Flow path chip

Abstract

Provided is a flow path chip capable of capturing impurities contained in a liquid and suppressing the accumulation or adhesion of particles on the downstream side of a capturing body. The flow path chip is provided with a first flow path and a capturing body. A liquid containing particles flows in the first flow path. The capturing body is disposed in the first flow path. The capturing body captures impurities contained in the liquid. The capturing body has a blade-shaped cross section. The capturing body has a wide portion disposed on the upstream side in the flow direction of the liquid flowing through the first flow path, and a narrow portion disposed on the downstream side in the flow direction. The width of the narrow portion in an intersecting direction intersecting the flow direction is smaller than the width of the wide portion in the intersecting direction.

Description

Flow channel chip Related Applications

[0001] This application claims priority from Japanese Patent Application No. 2023-108067, filed on June 30, 2023, the entire contents of which are incorporated herein by reference.

[0002] The present invention relates to a channel chip.

[0003] Conventionally, a channel chip for separating specific cells from blood has been known (see, for example, Patent Document 1). Patent Document 1 describes a channel chip equipped with a hydrodynamic filtration (HDF) section including a main channel and multiple branch channels branching from the main channel. The channel chip further includes two inlet channels connected to the inlet of the main channel. Blood flows into one of the inlet channels as a sample liquid. A buffer solution flows into the other inlet channel. Each of the two inlet channels is provided with multiple pillars extending in the height direction of the channel chip.

[0004] Japanese Patent Application Laid-Open No. 2020-99256

[0005] In a channel chip such as that disclosed in Patent Document 1, a plurality of pillars are provided in the inlet channel, so that impurities contained in the sample solution or buffer solution can be captured.

[0006] However, after extensive research, the inventors of the present application found that in a channel chip such as that described in Patent Document 1, some particles (e.g., cancer cells) contained in blood may pass through multiple pillars and then become trapped or adhere downstream of the pillars. If particles become trapped or adhere downstream of the pillars, the number of particles (e.g., cancer cells) reaching the HDF section decreases. Furthermore, if particles become trapped or adhere downstream of the pillars, multiple particles may gather downstream of the pillars to form particle clumps, which may then flow downstream and clog the main and / or sub-channels of the HDF section. In particular, if the particles are cells, the cells may adhere to each other and form large clumps, easily clogging the channel.

[0007] The present invention has been made in consideration of the above-mentioned problems, and its purpose is to provide a flow path chip that can capture impurities contained in a liquid and prevent particles from accumulating or adhering downstream of the capture body.

[0008] A channel chip according to one aspect of the present invention includes a first channel and a capture body. A liquid containing particles flows through the first channel. The capture body is disposed within the first channel. The capture body captures impurities contained in the liquid. The capture body has a wing-shaped cross section. The capture body has a wide portion disposed upstream in the flow direction of the liquid flowing through the first channel, and a narrow portion disposed downstream in the flow direction. The width of the narrow portion in a cross direction intersecting the flow direction is smaller than the width of the wide portion in the cross direction.

[0009] In one aspect of the present invention, the liquid transport device may include a second flow path and a plurality of third flow paths. The second flow path may be disposed downstream of the first flow path, and the liquid may flow through the second flow path. The plurality of sub-flow paths may branch off from the second flow path, and some of the particles may flow through the sub-flow paths.

[0010] In one aspect of the present invention, a channel width of the first channel may be larger than a channel width of the second channel.

[0011] In one aspect of the present invention, a plurality of the capture bodies may be provided. The plurality of capture bodies may include a first row and a second row. The first row may have a plurality of first row capture bodies arranged at a predetermined interval from each other in the flow path width direction of the first flow path. The second row may be arranged adjacent to the downstream side of the first row. The second row may have a plurality of second row capture bodies arranged at a predetermined interval from each other in the flow path width direction. The second row capture bodies may be arranged at a position that does not overlap with a straight line passing through the tops of the wide portions of the first row capture bodies and the tops of the narrow portions of the first row capture bodies.

[0012] FIG. 1 is a plan view schematically showing the structure of a separation device including an HDF chip according to a first embodiment of the present invention. FIG. 2 is a plan view schematically showing the structure around a first capture body of the HDF chip according to the first embodiment. FIG. 3 is a diagram schematically showing the structure of a first capture body of the HDF chip according to the first embodiment. FIG. 4 is a plan view schematically showing the structure around an upstream junction of the HDF chip. FIG. 5 is a schematic diagram for explaining the operating principle of HDF. FIG. 6 is a plan view schematically showing the structure of an HDF chip according to a modified example of the first embodiment. FIG. 7 is a plan view schematically showing the structure of a separation device including an HDF chip according to a second embodiment of the present invention.

[0013] Hereinafter, embodiments of the present invention will be described with reference to the drawings. In the drawings, the same or corresponding parts are designated by the same reference characters and description thereof will not be repeated.

[0014] 1 to 5, a demultiplexer 100 including an HDF chip 1 according to a first embodiment of the present invention will be described. Fig. 1 is a plan view schematically showing the structure of a demultiplexer 100 including an HDF chip 1 according to the first embodiment of the present invention.

[0015] As shown in FIG. 1 , the separation device 100 of this embodiment includes an HDF (hydrodynamic filtration) chip 1. The HDF chip 1 functions as a hydrodynamic filter. For example, the HDF chip 1 is a microchannel chip intended for particle separation and / or concentration. In this embodiment, the HDF chip 1 can be used, for example, for pathological diagnosis. Furthermore, for example, the HDF chip 1 is configured with a transparent substrate or the like. The HDF chip 1 is an example of a "channel chip" of the present invention.

[0016] The HDF chip 1 includes at least a sample liquid supply channel 15 and a first capture body 31. In this embodiment, the HDF chip 1 includes a main channel 11, multiple sub-channels 13, a sample liquid supply channel 15, a first capture body 31, a transport liquid supply channel 17, a second capture body 33, an upstream junction 19, a collection section 21, a first outlet 23, and a second outlet 25. The sample liquid supply channel 15 is an example of the "first channel" of the present invention. The first capture body 31 is an example of the "capture body" of the present invention. The main channel 11 is an example of the "second channel" of the present invention. The sub-channel 13 is an example of the "third channel" of the present invention.

[0017] The main channel 11, the plurality of sub-channels 13, the sample liquid supply channel 15, the first capture body 31, the transport liquid supply channel 17, the second capture body 33, the upstream junction 19, the collection section 21, the first outlet 23, and the second outlet 25 are formed, for example, from a resin layer disposed on a transparent substrate. Specifically, all or part of the surfaces constituting the main channel 11, the sub-channels 13, the sample liquid supply channel 15, the first capture body 31, the transport liquid supply channel 17, the second capture body 33, the upstream junction 19, the collection section 21, the first outlet 23, and the second outlet 25 are made, for example, from a metal, an insulator, a semiconductor, PDMS (dimethylpolysiloxane), glass, and / or a photoresist.

[0018] Sample liquid 510 flows through sample liquid supply channel 15. Sample liquid supply channel 15 is a channel for supplying sample liquid 510 to main channel 11. In this embodiment, sample liquid supply channel 15 is inclined with respect to main channel 11, but the present invention is not limited to this. For example, sample liquid supply channel 15 may be parallel to main channel 11 or perpendicular to main channel 11.

[0019] The sample liquid 510 is a liquid containing particles. The sample liquid 510 is not particularly limited, but may be, for example, blood. The particle diameter is, for example, several tens of μm or less. In this embodiment, the particle diameter is, for example, 1 μm or more and 20 μm or less.

[0020] The shape of the particles is not particularly limited, but is preferably spherical, for example. However, the shape of the particles may be a shape other than spherical. In this embodiment, the particle may be a particle consisting of a single individual, or a group of fine particles formed by gathering a plurality of fine particles into a single mass. The particles may be formed point-symmetrically or line-symmetrically, or asymmetrically or line-symmetrically. The particles may have or may not have irregularities on the surface.

[0021] Sample liquid supplying flow path 15 has sample liquid inlet 151, upstream flow path 152, and downstream flow path 153. Sample liquid inlet 151 is disposed at the upstream end of sample liquid supplying flow path 15. Sample liquid 510 is supplied to sample liquid inlet 151, as will be described later.

[0022] Upstream flow path 152 is connected to sample liquid inlet 151. Sample liquid 510 supplied to sample liquid inlet 151 flows into upstream flow path 152. Upstream flow path 152 allows sample liquid 510 to flow from the upstream side (sample liquid inlet 151 side) to the downstream side (downstream flow path 153 side).

[0023] The downstream flow channel 153 is connected to the upstream flow channel 152. The downstream flow channel 153 allows the sample liquid 510 to flow from the upstream side (the upstream flow channel 152 side) to the downstream side (the main flow channel 11 side).

[0024] The flow path width of the portion of sample liquid supply flow path 15 where first capture body 31 is arranged (here, upstream flow path 152) is larger than the flow path width of main flow path 11. In addition, the flow path width of the portion of sample liquid supply flow path 15 where first capture body 31 is arranged (here, upstream flow path 152) is larger than the flow path width of downstream flow path 153.

[0025] 2 is a plan view schematically showing the structure around the first capture body 31 of the HDF chip 1 of the first embodiment. As shown in FIG. 2, the first capture body 31 is disposed in the sample liquid supply flow path 15. Specifically, the first capture body 31 is disposed in the upstream flow path 152. The first capture body 31 captures impurities 900 contained in the liquid (here, the sample liquid 510). In other words, the first capture body 31 functions as a filter. The impurities 900 are, for example, dirt, dust, or dirt.

[0026] The first capturing body 31 has a wing-shaped cross section. Specifically, the first capturing body 31 is formed, for example, in a columnar or rod shape. The cross section of the first capturing body 31 cut in a direction perpendicular to the extension direction of the first capturing body 31 has a wing shape. In other words, the cross section of the first capturing body 31 along the direction perpendicular to the extension direction has a wing shape.

[0027] The first capture body 31 is disposed across the upstream flow channel 152. In this embodiment, the first capture body 31 extends from the lower surface to the upper surface of the upstream flow channel 152. That is, the first capture body 31 extends within the upstream flow channel 152 in the thickness direction of the HDF chip 1 (perpendicular to the plane of FIG. 2 ). A gap may be formed between the first capture body 31 and the lower surface of the upstream flow channel 152 or between the first capture body 31 and the upper surface of the upstream flow channel 152. The first capture body 31 may extend within the upstream flow channel 152 in a flow channel width direction that intersects with the flow direction D1 of the liquid (here, the sample liquid 510). Here, the flow channel width direction is a direction perpendicular to the thickness direction of the HDF chip 1 and corresponds to the up-down direction of the plane of FIG. 2 .

[0028] FIG. 3 is a diagram schematically illustrating the structure of the first capture body 31 of the HDF chip 1 of the first embodiment. Note that in FIG. 3, the flow of liquid is depicted by dashed arrows. As shown in FIG. 3, the first capture body 31 has a wide portion 311 and a narrow portion 312. The wide portion 311 is disposed upstream in the flow direction D1 of the liquid (here, sample liquid 510) flowing through the sample liquid supply channel 15. That is, the wide portion 311 is disposed in the upstream portion of the first capture body 31. The narrow portion 312 is disposed downstream in the flow direction D1. That is, the narrow portion 312 is disposed downstream of the wide portion 311. The narrow portion 312 is also disposed in the downstream portion of the first capture body 31. The width of the narrow portion 312 in the intersecting direction (the flow channel width direction in this embodiment) intersecting the flow direction D1 is smaller than the width of the wide portion 311 in the direction intersecting the flow direction D1 (the flow channel width direction in this embodiment).

[0029] In this embodiment, as described above, the first capture body 31 having a wing-shaped cross section is disposed in the sample liquid supply flow path 15, with the wide portion 311 of the first capture body 31 disposed upstream and the narrow portion 312 of the first capture body 31 disposed downstream. Therefore, when liquid is flowed through the sample liquid supply flow path 15, flow separation can be prevented from occurring downstream of the first capture body 31. This prevents particles contained in the sample liquid 510 from accumulating or adhering downstream of the first capture body 31.

[0030] In this way, particles contained in the sample solution 510 can be prevented from accumulating or adhering downstream of the first capture body 31, thereby preventing a decrease in the number of particles (here, cells) reaching the main channel 11. Furthermore, particles can be prevented from gathering and forming clumps downstream of the first capture body 31. This prevents clumps of particles from flowing downstream and clogging the main channel 11 and / or the sub-channel 13. In particular, when the particles (hereinafter sometimes referred to as target particles) that are desired to reach the main channel 11 are cells, there is a risk that the cells will adhere to each other one after another and form large clumps. Therefore, when the target particles are cells, preventing particles from accumulating or adhering downstream of the first capture body 31 is particularly effective.

[0031] As described above, the first capture body 31 has a wing-shaped cross section. The type of wing shape is not particularly limited, but examples include NACA 4-digit, NACA 5-digit, NACA 6, and Joukowski blades. The type and / or size of the wing shape may be determined depending on, for example, the liquid flow rate, the liquid viscosity, the particle density, the particle size, the flow path width, or the flow path height. The first capture body 31 has a streamlined cross section. It is preferable that the entire cross section of the first capture body 31 be streamlined, but only a portion of the cross section of the first capture body 31 may be streamlined.

[0032] In addition, in this embodiment, the first capturing body 31 is formed symmetrically in the width direction of the first capturing body 31 (a direction intersecting the longitudinal direction). In this embodiment, the first capturing body 31 is formed symmetrically in the flow path width direction. However, the first capturing body 31 does not have to be formed symmetrically in the width direction of the first capturing body 31, the flow path width direction, or a predetermined direction. In other words, the first capturing body 31 may have an asymmetric shape.

[0033] In this embodiment, the first capturing body 31 is disposed substantially parallel to the flow direction D1. Specifically, the center line of the first capturing body 31, which extends from the upstream side to the downstream side, is disposed substantially parallel to the flow direction D1. The center line of the first capturing body 31 may be disposed at an angle with respect to the flow direction D1.

[0034] As shown in FIG. 2 , in this embodiment, a plurality of first capture bodies 31 are provided. That is, in this embodiment, a filter is formed by the plurality of first capture bodies 31. The plurality of first capture bodies 31 are arranged, for example, in a staggered pattern, although this is not particularly limited. Specifically, the plurality of first capture bodies 31 are formed in a plurality of rows. The plurality of first capture bodies 31 includes a first row 321 and a second row 322. In this embodiment, the plurality of first capture bodies 31 include a first row 321, a second row 322, and a third row 323. The first row 321 includes a plurality of first-row capture bodies 3211 arranged at a predetermined interval from each other in the flow path width direction of the sample liquid supply flow path 15. The second row 322 includes a plurality of second-row capture bodies 3221 arranged at a predetermined interval from each other in the flow path width direction. The third row 323 includes a plurality of third-row capture bodies 3231 arranged at a predetermined interval from each other in the flow path width direction. Therefore, the plurality of first capture bodies 31 includes a plurality of first row capture bodies 3211, a plurality of second row capture bodies 3221, and a plurality of third row capture bodies 3231. Note that the spacing (predetermined spacing) between the first row capture bodies 3211, the spacing (predetermined spacing) between the second row capture bodies 3221, and the spacing (predetermined spacing) between the third row capture bodies 3231 may be the same or different. In this embodiment, the spacing (predetermined spacing) between the first row capture bodies 3211, the spacing (predetermined spacing) between the second row capture bodies 3221, and the spacing (predetermined spacing) between the third row capture bodies 3231 are the same.

[0035] The second row 322 is disposed adjacent to the downstream side of the first row 321. The third row 323 is disposed adjacent to the downstream side of the second row 322.

[0036] Furthermore, in this embodiment, the second row capturing body 3221 is positioned at a position that does not overlap with the straight line L1 that passes through the top 3111 (see Figure 3) of the wide portion 311 of the first row capturing body 3211 and the top 3121 (see Figure 3) of the narrow portion 312 of the first row capturing body 3211. The top 3111 is the upstream end of the wide portion 311. The top 3121 is the downstream end of the narrow portion 312. Furthermore, in this embodiment, when viewed from the flow direction D1, the first row capturing body 3211 and the second row capturing body 3221 are positioned at a position that does not overlap. Note that in this embodiment, the straight line L1 is the center line of the first row capturing body 31.

[0037] Furthermore, in this embodiment, the third row capturing body 3231 is positioned so as not to overlap with the straight line L2 that passes through the top 3111 of the wide portion 311 of the second row capturing body 3221 and the top 3121 of the narrow portion 312 of the second row capturing body 3221. Furthermore, in this embodiment, the second row capturing body 3221 and the third row capturing body 3231 are positioned so as not to overlap when viewed from the flow direction D1.

[0038] The distance between adjacent first capture bodies 31 is preferably greater than the particle size (here, cells) contained in the liquid, but may be smaller than the particle size. In this embodiment, the distance between adjacent first capture bodies 31 is 1.1 to 5 times, and preferably 1.5 to 3 times, the particle size of the largest particle (e.g., cancer cell) contained in the liquid. Alternatively, in this embodiment, the distance between adjacent first capture bodies 31 is 1 μm to 100 μm greater, and preferably 5 μm to 50 μm greater, than the particle size of the largest particle (e.g., cancer cell) contained in the liquid. Note that the distance between adjacent first capture bodies 31 is preferably smaller than the particle size of impurities 900, but may be greater than the particle size of impurities 900.

[0039] As shown in FIG. 1 , a transport liquid 520 flows through the transport liquid supply channel 17. The transport liquid supply channel 17 is a channel for supplying the transport liquid 520 to the main channel 11. The transport liquid 520 is, for example, a liquid for transporting particles larger than a predetermined particle size. In this embodiment, the transport liquid 520 is a liquid for transporting particles that do not flow into the sub-channel 13 to the downstream side of the main channel 11. Note that in this embodiment, the transport liquid supply channel 17 is inclined with respect to the main channel 11, but the present invention is not limited to this. For example, the transport liquid supply channel 17 may be parallel to the main channel 11 or perpendicular to the main channel 11.

[0040] The transport liquid 520 is, for example, a liquid that does not contain particles. The transport liquid 520 is not particularly limited, but may be, for example, a liquid culture medium.

[0041] The transport liquid supply channel 17 has a transport liquid inlet 171, an upstream channel 172, and a downstream channel 173. The transport liquid inlet 171 is disposed at the upstream end of the transport liquid supply channel 17. As will be described later, a transport liquid 520 is supplied to the transport liquid inlet 171.

[0042] The upstream flow path 172 is connected to the transport liquid inlet 171. The transport liquid 520 supplied to the transport liquid inlet 171 flows into the upstream flow path 172. The upstream flow path 172 allows the transport liquid 520 to flow from the upstream side (the transport liquid inlet 171 side) to the downstream side (the downstream flow path 173 side).

[0043] The downstream flow path 173 is connected to the upstream flow path 172. The downstream flow path 173 allows the transport liquid 520 to flow from the upstream side (the upstream flow path 172 side) to the downstream side (the main flow path 11 side).

[0044] The flow path width of the upstream flow path 172 is larger than the flow path width of the main flow path 11. The flow path width of the upstream flow path 172 is also larger than the flow path width of the downstream flow path 173.

[0045] The second capture body 33 is disposed in the transport liquid supply flow path 17. Specifically, the second capture body 33 is disposed in the upstream flow path 172. The second capture body 33 captures impurities 900 contained in the liquid (here, the transport liquid 520). In other words, the second capture body 33 functions as a filter.

[0046] The second capture body 33 has a circular or rectangular cross section. Specifically, the second capture body 33 is formed in the shape of, for example, a cylinder or a square prism. The second capture body 33 extends from the lower surface to the upper surface of the upstream flow path 172.

[0047] Unlike the first capture body 31, the second capture body 33 does not have a wing-shaped cross section, and therefore flow separation occurs downstream of the second capture body 33. However, since the transport liquid 520 does not contain particles, particles do not stagnate or adhere downstream of the second capture body 33.

[0048] Furthermore, a plurality of second capture bodies 33 are provided. That is, in this embodiment, a filter is formed by a plurality of second capture bodies 33. The distance between adjacent second capture bodies 33 is, for example, the same as the distance between adjacent first capture bodies 31, or is smaller than the distance between adjacent first capture bodies 31. In this embodiment, the distance between adjacent second capture bodies 33 is smaller than the distance between adjacent first capture bodies 31.

[0049] The sample liquid supply channel 15 and the transport liquid supply channel 17 join at an upstream junction 19. The upstream junction 19 is disposed at the upstream end of the main channel 11. Therefore, the sample liquid 510 that has passed through the sample liquid supply channel 15 and the transport liquid 520 that has passed through the transport liquid supply channel 17 join at the upstream junction 19 and flow through the main channel 11.

[0050] The main channel 11 extends, for example, linearly in a predetermined direction. Liquid flows through the main channel 11. In this embodiment, a sample liquid 510 and a transport liquid 520 flow through the main channel 11.

[0051] The multiple sub-channels 13 branch off from the main channel 11. Specifically, the multiple sub-channels 13 are arranged, for example, at approximately equal intervals along the direction in which the main channel 11 extends. The multiple sub-channels 13 extend in a direction intersecting the main channel 11. In this embodiment, the multiple sub-channels 13 extend in a direction perpendicular to the main channel 11. In this embodiment, the multiple sub-channels 13 are connected perpendicular to the main channel 11. However, although it is preferable that the multiple sub-channels 13 are connected perpendicular to the main channel 11, they may also be connected at an angle other than perpendicular to the main channel 11.

[0052] The HDF 2 is composed of the main channel 11 and the multiple sub-channels 13. Specifically, some of the liquid flowing through the main channel 11 flows into the multiple sub-channels 13. Furthermore, some of the particles contained in the liquid flowing through the main channel 11 flow into the multiple sub-channels 13. Whether particles flow into the multiple sub-channels 13 depends on, for example, particle size. However, even particles with a particle size smaller than the width of the sub-channel 13 do not necessarily flow into the sub-channel 13. Particles with smaller particle sizes tend to flow into the sub-channel 13 more easily, while particles with larger particle sizes tend to flow less easily into the sub-channel 13. For example, when blood is used as the sample liquid 510, it is possible to flow plasma (also called plasma), red blood cells, and platelets, which are liquid components of blood, into the sub-channel 13, while preventing cancer cells and white blood cells contained in the blood from flowing into the sub-channel 13. In other words, it is possible to separate large particles, such as cancer cells and white blood cells, from the blood. The operating principle of the HDF 2 will be described later.

[0053] 4 is a plan view schematically showing the structure around the upstream confluence 19 of the HDF chip 1. As shown in FIG. 4, the sample liquid supply channel 15 is arranged so that the sample liquid 510 flows through the portion of the main channel 11 on the side of the sub-channel 13. On the other hand, the transport liquid supply channel 17 is arranged so that the transport liquid 520 flows through the portion of the main channel 11 on the side opposite the sub-channel 13. In this embodiment, the sample liquid supply channel 15 is connected to an inner wall 111 of the main channel 11 on the side of the sub-channel 13. On the other hand, the transport liquid supply channel 17 is connected to an inner wall 112 of the main channel 11 on the side opposite the sub-channel 13.

[0054] 1 , the collection unit 21 collects the liquid that has passed through the multiple sub-channels 13. The collection unit 21 is connected to multiple (here, all) of the sub-channels 13. The collection unit 21 is also connected to a first outlet 23. The collection unit 21 collects the liquid that has passed through the multiple sub-channels 13 and guides it to the first outlet 23.

[0055] The liquid that has passed through the plurality of sub-channels 13 is collected in a first collection unit (not shown) via the collection unit 21 and the first outlet 23. The first collection unit includes, for example, a collection container.

[0056] The second outlet 25 is connected to the downstream end of the main channel 11. Therefore, the liquid that has passed through the main channel 11 flows to the second outlet 25. At least particles larger than a predetermined particle size contained in the sample liquid 510 flow through the second outlet 25. In this embodiment, a transport liquid 520 containing particles larger than a predetermined particle size flows through the second outlet 25. The liquid that has passed through the main channel 11 (here, the transport liquid 520) is collected in a second collection unit (not shown) via the second outlet 25. The second collection unit includes, for example, a collection container.

[0057] Continuing to refer to FIG. 1 , the separation device 100 and the HDF chip 1 will be further described. The separation device 100 further includes a sample liquid delivery unit 35 and a transport liquid delivery unit 36. The separation device 100 may also include a control device (not shown) that drives the sample liquid delivery unit 35 and the transport liquid delivery unit 36. The sample liquid delivery unit 35 and the transport liquid delivery unit 36 ​​are not particularly limited, but may be, for example, a micropump. The micropump may be a mechanical pump or a non-mechanical pump.

[0058] The control device may include, for example, a control unit and a memory unit. The control unit may have, for example, a processor. The control unit may have, for example, a central processing unit (CPU) or a general-purpose computer. The memory unit may include, for example, a main memory unit and an auxiliary memory unit. The main memory unit is, for example, a semiconductor memory. The auxiliary memory unit is, for example, a semiconductor memory and / or a hard disk drive. The memory unit may include removable media.

[0059] Sample liquid delivery unit 35 is connected to sample liquid supply channel 15 and causes sample liquid 510 to flow through sample liquid supply channel 15. Specifically, sample liquid delivery unit 35 is connected to sample liquid inlet 151 of sample liquid supply channel 15. When sample liquid delivery unit 35 supplies sample liquid 510 to sample liquid inlet 151, sample liquid 510 flows through sample liquid supply channel 15 and main channel 11.

[0060] The transport liquid delivery unit 36 ​​is connected to the transport liquid supply flow path 17 and causes the transport liquid 520 to flow through the transport liquid supply flow path 17. Specifically, the transport liquid delivery unit 36 ​​is connected to the transport liquid inlet 171 of the transport liquid supply flow path 17. When the transport liquid delivery unit 36 ​​supplies the transport liquid 520 to the transport liquid inlet 171, the transport liquid 520 flows through the transport liquid supply flow path 17 and the main flow path 11.

[0061] In this embodiment, the sample liquid delivery unit 35 delivers the sample liquid 510 so that the sample liquid 510 forms a laminar flow. The transport liquid delivery unit 36 ​​delivers the transport liquid 520 so that the transport liquid 520 forms a laminar flow. Therefore, in this embodiment, each liquid forms a laminar flow in the HDF chip 1.

[0062] Next, the operating principle of the HDF 2 will be described with reference to FIG. 5 . FIG. 5 is a schematic diagram for explaining the operating principle of the HDF 2. As shown in FIG. 5 , when the sample liquid delivery unit 35 supplies the sample liquid 510 and the transport liquid delivery unit 36 ​​supplies the transport liquid 520, the sample liquid 510 and the transport liquid 520 flow through the main channel 11. The sample liquid 510 flows along the inner wall 111 on the sub-channel 13 side, and the transport liquid 520 flows along the inner wall 112 on the opposite side from the sub-channel 13. At this time, the centers (more specifically, the centers of gravity) of the various particles pass through positions spaced apart from the inner wall 111 of the main channel 11 by at least the radius of the particles.

[0063] Of the fluid flowing through the main channel 11, a portion of the fluid flowing within a certain distance from the inner wall 111 on the side of the sub-channel 13 flows into the sub-channel 13, and particles flow into the sub-channel 13 along with this portion of the fluid. More specifically, particles whose centers of gravity are located within the certain distance flow into the sub-channel 13. The certain distance is a design parameter that can be adjusted by the design of the main channel 11 and the sub-channel 13 (more specifically, the channel resistance). Therefore, the main channel 11 and the sub-channel 13 are designed so that the centers of gravity of particles equal to or smaller than a certain size are located within the certain distance from the inner wall 111, and the centers of gravity of particles exceeding the certain size are located outside the certain distance from the inner wall 111. Typically, the main channel 11 and the sub-channel 13 are designed so that the certain distance is approximately half the particle size of the certain size.

[0064] Therefore, particles with small particle diameters and centers of gravity located near the inner wall 111 tend to flow into the sub-channel 13. On the other hand, particles with large particle diameters and centers of gravity located far from the inner wall 111 do not flow into the sub-channel 13 but travel straight through the main channel 11. In other words, under predetermined conditions, such as a constant supply of the sample solution 510 and the transport liquid 520, particles larger than a predetermined size are not discharged from the main channel 11, while particles smaller than the predetermined size are discharged from the main channel 11. Because discharge from the main channel 11 to the sub-channels 13 is repeated via multiple sub-channels 13, particles smaller than the predetermined size do not reach the downstream end of the main channel 11. Note that plasma, which is a liquid component, also does not reach the downstream end of the main channel 11. Therefore, the HDF chip 1 can separate large particles, such as cancer cells and white blood cells, from blood, for example.

[0065] As described above with reference to FIGS. 1 to 5 , in this embodiment, a first capture body 31 having a wing-shaped cross section is disposed in the sample liquid supply flow channel 15. The wide portion 311 of the first capture body 31 is disposed upstream, and the narrow portion 312 of the first capture body 31 is disposed downstream. Therefore, when a liquid is flowed through the sample liquid supply flow channel 15, flow separation downstream of the first capture body 31 can be suppressed. This prevents particles contained in the sample liquid 510 from accumulating or adhering downstream of the first capture body 31. Therefore, the HDF chip 1 can be used for highly viscous particles (e.g., cells), thereby improving the versatility of the HDF chip 1.

[0066] As described above, the HDF chip 1 includes the main channel 11 located downstream of the sample liquid supply channel 15 and multiple sub-channels 13 branching off from the main channel 11. That is, the HDF chip 1 includes the HDF 2 (the main channel 11 and multiple sub-channels 13) downstream of the sample liquid supply channel 15 in which the first capture body 31 is located. Therefore, by preventing particles from accumulating or adhering downstream of the first capture body 31, a decrease in the number of particles (here, cells) reaching the main channel 11 can be prevented. Furthermore, by preventing particles from accumulating or adhering downstream of the first capture body 31, a decrease in the number of particles (here, cells) reaching the main channel 11 can be prevented. Furthermore, by preventing particles from accumulating or adhering downstream of the first capture body 31, a decrease in the number of particles gathering downstream of the first capture body 31 can be prevented. This prevents particle clumps from flowing downstream and clogging the main channel 11 and / or the sub-channels 13. Therefore, particles smaller than a predetermined size and / or liquid components of the sample liquid 510 can be prevented from reaching the downstream end of the main channel 11. In other words, the durability and / or robustness of the HDF chip 1 can be improved. In particular, when the particles are cells, there is a risk that the cells will adhere one after another to form large clumps. Therefore, in a configuration in which the particles are cells and the HDF 2 is disposed downstream of the sample liquid supply channel 15, it is particularly effective to prevent the particles from remaining or adhering downstream of the first capture body 31.

[0067] As described above, the flow path width of sample liquid supply flow path 15 is greater than the flow path width of main flow path 11. Specifically, the flow path width of the portion of sample liquid supply flow path 15 where first capture body 31 is arranged (here, upstream flow path 152) is greater than the flow path width of main flow path 11. Therefore, for example, impurities 900 can be captured in a portion with a wider flow path width compared to when first capture body 31 is arranged in main flow path 11. Therefore, clogging of the flow path by impurities 900 can be suppressed.

[0068] Furthermore, as described above, the second row capture bodies 3221 are positioned so as not to overlap the straight line L1 that passes through the top 3111 of the wide portion 311 of the first row capture body 3211 and the top 3121 of the narrow portion 312 of the first row capture body 3211. Therefore, even if the impurities 900 pass between adjacent first row capture bodies 3211, the impurities 900 can be easily captured by the second row capture bodies 3221 of the second row 322.

[0069] (Modification) Next, an HDF chip 1 according to a modification of the first embodiment will be described with reference to Fig. 6. Fig. 6 is a plan view schematically showing the structure of an HDF chip 1 according to a modification of the first embodiment.

[0070] 6 , in the HDF chip 1 according to the modification of the first embodiment, some of the multiple first capture bodies 31 are formed integrally with the inner wall of the sample liquid supply channel 15. Specifically, the first capture bodies 31 arranged on the outer side in the channel width direction are formed integrally with the inner wall of the sample liquid supply channel 15. In other words, the first capture bodies 31 arranged on the outer side in the channel width direction and the sample liquid supply channel 15 are a single member. Furthermore, the outer surface of the first capture body 31 arranged on the outer side in the channel width direction is formed continuously with the inner surface of the sample liquid supply channel 15. In this modification, the first capture bodies 31 arranged at both ends in the channel width direction of each of the first row 321 and the third row 323 are formed integrally with the inner wall of the sample liquid supply channel 15.

[0071] Other configurations and effects of the modified example of the first embodiment are similar to those of the first embodiment.

[0072] Second Embodiment Next, a demultiplexer 300 including an HDF chip 301 according to a second embodiment of the present invention will be described with reference to Fig. 7. Fig. 7 is a plan view schematically showing the structure of a demultiplexer 300 including an HDF chip 301 according to the second embodiment of the present invention.

[0073] 7 , in a separation device 300 according to the second embodiment of the present invention, an HDF chip 301 includes a main channel 11, a transport liquid supply channel 26, a separation channel 27, a first recovery channel 51, and a second recovery channel 53. Similarly to the HDF chip 1, the HDF chip 301 also includes a plurality of sub-channels 13, a sample liquid supply channel 15, a first capture body 31, a transport liquid supply channel 17, a second capture body 33, an upstream junction 19, a collection section 21, and a first outlet 23. The HDF chip 301 is an example of the “channel chip” of the present invention.

[0074] A transport liquid 530 flows through the transport liquid supply flow path 26. The transport liquid supply flow path 26 is a flow path for supplying the transport liquid 530 to the separation flow path 27. The transport liquid 530 is, for example, a liquid for transporting particles separated by dielectrophoresis (described later) to the first recovery path 51. The transport liquid 530 is, for example, a liquid that does not contain particles. The transport liquid 530 is not particularly limited, but may have the same components as the transport liquid 520, for example.

[0075] The separation channel 27 is connected to the downstream end of the main channel 11 and the downstream end of the transport liquid supply channel 26. For example, the channel width of the separation channel 27 is larger than the channel width of the main channel 11 and the channel width of the transport liquid supply channel 26. By making the channel width of the separation channel 27 larger than the channel width of the main channel 11 in this way, the flow rate of the liquid flowing through the separation channel 27 can be reduced. This makes it easy to separate particles by dielectrophoresis, which will be described later.

[0076] The first recovery channel 51 and the second recovery channel 53 are connected to the downstream end of the separation channel 27. In other words, the separation channel 27 is branched into the first recovery channel 51 and the second recovery channel 53.

[0077] In the HDF chip 301, the second outlet 25 includes a second outlet 251 and a second outlet 252. The second outlet 251 is connected to the downstream end of the first recovery channel 51, and the second outlet 252 is connected to the downstream end of the second recovery channel 53.

[0078] Here, the HDF chip 301 can further separate particles flowing through the separation channel 27 by dielectrophoresis (DEP). Specifically, the HDF chip 301 further includes an electrode 55 and an electrode 57 that are arranged to overlap the separation channel 27. The electrodes 55 and 57 are comb-shaped electrodes that face each other. The electrode 55 is connected to, for example, an AC power supply 61. The electrode 57 is grounded, for example. In the second embodiment, the separation device 300 includes the AC power supply 61. Note that the separation device 300 does not necessarily have to include the AC power supply 61.

[0079] The teeth of electrodes 55 and 57 are inclined at an angle of, for example, 10° to 60° with respect to separation channel 27. Dielectrophoresis can be caused by applying an AC voltage between electrodes 55 and 57 using AC power supply 61. Then, by adjusting the frequency of the applied AC voltage, it is possible to separate and recover desired particles from multiple types of particles passing through separation channel 27.

[0080] Specifically, when multiple types of particles passing through the separation channel 27 include dielectric particles, it is possible to separate specific dielectric particles from the multiple types of particles using DEP. For example, cancer cells and white blood cells are dielectric particles. When the multiple types of particles passing through the separation channel 27 include cancer cells and particles other than cancer cells that are larger than a predetermined size (e.g., white blood cells), for example, an AC voltage of a specific frequency is applied between the electrodes 55 and 57 so that the dielectrophoretic force acts more easily on the cancer cells. This allows the cancer cells to move along the electrodes 55 and 57, and therefore allows only the cancer cells to be guided to the second outlet 251 by dielectrophoresis. This makes it possible to separate the cancer cells from other particles (e.g., white blood cells).

[0081] Other structures of the separation device 300, HDF chip 301, main channel 11, multiple sub-channels 13, sample liquid supply channel 15, first capture body 31, transport liquid supply channel 17, second capture body 33, upstream junction 19, collection section 21, and first outlet 23 according to the second embodiment are similar to those of the separation device 100, HDF chip 1, main channel 11, multiple sub-channels 13, sample liquid supply channel 15, first capture body 31, transport liquid supply channel 17, second capture body 33, upstream junction 19, collection section 21, and first outlet 23 according to the first embodiment. Furthermore, other effects of the second embodiment are similar to those of the first embodiment.

[0082] The embodiments of the present invention have been described above with reference to the drawings. However, the present invention is not limited to the above embodiments and can be embodied in various forms without departing from the spirit and scope of the present invention. Furthermore, various inventions can be formed by appropriately combining multiple components disclosed in the above embodiments. For example, some components may be omitted from all components shown in the embodiments. Furthermore, components from different embodiments may be appropriately combined. The drawings mainly show each component in a schematic manner to facilitate understanding. The thickness, length, number, spacing, etc. of each component shown may differ from the actual thickness, length, number, spacing, etc. of each component shown in the above embodiments due to the convenience of drawing. Furthermore, the materials, shapes, dimensions, etc. of each component shown in the above embodiments are merely examples and are not particularly limited. Various modifications are possible within a scope that does not substantially deviate from the effects of the present invention.

[0083] For example, in the above embodiment, an example was described in which blood was used as sample liquid 510 and a liquid culture medium was used as transport liquid 520, but the present invention is not limited to this. For example, a liquid other than blood may be used as sample liquid 510, and a liquid other than a culture medium may be used as transport liquid 520.

[0084] In the first embodiment, an example was described in which the HDF chip 1 includes the HDF 2. In the second embodiment, an example was described in which the HDF chip 1 includes the HDF 2, the separation channel 27 that separates particles by dielectrophoresis, and the electrodes 55 and 57. However, the present invention is not limited to this. For example, the channel chip does not need to include both the HDF 2 and the separation channel 27 that separates particles by dielectrophoresis, the electrodes 55 and 57. Alternatively, the channel chip may include the separation channel 27 that separates particles by dielectrophoresis, the electrodes 55 and 57, and the electrodes 57, without including the HDF 2.

[0085] In the above embodiment, all of the first capturing bodies 31 have the same cross-sectional shape and the same size, but the present invention is not limited to this. For example, some of the first capturing bodies 31 may have the same cross-sectional shape and the same size. Furthermore, for example, the first capturing bodies 31 may have different widths, lengths, or shapes.

[0086] In the above embodiment, the first capturing bodies 31 are arranged in a regular pattern, but the present invention is not limited to this. For example, the first capturing bodies 31 may be arranged in an irregular pattern.

[0087] Furthermore, in the above embodiment, for example, an example has been described in which one filter constituted by a plurality of first capture bodies 31 is provided in sample liquid supply flow path 15, but the present invention is not limited to this. For example, a plurality of filters constituted by a plurality of first capture bodies 31 may be provided in series in a single flow path. Furthermore, for example, sample liquid supply flow path 15 may be branched, and one or more filters may be provided in each of the branched flow paths.

[0088] In the above embodiment, sample liquid supply channel 15 includes upstream channel 152 and downstream channel 153, but the present invention is not limited to this. For example, sample liquid supply channel 15 may be configured as a single channel with a constant channel width. In this case, the channel width of sample liquid supply channel 15 is preferably larger than that of main channel 11, but may also be the same as that of main channel 11.

[0089] In the first embodiment, the particles (e.g., cancer cells and white blood cells) collected from the second outlet 25 are used as an example of the target collected material, but the present invention is not limited to this. For example, the particles or liquid components collected from the first outlet 23 may be the target collected material.

[0090] In the second embodiment, an example has been described in which target particles (e.g., cancer cells) are collected from the second outlet 251. However, the present invention is not limited to this. For example, target particles may be collected from the second outlet 252.

[0091] In the above embodiment, an example has been described in which a liquid that does not contain particles (e.g., transport liquid 520) is used. That is, an example has been described in which a liquid that does not contain particles (e.g., transport liquid 520) is flowed through the main channel 11 in addition to a liquid that contains particles (e.g., sample liquid 510). However, the present invention is not limited to this. For example, only a liquid that contains particles (e.g., sample liquid 510) may be flowed through the main channel 11. Furthermore, for example, seawater containing particles may be used as the liquid that contains particles (e.g., sample liquid 510), and the particles may be separated from the seawater.

[0092] In the above embodiment, the sub-channel 13 is connected to one of the inner walls 111 and 112 of the main channel 11 (the inner wall 111). However, the present invention is not limited to this. For example, the sub-channel 13 may be connected to both the inner wall 111 and the inner wall 112.

[0093] In the above embodiment, an example has been described in which no structures such as sensors are disposed in the channels of the HDF chip 1 (e.g., the main channel 11 and the sub-channel 13), but the present invention is not limited to this. For example, as long as it is possible to separate particles, structures such as physical, electrical, or magnetic sensors may be disposed in the channels of the HDF chip 1 (e.g., the sample liquid supply channel 15, the main channel 11, the sub-channel 13, or the separation channel 27).

[0094] The present invention can be used in the field of channel chips.

[0095] 1, 301: HDF chip (channel chip) 11: Main channel (second channel) 13: Sub-channel (third channel) 15: Sample liquid supply channel (first channel) 31: First capture body (capture body) 311: Wide section 312: Narrow section 321: First row 322: Second row 900: Impurities 3111: Top 3121: Top 3211: First row capture body 3221: Second row capture body D1: Flow direction L1: Straight line

Claims

1. A flow path chip comprising: a first flow path through which a liquid containing particles flows; and a capture body disposed within the first flow path for capturing impurities contained in the liquid, wherein the capture body has a wing-shaped cross section and has a wide portion disposed upstream in a flow direction of the liquid flowing through the first flow path and a narrow portion disposed downstream in the flow direction, and the width of the narrow portion in a cross direction that intersects with the flow direction is smaller than the width of the wide portion in the cross direction.

2. The flow path chip according to claim 1, comprising: a second flow path arranged downstream of the first flow path, through which the liquid flows; and a plurality of third flow paths branching off from the second flow path, through which some of the particles flow.

3. The channel chip according to claim 2, wherein the channel width of the first channel is greater than the channel width of the second channel.

4. A flow path chip as described in any one of claims 1 to 3, wherein a plurality of the capture bodies are provided, the plurality of capture bodies including a first row having a plurality of first row capture bodies arranged at a predetermined interval from each other in the flow path width direction of the first flow path, and a second row having a plurality of second row capture bodies arranged adjacent to the downstream side of the first row and arranged at a predetermined interval from each other in the flow path width direction, and the second row capture bodies are arranged at a position that does not overlap with a straight line passing through the tops of the wide portions of the first row capture bodies and the tops of the narrow portions of the first row capture bodies.

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