Channel chip

The flow path chip simplifies design by using constant-width sub-channels with decreasing length, reducing material and cost, and effectively separates particles like cancer cells from blood, with additional dielectrophoretic capabilities.

JP2025018650APending Publication Date: 2025-02-06SCREEN HOLDINGS CO LTD
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Patent Information

Application Number
JP2023122545
Authority / Receiving Office
JP · JP
Patent Type
Applications
Current Assignee / Owner
Filing Date
2023-07-27
Publication Date
2025-02-06

AI Technical Summary

Technical Problem

The design of conventional flow path chips for separating specific cells from blood becomes complicated due to the need to accurately set flow path resistance values for branching flow paths, requiring complex calculations of width and length.

Method used

The flow path chip design includes a main flow path with branching sub-channels of constant width, where the length of the sub-channels decreases downstream, simplifying the design by eliminating the need for complex calculations of flow path resistance.

Benefits of technology

This simplification reduces the complexity of the flow path design, decreases the required material and cost, and allows for efficient separation of particles such as cancer cells from blood, while also enabling further separation by dielectrophoresis.

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Abstract

To provide a channel chip that can inhibit a flow channel design from being complicated.SOLUTION: An HDF chip 1 (channel chip) includes a main flow channel 11 and a plurality of sub-flow channels 13. The main flow channel 11 flows a liquid containing particulates therethrough. The sub-flow channels 13 branch from the main flow channel 11. The sub-flow channels 13 have a flow channel width ln that is constant. The sub-flow channels 13 have lengths that become short as proceeding downstream of a circulation direction D1 of the liquid flowing through the main flow channel 11.SELECTED DRAWING: Figure 1
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Description

[Technical field]

[0001] The present invention relates to a channel chip. [Background technology]

[0002] Conventionally, a channel chip that separates specific cells from blood is known (see, for example, Patent Document 1). Patent Document 1 describes a channel chip that includes a main channel and multiple branch channels branching off from the main channel. Blood is passed through the main channel as a sample liquid. Cancer cells present in the blood reach the downstream end of the main channel. Meanwhile, blood components other than cancer cells flow into the multiple branch channels. In this manner, cancer cells are separated from blood.

[0003] In the channel chip of Patent Document 1, each branch channel is set to a first width at its starting end (main channel side) and set to a second width wider than the first width at its terminal end. The position at which the width switches from the first to the second width for each branch channel is set closer to the starting end for channels closer to the downstream end of the main channel. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] JP 2020-99256 A Summary of the Invention [Problem to be solved by the invention]

[0005] Incidentally, in a flow channel chip such as that in Patent Document 1, it is necessary to appropriately set the flow channel resistance value of each branch flow channel. Therefore, when designing the flow channels of a flow channel chip, the flow channel resistance value to be set for each branch flow channel is calculated, and the width, length, etc. of the branch flow channel are set based on the calculation result.

[0006] However, in the flow channel chip of Patent Document 1, each branch flow channel has a portion having a first width (hereinafter, sometimes referred to as a base end portion) and a portion having a second width wider than the first width (hereinafter, sometimes referred to as a tip end portion). Since the flow channel resistance value of the branch flow channel is calculated using the length and width of the base end portion and the length and width of the tip end portion, the flow channel design of the flow channel chip is complicated.

[0007] The present invention has been made in view of the above problems, and has an object to provide a channel chip capable of preventing the channel design from becoming complicated. [Means for solving the problem]

[0008] A channel chip according to one aspect of the present invention includes a main channel and a plurality of sub-channels. A liquid containing particles flows through the main channel. The plurality of sub-channels branch off from the main channel. The width of the sub-channels is constant. The lengths of the plurality of sub-channels become shorter toward the downstream side in the flow direction of the liquid flowing through the main channel.

[0009] In one aspect of the present invention, the plurality of sub-channels may have the same flow path width.

[0010] In one aspect of the present invention, a collection section may be provided that collects the liquid that has passed through the plurality of sub-flow paths. The plurality of sub-flow paths may have a most upstream sub-flow path arranged most upstream in the flow direction, and a most downstream sub-flow path arranged most downstream in the flow direction. At least a part of the collection section may be arranged within a rectangular region. The rectangular region may have two sides defined by a portion of the main flow path between the most upstream sub-flow path and the most downstream sub-flow path, and the most upstream sub-flow path.

[0011] In one aspect of the present invention, the liquid collecting device may further include a discharge section connected to the collecting section and configured to discharge the liquid collected by the collecting section. The entire discharge section may be disposed within the rectangular area.

[0012] In one aspect of the present invention, the liquid supply system may include a downstream flow path and an electrode. The downstream flow path may be connected to a downstream end of the main flow path, and the liquid that has passed through the main flow path may pass through the downstream flow path. The electrode causes dielectrophoresis of dielectric particles contained in the liquid passing through the downstream flow path. Effect of the Invention

[0013] According to the present invention, it is possible to provide a channel chip capable of preventing the channel design from becoming complicated. [Brief description of the drawings]

[0014] [Figure 1] FIG. 1 is a plan view showing a schematic structure of a separation device including an HDF chip according to one embodiment of the present invention. [Diagram 2] FIG. 2 is a plan view showing a schematic structure of the periphery of the upstream junction of the HDF chip. [Diagram 3] FIG. 4 is a diagram showing a schematic structure around a plurality of sub-flow paths; [Figure 4] FIG. 1 is a schematic diagram for explaining the operating principle of HDF. [Diagram 5] FIG. 1 is a schematic diagram showing the structure around a sub-channel of a conventional HDF chip. [Figure 6] FIG. 2 is a schematic diagram showing a channel model having a rectangular parallelepiped shape. [Figure 7] FIG. 2 is a schematic diagram showing the structure around a sub-channel of the HDF chip of the present embodiment. [Figure 8] FIG. 11 is a plan view showing a schematic structure of a separation device including an HDF chip according to a modified example of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0015] 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.

[0016] A separation device 100 including an HDF chip 1 according to one embodiment of the present invention will be described with reference to Figures 1 to 7. Figure 1 is a plan view that illustrates a schematic structure of a separation device 100 including an HDF chip 1 according to one embodiment of the present invention.

[0017] 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.

[0018] The HDF chip 1 includes at least a main channel 11 and a plurality of sub-channels 13. In this embodiment, the HDF chip 1 includes the main channel 11, a plurality of sub-channels 13, a sample liquid supply channel 15, a transport liquid supply channel 17, an upstream junction 19, a collection section 21, a first outlet 23, and a second outlet 25. The first outlet 23 is an example of the "discharge section" of the present invention. The main channel 11, the plurality of sub-channels 13, the sample liquid supply channel 15, the transport liquid supply channel 17, 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 arranged on a transparent substrate. Specifically, all or part of the surfaces constituting the main flow path 11, the secondary flow path 13, the sample liquid supply flow path 15, the transport liquid supply flow path 17, the upstream junction 19, the collection section 21, the first outlet 23 and the second outlet 25 are made of, for example, a metal, an insulator, a semiconductor, PDMS (dimethylpolysiloxane), glass and / or photoresist.

[0019] The main channel 11 extends, for example, in a straight line in a predetermined direction. A liquid flows in the main channel 11. In this embodiment, a sample liquid 510 flows in the main channel 11. In this embodiment, the sample liquid 510 and a transport liquid 520 flow in the main channel 11. The sample liquid 510 is a liquid containing particles. The sample liquid 510 is not particularly limited, but is, for example, blood. The transport liquid 520 is a liquid that does not contain particles. The transport liquid 520 is not particularly limited, but is, for example, a liquid culture medium. The particle size of the particles is, for example, several tens of μm or less. In this embodiment, the particle size of the particles 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] 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.

[0022] 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 blood. The operating principle of the HDF2 will be described later.

[0023] Moreover, the multiple sub-channels 13 are formed so that the flow path resistance gradually decreases from the upstream side to the downstream side of the main channel 11. Specifically, in this embodiment, the flow path width of each sub-channel 13 is constant. That is, the flow path width of each sub-channel 13 is constant from the end on the base end side (the main channel 11 side) to the end on the tip end side (the side farther from the main channel 11). Therefore, the entire sub-channel 13 contributes to particle separation. That is, when designing the sub-channel 13 as described later, the flow path resistance of the entire sub-channel 13 is used.

[0024] In addition, the lengths of the multiple sub-channels 13 become shorter toward the downstream side in the flow direction D1 of the liquid flowing through the main channel 11. In other words, the lengths of the sub-channels 13 become shorter toward the downstream end of the main channel 11. In this embodiment, the lengths of the sub-channels 13 gradually become shorter toward the downstream end of the main channel 11. Note that in this embodiment, all of the sub-channels 13 are formed to have different lengths from one another. In other words, all of the multiple sub-channels 13 have different lengths from one another. In this embodiment, the multiple sub-channels 13 have the same flow path width. The flow path width of the sub-channels 13 is not particularly limited, but is, for example, about 10 μm to several tens of μm. Note that in this embodiment, the type of particles to be separated is the same in all of the sub-channels 13.

[0025] 2 is a plan view showing a schematic structure of the periphery of upstream junction 19 of HDF chip 1. As shown in FIG. 2, sample liquid 510 flows through sample liquid supplying flow channel 15. Sample liquid supplying flow channel 15 is a flow channel for supplying sample liquid 510 to main flow channel 11. In this embodiment, sample liquid supplying flow channel 15 is inclined with respect to main flow channel 11, but the present invention is not limited to this. For example, sample liquid supplying flow channel 15 may be parallel to main flow channel 11 or perpendicular to main flow channel 11.

[0026] 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 other words, 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. 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 to this. 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.

[0027] Moreover, the sample liquid supply flow channel 15 is disposed so that the sample liquid 510 flows in a portion of the main flow channel 11 on the side of the sub-flow channel 13. On the other hand, the transport liquid supply flow channel 17 is disposed so that the transport liquid 520 flows in a portion of the main flow channel 11 on the opposite side to the sub-flow channel 13. In this embodiment, the sample liquid supply flow channel 15 is connected to an inner wall 111 of the main flow channel 11 on the side of the sub-flow channel 13. On the other hand, the transport liquid supply flow channel 17 is connected to an inner wall 112 of the main flow channel 11 on the opposite side to the sub-flow channel 13.

[0028] At the upstream junction 19, the sample liquid supplying flow channel 15 and the transport liquid supplying flow channel 17 join together. 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 together at the upstream junction 19 and flow through the main flow channel 11.

[0029] 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.

[0030] 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.

[0031] 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.

[0032] Next, the structure around the multiple sub-flow paths 13 will be described with reference to Fig. 3. Fig. 3 is a diagram showing a schematic structure around the multiple sub-flow paths 13. Note that in Fig. 3, the number of sub-flow paths 13 is reduced for ease of understanding.

[0033] 3, the sub-channels 13 include a most upstream sub-channel 131 arranged at the most upstream position in the flow direction D1, and a most downstream sub-channel 132 arranged at the most downstream position in the flow direction D1. The most upstream sub-channel 131 is connected to a portion of the main channel 11 that is most upstream in the flow direction D1 compared to the other sub-channels 13. The most downstream sub-channel 132 is connected to a portion of the main channel 11 that is most downstream in the flow direction D1 compared to the other sub-channels 13.

[0034] Here, a portion of the main channel 11 that is disposed between the most upstream sub-channel 131 and the most downstream sub-channel 132 is defined as portion 115. A rectangular region having two sides, which are the portion 115 and the most upstream sub-channel 131, is defined as region 600. In this embodiment, at least a part of the collecting section 21 is disposed within region 600. Specifically, a part of the collecting section 21 excluding the periphery of the most upstream sub-channel 131 is disposed within region 600. In other words, most of the collecting section 21 is disposed within region 600.

[0035] In this embodiment, the first outlet 23 is disposed within the region 600. Specifically, the entire first outlet 23 is disposed within the region 600 having a rectangular shape.

[0036] 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 31 and a transport liquid delivery section 33. The separation device 100 may include a control device that drives the sample liquid delivery section 31 and the transport liquid delivery section 33. The sample liquid delivery section 31 and the transport liquid delivery section 33 are not particularly limited, but are, for example, micropumps. The micropump may be a mechanical pump or a non-mechanical pump.

[0037] 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.

[0038] Sample liquid delivery unit 31 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 supplying flow path 15 has sample liquid inlet 151. Sample liquid inlet 151 is disposed at the upstream end of sample liquid supplying flow path 15. Sample liquid delivery unit 31 is connected to sample liquid inlet 151. Sample liquid delivery unit 31 supplies sample liquid 510 to sample liquid inlet 151, causing sample liquid 510 to flow through sample liquid supplying flow path 15 and main flow path 11.

[0039] The transport liquid delivery unit 33 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 supply flow path 17 has a transport liquid inlet 171. The transport liquid inlet 171 is disposed at the upstream end of the transport liquid supply flow path 17. The transport liquid delivery unit 33 is connected to the transport liquid inlet 171. The transport liquid delivery unit 33 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.

[0040] In this embodiment, the sample liquid delivery unit 31 delivers the sample liquid 510 so that the sample liquid 510 becomes a laminar flow. The transport liquid delivery unit 33 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.

[0041] Next, the operation principle of the HDF2 will be described with reference to Fig. 4. Fig. 4 is a schematic diagram for explaining the operation principle of the HDF2. As shown in Fig. 4, when the sample liquid delivery section 31 supplies the sample liquid 510 and the transport liquid delivery section 33 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.

[0042] Here, the flow velocity changes depending on the position in the width direction of the main flow channel 11. Specifically, the flow velocity is small in the vicinity of the inner walls 111 and 112 of the main flow channel 11. On the other hand, the flow velocity is greatest in the position of the main flow channel 11 far from the inner walls 111 and 112 (the center of the main flow channel 11 in the width direction).

[0043] 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.

[0044] Next, a method for setting the length and width of the sub-channel 13 will be described with reference to Figs. 5 to 7. In other words, a method for designing the sub-channel 13 will be described. Here, in order to facilitate understanding of the effects of this embodiment, a method for designing the sub-channel 1013 in a conventional HDF chip will be described first with reference to Figs. 5 and 6. Fig. 5 is a schematic diagram showing the structure around the sub-channel 1013 in a conventional HDF chip. Fig. 6 is a schematic diagram showing a channel model having a rectangular parallelepiped shape.

[0045] 5, in a conventional HDF chip, a portion 10131 on the base end side (the side closer to the main channel 1011) of each sub-channel 1013 is formed to have a first width. On the other hand, a portion 10132 on the tip end side (the side farther from the main channel 1011) of each sub-channel 1013 is formed to have a second width larger than the first width. The position where the width changes from the first width to the second width toward the downstream side in the flow direction D1 is located on the base end side.

[0046] Here, the length of the sub-channel 1013 is L, the length of the portion 10131 is Ln, and the length of the portion 10132 is Lw. The channel width of the portion 10131 is ln, and the channel width of the portion 10132 is lw. The height of the sub-channel 1013 is T. The formulas used in the following description are formulas used when the height T>channel width ln and the height T>channel width lw. However, when the height T≦channel width ln, for example, in the following formulas, f(T, ln) may be replaced with f(ln, T). When the height T≦channel width lw, for example, in the following formulas, f(T, lw) may be replaced with f(lw, T).

[0047] The height T of the sub-channel 1013 is the size in the direction perpendicular to the length and width directions of the sub-channel 1013. In other words, the height T of the sub-channel 1013 is the size in the direction perpendicular to the paper surface of FIG. 5. The height T of the sub-channel 1013 is constant. The height of the portion 10131 of the sub-channel 1013 is the same as the height of the portion 10132. The flow path resistance of the sub-channel 1013 is R. The proportional constant is k.

[0048] In this case, the length Ln of the portion 10131 can be expressed by the following formula (1): Moreover, the length Lw of the portion 10132 can be expressed by the following formula (2): k>0, and g(T, lw, ln)>0.

[0049]

number

[0050]

number

[0051] The function f in the above formulas (1) and (2) is based on the following known formula (3). Specifically, as shown in Fig. 6, the larger of the height and width of the flow channel 1113 having a rectangular parallelepiped shape is a, and the smaller of the height and width of the flow channel 1113 is b. In this case, the function f(a, b) is expressed by formula (3). Here, for example, the height is a and the flow channel width is b.

[0052]

number

[0053] Furthermore, since the length Ln is a positive value in the above formula (1), the following formula (4) must be satisfied.

[0054]

number

[0055] Furthermore, since the length Lw is a positive value in the above formula (2), the following formula (5) must be satisfied.

[0056]

number

[0057] The flow path resistance R to be set for each sub-path 1013 is calculated in advance by a known method. Furthermore, the lengths L, flow path widths ln, flow path widths lw, and heights T of all the sub-paths 1013 are equal to one another. That is, the lengths L of all the sub-paths 1013 are equal to one another. Furthermore, the flow path widths ln of all the sub-paths 1013 are equal to one another. Furthermore, the flow path widths lw of all the sub-paths 1013 are equal to one another. Furthermore, the heights T of all the sub-paths 1013 are equal to one another.

[0058] Therefore, when designing the sub-channels of a conventional HDF chip, the length Ln and length Lw of each sub-channel 1013 are calculated using the above formulas (1) and (2) so that the length L, channel width ln, channel width lw, and height T of all the sub-channels 1013 are equal to one another and the channel resistance R of each sub-channel 1013 is a predetermined value. At this time, it is also necessary to set the length L, channel width ln, channel width lw, and height T so as to satisfy the above formulas (4) and (5).

[0059] On the other hand, the sub-channel 13 of the HDF chip 1 of this embodiment can be designed as follows: Fig. 7 is a schematic diagram showing the structure around the sub-channel 13 of the HDF chip 1 of this embodiment.

[0060] Specifically, as shown in FIG. 7, the length of the sub-channel 13 is L, the channel width is ln, and the height is T. The height T of the sub-channel 13 is the size in the direction perpendicular to the length and width directions of the sub-channel 13. In other words, the height T of the sub-channel 13 is the size in the direction perpendicular to the paper surface of FIG. 7. The height T of the sub-channel 13 is constant. The channel width ln of the sub-channel 13 is also constant. The channel resistance of the sub-channel 13 is R. The proportionality constant is k.

[0061] In this case, the length L of the sub-channel 13 is expressed by the following known formula (6), where k>0.

[0062]

number

[0063] The flow path resistance R to be set for each sub-flow path 13 is calculated in advance by a known method. Furthermore, the lengths L and heights T of all the sub-flow paths 13 are equal to each other. That is, the lengths L of all the sub-flow paths 13 are equal to each other. Furthermore, the heights T of all the sub-flow paths 13 are equal to each other.

[0064] Therefore, when designing the sub-channels 13 of the HDF chip 1 of this embodiment, the length L of each sub-channel 13 is calculated using the above formula (6) so that the channel width ln and height T of all the sub-channels 13 are equal to each other and the channel resistance R of each sub-channel 13 is a predetermined value. Note that, in this embodiment, unlike the case of calculating the length Ln and length Lw of the sub-channel 1013 shown in Fig. 5, it is not necessary to satisfy the constraints shown in the above formulas (4) and (5).

[0065] In this manner, in this embodiment, the number of parameters (e.g., length and flow path width) required when designing the sub-flow path 13 is reduced, and it is not necessary to satisfy the constraints such as those shown in the above equations (4) and (5).

[0066] As described above with reference to Figs. 1 to 7, in this embodiment, the flow path width of the sub-flow paths 13 is constant. In addition, the length of the multiple sub-flow paths 13 becomes shorter toward the downstream side of the flow direction D1 of the liquid flowing through the main flow path 11. Therefore, when designing the flow paths (main flow path 11 and multiple sub-flow paths 13) of the HDF chip 1, the number of parameters required for design can be reduced compared to when designing the flow paths of a conventional HDF chip. Furthermore, when designing the flow paths of the HDF chip 1, unlike when designing the flow paths of a conventional HDF chip, it is not necessary to satisfy the constraints shown in the above formulas (4) and (5). Therefore, in the HDF chip 1 of this embodiment, it is possible to prevent the flow path design from becoming complicated.

[0067] Furthermore, since it is not necessary to satisfy the constraints such as those shown in the above expressions (4) and (5), the degree of freedom in design can be improved.

[0068] Furthermore, since the length of the multiple sub-channels 13 becomes shorter toward the downstream side in the flow direction D1 of the liquid flowing through the main channel 11, the area of ​​the HDF 2 can be reduced. This allows the amount of material used in the HDF chip 1 to be reduced. This leads to a reduction in the cost of the HDF chip 1. According to calculations by the inventors of the present application, the area of ​​the HDF 2 in the HDF chip 1 of this embodiment can be reduced by approximately 43% compared to the HDF in the conventional HDF chip.

[0069] As described above, the flow path widths of the multiple sub-flow paths 13 are the same as each other. This makes it possible to easily prevent calculations from becoming complicated when designing the flow paths of the HDF chip 1.

[0070] As described above, at least a part of the collecting part 21 is disposed within a rectangular region 600 having two sides defined by the portion 115 and the most upstream sub-channel 131. Therefore, at least a part of the collecting part 21 can be disposed in the region where the sub-channel 1013 was disposed in the conventional HDF chip. This makes it easy to reduce the area of ​​the HDF chip 1. This makes it easy to reduce the amount of material used in the HDF chip 1. The region 600 corresponds to the region where the HDF (main channel 1011 and multiple sub-channels 1013) was disposed in the conventional HDF chip.

[0071] As described above, the entire first outlet 23 is disposed within the rectangular region 600. Therefore, the entire first outlet 23 can be disposed in the region where the sub-channel 1013 was disposed in the conventional HDF chip. This allows the area of ​​the HDF chip 1 to be further reduced. Therefore, the amount of material used in the HDF chip 1 can be further reduced.

[0072] Next, a separation apparatus 300 according to a modified example of the present invention will be described with reference to Fig. 8. Fig. 8 is a plan view that shows a schematic structure of a separation apparatus 300 including an HDF chip 301 according to a modified example of the present invention.

[0073] 8, in a separation device 300 according to a modified example of the present invention, an HDF chip 301 includes a main channel 11, a transport liquid supply channel 26, a downstream 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 transport liquid supply channel 17, 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 downstream 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 downstream side flow channel 27 is connected to the downstream end of the main flow channel 11 and the downstream end of the transport liquid supply flow channel 26. For example, the flow channel width of the downstream side flow channel 27 is larger than the flow channel width of the main flow channel 11 and the flow channel width of the transport liquid supply flow channel 26. In this modified example, the flow channel width of the downstream side flow channel 27 is larger than the sum of the flow channel width of the main flow channel 11 and the flow channel width of the transport liquid supply flow channel 26. In addition, the height of the downstream side flow channel 27 is the same as the height of the main flow channel 11 and the height of the transport liquid supply flow channel 26.

[0076] In this way, by making the flow path width of the downstream side flow path 27 larger than the flow path width of the main flow path 11, it is possible to reduce the flow velocity of the liquid flowing through the downstream side flow path 27. This makes it possible to easily separate particles by dielectrophoresis, which will be described later.

[0077] The first recovery path 51 and the second recovery path 53 are connected to the downstream end of the downstream side flow path 27. In other words, the downstream side flow path 27 is branched into the first recovery path 51 and the second recovery path 53.

[0078] 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.

[0079] Here, the HDF chip 301 can further separate particles flowing through the downstream flow path 27 by dielectrophoresis (DEP). Specifically, the HDF chip 301 further includes an electrode 55 and an electrode 57 arranged to overlap with the downstream flow path 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 this modification, the separation device 300 includes the AC power source 61. It is to be noted that the separation device 300 does not necessarily need to include the AC power source 61.

[0080] The teeth of electrode 55 and electrode 57 are inclined, for example, at an angle of 10° to 60° with respect to downstream flow path 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 collect desired particles from multiple types of particles passing through downstream flow path 27.

[0081] Specifically, when the multiple types of particles passing through the downstream flow path 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 downstream flow path 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.).

[0082] Other structures of the separation device 300, HDF chip 301, main channel 11, multiple sub-channels 13, sample liquid supply channel 15, transport liquid supply channel 17, upstream junction 19, collection section 21, and first outlet 23 according to the modification of the present invention are similar to those of the separation device 100, HDF chip 1, main channel 11, multiple sub-channels 13, sample liquid supply channel 15, transport liquid supply channel 17, upstream junction 19, collection section 21, and first outlet 23 of the above embodiment. Other effects of the modification of the present invention are similar to those of the above embodiment.

[0083] As described above, the HDF chip 301 according to the modified example of the present invention includes the downstream channel 27 connected to the downstream end of the main channel 11 and through which the liquid that has passed through the main channel 11 passes, and the electrodes 55 and 57 that cause dielectrophoresis of the dielectric particles (cancer cells in this case) contained in the liquid passing through the downstream channel 27. Therefore, specific dielectric particles (cancer cells in this case) can be easily separated from the liquid that has passed through the main channel 11.

[0084] 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.

[0085] 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.

[0086] In the above 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.

[0087] In the above modified example, the target particles (for example, cancer cells) are collected from the second outlet 251. However, the present invention is not limited to this. For example, the target particles may be collected from the second outlet 252.

[0088] 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. 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.

[0089] In the above embodiment, an example has been described in which a liquid containing particles (e.g., sample liquid 510) and a liquid not containing particles (e.g., transport liquid 520) are joined on the HDF chip 1, but the present invention is not limited to this. For example, a mixed liquid obtained by mixing a liquid containing particles (e.g., sample liquid 510) and a liquid not containing particles (e.g., transport liquid 520) may be supplied to the HDF chip 1.

[0090] In the above embodiment, an example has been described in which liquid that has passed through all of the sub-flow paths 13 is collected in one collection section 21, but the present invention is not limited to this. For example, a collection section that collects liquid that has passed through some of the sub-flow paths 13 and a collection section that collects liquid that has passed through the remaining sub-flow paths 13 may be provided separately. Also, three or more collection sections may be provided. Also, a collection section and / or a first outlet may not be provided.

[0091] In the above embodiment, the sub-flow paths 13 extend in a straight line, but the present invention is not limited to this. For example, some or all of the sub-flow paths 13 may be bent midway along the flow path.

[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 has been described in which no structures such as sensors are arranged in the channels (e.g., the main channel 11 and the sub-channel 13) of the HDF chip 1, 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 (e.g., the main channel 11 and the sub-channel 13) of the HDF chip 1.

[0094] In the above embodiment, as shown in Fig. 7, an example has been shown in which no sidewall other than the sub-channel 13 is connected to the sidewall of the sub-channel 13 in the flow path width direction at the end of the sub-channel 13, but the present invention is not limited to this. For example, a sidewall extending outward from the end of the sub-channel 13 may be formed. However, the sidewall connected to the end of the sub-channel 13 is a sidewall that does not effectively contribute to particle separation. In other words, as long as the flow path resistance can be ignored when designing the sub-channel 13, the sidewall may be connected to the end of the sub-channel 13. [Industrial Applicability]

[0095] The present invention can be used in the field of channel chips. [Explanation of symbols]

[0096] 1, 301: HDF chip (fluid chip) 11: Main channel 13: Sub-channel 21: Collection Department 23: 1st outlet (discharge part) 27: Downstream flow path 55: Electrode 57: Electrode 115 :part 131: Uppermost secondary channel 132: Most downstream secondary channel 510: Sample liquid (liquid) 600: area D1: Distribution direction L: Length ln: channel width

Claims

1. a main flow path through which a liquid containing particles flows; A plurality of sub-flow paths branched from the main flow path; Equipped with The flow path width of the sub-flow path is constant, The channel chip, wherein the lengths of the plurality of sub-channels become shorter toward the downstream side in the flow direction of the liquid flowing through the main channel.

2. The channel chip according to claim 1 , wherein the sub-channels have the same channel width.

3. a collection section that collects the liquid that has passed through the plurality of sub-flow paths; the plurality of sub-flow paths include a most upstream sub-flow path arranged at a most upstream position in the flow direction and a most downstream sub-flow path arranged at a most downstream position in the flow direction, 3. The channel chip according to claim 1, wherein at least a part of the collection portion is disposed within a rectangular region having two sides including a portion of the main channel between the most upstream sub-channel and the most downstream sub-channel and the most upstream sub-channel.

4. a discharge part connected to the collection part and configured to discharge the liquid collected by the collection part; The channel chip according to claim 3 , wherein the entirety of the discharge portion is disposed within the rectangular region.

5. a downstream side flow path connected to a downstream end of the main flow path and through which the liquid that has passed through the main flow path passes; an electrode that causes dielectrophoresis of dielectric particles contained in the liquid passing through the downstream flow path; The channel chip according to claim 1 , comprising:

Citation Information

Patent Citations

  • Separation method

    JP2020099256A