Patent Publication Number: US-2023152191-A1

Title: Flow path device

Description:
CROSS-REFERENCE TO RELATED APPLICATION 
     The present application is a National Phase entry based on PCT Application No. PCT/JP2021/010733 filed on Mar. 17, 2021, entitled “FLOW PATH DEVICE”, which claims the benefit of Japanese Patent Application No. 2020-052362, filed on Mar. 24, 2020, entitled “FLOW PATH DEVICE”. 
    
    
     TECHNICAL FIELD 
     Embodiments of the present disclosure relate generally to a flow path device. 
     BACKGROUND 
     Techniques have been developed for separating a specific type of particles (hereafter, separating target particles) from other types of particles in a fluid containing multiple types of particles and for performing a predetermined process on separating target particles (e.g., WO 2019/151150). A device for separating target particles in a fluid may include different components from a device for evaluating separated particles. 
     SUMMARY 
     A flow path device includes a first device including a groove, a second device including a first surface, a second surface opposite to the first surface and in contact with the first device, and a first hole extending through and between the first surface and the second surface and being continuous with the groove, and a third device including a third surface in contact with the first surface, a second hole open in the third surface and continuous with the first hole, and a flow path continuous with the second hole and open in the third surface. 
     As viewed in a first direction from the first surface to the second surface, the second hole has a diameter greater than a dimension of the flow path in a third direction orthogonal to a second direction in which the flow path extends. The first hole has a diameter greater than the diameter of the second hole. 
     In a first aspect of the flow path device, the second hole has a center surrounded by the first hole. The flow path intersects with the first hole at not more than one point or does not intersect with the first hole. 
     In a second aspect of the flow path device, the second hole has an edge intersecting with an edge of the flow path at two intersections. At least one of the two intersections is located outward from an edge of the first hole. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG.  1    is a schematic plan view of a flow path device according to an embodiment as viewed vertically downward (in the −Z direction). 
         FIG.  2    is a schematic plan view of a processing device as viewed vertically downward (in the −Z direction). 
         FIG.  3 A  is a schematic and partially cut imaginary sectional view of the flow path device at position A-A as viewed in the Y direction,  FIG.  3 B  is a schematic and partially cut imaginary sectional view of the flow path device at position B-B as viewed in the Y direction, and  FIG.  3 C  is a schematic and partially cut imaginary sectional view of the flow path device at position E-E as viewed in the Y direction. 
         FIG.  4    is a schematic plan view of a connection device as viewed vertically downward. 
         FIG.  5 A  is a schematic and partially cut imaginary sectional view of the flow path device at position C-C as viewed in a direction orthogonal to the Z direction,  FIG.  5 B  is a schematic and partially cut imaginary sectional view of the flow path device at position D-D as viewed in the −X direction, and  FIG.  5 C  is a schematic and partially cut imaginary sectional view of the flow path device at position F-F as viewed in the −X direction. 
         FIG.  6    is a schematic plan view of a separating device as viewed vertically downward (in the −Z direction). 
         FIG.  7    is a plan view illustrating an area M in  FIG.  6   . 
         FIG.  8    is a schematic and partially cut sectional view of the connection device and the separating device at position H-H in  FIG.  9    as viewed vertically downward (in the −Z direction). 
         FIG.  9    is a schematic and partially cut imaginary sectional view of the connection device and the separating device at position G-G in  FIG.  8    as viewed in the Y direction. 
         FIG.  10    is a schematic plan view of an exit hole, a flow path, and a through-hole illustrating the positional relationship between their edges as viewed vertically downward (in the −Z direction). 
         FIG.  11    is a schematic plan view of the exit hole, the flow path, and the through-hole illustrating the positional relationship between their edges as viewed vertically downward (in the −Z direction). 
         FIG.  12    is a schematic plan view of the exit hole, the flow path, and the through-hole illustrating the positional relationship between their edges as viewed vertically downward (in the −Z direction). 
         FIG.  13    is a schematic plan view of the exit hole, the flow path, and the through-hole illustrating the positional relationship between their edges as viewed vertically downward (in the −Z direction). 
         FIG.  14    is a schematic plan view of the exit hole, the flow path, and the through-hole illustrating the positional relationship between their edges as viewed vertically downward (in the −Z direction). 
         FIG.  15    is a schematic plan view of the exit hole, the flow path, and the through-hole illustrating the positional relationship between their edges as viewed vertically downward (in the −Z direction). 
         FIG.  16    is a schematic plan view of the exit hole, the flow path, and the through-hole illustrating the positional relationship between their edges as viewed vertically downward (in the −Z direction). 
         FIG.  17    is a schematic plan view of the exit hole, the flow path, and the through-hole illustrating the positional relationship between their edges as viewed vertically downward (in the −Z direction). 
         FIG.  18    is a schematic plan view of the exit hole, the flow path, and the through-hole illustrating the positional relationship between their edges as viewed vertically downward (in the −Z direction). 
         FIG.  19    is a schematic plan view of the exit hole, the flow path, and the through-hole illustrating the positional relationship between their edges as viewed vertically downward (in the −Z direction). 
         FIG.  20    is a schematic plan view of the exit hole, the flow path, and the through-hole illustrating the positional relationship between their edges as viewed vertically downward (in the −Z direction). 
     
    
    
     DESCRIPTION OF EMBODIMENTS 
     Various embodiments and variations are described below with reference to the drawings. Throughout the drawings, components with the same or similar structures and functions are given the same reference numerals and will not be described repeatedly. The drawings are schematic. 
     The drawings include the right-handed XYZ coordinate system for convenience. The Z direction herein is defined as the vertically upward direction. A first direction may be the vertically downward direction. The vertically downward direction is also referred to as the −Z direction. A second direction may be the X direction. The direction opposite to the X direction is also referred to as the −X direction. A third direction may be the Y direction. The direction opposite to the Y direction is also referred to as the −Y direction. 
     The flow path herein has a structure that allows a fluid to flow. The dimension of the flow path in the direction orthogonal to the direction in which the flow path extends is referred to as the width of the flow path. 
     1. Example Structure 
       FIG.  1    is a plan view of a flow path device  100  according to an embodiment. The flow path device  100  includes a processing device  1 , a connection device  2 , and a separating device  3 . The processing device  1 , the connection device  2 , and the separating device  3  are stacked in this order in the Z direction. 
     The processing device  1  includes surfaces  1   a  and  1   b . The surface  1   a  is located in the Z direction from the surface  1   b . The connection device  2  includes surfaces  2   a  and  2   b . The surface  2   a  is located in the Z direction from the surface  2   b . The surface  2   b  is in contact with the surface  1   a . The surface  2   b  is bonded to the surface  1   a  with, for example, plasma or light. 
     The separating device  3  includes surfaces  3   a  and  3   b . The surface  3   a  is located in the Z direction from the surface  3   b . The surface  3   b  is in contact with the surface  2   a . The surface  3   b  is bonded to the surface  2   a  with, for example, plasma or light. 
     For bonding with plasma, for example, oxygen plasma is used. For bonding with light, for example, ultraviolet light from an excimer lamp is used. 
     Each of the processing device  1 , the connection device  2 , and the separating device  3  is a rectangular plate as viewed in plan (hereafter, as viewed in the −Z direction unless otherwise specified). The surfaces  1   a ,  1   b ,  2   a ,  2   b ,  3   a , and  3   b  are orthogonal to the Z direction. 
       FIG.  2    is a plan view of the processing device  1 . The dot-dash line indicates an area R 2  at which the surface  2   b  of the connection device  2  is to be bonded. The processing device  1  has a thickness (a dimension in the Z direction) of, for example, about 0.5 to 5 mm (millimeters). The surfaces  1   a  and  1   b  each have a width (a dimension in the X direction) of, for example, about 10 to 30 mm. The surfaces  1   a  and  1   b  each have a length (a dimension in the Y direction) of, for example, about 20 to 50 mm. 
     The processing device  1  includes entry holes  121 ,  122 ,  124 ,  126 ,  128 , and  129 , exit holes  125  and  127 , and a mixing-fluid hole  123 . The entry holes  126 ,  128 , and  129  and the exit holes  125  and  127  are open in the surface  1   a  in the area R 2 . The entry holes  121 ,  122 , and  124  and the mixing-fluid hole  123  are open in the surface  1   a  outside the area R 2 . The entry holes  121 ,  122 ,  124 ,  126 ,  128 , and  129 , the exit holes  125  and  127 , and the mixing-fluid hole  123  are not open in the surface  1   b.    
     The processing device  1  includes exit holes  141 ,  142 , and  143 . The exit holes  141 ,  142 , and  143  are open in the surface  1   b  outside the area R 2  as viewed in plan. The exit holes  141 ,  142 , and  143  are not open in the surface  1   a.    
     The processing device  1  includes a mixing flow path  115 , flow paths  111 ,  112 ,  113 ,  114 ,  116 ,  117 ,  118 , and  119 , a measurement flow path  151 , and a reference flow path  152 . The mixing flow path  115 , the flow paths  111 ,  112 ,  113 ,  114 ,  116 ,  117 ,  118 , and  119 , the measurement flow path  151 , and the reference flow path  152  are grooves that are not open in the surface  1   a  or  1   b.    
     Elements continuous with each other refer to the elements being connected to allow a fluid to flow through the elements. The flow path  111  is continuous with the entry hole  121  and the exit hole  127 . The flow path  112  is continuous with the entry hole  128  and the exit hole  141 . The flow path  113  is continuous with the entry hole  122  and the exit hole  125 . The flow path  114  is continuous with the entry hole  126  and the exit hole  142 . 
     The mixing flow path  115  is continuous with the mixing-fluid hole  123  and is between the mixing-fluid hole  123  and the flow path  117 . The flow path  116  is between the flow path  117  and the reference flow path  152 . The flow path  117  is continuous with the mixing flow path  115  and is between the measurement flow path  151  and the flow path  116 . The flow path  118  is continuous with the entry hole  124  and is between the entry hole  124  and the reference flow path  152 . The flow path  119  is continuous with the exit hole  143  and is between the exit hole  143  and the measurement flow path  151 . 
     The measurement flow path  151  is between the flow path  117  and the flow path  119 . The measurement flow path  151  extends in the Y direction. The measurement flow path  151  has the end in the Y direction continuous with the flow path  117  and the opposite end continuous with the flow path  119 . The measurement flow path  151  includes a portion continuous with the flow path  117  in the area R 2  as viewed in plan. The measurement flow path  151  is continuous with the entry hole  129 . 
     The reference flow path  152  is between the flow path  116  and the flow path  118 . The reference flow path  152  extends in the Y direction. The reference flow path  152  has the end in the Y direction continuous with the flow path  116  and the opposite end continuous with the flow path  118 . In the present embodiment, the measurement flow path  151  and the reference flow path  152  both extend in the Y direction. However, the measurement flow path  151  and the reference flow path  152  may extend in different directions. 
       FIG.  3 A  is an imaginary sectional view of the flow path device  100 . The mixing flow path  115  extends from the mixing-fluid hole  123  substantially in the Y direction, substantially in the −Y direction, substantially in the Y direction, and then in the −X direction, and is continuous with the flow path  117 . 
       FIGS.  3 B and  3 C  are imaginary sectional views of the flow path device  100 . The processing device  1  includes cylinders  101 ,  102 ,  103 , and  104  protruding from the surface  1   a  in the Z direction. The cylinder  101  surrounds the entry hole  121  about Z-axis. The cylinder  102  surrounds the entry hole  122  about Z-axis. The cylinder  103  surrounds the mixing-fluid hole  123  about Z-axis. The cylinder  104  surrounds the entry hole  124  about Z-axis. 
     The processing device  1  includes cylinders  131 ,  132 , and  133  protruding from the surface  1   b  in the direction opposite to the Z direction. The cylinder  131  surrounds the exit hole  141  about Z-axis. The cylinder  132  surrounds the exit hole  142  about Z-axis. The cylinder  133  surrounds the exit hole  143  about Z-axis. 
       FIG.  4    is a plan view of the connection device  2 . An area R 3  is an area at which the surface  3   b  is to be bonded. The connection device  2  includes through-holes  225 ,  226 ,  227 ,  228 , and  229 . The through-holes  225 ,  226 ,  227 ,  228 , and  229  extend through and between the surface  2   a  and the surface  2   b  in the area R 3 . 
       FIGS.  5 A,  5 B, and  5 C  are imaginary sectional views of the flow path device  100 . The through-hole  225  is continuous with the exit hole  125 . The through-hole  225  is continuous with the entry hole  122  through the exit hole  125  and the flow path  113  in this order. The through-hole  226  is continuous with the entry hole  126 . The through-hole  226  is continuous with the exit hole  142  through the entry hole  126  and the flow path  114  in this order. The through-hole  227  is continuous with the exit hole  127 . The through-hole  227  is continuous with the entry hole  121  through the exit hole  127  and the flow path  111  in this order. The through-hole  228  is continuous with the entry hole  128 . The through-hole  228  is continuous with the exit hole  141  through the entry hole  128  and the flow path  112  in this order. The through-hole  229  is continuous with the entry hole  129 . The through-hole  229  is continuous with the measurement flow path  151  through the entry hole  129 . 
       FIG.  6    is a plan view of the separating device  3 . The separating device  3  has a thickness (a dimension in the Z direction) of, for example, about 1 to 5 mm. The surfaces  3   a  and  3   b  each have a width (a dimension in the X direction) of, for example, about 10 to 50 mm. The surfaces  3   a  and  3   b  each have a length (a dimension in the Y direction) of, for example, about 10 to 30 mm. 
     The separating device  3  includes entry holes  325  and  327 , exit holes  326 ,  328 , and  329 , a separating flow path  30 , and flow paths  35 ,  37 ,  38 , and  39 . The entry holes  325  and  327  and the exit holes  326 ,  328 , and  329  are open in the surface  3   b  without being open in the surface  3   a . The separating flow path  30  and the flow paths  35 ,  37 ,  38 , and  39  are grooves that are open in the surface  3   b  without being open in the surface  3   a.    
     The surface  3   b  is in contact with the surface  2   a  excluding a portion with the entry holes  325  and  327 , the exit holes  326 ,  328 , and  329 , the separating flow path  30 , and the flow paths  35 ,  37 ,  38 , and  39 . A fluid does not enter between portions of the surface  3   b  and the surface  2   a  that are in contact with each other. The separating flow path  30  and the flow paths  35 ,  37 ,  38 , and  39 , together with the surface  2   a , allow a fluid to move. 
     The separating flow path  30  includes a main flow path  34  and an output port  303 . The main flow path  34  includes an input port  341  and an output port  342 . The main flow path  34  extends in the −Y direction from the input port  341  to the output port  342 . 
       FIG.  7    partially illustrates the separating device  3 . The separating flow path  30  and the flow paths  35  and  37  are illustrated with solid lines for convenience. The separating flow path  30  includes multiple branch flow paths  301 . The branch flow paths  301  branch from the main flow path  34  at different positions in the Y direction. The branch flow paths  301  each extend in the X direction. The branch flow paths  301  are each continuous with the output port  303  opposite to the main flow path  34 . 
     The entry hole  325  is continuous with the through-hole  225 . The entry hole  325  is continuous with the entry hole  122  through the through-hole  225 , the exit hole  125 , and the flow path  113  in this order. The entry hole  327  is continuous with the through-hole  227 . The entry hole  327  is continuous with the entry hole  121  through the through-hole  227 , the exit hole  127 , and the flow path  111  in this order. The exit hole  326  is continuous with the through-hole  226 . The exit hole  326  is continuous with the exit hole  142  through the through-hole  226 , the entry hole  126 , and the flow path  114  in this order. The exit hole  328  is continuous with the through-hole  228 . The exit hole  328  is continuous with the exit hole  141  through the through-hole  228 , the entry hole  128 , and the flow path  112  in this order. The exit hole  329  is continuous with the through-hole  229 . The exit hole  329  is continuous with the measurement flow path  151  through the through-hole  229  and the entry hole  129 . 
     The flow path  35  joins the entry hole  325  and the input port  341 . The flow path  35  is continuous with the main flow path  34  at the input port  341 . The flow path  35  extends in the −Y direction and is joined to the input port  341 . The flow path  35  includes a portion extending in the Y direction near the input port  341 . 
     The flow path  37  extends in the X direction and is joined to the portion of the flow path  35  extending in the Y direction near the input port  341 . The entry hole  327  is continuous with the main flow path  34  through the flow path  37 . 
     The flow path  36  joins the exit hole  326  and the output port  303 . The flow path  36  extends in the X direction. 
     The flow path  38  joins the exit hole  328  and the output port  342 . The flow path  38  extends in the Y direction and is joined to the output port  342 . The flow path  38  extends from the output port  342  in the −Y direction, in the −X direction, in the −Y direction, and then in the X direction to the exit hole  328 . 
     The flow path  39  extends in the −X direction and is joined to a portion of the flow path  38  extending in the Y direction near the output port  342 . The exit hole  329  is continuous with the output port  342  through the flow path  39 . The flow path  39  extends from the flow path  38  in the X direction, in the −Y direction, and then in the −X direction to the exit hole  329 . 
     2. Example Functions 
     The flow path device  100  has functions generally described below. 
     A fluid containing multiple types of particles P 100  and P 200  (hereafter also a processing target fluid; refer to  FIG.  7   ) is introduced into the separating device  3 . The separating device  3  separates separating target particles P 100  as a specific type of particles from other types of particles (hereafter also non-target particles) P 200  and discharges the separating target particles P 100 . The fluid may contain three or more types of particles. In the example described below, the separating target particles P 100  are of a single type, and the non-target particles P 200  are of another single type. 
     The processing device  1  is used to perform a process on the separating target particles P 100 . The process includes, for example, counting the separating target particles P 100  (detection of the number). To describe the process, the separating target particles P 100  and the fluid containing the separating target particles P 100  are both herein also referred to as a sample. 
     The connection device  2  guides the separating target particles P 100  (specifically, the sample) discharged from the separating device  3  to the processing device  1 . 
     A pressing fluid is introduced into the flow path device  100  through the entry hole  121 . A processing target fluid is introduced into the flow path device  100  through the entry hole  122 . A mixing fluid is fed into the flow path device  100  through the mixing-fluid hole  123 . The mixing fluid is discharged from the flow path device  100  through the mixing-fluid hole  123 . A dispersing fluid is introduced into the flow path device  100  through the entry hole  124 . Specific examples and the functions of the pressing fluid, the mixing fluid, and the dispersing fluid are described later. 
     A tube is externally connectable to the flow path device  100  to introduce the pressing fluid into the flow path device  100  through the entry hole  121  using the cylinder  101 . 
     A tube is externally connectable to the flow path device  100  to introduce the processing target fluid into the flow path device  100  through the entry hole  122  using the cylinder  102 . 
     A tube is externally connectable to the flow path device  100  to feed the mixing fluid into the flow path device  100  through the mixing-fluid hole  123  using the cylinder  103 . 
     A tube is externally connectable to the flow path device  100  to introduce the dispersing fluid into the flow path device  100  through the entry hole  124  using the cylinder  104 . 
     The processing target fluid introduced into the flow path device  100  through the entry hole  122  flows through the flow path  113 , the exit hole  125 , the through-hole  225 , the entry hole  325 , the flow path  35 , and the input port  341  in this order, and then flows into the main flow path  34 . 
     The pressing fluid introduced into the flow path device  100  through the entry hole  121  flows through the flow path  111 , the exit hole  127 , the through-hole  227 , the entry hole  327 , and the flow path  37  in this order, and then flows into the main flow path  34 . 
     In  FIG.  7   , the arrows Fp 1  drawn with two-dot chain lines indicate the direction of flow of the pressing fluid. The direction is the X direction. In  FIG.  7   , the arrows Fm 1  drawn with two-dot chain lines thicker than the arrows Fp 1  indicate the direction of the main flow of the processing target fluid (also referred to as a main flow) in the main flow path  34 . The direction is the −Y direction. 
       FIG.  7    schematically illustrates the separating target particles P 100  with a greater diameter than the non-target particles P 200  being separated from the non-target particles P 200 . More specifically, in the illustrated example, the branch flow paths  301  each have a width (a dimension of the branch flow path  301  in the Y direction) greater than the diameter of the non-target particles P 200  and less than the diameter of the separating target particles P 100 . 
     At least the main flow path  34  and the flow path  35  each have a width greater than the diameter of the separating target particles P 100  and the diameter of the non-target particles P 200 . The width of the main flow path  34  refers to the dimension of the main flow path  34  in the X direction. The width of the flow path  35  refers to the dimension of the flow path  35  in the X direction for its portion near the main flow path  34 . The width of the flow path  35  refers to the dimension of the flow path  35  in the Y direction for its portion extending in the −X direction. 
     The non-target particles P 200  move along the main flow path  34  in the −Y direction and mostly flow into the branch flow paths  301 . The non-target particles P 200  mostly flow through the branch flow paths  301 , the output port  303 , the flow path  36 , the exit hole  326 , the through-hole  226 , the entry hole  126 , and the flow path  114 , and are then discharged through the exit hole  142 . 
     The branch flow paths  301  connected to the main flow path  34  each have the cross-sectional area and the length adjusted to cause the non-target particles P 200  to flow from the main flow path  34  into the branch flow paths  301  and to be separated from the separating target particles P 100 . In the present embodiment, a process to be performed on the discharged non-target particles P 200  is not specified. 
     The separating target particles P 100  move along the main flow path  34  in the −Y direction substantially without flowing into the branch flow paths  301 . The separating target particles P 100  mostly flow through the main flow path  34 , the output port  342 , the flow path  39 , the exit hole  329 , the through-hole  229 , and the entry hole  129  into the measurement flow path  151 . 
     While the separating target particles P 100  flow through the flow path  39 , a component of the processing target fluid other than the separating target particles P 100  flows through the flow path  38  and is discharged. An example of the component is described later. The flow path  39  has a width greater than the size of the separating target particles P 100 . The separating target particles P 100  flow from the output port  342  into the flow path  39  rather than into the flow path  38 , similarly to the non-target particles P 200  flowing into the branch flow paths  301  from the main flow path  34 . 
     The component flows into the flow path  38 , further flows through the exit hole  328 , the through-hole  228 , the entry hole  128 , and the flow path  112 , and is then discharged through the exit hole  141 . In the present embodiment, a process to be performed on the discharged component is not specified. 
     In the present embodiment, the processing target fluid is directed into the branch flow paths  301  using a flow (hereafter, a fluid-drawing flow). The fluid-drawing flow allows the separating target particles P 100  to be separated from the non-target particles P 200  using the main flow path  34  and the branch flow paths  301 . The fluid-drawing flow is indicated by a hatched area Ar 1  with a dot pattern in  FIG.  7   . The state of the fluid-drawing flow indicated by the area Ar 1  in  FIG.  7    is a mere example and may be changed in accordance with the relationship between the flow velocity and the flow rate of the introduced processing target fluid (main flow) and the flow velocity and the flow rate of the pressing fluid. The area Ar 1  may be adjusted as appropriate to efficiently separate the separating target particles P 100  from the non-target particles P 200 . 
     The pressing fluid directs the processing target fluid toward the branch flow paths  301  in the X direction from a position opposite to the branch flow paths  301 . The pressing fluid can create the fluid-drawing flow. 
     In  FIG.  7   , the fluid-drawing flow in the main flow path  34  has a width W 1  (a dimension of the fluid-drawing flow in the X direction) near a branch of the main flow path  34  to each branch flow path  301 . The width W 1  may be adjusted by, for example, the cross-sectional areas and the lengths of the main flow path  34  and the branch flow paths  301  and by the flow rates of the processing target fluid and the pressing fluid. 
     At the width W 1  illustrated in  FIG.  7   , the area Ar 1  of the fluid-drawing flow does not include the center of gravity of each separating target particle P 100  and includes the center of gravity of each non-target particle P 200 . 
     The processing target fluid is, for example, blood. In this case, the separating target particles P 100  are, for example, white blood cells. The non-target particles P 200  are, for example, red blood cells. The process on the separating target particles P 100  includes, for example, counting white blood cells. The component flowing through the flow path  38  and the exit hole  328  before being discharged from the separating device  3  is, for example, blood plasma. In this case, the pressing fluid is, for example, PBS (phosphate-buffered saline). 
     A red blood cell has the center of gravity at, for example, about 2 to 2.5 μm (micrometers) from its outer rim. A red blood cell has a maximum diameter of, for example, about 6 to 8 μm. A white blood cell has the center of gravity at, for example, about 5 to 10 μm from its outer rim. A white blood cell has a maximum diameter of, for example, about 10 to 30 μm. To effectively separate red blood cells and white blood cells in blood, the fluid-drawing flow has the width W 1  of about 2 to 15 μm. 
     The main flow path  34  has an imaginary cross-sectional area of, for example, about 300 to 1000 μm 2  (square micrometers) along the XZ plane. The main flow path  34  has a length of, for example, about 0.5 to 20 mm in the Y direction. Each branch flow path  301  has an imaginary cross-sectional area of, for example, about 100 to 500 μm 2  along the YZ plane. Each branch flow path  301  has a length of, for example, about 3 to 25 mm in the X direction. The flow velocity in the main flow path  34  is, for example, about 0.2 to 5 m/s (meters per second). The flow rate in the main flow path  34  is, for example, about 0.1 to 5 μl/s (microliters per second). 
     The material for the separating device  3  is, for example, PDMS (polydimethylsiloxane). PDMS is highly transferable in resin molding using molds. A transferrable material can produce a resin-molded product including fine protrusions and recesses corresponding to a fine pattern on the mold. The separating device  3  is resin-molded using PDMS for easy manufacture of the flow path device  100 . The material for the connection device  2  is, for example, a silicone resin. 
     The dispersing fluid introduced into the flow path device  100  through the entry hole  124  flows through the flow path  118 , the reference flow path  152 , and the flow paths  116  and  117  in this order, and then flows into the measurement flow path  151 . 
     The dispersing fluid disperses the separating target particles P 100  introduced into the measurement flow path  151  through the entry hole  129 . Dispersing herein is an antonym of clumping or aggregation of the separating target particles P 100 . Dispersing the separating target particles P 100  allows a predetermined process (e.g., counting in the present embodiment) to be performed easily or accurately or both. For the processing target fluid being blood, the dispersing fluid is, for example, PBS. 
     The mixing fluid introduced into the flow path device  100  through the mixing-fluid hole  123  flows into the mixing flow path  115 . The mixing fluid flows back and forth through the mixing flow path  115  with an external operation. For example, the mixing fluid may be air. In this case, the air pressure at the mixing-fluid hole  123  is controlled to cause air to flow back and forth through the mixing flow path  115 . For example, the mixing fluid may be PBS. In this case, PBS flows back and forth through the mixing flow path  115  as it flows into and out of the mixing-fluid hole  123 . 
     The mixing fluid flowing back and forth through the mixing flow path  115  allows mixing of the dispersing fluid and the sample. The dispersing fluid being mixed with the sample can disperse the separating target particles P 100 . 
     The sample, the dispersing fluid, and optionally the mixing fluid, flow through the measurement flow path  151  toward the flow path  119 . The measurement flow path  151  is used to perform a predetermined process on the separating target particles P 100 . 
     In the illustrated example, the predetermined process includes counting the separating target particles P 100 . The separating target particles P 100  in the measurement flow path  151  can be counted with known optical measurement. For example, the separating target particles P 100  are counted by using illumination of the surface  1   b  with light that is transmitted through the processing device  1  to the surface  1   a  and measuring the transmitted light at the measurement flow path  151 . 
     The processing device  1  may be light-transmissive for efficient counting of the separating target particles P 100 . In  FIGS.  1 ,  3 A,  3 B,  3 C,  5 A,  5 B,  5 C, and  9   , the processing device  1  is hatched to indicate its light transmissiveness. 
     The same or similar optical measurement is performed on, for example, the reference flow path  152 . The measurement result may be used as a reference value for counting at the measurement flow path  151 . The reference value can reduce counting error. 
     The sample, the dispersing fluid, and optionally the mixing fluid, flow through the flow path  119  and are discharged through the exit hole  143  after the predetermined process is performed on the separating target particles P 100 . In the present embodiment, a process to be performed on the discharged separating target particles P 100  is not specified. 
     The material for the processing device  1  is, for example, a COP (cycloolefin polymer). The device made of a COP is highly light-transmissive and less flexible. 
     With the separating flow path  30  and the flow paths  35 ,  37 ,  38 , and  39 , together with the surface  2   a , allowing a fluid to move, the connection device  2  and the separating device  3  are less flexible. The separating device  3  made of PDMS and the connection device  2  made of a silicone resin are flexible. The processing device  1  made of a COP is less likely to deteriorate the function of the separating device  3 . 
     3. Fluid Movement from Exit Hole  329  to Through-Hole  229   
     The structure will now be described with reference to  FIGS.  2 ,  5 C,  8 , and  9   . For simplicity, the through-hole  229  and the exit hole  329  each may have a circular edge as viewed in plan (hereafter simply an edge). The through-hole  229  has an edge defined by the rim of the opening in the surface  2   a . The exit hole  329  has an edge defined by the rim of the opening in the separating device  3  as viewed in plan. The same applies to  FIG.  8   . In  FIG.  8   , the boundary between the exit hole  329  and the flow path  39  is indicated by an are drawn with an imaginary dot-dash line. 
     A fluid moves from the flow path  39  through the exit hole  329 , the through-hole  229 , and the entry hole  129  before reaching the measurement flow path  151 . The fluid moves from the flow path  39  in the −X direction on the surface  2   a  before reaching the exit hole  329 . 
     The through-hole  229  typically has an edge surrounding the edge of the exit hole  329  as viewed in plan. The through-hole  229  and the exit hole  329  located in this manner allow the fluid to easily move from the exit hole  329  to the through-hole  229  with any misalignment of these holes. For this layout, the through-hole  229  has an edge with a diameter W 2  greater than a diameter W 3  of the edge of the exit hole  329 . 
     The entry hole  129  herein may have any size. For example, the entry hole  129  may be aligned with the through-hole  229  as viewed in plan. The same applies to  FIG.  9   . The diameter W 2  is greater than or equal to the diameter W 3 . For example, the diameter W 2  is 2.4 mm. For example, the diameter W 3  is 2.0 mm. 
     The diameter W 3  is greater than a width d 0  of the flow path  39  near the exit hole  329  (a dimension of the flow path  39  in the Y direction in the portion extending in the −X direction toward the exit hole  329 ). The flow path  39  and the exit hole  329  with such sizes facilitate movement of the fluid from the flow path  39  to the exit hole  329 . For example, the width d 0  is 0.9 mm. 
     For example, a fluid is introduced into the flow path device  100  through the entry hole  121  in a process before the processing target fluid is introduced into the flow path device  100 . Such a fluid (hereafter, a preprocessing fluid) facilitates movement of the processing target fluid and the sample in the separating device  3 . 
     The preprocessing fluid is introduced through the entry hole  327 . For example, the preprocessing fluid also serves as the pressing fluid and flows through the entry hole  121 , the flow path  111 , the exit hole  127 , the through-hole  227 , and the entry hole  327  in this order and reaches the flow path  37 . 
     The preprocessing fluid flows from the flow path  37  through the flow path  35  to at least the entry hole  325 , or further flows through the through-hole  225 , the exit hole  125 , and the flow path  113  in this order, and is then discharged through the entry hole  122 . The preprocessing fluid flows through the flow path  35  and the entry hole  325  or further through the through-hole  225 , the exit hole  125 , the flow path  113 , and the entry hole  122  in the direction opposite to the direction of the processing target fluid. 
     The preprocessing fluid flows from the flow path  37  through the main flow path  34  and the flow path  38  to at least the exit hole  328 , or further flows through the through-hole  228 , the entry hole  128 , and the flow path  112  in this order, and is then discharged through the exit hole  141 . 
     The preprocessing fluid flows from the flow path  37  through the main flow path  34  and the flow path  39  to at least the exit hole  329 , or further flows through the through-hole  229  and the entry hole  129  to the measurement flow path  151 . 
     The preprocessing fluid flows from the flow path  37  through the main flow path  34 , the branch flow paths  301 , and the flow path  36  in this order to at least the exit hole  326 , or further flows through the through-hole  226 , the entry hole  126 , and the flow path  114  in this order, and is then discharged through the exit hole  142 . 
       FIG.  9    illustrates a fluid  4  that does not reach the exit hole  329  and thus does not reach the through-hole  229 . The fluid  4  has a surface  41  out of contact from the connection device  2  and the separating device  3  and protruding from the flow path  39  into the exit hole  329  at the edge of the through-hole  229 . 
     The fluid  4  can have the surface  41  that is more likely to protrude when the fluid  4  is a hydrophilic liquid and the surface  2   a  is water repellent. In this case, the fluid  4  and the surface  2   a  define a greater contact angle. Under a constant pressure on the fluid  4 , the contact angle has a cosine inversely proportional to the surface tension (refer to, for example, Laplace&#39;s equation). The surface tension increases as the contact angle increases. The fluid  4  with an increased surface tension moves less smoothly from the flow path  39  into the exit hole  329 . 
     The preprocessing fluid is, for example, saline (e.g., PBS), which is hydrophilic. For the connection device  2  made of a silicone resin, the preprocessing fluid is less likely to reach the through-hole  229  similarly to the fluid  4 . 
     As described above, for example, the surface  2   a  may be bonded to the surface  3   b  with plasma or light. This causes the surface  2   a  to be hydrophilic. After being bonded with plasma or light, the surface  2   a  becomes less hydrophilic over time. The preprocessing fluid is to smoothly move from the exit hole  329  to the through-hole  229  over a long time after the connection device  2  is bonded to the separating device  3 . 
     The flow path  39  may have a fixed width d 0  and a fixed cross-sectional area (the area of the section orthogonal to the X direction). In this case, the edge of the through-hole  229  may include a longer portion (hereafter, a contact portion) that comes in contact with the fluid  4  (refer to  FIG.  9   ) flowing through the flow path  39  and the exit hole  329  toward the through-hole  229 . The longer contact portion reduces the velocity head of preprocessing fluid moving from the exit hole  329  to the through-hole  229 . The reduced velocity head causes the pressure head to increase (refer to, for example, Bernoulli&#39;s theorem). As the pressure head increases, the fluid  4  can flow more easily from the flow path  39  toward the exit hole  329 . 
       FIGS.  10  to  20    each illustrate an edge  39   c  of the flow path  39 , an edge  329   c  of the exit hole  329 , and an edge  229   c  of the through-hole  229 . 
       FIGS.  10  to  20    each illustrate the edge  329   c  as a circle around a point  329   d  with a dot-dash line indicating an imaginary line  329   x  through the point  329   d  and parallel to the X direction and a dot-dash line indicating an imaginary line  329   y  through the point  329   d  and parallel to the Y direction. 
       FIGS.  10  to  20    each illustrate the edge  229   c  as a circle around a point  229   d  with a dot-dash line indicating an imaginary line  229   x  through the point  229   d  and parallel to the X direction and a dot-dash line indicating an imaginary line  229   y  through the point  229   d  and parallel to the Y direction. 
     In each of  FIGS.  10  to  20   , the edge  39   c  and the edge  329   c  intersect with each other at two intersections Q 1  and Q 2 . 
       FIGS.  10  to  13   , with reference to  FIG.  8   , illustrate structures as viewed in plan with the features (i) and (ii) below. (i) The diameter W 3  (that is also the diameter of the edge  329   c ) is greater than the dimension d 0  of the flow path  39  in the Y direction orthogonal to the X direction in which the flow path  39  extends. (ii) The diameter W 2  (that is also the diameter of edge  229   c ) is greater than the diameter W 3 . 
       FIGS.  10  to  13   , with reference to  FIG.  8   , illustrate the exit hole  329 , the through-hole  229 , and the flow path  39  as viewed in plan with the features (iii) and (iv-1) below. (iii) The exit hole  329  has its center (illustrated as the point  329   d ) surrounded by the through-hole  229  (or in other words, surrounded by the edge  229   c ). (iv-1) The flow path  39  intersects with the exit hole  329  at two or more intersections (illustrated as the two intersections Q 1  and Q 2 ). 
       FIGS.  10  to  13    illustrate the exit hole  329 , the through-hole  229 , and the flow path  39  as viewed in plan with the feature (v-1) below. (v-1) The flow path  39  intersects with the exit hole  329  at intersections (illustrated as the two intersections Q 1  and Q 2 ) all located inward from the through-hole  229  (or in other words, located inward from the edge  229   c ). 
     The example of  FIG.  10    will now be described. The imaginary line  229   x  is aligned with the imaginary line  329   x . The imaginary line  229   y  is located in the X direction from the imaginary line  329   y . The edge  229   c  intersects with the edge  329   c  at points P 19  and P 20 . The edge  229   c  intersects with the edge  39   c  at points P 21  and P 22 . The contact portion is an arc of the edge  229   c  defined by the points P 21  and P 22  and located in the X direction. 
     The example of  FIG.  11    will now be described. The imaginary line  229   x  is aligned with the imaginary line  329   x . The imaginary line  329   y  is located in the X direction from the imaginary line  229   y . The edge  229   c  intersects with the edge  329   c  at points P 23  and P 24 . The point P 23  is at the same position as the intersection Q 1 . The point P 24  is at the same position as the intersection Q 2 . The contact portion is an arc of the edge  229   c  defined by the points P 23  and P 24  and located in the X direction as viewed in plan. 
     For the through-hole  229  and the exit hole  329  in the positional relationship illustrated in  FIG.  8    as well, the arc corresponding to the arcs illustrated in  FIGS.  10  and  11    is the contact portion. 
     The example of  FIG.  12    will now be described. The imaginary line  329   x  is located in the Y direction from the imaginary line  229   x . The imaginary line  229   y  is located in the X direction from the imaginary line  329   y . The edge  229   c  intersects with the edge  329   c  at points P 25  and P 26 . The edge  229   c  intersects with the edge  39   c  at points P 27  and P 28 . The contact portion is an arc of the edge  229   c  defined by the points P 27  and P 28  and excluding the points P 25  and P 26  as viewed in plan. 
     The example of  FIG.  13    will now be described. The imaginary line  229   x  is located in the Y direction from the imaginary line  329   x . The imaginary line  229   y  is located in the X direction from the imaginary line  329   y . The edge  229   c  intersects with the edge  329   c  at points P 29  and P 30 . The edge  229   c  intersects with the edge  39   c  at points P 31  and P 32 . The contact portion is an arc of the edge  229   c  defined by the points P 31  and P 32  and excluding the points P 29  and P 30  as viewed in plan. 
     As illustrated in  FIGS.  10  to  13   , the device with the features (iii) and (iv-1) or with the feature (v-1) includes the contact portion surrounded by the edge  39   c  but not surrounded by the edge  329   c . Such a device cannot easily include a long contact portion. 
       FIGS.  14  to  20   , with reference to  FIG.  8   , illustrate the exit hole  329 , the through-hole  229 , and the flow path  39  as viewed in plan with the features (iii) and (iv-2) below. (iii) The exit hole  329  has its center (illustrated as the point  329   d ) surrounded by the through-hole  229  (or in other words, surrounded by the edge  229   c ). (iv-2) The flow path  39  intersects with the through-hole  229  at not more than one point or does not intersect with the through-hole  229 . 
       FIGS.  14  to  20    illustrate the exit hole  329 , the through-hole  229 , and the flow path  39  as viewed in plan with the feature (v-2) below. (v-2) The flow path  39  intersects with the exit hole  329  at intersections (illustrated as the two intersections Q 1  and Q 2 ), and at least one of the intersections is located outward from the through-hole  229  (or in other words, located outward from the edge  229   c ). 
     The example of  FIG.  14    will now be described. The imaginary line  229   y  is aligned with the imaginary line  329   y . The imaginary line  229   x  is located in the Y direction from the imaginary line  329   x . The edge  229   c  intersects with the edge  329   c  at points P 1  and P 2 . The edge  229   c  intersects with the edge  39   c  at a point P 3 . The contact portion is an arc of the edge  229   c  defined by the points P 1  and P 3  and passing through the point P 2  as viewed in plan. 
     The example of  FIG.  15    will now be described. The imaginary line  229   y  is aligned with the imaginary line  329   y . The imaginary line  329   x  is located in the Y direction from the imaginary line  229   x . The edge  229   c  intersects with the edge  329   c  at points P 4  and P 5 . The edge  229   c  intersects with the edge  39   c  at a point P 6 . The contact portion is an arc of the edge  229   c  defined by the points P 4  and P 6  and passing through the point P 5  as viewed in plan. 
     The example of  FIG.  16    will now be described. The imaginary line  229   x  is located in the Y direction from the imaginary line  329   x . The imaginary line  329   y  is located in the X direction from the imaginary line  229   y . The edge  229   c  intersects with the edge  329   c  at points P 7  and P 8 . The edge  229   c  does not intersect with the edge  39   c . The contact portion is an arc of the edge  229   c  defined by the points P 7  and P 8  and nearer the intersections Q 1  and Q 2  as viewed in plan. 
     The example of  FIG.  17    will now be described. The imaginary line  329   x  is aligned with the imaginary line  229   x . The imaginary line  329   y  is located in the X direction from the imaginary line  229   y . The edge  229   c  intersects with the edge  329   c  at points P 9  and P 10 . The edge  229   c  does not intersect with the edge  39   c . The contact portion is an arc of the edge  229   c  defined by the points P 9  and P 10  and nearer the intersections Q 1  and Q 2  as viewed in plan. 
     The example of  FIG.  18    will now be described. The imaginary line  329   x  is located in the Y direction from the imaginary line  229   x . The imaginary line  329   y  is located in the X direction from the imaginary line  229   y . The edge  229   c  intersects with the edge  329   c  at points P 11  and P 12 . The edge  229   c  does not intersect with the edge  39   c . The contact portion is an arc of the edge  229   c  defined by the points P 11  and P 12  and nearer the intersections Q 1  and Q 2  as viewed in plan. 
     The example of  FIG.  19    will now be described. The imaginary line  229   x  is located in the Y direction from the imaginary line  329   x . The imaginary line  229   y  is located in the X direction from the imaginary line  329   y . The edge  229   c  intersects with the edge  329   c  at points P 13  and P 14 . The edge  229   c  intersects with the edge  39   c  at a point P 15 . The contact portion is an arc of the edge  229   c  defined by the points P 13  and P 15  and passing through the point P 14  as viewed in plan. 
     The example of  FIG.  20    will now be described. The imaginary line  329   x  is located in the Y direction from the imaginary line  229   x . The imaginary line  229   y  is located in the X direction from the imaginary line  329   y . The edge  229   c  intersects with the edge  329   c  at points P 16  and P 17 . The edge  229   c  intersects with the edge  39   c  at a point P 18 . The contact portion is an arc of the edge  229   c  defined by the points P 16  and P 18  and passing through the point P 17  as viewed in plan. 
     As illustrated in  FIGS.  14  to  20   , the device with the features (iii) and (iv-2) or with the feature (v-2) includes the contact portion surrounded by the edge  329   c  or surrounded by the edge  329   c  and the edge  39   c . The device with these features is likely to include a longer contact portion with the diameter W 3  greater than the width d 0 . 
     As illustrated and described above, the device with the features (iii) and (iv-2) is likely to include a longer contact portion than with the features (iii) and (iv-1). The device with the features (iii) and (iv-2) facilitates flow of the preprocessing fluid from the exit hole  329  to the through-hole  229 , and thus facilitates flow from the exit hole  329  to the entry hole  129 . 
     The device with the feature (v-2) is likely to include a longer contact portion than with the feature (v-1). The device with the feature (v-2) facilitates flow of the preprocessing fluid from the exit hole  329  to the through-hole  229 , and thus facilitates flow from the exit hole  329  to the entry hole  129 . 
     4. Variations 
     The exit hole  329  is not limited to a circular hole but may be an elliptical hole. The edge  329   c  may be in the shape of an ellipse including a circle. The through-hole  229  is not limited to a circular hole but may be an elliptical hole. The edge  229   c  may be in the shape of an ellipse including a circle. The entry hole  129  is not limited to a circular hole but may be an elliptical hole. 
     The preprocessing fluid is optional. The above features that allow the contact portion to be longer facilitate movement of the processing target fluid from the exit hole  329  to the entry hole  129 . 
     The material for the processing device  1  may be an acrylic resin (e.g., polymethyl methacrylate), polycarbonate, or a COP. 
     The processing device  1  may be a stack of multiple members such as plates. The processing device  1  may be a stack of, for example, a first member and a second member. In this case, the first member may include a bonding surface including grooves corresponding to the mixing flow path  115 , the flow paths  111 ,  112 ,  113 ,  114 ,  116 ,  117 ,  118 , and  119 , the measurement flow path  151 , and the reference flow path  152 . The second member may include a flat surface. The bonding surface of the first member excluding a portion with the grooves may be bonded to the surface of the second member. 
     The first member may include recesses and protrusions around the grooves on its bonding surface. The second member may include protrusions and recesses on its surface to be fitted to the recesses and protrusions on the first member. 
     The components described in the above embodiments and variations may be entirely or partially combined as appropriate unless any contradiction arises.