%. In contrast, the maximum white blood cell purity in the white blood cell collection solution obtained in the fifth example of the above experiment, in which the angle θ was 15 degrees, was approximately 69%, and the maximum white blood cell purity in the white blood cell collection solution obtained in the sixth example of the above experiment, in which the angle θ was 45 degrees, was approximately 75%. Therefore, it was confirmed that when the connection surface Cs1 is present and the angle θ formed by the first direction D1 along the extension directions of the first connection portion Cp1 of the first introduction flow channel 23 and the main flow channel 21 and the third direction D3 along the extension direction of the second connection portion Cp2 of the second introduction flow channel 24 is 30 degrees, the white blood cell purity in the white blood cell collection solution can be further improved compared to when the connection surface Cs1 is not present. In other words, it was confirmed that if a connection surface Cs1 exists and the angle θ formed by the first direction D1 along the direction in which the first connection portion Cp1 of the first introduction flow path 23 and the main flow path 21 extend, and the third direction D3 along the direction in which the second connection portion Cp2 of the second introduction flow path 24 extends, is 30 degrees, the proportion of particles of a specific species (e.g., multiple specific species of particles) among the multiple particles contained in the recovery liquid can be further improved.
[0154] <4. Summary of one embodiment> In the flow channel device 1 according to one embodiment, the main channel 21 extends along a first direction D1 and has a first upstream portion 21u and a first downstream portion 21d. Each of the branch channels 22, which are narrower than the main channel 21, is connected to the main channel 21 by opening at a first side surface Sw1 between the first downstream portion 21d and the first upstream portion 21u. A first connection portion Cp1 of the first inlet channel 23, which is connected to the first upstream portion 21u, extends along the first direction D1. A second connection portion Cp2 of the second inlet channel 24, which is 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 channel section 2 has a connection surface Cs1 that connects the second side surface Sw2 of the main channel 21 to a third side surface Sw3 of the second connection portion Cp2, which is located on the first connection portion Cp1 side. The distance (first distance) Le1 between the third portion P1 where the second side surface Sw2 of the main flow path 21 is connected to the connection surface Cs1 and the fourth portion P2 where the third side surface Sw3 of the second connection portion Cp2 is connected to the connection surface Cs1 is set to be equal to or less than 1 time the width (first width) W1 of the main flow path 21.
[0155] According to this configuration, in the flow channel device 1, when the first liquid L1 is introduced from the first inlet flow channel 23 into the first upstream portion 21u of the main flow channel 21 and the second liquid L2 is introduced from the second inlet flow channel 24 into the first upstream portion 21u of the main flow channel 21 and a particle separation process is performed, for example, in the main flow channel 21, turbulence in the introduced flow is reduced and the force with which the second liquid L2 presses the first liquid L1 toward the plurality of branch flow channels 22 can be increased. As a result, the proportion of the second particles Pa12 (e.g., one or more second particles Pa12) that flow to the first downstream portion 21d among the plurality of second particles Pa12 in the first liquid L1 can be reduced. Therefore, for example, the number of second particles Pa12 mixed into the recovery liquid recovered from the first downstream portion 21d via the first discharge hole 33 or the like can be reduced. Therefore, the proportion of first particles Pa11 (e.g., a plurality of first particles Pa11) as a specific type of particle among the plurality of particles contained in the recovery liquid can be increased. Here, for example, if blood or a liquid in which blood is 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 white blood cell purity, which is the proportion of white blood cells (e.g., multiple white blood cells) among all blood cells in the white blood cell recovery liquid as the recovery liquid, can be improved.
[0156] <5. Other embodiments> The present disclosure is not limited to the above-described embodiment, and various modifications and improvements can be made without departing from the spirit and scope of the present disclosure.
[0157] In the above embodiment, the connection surface Cs1 is, for example, a flat surface, but is not limited thereto. For example, the connection surface Cs1 may be a slightly curved surface or a surface having slight irregularities. Here, for example, the portion of the connection surface Cs1 that connects to the second side surface Sw2 of the main flow path 21 may form a sharp corner between the second side surface Sw2 and the second side surface Sw2, or may form a blunt corner between the second side surface Sw2 and the second side surface Sw2. For example, the portion of the connection surface Cs1 that connects to the third side surface Sw3 of the second connection portion Cp2 may form a sharp corner between the third side surface Sw3 and the third side surface Sw3, or may form a blunt corner between the third side surface Sw3 and the third side surface Sw3.
[0158] In the above embodiment, when the extension portion Ac1 is viewed in a plane, the shape of the extension portion Ac1 is an isosceles triangle along an isosceles triangle whose base is the side along the connection surface Cs1, but this is not limited to this. For example, when the extension portion Ac1 is viewed in a plane, the shape of the extension portion Ac1 may be a right triangle along a right triangle whose adjacent side is the side along the connection surface Cs1, or may be a shape along another triangle.
[0159] In other words, in the above embodiment, 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 not necessarily the same or substantially the same. For example, the angle α and the angle β may be different.
[0160] 14 and 15 are plan views each schematically showing a portion of the flow path section 2. More specifically, FIG. 14 is a plan view schematically showing a first alternative configuration example for a region corresponding to region IV surrounded by a dashed-dotted rectangular line in FIG. 3. FIG. 15 is a plan view schematically showing a second alternative configuration example for a region corresponding to region IV surrounded by a dashed-dotted rectangular line in FIG. 3. In each of FIGS. 14 and 15, the outer edge of the flow path section 2 is depicted with a solid line. In each of FIGS. 14 and 15, when a particle separation process is performed using the flow path device 1, an example of the direction in which the first liquid L1 flows is schematically shown by a thick, double-dashed arrow, and an example of the direction in which the second liquid L2 flows is also schematically shown by a double-dashed arrow at the most upstream portion of the portion where the flow of the first liquid L1 and the flow of the second liquid L2 join.
[0161] For example, as shown in FIG. 14 , angle β may be greater than angle α. For example, angle β may be an obtuse angle, and angle α may be an acute angle. In this case, when a particle separation process is performed using the flow path device 1, for example, the first liquid L1, which is part of the first liquid L1, flows along the second side surface Sw2 and then flows along the connection surface Cs1, may be pushed toward the first side surface Sw1 by the second liquid L2, which is part of the second liquid L2, flowing along the third side surface Sw3. In this configuration, at a location where the liquids converge, for example, the direction in which the second liquid L2, which is part of the flow of the second liquid L2, flows along the third side surface Sw3, pushes the first liquid L1, which has flowed along the connection surface Cs1, toward the first side surface Sw1 may approach a perpendicular direction to the flow direction of the first liquid L1, which has flowed along the connection surface Cs1. This can increase the force with which the second liquid L2 presses the first liquid L1 toward the branch flow paths 22, while reducing turbulence in the introduced flow in the main flow path 21. As a result, the proportion of the second particles Pa12 (e.g., one or more second particles Pa12) among the second particles Pa12 in the first liquid L1 that flow to the first downstream portion 21d can be reduced. Therefore, for example, the number of second particles Pa12 mixed into the recovery liquid recovered from the first downstream portion 21d via the first discharge hole 33 or the like can be reduced. Therefore, the proportion of first particles Pa11 (e.g., multiple first particles Pa11) as specific types of particles among the multiple particles contained in the recovery liquid can be increased. Here, for example, when blood or a liquid obtained by diluting blood with physiological saline is used as the first liquid L1 and physiological saline is used as an example of the second liquid L2, the white blood cell purity, which is the proportion of white blood cells (e.g., multiple white blood cells) among all blood cells in the white blood cell recovery liquid that is the recovery liquid, can be improved. Here, for example, when the angle α approaches 90 degrees, the direction in which the second liquid L2 flowing along the third side surface Sw3 as part of the flow of the second liquid L2 pushes the first liquid L1 flowing along the connection surface Cs1 toward the first side surface Sw1 can become closer to being perpendicular to the direction in which the first liquid L1 flowing along the connection surface Cs1 flows.
[0162] For example, as shown in FIG. 15 , angle α may be greater than angle β. For example, angle α may be an obtuse angle, and angle β may be an acute angle. In this case, when a particle separation process is performed using the flow path device 1, for example, the first liquid L1, which is part of the first liquid L1, flowing along the second side surface Sw2, may be pushed toward the first side surface Sw1 by the second liquid L2, which flows along the third side surface Sw3, which is part of the second liquid L2, and then flows along the connection surface Cs1. In this configuration, at a location where the liquids converge, for example, the direction in which the second liquid L2, which flows along the third side surface Sw3 as part of the flow of the second liquid L2 and then flows along the connection surface Cs1, pushes the first liquid L1, which has flowed along the second side surface Sw2, toward the first side surface Sw1 may be nearly perpendicular to the direction in which the first liquid L1, which has flowed along the second side surface Sw2, flows. This can increase the force with which the second liquid L2 presses the first liquid L1 toward the branch flow paths 22, while reducing turbulence in the introduced flow in the main flow path 21. As a result, the proportion of the second particles Pa12 (e.g., one or more second particles Pa12) among the second particles Pa12 in the first liquid L1 that flow to the first downstream portion 21d can be reduced. Therefore, for example, the number of second particles Pa12 mixed into the recovery liquid recovered from the first downstream portion 21d via the first discharge hole 33 or the like can be reduced. Therefore, the proportion of first particles Pa11 (e.g., multiple first particles Pa11) as specific types of particles among the multiple particles contained in the recovery liquid can be increased. Here, for example, when blood or a liquid obtained by diluting blood with physiological saline is used as the first liquid L1 and physiological saline is used as an example of the second liquid L2, the white blood cell purity, which is the proportion of white blood cells (e.g., multiple white blood cells) among all blood cells in the white blood cell recovery liquid that is the recovery liquid, can be improved. Here, for example, when the angle β approaches 90 degrees, the direction in which the second liquid L2, which has flowed along the third side surface Sw3 as part of the flow of the second liquid L2 and then flowed along the connection surface Cs1, pushes the first liquid L1, which has flowed along the second side surface Sw2, toward the first side surface Sw1, can become closer to being perpendicular to the direction in which the first liquid L1, which has flowed along the second side surface Sw2, flows.
[0163] The inventors have confirmed that the occurrence of turbulence in the introduced flow in the main flow path 21 is reduced to the same extent in each of the following cases: when the angle θ is fixed at 30 degrees and the angles α and β are each set to 105 degrees; when the angle α is set to 60 degrees and the angle β is set to 150 degrees; and when the angle α is set to 150 degrees and the angle β is set to 60 degrees. Therefore, for example, when the angle θ is 30 degrees and the sum of the angles α and β is 210 degrees, each of the angles α and β may be equal to or greater than 60 degrees and equal to or less than 150 degrees.
[0164] In the above embodiment, for example, the first inlet hole 31, the second inlet hole 32, the first discharge hole 33, the second discharge hole 34, and the third discharge hole 35 each open on the lower surface 1b, but this is not limited to this. For example, at least one of the first inlet hole 31, the second inlet hole 32, the first discharge hole 33, the second discharge hole 34, and the third discharge hole 35 may not open on the lower surface 1b but may open on the upper surface 1a. In other words, for example, the first inlet hole 31, the second inlet hole 32, the first discharge hole 33, the second discharge hole 34, and the third discharge hole 35 each may open on either the upper surface 1a or the lower surface 1b.
[0165] In the above embodiment, the flow path device 1 has, for example, one set of the first inlet hole 31 and the first inlet flow channel 23 as an inlet for the first liquid L1. However, this is not limited thereto. For example, the flow path device 1 may have two or more sets of the first inlet hole 31 and the first inlet flow channel 23 as an inlet for the first liquid L1. Furthermore, in the above embodiment, the flow path device 1 has, for example, one set of the second inlet hole 32 and the second inlet flow channel 24 as an inlet for the second liquid L2. However, this is not limited thereto. For example, the flow path device 1 may have two or more sets of the second inlet hole 32 and the second inlet flow channel 24 as an inlet for the second liquid L2. Here, each of the inlet for the first liquid L1 and the inlet for the second liquid L2 may be connected to the main flow channel 21 in an appropriate relationship within a range that can improve the proportion of first particles Pa11 (e.g., multiple first particles Pa11) as specific species of particles among multiple particles contained in a recovery liquid when the flow path device 1 is used to perform a particle separation process.
[0166] In the above embodiment, for example, when the second liquid L2 is introduced into the flow path device 1 from the second inlet 2i, a liquid suction unit for sucking the second liquid L2 from the main flow path 21 via the plurality of branch flow paths 22 and the second discharge hole 34 may be connected to the second discharge hole 34. In this case, for example, a tubular member for connecting the liquid suction unit to the second discharge hole 34 may be connected to the flow path device 1 from the outside of the flow path device 1. Here, connecting the liquid suction unit to the second discharge hole 34 by a tubular member means that a fluid can flow between the liquid suction unit 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 is positioned so as to surround the second discharge hole 34 around the Z axis in a plan view and protrudes in the −Z direction.
[0167] In the above embodiment, for example, the flow path section 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 as the first direction D1, similar to the main flow path 21. For example, the main flow path 21 may include the first discharge flow path 25 as the fifth flow path. Here, the first discharge hole 33 may be directly connected to the first downstream portion 21d of the main flow path 21. Furthermore, for example, the recovery liquid may be recovered from the first downstream portion 21d via various routes.
[0168] In the above embodiment, 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 or may not be constant from upstream to downstream. For example, the first inlet flow path 23 may have a portion whose width decreases continuously or in steps 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 have a portion whose width decreases continuously or in steps as it approaches the main flow path 21. For example, the second inlet flow path 24 may have a portion whose width decreases continuously or in steps 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 have a portion whose width decreases continuously or in steps as it approaches the main flow path 21. For example, the first outlet flow path 25 may have a portion whose width increases continuously or in steps as it approaches the main flow path 21 from the main flow path 21 to the first outlet hole 33. In other words, for example, the first discharge flow path 25 may have a portion whose width increases continuously or in stages as it becomes farther away from the main flow path 21. For example, the third discharge flow path 27 may have a portion whose width increases continuously or in stages as it becomes closer to the third discharge hole 35 from the main flow path 21. In other words, for example, the third discharge flow path 27 may have a portion whose width increases continuously or in stages as it becomes farther away from the main flow path 21.
[0169] In the above embodiment, for example, the first liquid L1 may be a liquid containing multiple types of particles Pa1 other than blood. In this case, for example, various liquids that are combined with the first liquid L1 may be used as the second liquid L2. For example, water may be used as the various liquids.
[0170] Although the flow path device has been described in detail above, the above description is illustrative in all respects and the disclosure is not limited thereto. Furthermore, the various examples described above may be combined unless they are mutually inconsistent. Furthermore, countless examples not illustrated may be envisioned without departing from the scope of the disclosure.
[0171] This disclosure includes the following:
[0172] In one embodiment, (1) a flow path device includes a flow path portion that is not open on an outer surface, and a plurality of holes that are in communication with the flow path portion and that 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 a side of the first direction and a first upstream portion located on an opposite side to the first downstream portion, and the first flow path is perpendicular to the first direction. a third flow path having a first side surface in a second direction and a second side surface in a fourth direction opposite to the second direction, each of the plurality of second flow paths being connected to the first flow path and narrower than the first flow path, each of the plurality of second flow paths being open at the first side surface between the first upstream portion and the first downstream portion of the first flow path, each of the plurality of second flow paths including a second downstream portion on the opposite side to the first flow path, and the third flow path including a first connecting portion connected to the first upstream portion, the first connecting portion being connected to the first upstream portion the fourth flow path includes a second connection portion connected to the first upstream portion along the first direction, the second connection portion having an opening at the second side surface, the second connection portion extending linearly toward the first upstream portion along a third direction that forms an acute angle with the first direction, the second connection portion having a third side surface located on the side of the first connection portion, and the plurality of holes includes a first hole, a second hole, a third hole, and a fourth hole, and the first hole is connected to the third flow path 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 connection surface connecting the second side surface and the third side surface, and a distance between a third portion where the second side surface and the connection surface are connected and a fourth portion where the third side surface and the connection surface are connected is equal to or less than one time the width of the first flow path in the second direction.
[0173] (2) In the flow path device of (1) above, the angle formed between the first direction and the third direction may be equal to or greater than 15 degrees and equal to or less than 45 degrees.
[0174] (3) In the flow path device of (2) above, the angle between the first direction and the third direction may be 30 degrees.
[0175] (4) In the flow path device of (2) or (3) above, the distance between the third portion and the fourth portion may be 0.1 times or more and 0.5 times or less the width of the first flow path in the second direction. [Explanation of symbols]
[0176] 1. Flow path device 2 Flow path section 21 Main channel 21d 1st downstream section 21u 1st upstream section 22 Branch channel 22d 2nd downstream section 23 First inlet channel 24 Second inlet channel 3 holes 31 1st introduction hole 32 2nd introduction hole 33 1st discharge hole 34 2nd discharge hole 35 3rd discharge hole Cp1 First connection part Cp2 Second connection part Cs1 connection surface D1 1st direction D2 2nd direction D3 Third direction D4 4th direction L1 1st liquid L2 2nd liquid Le1 First distance P1 3rd part P2 Part 4 Pa1 Multiple particle types Pa11 1st particle Pa12 2nd particle Sw1 1st side Sw2 Side 2 Sw3 3rd side W1 No. 1
Claims
1. 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 a direction opposite to the first portion, the first flow path has a first side surface and a second side surface facing the first side surface in a second direction perpendicular to the first direction, each of the plurality of second flow paths is connected to the first flow path by opening at the first side surface between the first portion and the second portion, and is narrower than the first flow path; the third flow path includes a first connection portion connected to the second portion; The first connection portion extends along the first direction, the fourth flow path includes a second connection portion connected to the second portion; the second connection portion extends along a third direction that forms an acute angle with the first direction; the second connection portion has a third side surface located on the first connection portion side; the flow path portion has a connection surface connecting the second side surface and the third side surface, A flow path device, wherein the distance between a third portion where the second side surface and the connection surface are connected and a fourth portion where the third side surface and the connection surface are connected is less than or equal to one time the width of the first flow path in the second direction.
2. The flow path device according to claim 1 , The angle formed between the first direction and the third direction is equal to or greater than 15 degrees and equal to or less than 45 degrees.
3. The flow path device according to claim 2, A flow path device, 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, A flow path device, wherein the distance between the third portion and the fourth portion is 0.1 times or more and 0.5 times or less the width of the first flow path in the second direction.
Citation Information
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