Patent Publication Number: US-2023144961-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/JP2021/010800 filed on Mar. 17, 2021, entitled “FLOW PATH DEVICE”, which claims the benefit of Japanese Patent Application No. 2020-052386, 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). 
     SUMMARY 
     A flow path device includes a first surface including a first hole open in a first direction, a second surface opposite to the first surface in the first direction, a first groove connected to and continuous with the first hole without being open in the first surface or the second surface, a second groove connected to and continuous with the first groove without being open in the first surface or the second surface, and a third groove connected to and continuous with the second groove without being open in the first surface or the second surface. The third groove is connected to the second groove at a position on the second groove spaced from the first groove. The first groove extends toward a position opposite to the second groove with respect to the first hole. 
     As viewed in a direction parallel to the first direction, the second groove and the third groove define a first minor angle adjacent to the first hole and define a second minor angle opposite to the first hole. The first minor angle is larger than the second minor angle. 
    
    
     
       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 flowchart illustrating counting separating target particles. 
         FIG.  9    is a schematic partial plan view of the processing device immediately after the processing in step S 2  in the flowchart of  FIG.  8    is complete. 
         FIG.  10    is a schematic partial plan view of the processing device immediately after the processing in step S 4  in the flowchart of  FIG.  8    is complete. 
         FIG.  11    is a schematic partial plan view of the processing device immediately after the processing in step S 5  in the flowchart of  FIG.  8    is complete. 
         FIG.  12    is a schematic partial plan view of the processing device immediately after the processing in step S 6  in the flowchart of  FIG.  8    is complete. 
         FIG.  13    is a schematic partial plan view of the processing device immediately after the processing in step S 7  in the flowchart of  FIG.  8    is complete. 
         FIG.  14    is a plan view illustrating an area G 1  in  FIG.  13   . 
         FIG.  15    is a schematic partial plan view of the processing device immediately after the processing in step S 2  in the flowchart of  FIG.  8    is complete. 
         FIG.  16    is a schematic partial plan view of the processing device immediately after the processing in step S 4  in the flowchart of  FIG.  8    is complete. 
         FIG.  17    is a schematic partial plan view of the processing device immediately after the processing in step S 5  in the flowchart of  FIG.  8    is complete. 
         FIG.  18    is a schematic partial plan view of the processing device immediately after the processing in step S 6  in the flowchart of  FIG.  8    is complete. 
         FIG.  19    is a schematic partial plan view of the processing device immediately after the processing in step S 7  in the flowchart of  FIG.  8    is complete. 
         FIG.  20 A  is a plan view illustrating an area G 2  in  FIG.  19   , and  FIG.  20 B  is a partial plan view of a processing device in a variation. 
     
    
    
     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 may 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 . 
     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 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 . 
     In the illustrated example, the predetermined process on the separating target particles P 100  includes counting the separating target particles P 100 . In  FIG.  8   , counting the separating target particles P 100  is abbreviated as particle counting. 
     In step S 1 , 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) cleans the flow path device  100  and facilitates movement of the processing target fluid and the sample in the separating device  3 . Step S 1  may be eliminated. 
     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 , 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 . 
     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 reaching the measurement flow path  151  further flows through the flow path  119  and is discharged through the exit hole  143 . 
     After step S 1  is performed, the dispersing fluid is introduced through the entry hole  124 , the flow path  118 , the reference flow path  152 , and the flow path  116  in this order to a position before the entry hole  129  (step S 2 ). The position before the entry hole  129  herein refers to a position on the measurement flow path  151  nearer the flow path  117  than the entry hole  129  or a position on the flow path  117  nearer the measurement flow path  151  than the mixing flow path  115 . 
     The processing in step S 2  is complete when the dispersing fluid flows to the position before the entry hole  129 . Another dispersing fluid is introduced later, and thus the processing in step S 2  is referred to as first introduction. 
     For simplicity, in  FIG.  9    and subsequent figures, the elements located in the Z direction from the surface  1   b  are indicated by solid lines when the elements are actually hidden under the surface  1   a . The sample described with reference to  FIG.  9    and subsequent figures refers to a fluid containing the separating target particles P 100 . 
     In the example of  FIG.  9   , the dispersing fluid fills the entry hole  124 , the flow path  118 , the reference flow path  152 , the flow path  116 , and the flow path  117  and reaches the junction between the flow path  117  and the measurement flow path  151 . Step S 2  is performed to cause the dispersing fluid to flow also into the mixing flow path  115  through the flow path  117 . In  FIG.  9   , the area with the dispersing fluid is hatched with diagonal lines from the lower left to the upper right. 
     In the processing in step S 2 , the dispersing fluid pushes any preprocessing fluid remaining in the entry hole  129  and the measurement flow path  151  before step S 2 . This causes the preprocessing fluid to be discharged from the measurement flow path  151  through the flow path  119  and the exit hole  143 . The area with the preprocessing fluid is not illustrated in the figures. 
     Upon completion of the processing in step S 2 , the processing target fluid is introduced through the entry hole  122 , and the pressing fluid is introduced through the entry hole  121  (step S 3 ). 
     Step S 3  is performed to prepare the sample as illustrated in  FIG.  7   . The sample flows through the flow path  39 , the exit hole  329 , the through-hole  229 , and the entry hole  129  in this order and reaches the measurement flow path  151 . 
     In step S 4  in  FIG.  8   , the sample is introduced through the entry hole  129  into the measurement flow path  151 . This process can accompany the processing in step S 3 . Step S 4  is enclosed in a dashed block, indicating that the processing in step S 4  accompanies the processing in step S 3 . Step S 4  is complete upon completion of introduction of the sample through the entry hole  129 . 
     The processing in step S 4  causes the fluid to flow into the measurement flow path  151 . In  FIG.  10   , the area with the dispersing fluid and the sample is hatched with diagonal lines from the lower left to the upper right without distinguishing the dispersing fluid from the sample. In the subsequent figures, hatching is used in the same or similar manner unless otherwise specified. In the example of  FIG.  10   , the fluid in the measurement flow path  151  is mostly the sample introduced into the measurement flow path  151  in step S 4 . 
     The separating target particles P 100  (not illustrated in  FIG.  9    and subsequent figures) have not spread widely in the measurement flow path  151  immediately after the processing in step S 4  is complete. The separating target particles P 100  may aggregate in a portion of the measurement flow path  151  continuous with the entry hole  129  and may further aggregate in the entry hole  129 . 
     Upon completion of the processing in step S 4 , an additional dispersing fluid is introduced in step S 5 . The introduction is referred to as second introduction. The dispersing fluid is introduced through the entry hole  124 , the flow path  118 , the reference flow path  152 , and the flow path  116  in this order to the flow path  117 . The dispersing fluid introduced in the first introduction is pushed into the measurement flow path  151  by the dispersing fluid introduced in the second introduction. Step S 5  is complete upon completion of introduction of the dispersing fluid. 
     The second introduction causes the sample and the dispersing fluid to occupy a larger area in the measurement flow path  151  as illustrated in  FIG.  11    as compared with  FIG.  10   . 
     The separating target particles P 100  spread more widely in the measurement flow path  151  immediately after the processing in step S 5  is complete than immediately after the processing in step S 4  is complete. However, the separating target particles P 100  may aggregate in a portion of the measurement flow path  151  continuous with the entry hole  129  and may further aggregate in the entry hole  129 . 
     Steps S 6  and S 7  are repeatedly performed after the processing in step S 5  is complete. For example, a set of steps S 6  and S 7  is repeated five to ten times. 
     In the processing in step S 6 , the mixing fluid moves through the mixing flow path  115  toward the mixing-fluid hole  123 . For example, the mixing fluid may be air. In this case, the air pressure at the mixing-fluid hole  123  is controlled to evacuate the mixing flow path  115 . The air pressure can be controlled using any of known pumps. 
     The mixing flow path  115  is evacuated to cause the sample and the dispersing fluid to be drawn from the measurement flow path  151  into the mixing flow path  115 . The processing in step S 6  is thus referred to as fluid drawing. 
     As illustrated in  FIG.  12   , the processing in step S 6  is complete before the sample and the dispersing fluid reach the mixing-fluid hole  123 . Step S 6  is performed to cause substantially all the sample and the dispersing fluid to be drawn from the measurement flow path  151  into the mixing flow path  115 . The fluid drawing causes the separating target particles P 100  to move to an area R 1 . The area R 1  is an area with the sample or the dispersing fluid and relatively near the mixing-fluid hole  123 . 
     In the processing in step S 7 , the mixing fluid moves through the mixing flow path  115  toward the flow path  119  or toward the measurement flow path  151 . 
     The mixing fluid moves through the mixing flow path  115  toward the flow path  119  and causes the sample and the dispersing fluid to be pushed and mostly move from the mixing flow path  115  into the measurement flow path  151  through the flow path  117 . The processing in step S 7  is thus referred to as fluid pushing. The sample and the dispersing fluid mostly move toward the flow path  119  through the measurement flow path  151 . The measurement flow path  151  is used to perform a predetermined process on the separating target particles P 100  (step S 9  described later). 
     As illustrated in  FIG.  13   , the processing in step S 7  is complete before the sample and the dispersing fluid reach the flow path  119 . Step S 7  is performed to cause substantially all the sample and the dispersing fluid to be pushed from the mixing flow path  115  into the measurement flow path  151 . 
     Upon completion of the processing in step S 7 , the determination is performed as to whether steps S 6  and S 7  have been repeated a predetermined number of times in step S 8 . In response to a negative determination result (No in  FIG.  8   ), the processing in steps S 6  and S 7  is performed again. 
     Steps S 6  and S 7  are repeatedly performed to cause the mixing fluid to move back and forth through the mixing flow path  115 . The moving mixing fluid mixes the dispersing fluid and the sample. The mixed dispersing fluid can disperse the separating target particles P 100 . Dispersing the separating target particles P 100  allows a predetermined process to be performed on the separating target particles P 100  accurately or easily. 
     In response to an affirmative determination result in step S 8  (Yes in  FIG.  8   ), the processing in step S 9  is performed. Step S 9  corresponds to the above predetermined process. The predetermined process herein includes, for example, optical measurement of the separating target particles P 100 . For example, the optical measurement is performed using both the measurement flow path  151  and the reference flow path  152 . 
     For example, the separating target particles P 100  in the measurement flow path  151  can be counted with known optical measurement. At least the measurement flow path  151  in the processing device  1  may be light-transmissive for efficient counting of the separating target particles P 100 . 
     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  made of a COP can be light-transmissive. In  FIGS.  1 ,  3 A,  3 B,  3 C,  5 A,  5 B, and  5 C , 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. 
     3. Improvement with Fluid Drawing 
       FIG.  14    illustrates the state immediately after the processing in step S 7  is complete similarly to  FIG.  13   . In  FIGS.  14  and  20   , areas S and T are hatched differently. The fluid contains more separating target particles P 100  in the area S than in the area T. In  FIG.  14   , the flow path  117  is connected to the measurement flow path  151  at a position  71 . In the illustrated example, the position  71  is spaced from the entry hole  129 . 
     The fluid to be drawn into the mixing flow path  115  in the processing in step S 6  is mostly the fluid located in the measurement flow path  151  immediately after the processing in step S 5 . Through the processing in step S 7 , the fluid drawn into the mixing flow path  115  is mostly pushed back into the measurement flow path  151  through the flow path  117 . 
     However, the fluid drawn into the mixing flow path  115  is partially pushed back also into the flow path  116  through the flow path  117 . The area S is located in the mixing flow path  115  beyond a boundary  57  between the mixing flow path  115  and the flow path  117 , and is also located in the flow path  116  beyond a boundary  67  between the flow path  116  and the flow path  117 . This occurs when the mixing flow path  115  is orthogonally connected to the flow path  117 . The fluid moving from the mixing flow path  115  to the flow path  117  branches at the boundary  57  in both the Y direction and the −Y direction. 
     In the state illustrated in  FIG.  14   , the fluid at and near the boundary  67  cannot easily move into the measurement flow path  151  when an increased amount of fluid is pushed from the mixing flow path  115  toward the flow path  117  in step S 7 . With the area S located at and near the boundary  67  and containing a substantial amount of separating target particles P 100 , the separating target particles P 100  at and near the boundary  67  cannot be fully used for the predetermined process in the measurement flow path  151 . Such a situation may reduce the accuracy of the predetermined process, such as detecting fewer separating target particles P 100  than actually included separating target particles P 100 . 
     A processing device  1  described with reference to  FIGS.  15  to  20 A  includes a mixing flow path  115 A instead of the mixing flow path  115  in the processing device  1  described with reference to  FIG.  14    and figures preceding  FIG.  14   . The mixing flow path  115 A is a groove that is not open in the surface  1   a  or  1   b . The mixing flow path  115  is connected to the flow path  117 , whereas the mixing flow path  115 A is connected to the flow path  116 . 
     The mixing flow path  115 A differs from the mixing flow path  115  substantially in the connection to the flow paths  116  and  117  and in the positional relationship with the flow paths  116  and  117 . The processing device  1  including the mixing flow path  115 A can also be included in the flow path device  100  together with the connection device  2  and the separating device  3 . 
       FIG.  15    illustrates the state after the processing in step S 2  is complete similarly to  FIG.  9   .  FIG.  16    illustrates the state after the processing in step S 4  is complete similarly to  FIG.  10   .  FIG.  17    illustrates the state after the processing in step S 5  is complete similarly to  FIG.  11   .  FIG.  18    illustrates the state after the processing in step S 6  is complete similarly to  FIG.  12   .  FIG.  19    illustrates the state after the processing in step S 7  is complete similarly to  FIG.  13   . 
       FIG.  20 A  illustrates the mixing flow path  115 A connected to the flow path  116  at a position  56 , and illustrates the boundary  67  between the flow path  116  and the flow path  117  as viewed in plan (as viewed in the −Z direction in this example). 
     As viewed in plan (as viewed in the −Z direction in this example), the flow path  116  and the mixing flow path  115 A define a minor angle θ 1  (also referred to as a first minor angle) adjacent to the entry hole  129 , and define a minor angle θ 2  (also referred to as a second minor angle) opposite to the entry hole  129 . The minor angle θ 1  is larger than the minor angle θ 2 . For the mixing flow path  115  as illustrated in  FIG.  14   , θ 1 =θ 2 . 
     The minor angle θ 1  is larger than the minor angle θ 2  to cause the sample to easily move toward the measurement flow path  151  through the flow path  117  after being pushed from the mixing flow path  115 A into the flow path  116 . A flow path with a smaller degree of bending allows easier flow of a fluid. As illustrated in  FIG.  20 A , the fluid in the area S less easily flows beyond the position  56  toward the reference flow path  152  (in the X direction in the area G 2 ). 
     The fluid in the area S less easily flows beyond the position  56  toward the reference flow path  152  to allow more separating target particles P 100  to move into the measurement flow path  151  after repeated processing in steps S 6  and S 7 . The mixing flow path  115 A may increase the accuracy of the predetermined process on the separating target particles P 100  than the mixing flow path  115 . 
     In the above example, the flow path  116  and the flow path  117  are connected with the boundary  67  in between. The flow paths  116  and  117  define a corner K. The corner K does not compromise the efficiency of the mixing flow path  115 A as compared with the mixing flow path  115 . 
     The corner K allows the measurement flow path  151  and the reference flow path  152  to be arranged in the X direction. The measurement flow path  151  and the reference flow path  152  arranged in the X direction allow optical measurement with an optical measurement device moved in a simple manner. 
     The flow paths  116  and  117  are grooves as described above and may be referred to as a single groove. The measurement flow path  151  and the mixing flow path  115 A are also grooves. The flow paths  116  and  117 , the measurement flow path  151 , and the mixing flow path  115 A can be described as below. 
     The measurement flow path  151  is a first groove connected to and continuous with the entry hole  129  (the first hole) without being open in the surface  1   a  or  1   b.    
     The flow paths  116  and  117  together form a second groove connected to and continuous with the measurement flow path  151  (the first groove) without being open in the surface  1   a  or  1   b.    
     The mixing flow path  115 A is a third groove connected to and continuous with the second groove (the flow paths  116  and  117 ) without being open in the surface  1   a  or  1   b . The third groove is connected to the second groove at the position  56  on the second groove spaced from the measurement flow path  151  (the first groove). 
     The first groove (the measurement flow path  151 ) extends toward a position opposite to the second groove (the flow paths  116  and  117 ) with respect to the first hole ( 129 ) (in the −Y direction in this example). 
     As viewed in plan, the second groove and the third groove define the minor angle θ 1  (the first minor angle) adjacent to the first hole and define the minor angle θ 2  (the second minor angle) opposite to the first hole, and the minor angle θ 1  is larger than the minor angle θ 2 . 
     In the example of  FIG.  20 A , the second groove extends from the reference flow path  152  in the Y direction, in the −X direction, and then in the −Y direction at the corner K, and is connected to the measurement flow path  151  at the position  71 . 
     In the example of  FIG.  20 A , the mixing flow path  115 A is connected to the second groove at the position  56  at which the flow path  116  extends straight. In this case, the minor angle θ 1  is obtuse. 
     The structures in  FIG.  14    and  FIG.  20 A  are compared. The flow path  117  extends parallel to the Y direction similarly to the measurement flow path  151 . The mixing flow path  115  extends parallel to the X direction and is connected to the flow path  117 . The mixing flow path  115 A is connected to the flow path  116  extending in the X direction. The mixing flow path  115 A is connected differently from the mixing flow path  115 , thus shortening the flow path  117 . More specifically, a distance D between the boundary  67  and the position  71  is shorter with the mixing flow path  115 A than with the mixing flow path  115 . 
     4. Variations 
       FIG.  20 B  illustrates a processing device  1  including a mixing flow path  115 B instead of the mixing flow path  115 A. A fluid is not illustrated. The mixing flow path  115 B is a groove that is not open in the surface  1   a  or  1   b . The mixing flow path  115 B can also be referred to as the above third groove. 
     The mixing flow path  115 B is also connected to the flow path  116  at the position  56 . The boundary  67  has the end in the X direction at the same position as the end of the mixing flow path  115 B in the −X direction at the position  56 . This structure can also define the minor angle θ 1  with the second groove being the flow paths  116  and  117 . The minor angle θ 1  is defined by the flow path  117  and the mixing flow path  115 B. In this variation as well, the minor angle θ 1  may be larger than the minor angle θ 2  to increase the accuracy of the predetermined process on the separating target particles P 100 . 
     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.