Flow path chip
The channel chip addresses contaminant adherence and clogging by using wing-shaped capture bodies and branching channels to enhance particle capture efficiency and durability.
Patent Information
- Application Number
- JP2023108067
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2023-06-30
- Publication Date
- 2025-01-17
AI Technical Summary
Existing channel chips face issues with contaminants in sample liquids adhering to pillars, leading to reduced particle capture efficiency and potential clogging due to particle clumping.
A channel chip design featuring a first channel with capture bodies having a wing-shaped cross section, where the wide portion is upstream and the narrow portion is downstream, along with a second flow path and branching sub-channels, to prevent particle adherence and clumping.
The design effectively captures contaminants and prevents particle adherence, enhancing the efficiency and durability of the channel chip by reducing clogging and maintaining particle flow.
Smart Images

Figure 2025006982000001_ABST
Abstract
Description
[Technical field]
[0001] The present invention relates to a channel chip. [Background technology]
[0002] Conventionally, a channel chip for separating specific cells from blood is known (see, for example, Patent Document 1). Patent Document 1 describes a channel chip equipped with an HDF section including a main channel and multiple branch channels branching off 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 liquid 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. [Prior art documents] [Patent documents]
[0003] [Patent Document 1] JP 2020-99256 A Summary of the Invention [Problem to be solved by the invention]
[0004] In a channel chip such as that disclosed in Patent Document 1, a plurality of pillars are provided in the inlet channel, making it possible to capture impurities contained in the sample liquid or buffer liquid.
[0005] However, as a result of intensive research by the inventors of the present application, it was found that in a flow channel chip such as that of Patent Document 1, some particles (e.g., cancer cells) contained in blood may pass through multiple pillars and then remain or adhere to the downstream side of the pillars. In this way, when particles remain or adhere to the downstream side of the pillars, the number of particles (e.g., cancer cells) that reach the HDF section decreases. In addition, when particles remain or adhere to the downstream side of the pillars, multiple particles gather on the downstream side of the pillars to form a particle clump, and the particle clump may flow downstream and clog the main flow channel and / or sub-flow channel of the HDF section. In particular, when the particles are cells, the cells may adhere to each other one after another to form large clumps, which are likely to clog the flow channel.
[0006] 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 remaining or adhering downstream of the capture body. [Means for solving the problem]
[0007] A flow path chip according to one aspect of the present invention comprises a first flow path and a capture body. A liquid containing particles flows through the first flow path. The capture body is disposed within the first flow path. 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 a flow direction of the liquid flowing through the first flow path, and a narrow portion disposed downstream in the flow direction. A width of the narrow portion in a cross direction intersecting the flow direction is smaller than a width of the wide portion in the cross direction.
[0008] In one aspect of the present invention, the liquid may flow through 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 plurality of sub-flow paths. 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.
[0009] 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.
[0010] 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 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. Effect of the Invention
[0011] According to the present invention, it is possible to provide a channel chip that is capable of trapping impurities contained in a liquid and suppressing the retention or adhesion of particles on the downstream side of the trapping body. [Brief description of the drawings]
[0012] [Figure 1] FIG. 1 is a plan view showing a schematic structure of a separation device including an HDF chip according to a first embodiment of the present invention. [Diagram 2] FIG. 2 is a plan view showing a schematic structure of a first capture body and its surroundings of the HDF chip of the first embodiment. [Diagram 3] FIG. 2 is a diagram showing a schematic structure of a first capture body of the HDF chip of the first embodiment. [Figure 4] FIG. 2 is a plan view showing a schematic structure of the periphery of the upstream junction of the HDF chip. [Diagram 5] FIG. 1 is a schematic diagram for explaining the operating principle of HDF. [Figure 6] FIG. 11 is a plan view illustrating a structure of an HDF chip according to a modified example of the first embodiment. [Figure 7] FIG. 11 is a plan view showing a schematic structure of a separation device including an HDF chip according to a second embodiment of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0013] Hereinafter, an embodiment 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] (First embodiment) A separation device 100 including an HDF chip 1 according to a first embodiment of the present invention will be described with reference to Figures 1 to 5. Figure 1 is a plan view that illustrates a schematic structure of a separation device 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 separating and / or concentrating particles. In this embodiment, the HDF chip 1 can be used, for example, for pathological diagnosis. For example, the HDF chip 1 is composed of a transparent substrate or the like. The HDF chip 1 is an example of the "channel chip" of the present invention.
[0016] The HDF chip 1 at least includes a sample liquid supply flow path 15 and a first capture body 31. In this embodiment, the HDF chip 1 includes a main flow path 11, a plurality of sub-flow paths 13, a sample liquid supply flow path 15, a first capture body 31, a transport liquid supply flow path 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 flow path 15 is an example of the "first flow path" of the present invention. The first capture body 31 is an example of the "capture body" of the present invention. The main flow path 11 is an example of the "second flow path" of the present invention. The sub-flow path 13 is an example of the "third flow path" of the present invention.
[0017] The main channel 11, the multiple 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, by a resin layer or the like disposed on a transparent substrate. Specifically, all or part of the surfaces constituting the main channel 11, the sub-channel 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, by a metal, an insulator, a semiconductor, PDMS (dimethylpolysiloxane), glass, and / or a photoresist.
[0018] Sample liquid 510 flows through sample liquid supplying flow path 15. Sample liquid supplying flow path 15 is a flow path for supplying sample liquid 510 to main flow path 11. In this embodiment, sample liquid supplying flow path 15 is inclined with respect to main flow path 11, but the present invention is not limited to this. For example, sample liquid supplying flow path 15 may be parallel to main flow path 11 or perpendicular to main flow path 11.
[0019] The sample liquid 510 is a liquid containing particles. The sample liquid 510 is not particularly limited, but is, for example, blood. The particle diameter of the particles 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, for example, spherical. However, the shape of the particles may be a shape other than spherical. In the present embodiment, the particles may be a particle consisting of one solid, or a group of fine particles formed into one mass of fine particles. The particles may be formed point-symmetrically or line-symmetrically, or may be formed asymmetrically or line-symmetrically. The particles may not have unevenness on the surface, or may have unevenness on the surface.
[0021] Sample liquid supplying flow path 15 has sample liquid inlet 151, an upstream flow path 152, and a 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 described below.
[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] Downstream flow channel 153 is connected to upstream flow channel 152. Downstream flow channel 153 allows sample liquid 510 to flow from the upstream side (upstream flow channel 152 side) to the downstream side (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] Fig. 2 is a plan view showing a schematic structure around a 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, 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. A 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, a cross section of the first capturing body 31 along a direction perpendicular to the extension direction has a wing shape.
[0027] The first capturing body 31 is disposed so as to cross the inside of the upstream flow channel 152. In this embodiment, the first capturing body 31 extends from the lower surface to the upper surface of the upstream flow channel 152. That is, the first capturing body 31 extends in the thickness direction of the HDF chip 1 (perpendicular to the paper surface of FIG. 2) in the upstream flow channel 152. A gap may be formed between the first capturing body 31 and the lower surface of the upstream flow channel 152, or between the first capturing body 31 and the upper surface of the upstream flow channel 152. The first capturing body 31 may extend in the upstream flow channel 152 in a flow channel width direction intersecting with the flow direction D1 of the liquid (here, the sample liquid 510).
[0028] FIG. 3 is a diagram showing a schematic structure of the first capture body 31 of the HDF chip 1 of the first embodiment. In FIG. 3, the flow of the 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 of the flow direction D1 of the liquid (here, the sample liquid 510) flowing through the sample liquid supply flow 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 of the flow direction D1. That is, the narrow portion 312 is disposed downstream of the wide portion 311. The narrow portion 312 is disposed in the downstream portion of the first capture body 31. The width of the narrow portion 312 in the cross direction crossing the flow direction D1 is smaller than the width of the wide portion 311 in the cross direction crossing the flow direction D1.
[0029] In this embodiment, as described above, first capture body 31 having a wing-shaped cross section is disposed in sample liquid supply flow path 15, with wide portion 311 of first capture body 31 disposed upstream and narrow portion 312 of first capture body 31 disposed downstream. Therefore, when liquid is caused to flow in sample liquid supply flow path 15, flow separation can be suppressed from occurring downstream of first capture body 31. This makes it possible to suppress particles contained in sample liquid 510 from remaining or adhering downstream of first capture body 31.
[0030] In this way, since the particles contained in the sample liquid 510 can be prevented from staying or adhering downstream of the first capture body 31, the number of particles (here, cells) reaching the main channel 11 can be prevented from decreasing. In addition, the number of particles that gather downstream of the first capture body 31 and form a particle clump can be prevented. This prevents the particle clump 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 the 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 a large clump. Therefore, when the target particles are cells, it is particularly effective to prevent the particles from staying or adhering downstream of the first capture body 31.
[0031] As described above, the first capturing body 31 has a wing-shaped cross section. The type of wing shape is not particularly limited, but for example, NACA 4-digit system, NACA 5-digit system, NACA 6 system, Joukowski system, etc. can be used. The type and / or size of the wing shape may be determined according to, for example, the flow rate of the liquid, the viscosity of the liquid, the density of the particles, the size of the particles, the flow path width, or the flow path height. The first capturing body 31 has a streamlined cross section. It is preferable that the entire cross section of the first capturing body 31 is streamlined, but a part of the cross section of the first capturing body 31 may be streamlined.
[0032] Furthermore, in this embodiment, first capturing body 31 is formed symmetrically in the width direction of first capturing body 31 (direction intersecting the longitudinal direction). In this embodiment, first capturing body 31 is formed symmetrically in the flow channel width direction. However, first capturing body 31 does not have to be formed symmetrically in the width direction of first capturing body 31, the flow channel width direction, or a specified direction. In other words, 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 extending in a direction 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 a plurality of first capture bodies 31. The plurality of first capture bodies 31 are arranged, for example, in a staggered manner, 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 include 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 has 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 has 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 has 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 capturing bodies 31 includes a plurality of first row capturing bodies 3211, a plurality of second row capturing bodies 3221, and a plurality of third row capturing bodies 3231. The interval (predetermined interval) between the first row capturing bodies 3211, the interval (predetermined interval) between the second row capturing bodies 3221, and the interval (predetermined interval) between the third row capturing bodies 3231 may be the same or different. In this embodiment, the interval (predetermined interval) between the first row capturing bodies 3211, the interval (predetermined interval) between the second row capturing bodies 3221, and the interval (predetermined interval) between the third row capturing 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] In addition, in this embodiment, the second row capturing body 3221 is arranged at a position that does not overlap with a straight line L1 that passes through the top 3111 (see FIG. 3) of the wide portion 311 of the first row capturing body 3211 and the top 3121 (see FIG. 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. In this embodiment, the first row capturing body 3211 and the second row capturing body 3221 are arranged at a position that does not overlap when viewed from the flow direction D1. Note that in this embodiment, the straight line L1 is the center line of the first row capturing body 31.
[0037] Moreover, in this embodiment, the third row capturing body 3231 is arranged at a position that does not overlap with a 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. Moreover, in this embodiment, the second row capturing body 3221 and the third row capturing body 3231 are arranged at positions that do not overlap when viewed from the flow direction D1.
[0038] The distance between adjacent first capture bodies 31 is preferably larger than the particle (here, cell) contained in the liquid, but may be smaller than the particle. In this embodiment, the distance between adjacent first capture bodies 31 is 1.1 to 5 times, 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 larger, preferably 5 μm to 50 μm larger, 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 impurities 900, but may be larger than the impurities 900.
[0039] As shown in FIG. 1, a transport liquid 520 flows through the transport liquid supply flow path 17. The transport liquid supply flow path 17 is a flow path for supplying the transport liquid 520 to the main flow path 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-flow path 13 to the downstream side of the main flow path 11. Note that, in this embodiment, the transport liquid supply flow path 17 is inclined with respect to the main flow path 11, but the present invention is not limited thereto. For example, the transport liquid supply flow path 17 may be parallel to the main flow path 11 or perpendicular to the main flow path 11.
[0040] The transport liquid 520 is, for example, a liquid that does not contain particles. The transport liquid 520 is, but is not particularly limited to, a liquid culture medium.
[0041] The transport liquid supply flow path 17 has a transport liquid inlet 171, an upstream flow path 172, and a downstream flow path 173. The transport liquid inlet 171 is disposed at the upstream end of the transport liquid supply flow path 17. The transport liquid inlet 171 is supplied with a transport liquid 520, as described below.
[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 distributes the transport liquid 520 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. In addition, the flow path width of the upstream flow path 172 is 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 trapping body 33 has a circular or rectangular cross section. Specifically, the second trapping body 33 is formed, for example, in the shape of a circular cylinder or a rectangular prism. The second trapping body 33 extends from the lower surface to the upper surface of the upstream flow path 172.
[0047] Unlike the first trapping body 31, the second trapping body 33 does not have a wing-shaped cross section, and therefore flow separation occurs downstream of the second trapping body 33. However, since the transport liquid 520 does not contain particles, the particles do not remain or adhere downstream of the second trapping body 33.
[0048] Further, a plurality of second capturing bodies 33 are provided. That is, in this embodiment, a filter is configured by a plurality of second capturing bodies 33. The distance between adjacent second capturing bodies 33 is, for example, the same as the distance between adjacent first capturing bodies 31, or is smaller than the distance between adjacent first capturing bodies 31. In this embodiment, the distance between adjacent second capturing bodies 33 is smaller than the distance between adjacent first capturing bodies 31.
[0049] The sample liquid supplying flow channel 15 and the transport liquid supplying flow channel 17 join at an upstream junction 19. The upstream junction 19 is disposed at the upstream end of the main flow channel 11. Therefore, the sample liquid 510 that has passed through the sample liquid supplying flow channel 15 and the transport liquid 520 that has passed through the transport liquid supplying flow channel 17 join at the upstream junction 19 and flow through the main flow channel 11.
[0050] The main channel 11 extends, for example, in a straight line in a predetermined direction. A 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 pitches 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 be connected at an angle other than perpendicular to the main channel 11.
[0052] The HDF2 is composed of the main channel 11 and the multiple sub-channels 13. Specifically, a part of the liquid flowing through the main channel 11 flows into the multiple sub-channels 13. Also, a part of the particles contained in the liquid flowing through the main channel 11 flows into the multiple sub-channels 13. Whether the particles flow into the multiple sub-channels 13 depends on, for example, their particle size. However, even if the particle has a particle size smaller than the flow width of the sub-channel 13, it does not necessarily flow into the sub-channel 13. The smaller the particle size, the easier it is to flow into the sub-channel 13, and the larger the particle size, the harder it is to flow into the sub-channel 13. For example, when blood is used as the sample liquid 510, it is possible to flow blood plasma (also called plasma), which is a liquid component of blood, red blood cells, and platelets into the sub-channel 13, and to prevent cancer cells and white blood cells contained in the blood from flowing into the sub-channel 13. That is, for example, it is possible to separate particles with a large particle size, such as cancer cells and white blood cells, from the blood. The operating principle of the HDF2 will be described later.
[0053] 4 is a plan view showing a schematic structure of the periphery of the upstream junction 19 of the HDF chip 1. As shown in FIG. 4, the sample liquid supplying channel 15 is arranged so that the sample liquid 510 flows in a portion of the main channel 11 on the side of the sub-channel 13. Meanwhile, the transport liquid supplying channel 17 is arranged so that the transport liquid 520 flows in a portion of the main channel 11 on the side opposite the sub-channel 13. In this embodiment, the sample liquid supplying channel 15 is connected to an inner wall 111 of the main channel 11 on the side of the sub-channel 13. Meanwhile, the transport liquid supplying 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 collecting unit 21 collects the liquid that has passed through the multiple sub-flow paths 13. The collecting unit 21 is connected to multiple (here, all) sub-flow paths 13. The collecting unit 21 is also connected to a first outlet 23. The collecting unit 21 collects the liquid that has passed through the multiple sub-flow paths 13, and guides it to the first outlet 23.
[0055] The liquid that has passed through the multiple sub-flow paths 13 is collected in a first collection section (not shown) via the collection section 21 and the first outlet 23. The first collection section 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. The liquid that has passed through the main channel 11 (here, the transport liquid 520) is collected in a second collection section (not shown) via the second outlet 25. The second collection section 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 section 35 and a transport liquid delivery section 36. The separation device 100 may include a control device (not shown) that drives the sample liquid delivery section 35 and the transport liquid delivery section 36. The sample liquid delivery section 35 and the transport liquid delivery section 36 are not particularly limited, but are, for example, micropumps. 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 has, for example, a processor. The control unit may have, for example, a central processing unit (CPU) or a general-purpose computing machine. The memory unit includes, for example, a main memory device and an auxiliary memory device. The main memory device is, for example, a semiconductor memory. The auxiliary memory device 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 supplying flow path 15, and causes sample liquid 510 to flow through sample liquid supplying flow path 15. Specifically, sample liquid delivery unit 35 is connected to sample liquid inlet 151 of sample liquid supplying flow path 15. When sample liquid delivery unit 35 supplies sample liquid 510 to sample liquid inlet 151, sample liquid 510 flows through sample liquid supplying flow path 15 and main flow path 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. The transport liquid delivery unit 36 supplies the transport liquid 520 to the transport liquid inlet 171, whereby 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 becomes a laminar flow. The transport liquid delivery unit 36 delivers the transport liquid 520 so that the transport liquid 520 becomes a laminar flow. Therefore, in this embodiment, each liquid becomes a laminar flow in the HDF chip 1.
[0062] Next, the operation principle of the HDF2 will be described with reference to Fig. 5. Fig. 5 is a schematic diagram for explaining the operation principle of the HDF2. As shown in Fig. 5, when the sample liquid delivery section 35 supplies the sample liquid 510 and the transport liquid delivery section 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 side of the sub-channel 13, and the transport liquid 520 flows along the inner wall 112 on the opposite side to the sub-channel 13. At this time, the centers of the various particles pass through a position separated from the inner wall 111 of the main channel 11 by the radius of the particle or more.
[0063] Here, the flow velocity changes depending on the position in the flow path width direction of main flow path 11. Specifically, the flow velocity is small in the vicinity of inner walls 111 and 112 of main flow path 11. On the other hand, the flow velocity is greatest in a position in main flow path 11 far from inner walls 111 and 112 (the center of main flow path 11 in the flow path width direction).
[0064] Therefore, particles with a small particle size passing near the inner wall 111 have a low flow rate and therefore tend to flow into the sub-channel 13. On the other hand, particles with a large particle size passing a position far from the inner wall 111 have a high flow rate and therefore do not flow into the sub-channel 13 but move straight through the main channel 11. In other words, under a predetermined condition such as a constant supply amount of the sample liquid 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. Discharge from the main channel 11 to the sub-channels 13 is repeated by a plurality of sub-channels 13, so particles smaller than the predetermined size do not reach the downstream end of the main channel 11. Incidentally, plasma, which is a liquid component, does not reach the downstream end of the main channel 11. Therefore, the HDF chip 1 can separate particles with a large particle size, 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, the first capturing body 31 having a wing-shaped cross section is placed in the sample liquid supply flow channel 15. In addition, the wide portion 311 of the first capturing body 31 is placed on the upstream side, and the narrow portion 312 of the first capturing body 31 is placed on the downstream side. Therefore, when liquid is flowed in the sample liquid supply flow channel 15, flow separation can be suppressed from occurring downstream of the first capturing body 31. Therefore, it is possible to suppress the particles contained in the sample liquid 510 from staying or adhering downstream of the first capturing body 31. Therefore, the HDF chip 1 can be used for particles with high viscosity (e.g., cells), and the versatility of the HDF chip 1 can be improved.
[0066] As described above, the HDF chip 1 includes the main channel 11 disposed downstream of the sample liquid supply channel 15, and a plurality of sub-channels 13 branching from the main channel 11. That is, the HDF chip 1 includes the HDF 2 (the main channel 11 and a plurality of sub-channels 13) downstream of the sample liquid supply channel 15 in which the first capture body 31 is disposed. Therefore, by suppressing the retention or adhesion of particles downstream of the first capture body 31, it is possible to suppress a decrease in the number of particles (here, cells) that reach the main channel 11. Also, by suppressing the retention or adhesion of particles downstream of the first capture body 31, it is possible to suppress a plurality of particles gathering to form a particle clump downstream of the first capture body 31. Therefore, it is possible to suppress the particle clump from flowing downstream and clogging the main channel 11 and / or the sub-channel 13. Therefore, it is possible to suppress particles of a predetermined size or less and / or liquid components of the sample liquid 510 from reaching the downstream end of the main channel 11. In other words, it is possible to improve the durability and / or robustness of the HDF chip 1. 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 HDF2 is disposed downstream of sample liquid supply flow path 15, it is particularly effective to prevent the particles from remaining or adhering downstream of first capture body 31.
[0067] As described above, the flow path width of sample liquid supply flow path 15 is larger 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 larger than the flow path width of main flow path 11. Therefore, for example, compared to the case where first capture body 31 is arranged in main flow path 11, impurities 900 can be captured in the portion with the larger flow path width. Therefore, clogging of the flow path by impurities 900 can be suppressed.
[0068] As described above, the second row capture bodies 3221 are arranged at positions that do not overlap with 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 the 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, the 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 that illustrates a schematic structure of the HDF chip 1 according to a modification of the first embodiment.
[0070] As shown in FIG. 6, in the HDF chip 1 according to the modification of the first embodiment, some of the first capture bodies 31 are formed integrally with the inner wall of the sample liquid supply flow channel 15. Specifically, the first capture body 31 arranged on the outer side in the flow channel width direction is formed integrally with the inner wall of the sample liquid supply flow channel 15. That is, the first capture body 31 arranged on the outer side in the flow channel width direction and the sample liquid supply flow channel 15 are a single member. In addition, the outer surface of the first capture body 31 arranged on the outer side in the flow channel width direction is formed continuously with the inner surface of the sample liquid supply flow channel 15. In this modification, the first capture bodies 31 arranged at both ends in the flow 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 flow 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 separation device 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 showing a schematic structure of a separation device 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 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, which will be 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, and may, for example, have the same components as the transport liquid 520.
[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 possible to easily 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 path 51, and the second outlet 252 is connected to the downstream end of the second recovery path 53.
[0078] Here, the HDF chip 301 can further separate the particles flowing through the separation channel 27 by dielectrophoresis (DEP). Specifically, the HDF chip 301 further includes an electrode 55 and an electrode 57 arranged to overlap the separation channel 27. The electrodes 55 and 57 are comb-shaped electrodes facing each other. The electrode 55 is connected to, for example, an AC power source 61. The electrode 57 is grounded, for example. In the second embodiment, the separation device 300 includes the AC power source 61. It is to be noted that the separation device 300 does not necessarily include the AC power source 61.
[0079] The teeth of electrode 55 and electrode 57 are inclined, for example, at an angle of 10° to 60° with respect to separation channel 27. Dielectrophoresis can be caused by applying an AC voltage between electrode 55 and electrode 57 by AC power source 61. Then, by adjusting the frequency of the applied AC voltage, it is possible to separate and recover desired particles from the multiple types of particles passing through separation channel 27.
[0080] Specifically, when the multiple types of particles passing through the separation channel 27 include dielectric particles, it is possible to separate a specific dielectric particle from the multiple types of particles by 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 (white blood cells, etc.) other than cancer cells that are larger than a predetermined size, for example, an AC voltage of a specific frequency is applied between the electrodes 55 and 57 so that the dielectrophoretic force is easily applied to the cancer cells. This makes it possible to move the cancer cells along the electrodes 55 and 57, so that only the cancer cells can be guided to the second outlet 251 by dielectrophoresis. Therefore, it is possible to separate the cancer cells from other particles (white blood cells, etc.).
[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. 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 implemented in various aspects without departing from the gist of the present invention. In addition, various inventions can be formed by appropriately combining multiple components disclosed in the above embodiments. For example, some components may be deleted from all components shown in the embodiments. Furthermore, components across different embodiments may be appropriately combined. The drawings are mainly shown schematically for ease of understanding, and the thickness, length, number, spacing, etc. of each component shown in the drawings may differ from the actual ones due to the convenience of drawing. In addition, the material, shape, dimensions, etc. of each component shown in the above embodiments are examples and are not particularly limited, and various changes are possible within a range 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 above first embodiment, an example was described in which the HDF chip 1 includes the HDF 2. In the above 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. In addition, the channel chip may not include the HDF 2, and may include the separation channel 27 that separates particles by dielectrophoresis, the electrodes 55 and 57.
[0085] In the above embodiment, an example in which all the first capturing bodies 31 have the same cross-sectional shape and the same size has been described, but the present invention is not limited to this. For example, some of the first capturing bodies 31 among the multiple first capturing bodies 31 may have the same cross-sectional shape and the same size. Also, for example, the multiple first capturing bodies 31 may have different widths, lengths, or shapes.
[0086] In the above embodiment, the example in which the first capturing bodies 31 are regularly arranged has been described, but the present invention is not limited to this. For example, the first capturing bodies 31 may be irregularly arranged.
[0087] 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 supplying 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 one flow path. Also, for example, sample liquid supplying 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, an example has been described in which sample liquid supplying channel 15 has upstream channel 152 and downstream channel 153, but the present invention is not limited to this. For example, sample liquid supplying channel 15 may be configured by a single channel with a constant channel width. In this case, the channel width of sample liquid supplying channel 15 is preferably larger than the channel width of main channel 11, but may be the same as the channel width of main channel 11.
[0089] In the above first embodiment, the particles (e.g., cancer cells and white blood cells) collected from the second outlet 25 are taken as an example of the target collected material, but the present invention is not limited thereto. For example, the particles or liquid components collected from the first outlet 23 may be the target collected material.
[0090] In the above second embodiment, an example has been described in which target particles (for example, cancer cells) are collected from the second outlet 251, but 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 not containing particles (e.g., transport liquid 520) is used. That is, an example has been described in which a liquid not containing particles (e.g., transport liquid 520) is flowed through main channel 11 in addition to a liquid containing particles (e.g., sample liquid 510). However, the present invention is not limited to this. For example, only a liquid containing particles (e.g., sample liquid 510) may be flowed through main channel 11. Also, for example, seawater containing particles may be used as the liquid containing 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), but 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 was described in which no structures such as sensors are arranged in the channels of the HDF chip 1 (for example, the main channel 11 and the sub-channel 13), but the present invention is not limited to this. For example, if it is possible to separate particles, structures such as physical, electrical, or magnetic sensors may be arranged in the channels of the HDF chip 1 (for example, the sample liquid supply channel 15, the main channel 11, the sub-channel 13, or the separation channel 27). [Industrial Applicability]
[0094] The present invention can be used in the field of channel chips. [Explanation of symbols]
[0095] 1, 301: HDF chip (fluid chip) 11: Main flow path (second flow path) 13: Sub-channel (third channel) 15: Sample liquid supply flow path (first flow path) 31: First capture body (capture body) 311: Wide section 312: Narrow part 321 :1st column 322: 2nd column 900: Impurities 3111 :Top 3121 :Top 3211: 1st row capture object 3221: 2nd row capture object D1: Distribution direction L1: Straight line
Claims
1. A first flow path through which a liquid containing particles flows; a capture body disposed in the first flow path and configured to capture impurities contained in the liquid; Equipped with The capture body is A cross section of a wing shape, 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, The narrow width portion has a width in a direction intersecting the flow direction that is smaller than a width in the intersecting direction of the wide width portion.
2. a second flow path disposed downstream of the first flow path and through which the liquid flows; a plurality of third flow paths branching from the second flow path and through which some of the particles flow; The channel chip according to claim 1 , comprising:
3. The channel chip according to claim 2 , wherein a channel width of the first channel is larger than a channel width of the second channel.
4. The capture body is provided in plurality, The plurality of capture bodies are a first row having a plurality of first row capture bodies arranged at predetermined intervals in a flow path width direction of the first flow path; a second row having a plurality of second row capture bodies arranged adjacent to the downstream side of the first row and spaced apart from each other at a predetermined interval in the width direction of the flow channel; Including, A flow path chip described in any one of claims 1 to 3, wherein 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.
Citation Information
Patent Citations
Separation method
JP2020099256A