Flow passage structure, method for manufacturing flow passage structure
The flow path structure with recessed holes and adjustable flow rates addresses the issue of irregular cell spacing in flow cytometry, enhancing operating speed and simplifying the alignment process.
Patent Information
- Application Number
- JP2023183027
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2023-10-25
- Publication Date
- 2025-05-12
AI Technical Summary
The irregular spacing of cells in flow cytometry due to the Poisson distribution leads to reduced operating speed and increased complexity in maintaining equal cell intervals.
A flow path structure with recessed holes at regular intervals on the inner wall surface, where vortices are generated by varying the flow rate, allowing cells to be captured and aligned at equal intervals.
This approach simplifies the process of maintaining equal cell intervals, thereby improving the operating speed of flow cytometers without increasing device complexity.
Smart Images

Figure 2025072744000001_ABST
Abstract
Description
[Technical field]
[0001] The present invention relates to a flow path structure and a method for manufacturing the flow path structure. [Background technology]
[0002] Flow cytometry is known as a technique for measuring cell characteristics such as cell size, cell type, cell cycle, etc. (For example, see Non-Patent Document 1). A flow cytometer is known as an analytical device used in this analytical technique called flow cytometry. This flow cytometer lines up cells one by one in a line in a microchannel, irradiates them with laser light, and obtains scattered light signals, fluorescent signals, and image information to obtain information about each cell.
[0003] Thus, when measuring cells with such a flow cytometer, a configuration called a flow cell is known that is used to line up the cells one by one in the sheath liquid. This flow cell will be specifically described with reference to Figure 9(a).
[0004] The flow cell 100 shown in FIG. 9(a) is composed of a tapered flow chamber 101 and a microchannel 102 provided inside the center of the flow chamber 101. Then, as shown in FIG. 9(a), a sheath liquid L1 is flowed into the flow chamber 101 at a constant flow rate. Furthermore, in this state, a sample liquid L2 containing a plurality of cells CE to be measured is flowed into the microchannel 102. This makes it possible to create a flow of sheath liquid L1 that envelops the flow of sample liquid L2. In this state, if the pressure of the flow of sample liquid L2 is made slightly lower than the pressure of the flow of sheath liquid L1, hydrodynamic constriction occurs in the process of forming a laminar flow, and a very thin flow of sample liquid L2 can be created. This makes it possible to arrange a plurality of cells CE in the sample liquid L2 in a line and continuously flow them through a very limited flow channel. Therefore, by irradiating this thin flow with a focused laser beam, it is possible to measure cells CE one by one with high sensitivity, high resolution, and high speed. [Prior art documents] [Non-patent literature]
[0005] [Non-Patent Document 1] "Introduction to flow cytometry | Explaining the principles, basics and general protocols of flow cytometry", [online], Cosmo Bio Co., Ltd., [Retrieved October 10, 2023], Internet (https: / / www.cosmobio.co.jp / product / detail / Introduction-flow-cytometry.asp?entry_id=35004) Summary of the Invention [Problem to be solved by the invention]
[0006] However, since the timing at which multiple cells CE flow into the microchannel 102 shown in FIG. 9(a) follows a Poisson distribution, the distance between the cells CE may become shorter or longer by 10 times or more than the average. To explain this in detail, as shown in FIG. 9(b), the sample liquid L2 containing multiple cells CE flows in the direction of the arrow Y1. At this time, the interval S1 between the cells CE shown in FIG. 9(b) is shorter than the average interval, and the interval S2 between the cells CE shown in FIG. 9(b) is longer than the average interval. Therefore, when such a phenomenon occurs, the operating speed of the flow cytometer decreases. This point will be explained in detail using FIG. 10.
[0007] Figure 10 is a graph showing the cell sorting success rate as a function of the operation time of the cell sorting device for one event based on the operating conditions of the latest cell sorting device in a flow cytometer (see A. Isozaki et al., “Intelligent image-activated cell sorting 2.0,” Lab on a Chip 20, 2263-2273, 2020.). In this graph, N represents the number of cells that can be processed per second (hereinafter referred to as throughput).
[0008] For example, if one wishes to perform an experiment with a throughput of 1000 eps (events per second) and maintain a cell sorting success rate of 95%, the operation time of the cell sorting device must be increased to approximately 0.1 ms, as shown in Figure 10.
[0009] Here, since the average interval between cell CEs at a throughput of 1000 eps is 1 ms, if the cell CEs are flowed at equal intervals, the operating time of the cell sorting device should be 1 ms. However, in reality, since it follows the Poisson distribution, the distance between cell CEs can be 10 times shorter or longer than the average. Therefore, if this is calculated probabilistically, as shown in Figure 10, a cell sorting device with 10 times the performance required for equal intervals is required. Therefore, when the phenomenon shown in Figure 9(b) occurs, the operating speed of the flow cytometer decreases.
[0010] However, conversely speaking, as long as the cell CE can be made to flow at equal intervals, the same device can be operated with 10 times the throughput, which means that the operating speed of the flow cytometer can be improved.
[0011] Therefore, in order to make the intervals between the cells CE equal, a method of applying force by an electrical method or a mechanical method can be considered, but such a method is not preferable because it makes the device complicated.
[0012] In view of the above problems, the present invention aims to provide a flow path structure and a method for manufacturing a flow path structure that can make the spacing between particles equal using a simple technique, thereby improving the operating speed of the device. [Means for solving the problem]
[0013] The above object of the present invention can be achieved by the following means. Note that the parentheses indicate reference symbols of the embodiments described below, but the present invention is not limited thereto.
[0014] The flow channel structure according to claim 1 has recesses (1c, Kc) provided at regular intervals on an inner wall surface of a flow channel (e.g., micro flow channels 1, 1A, 1B, liquid sending tube 1C) through which a fluid (e.g., sample liquid L2) containing particles (e.g., cells CE) to be measured flows, The particle (e.g., cell CE) can enter the cavity (1c, Kc), and a vortex (L2a) can be generated within the cavity (1c, Kc) by changing the flow rate of the fluid (e.g., sample liquid L2).
[0015] The flow path structure of claim 2 is characterized in that in the flow path structure described in claim 1, guide members (first guide member 2a, second guide member 2b) are provided on the inner wall surface facing the recesses (1c, Kc) provided at regular intervals in the inner wall surface of the flow path (e.g., microflow paths 1, 1A, 1B, liquid delivery tube 1C) to guide the particles (e.g., cells CE) into the recesses (1c, Kc).
[0016] The flow path structure according to claim 3 is the flow path structure according to claim 1, further comprising: a guide path (3) provided on an inner wall surface of the flow path (e.g., microflow paths 1, 1A, 1B, liquid sending tube 1C) facing recesses (1c, Kc) provided at regular intervals on the inner wall surface of the flow path; A specific fluid (liquid L3) is poured into the guide path (3), thereby guiding the particles (for example, cells CE) into the recesses (1c, Kc).
[0017] The flow path structure of claim 4 is characterized in that in the flow path structure of claim 1, the flow path through which a fluid (e.g., sample liquid L2) containing the particles to be measured (e.g., cells CE) flows is a microflow path (1, 1A, 1B).
[0018] The flow path structure of claim 5 is characterized in that in the flow path structure of claim 1, the flow path through which a fluid (e.g., sample liquid L2) containing the particles to be measured (e.g., cells CE) flows is formed in a tubular shape (see liquid delivery tube 1C shown in Figure 7(b)).
[0019] The flow path structure of claim 6 is characterized in that in the flow path structure of claim 1, the flow path through which a fluid (e.g., sample liquid L2) containing the particles to be measured (e.g., cells CE) flows is formed in an arc shape and has a specified plate (I) installed on the upper surface (see liquid delivery tube 1C shown in Figure 8(c)).
[0020] The flow path structure according to claim 7 is characterized in that in the flow path structure described in claim 5, protrusions (Kd) are provided at regular intervals on the outer wall surface of the flow path (liquid delivery tube 1C shown in Figure 7(b)) formed in a tubular shape.
[0021] The flow path structure of claim 8 is characterized in that, in the flow path structure of claim 6, protrusions (Kd) are provided at regular intervals on the outer peripheral wall surface of the flow path (liquid delivery tube 1C shown in Figure 8(c)) formed in an arc shape.
[0022] The flow path structure manufacturing method of claim 9 is characterized in that, in manufacturing a flow path (flow path 1C shown in Figure 7(b) and flow path 1C shown in Figure 8(c)) through which a fluid (e.g., sample liquid L2) containing particles (e.g., cells CE) to be measured in the flow path structure described in claim 5 or 6 flows, a base material (K) made of a stretchable elastic body having recesses (Kc) provided at regular intervals on at least one surface (surface Ka1) is stretched in a predetermined direction to form the base material (K) into a tubular or arc-shaped shape, thereby manufacturing a flow path through which a fluid (e.g., sample liquid L2) containing particles (e.g., cells CE) to be measured flows. Effect of the Invention
[0023] Next, the effects of the present invention will be described with reference to the drawings. Note that the reference symbols in the parentheses are those of the embodiments described below, but the present invention is not limited thereto.
[0024] According to the invention of claim 1, particles (e.g., cells CE) can enter the recesses (1c, Kc), and vortices (L2a) can be generated in the recesses (1c, Kc) by changing the flow rate of the fluid (e.g., sample liquid L2). This allows particles (e.g., cells CE) to be captured one by one in the recesses (1c, Kc) by adjusting the flow rate to generate vortices (L2a). Then, by adjusting the flow rate so that vortices (L2a) are not generated, the particles (e.g., cells CE) captured in the recesses (1c, Kc) provided at regular intervals will flow through the flow channel while maintaining equal intervals.
[0025] Therefore, according to the present invention, the intervals between particles can be made equal using a simple method, thereby improving the operating speed of the device.
[0026] According to the invention of claim 2, since guide members (first guide member 2a, second guide member 2b) are provided to guide particles (e.g., cells CE) into the recesses (1c, Kc), the particles (e.g., cells CE) can be more reliably captured one by one in the recesses (1c, Kc).
[0027] According to the invention of claim 3, particles (e.g., cells CE) are guided into the recesses (1c, Kc) by pouring a predetermined fluid (liquid L3) into the guide path (3), so that the particles (e.g., cells CE) can be more reliably captured one by one in the recesses (1c, Kc).
[0028] Thus, the flow paths of the inventions according to claims 1 to 3 are preferably microflow paths (1, 1A, 1B) as in the invention according to claim 4, or formed in a tube shape as in the invention according to claim 5 (see liquid supply pipe 1C shown in FIG. 7(b)), or formed in an arc shape as in the invention according to claim 6 with a specified plate (I) installed on the upper surface (see liquid supply pipe 1C shown in FIG. 8(c)).
[0029] According to the invention of claim 7, the outer peripheral wall surface of the flow path (liquid feed pipe 1C shown in FIG. 7(b)) formed in a tubular shape has projections (Kd) at regular intervals, and these projections (Kd) function as ribs. This makes it possible to reinforce the flow path (liquid feed pipe 1C shown in FIG. 7(b)) formed in a tubular shape.
[0030] According to the invention of claim 8, the outer peripheral wall surface of the flow path (liquid supply pipe 1C shown in FIG. 8(c)) formed in an arc shape has projections (Kd) at regular intervals, and these projections (Kd) function as ribs. This makes it possible to reinforce the flow path (liquid supply pipe 1C shown in FIG. 8(c)) formed in an arc shape.
[0031] According to the invention of claim 9, the base material (K) can be formed into a tube shape or an arc shape simply by stretching it in a predetermined direction, so that a flow path through which a fluid (e.g., sample liquid L2) containing particles to be measured (e.g., cells CE) flows can be simply and easily manufactured. [Brief description of the drawings]
[0032] [Figure 1] FIG. 1 is a cross-sectional view showing a microchannel according to an embodiment of the present invention, in which (a) shows a state where the flow rate is increased, (b) shows a state where the flow rate is decreased, and (c) shows a state where the intervals between cells are equal. [Diagram 2] FIG. 2(a) shows a simulation model of the microchannel shown in FIG. 1, and FIG. 2(b) is a graph showing the results of investigating whether or not vortices occur by changing the parameters of the protrusion height and the inlet velocity. [Diagram 3] 2(b) shows a streamline display indicating a state in which no vortex is generated at point A shown in FIG. 2(b), (b) shows a streamline display indicating a state in which a small vortex is generated at point B shown in FIG. 2(b), and (c) shows a streamline display indicating a state in which a large vortex is generated at point C shown in FIG. 2(b). [Figure 4] FIG. 2 is a cross-sectional view showing another microchannel different from that in FIG. [Diagram 5] FIG. 5 is a cross-sectional view showing another microchannel different from those in FIGS. 1 and 4. [Figure 6] 1 is a partial cross-sectional view showing a state in which a sample liquid is sent from a predetermined container to a conventional flow cell using a liquid sending tube. [Figure 7] 1A and 1B are perspective views showing a process for producing a liquid supply tube, in which FIG. 1A is a perspective view showing a base material, and FIG. 1B is a perspective view showing a tubular liquid supply tube after it has been produced. [Figure 8] 8 shows a process for manufacturing a liquid-transport tube different from that shown in FIG. 7, where (a) is an oblique view showing a base material, (b) is an oblique view showing the base material formed into an arc shape, and (c) is an oblique view showing the liquid-transport tube manufactured by providing a specified plate on the upper surface of the base material in the state shown in (b). [Figure 9]FIG. 1(a) is a cross-sectional view showing the state in which sheath liquid and sample liquid are flowing through a conventional flow cell, and FIG. 1(b) is an explanatory diagram for explaining the spacing between cells flowing near the outlet of a conventional microchannel. [Figure 10] This is a graph showing the success rate of cell sorting as a function of the operating time of the cell sorting device for one event, based on the operating conditions of the latest cell sorting device in a flow cytometer (see A. Isozaki et al., “Intelligent image-activated cell sorting 2.0,” Lab on a Chip 20, 2263-2273, 2020.). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0033] An embodiment of the flow channel structure according to the present invention applied to a flow cytometer will be specifically described below with reference to the drawings. In the following description, when directions such as up, down, left and right are indicated, they refer to up, down, left and right as viewed from the front of the figure.
[0034] <Outline of flow channel structure> The flow channel structure according to this embodiment can make the intervals between particles equal by a simple method, thereby improving the operation speed of the device. Specifically, the flow channel structure according to this embodiment is obtained by replacing the micro flow channel 102 of the flow cell 100 shown in FIG. 9(a) with the micro flow channel 1 shown in FIG. 1. This micro flow channel 1 will be described in detail below. In this embodiment, cells will be used as an example of particles.
[0035] <Explanation of microchannel> As shown in Fig. 1, the microchannel 1 is formed into a horizontally elongated cylindrical shape in cross section, and a sample liquid L2 containing a plurality of cells CE to be measured flows inside in the direction of arrow Y2 (from left to right in the figure). As shown in Fig. 1, acute angled mountain-shaped protrusions 1b are provided at regular intervals on the lower wall surface 1a of the microchannel 1 facing inward (upward in the figure). As a result, as shown in Fig. 1, recesses 1c are provided at regular intervals on the inner wall surface on the lower wall surface 1a side of the microchannel 1. The width W1 (see Fig. 1(a)) of the recesses 1c is formed to be slightly larger than the width of the cells CE.
[0036] <Explanation of examples of using microchannels> Thus, the microchannel 1 thus configured is used as follows.
[0037] First, a sample liquid L2 containing a plurality of cells CE to be measured is caused to flow at a high flow rate (e.g., 0.5 m / s) in the microchannel 1. This allows a vortex L2a to be generated in the recess 1c, as shown in Fig. 1(a). When such a vortex L2a is generated, the cells CE are caught in the vortex L2a and captured one by one in the recess 1c, as shown in Fig. 1(a).
[0038] Next, the flow rate is gradually decreased from a high flow rate (e.g., 0.5 m / s) to a low flow rate (e.g., 0.1 m / s) so that no vortex L2a is generated in the recess 1c, as shown in FIG. 1(b). In this way, as shown in FIG. 1(b), the cells CE captured in the recess 1c will escape from the recess 1c along the flow of the sample liquid L2 in the direction of the arrow Y2 (from the left to the right in the figure). At this time, since the flow rate is constant, the cells CE will flow in the direction of the arrow Y2 (from the left to the right in the figure) while maintaining the intervals between the recesses 1c, that is, constant intervals. As a result, the cells CE will flow in the direction of the arrow Y2 (from the left to the right in the figure) while maintaining the equal intervals between the cells CE, as shown in FIG. 1(c).
[0039] Thus, in this way, the micro flow channel 1 is configured as described above, and the intervals between the cells CE can be made equal simply by adjusting the flow rate.
[0040] Therefore, according to the present embodiment described above, the intervals between the cells CE can be made equal by a simple method, and therefore the operating speed of the flow cytometer device can be improved.
[0041] <Explanation of Experimental Example> Here, the inventors performed the following simulation (experiment) to confirm whether a vortex L2a as shown in Fig. 1(a) is generated in the recess 1c shown in Fig. 1 by changing the flow rate of the sample liquid L2 (see Fig. 1) using a microchannel 1 as shown in Fig. 1. The simulation software used was COMSOL Multiphysics (registered trademark) by COMSOL, Inc.
[0042] First, the inventors created a simulation model of the microchannel 1 shown in FIG. 1, as shown in FIG. 2(a). In this case, the height H1 of the microchannel 1 shown in FIG. 2(a) was set to 40 μm, the width W1 of the recessed hole 1c (see FIG. 1) was set to 40 μm, and the width W2 of the protrusion 1b (see FIG. 1) was set to 10 μm. Then, the sample liquid L2 was made to flow from the inlet shown in FIG. 2(a) toward the outlet. Thus, after making such settings, the height H2 (μm) of the protrusion 1b (see FIG. 1) shown in FIG. 2(a) and the velocity (m / s) of the inlet were changed as parameters to investigate the occurrence of a vortex L2a (see FIG. 1(a)). The results are shown in the graph in FIG. 2(b).
[0043] In the graph shown in FIG. 2(b), the horizontal axis indicates the velocity (m / s) of the inlet changed from 0 m / s to 1 m / s, and the vertical axis indicates the height H2 (μm) of the protrusion 1b (see FIG. 1), which is 0 to 1 times the height H1 of the microchannel 1, which is 40 μm. Then, the velocity (m / s) of the inlet and the height H2 (μm) of the protrusion 1b (see FIG. 1) were changed to check whether or not a vortex L2a (see FIG. 1(a)) was generated. As shown in FIG. 2(b), no vortex was generated in the blue area, small vortexes were generated in the light orange area, and large vortexes were generated in the dark orange area. To make this point easier to understand, three representative points (points A, B, and C) shown in FIG. 2(b) were selected, and the streamlines for each case were shown in FIG. 3. At point A shown in FIG. 2(b) (inlet speed 0.1 m / s, height of protrusion 1b (see FIG. 1) 20 μm), no vortex L2a (see FIG. 1(a)) is generated in recess 1c as shown in FIG. 3(a). At point B shown in FIG. 2(b) (inlet speed 0.25 m / s, height of protrusion 1b (see FIG. 1) 20 μm), vortex L2a is generated in recess 1c as shown in FIG. 3(b), but it is not enough to fill up recess 1c. That is, a small vortex L2a is generated. At point C shown in FIG. 2(b) (inlet speed 0.5 m / s, height of protrusion 1b (see FIG. 1) 20 μm), vortex L2a is generated to fill up recess 1c as shown in FIG. 3(c). That is, a large vortex L2a is generated.
[0044] From these results, it can be seen that if sample liquid L2 (see FIG. 1) is first made to flow at a high flow rate as shown at point C in FIG. 2(b), a vortex L2a is generated in hole 1c as shown in FIG. 1(a), and cells CE are captured one by one in hole 1c, then the flow rate is reduced to point B in FIG. 2(b), narrowing the area in which cells CE exist in hole 1c, and then the flow rate is reduced to point A in FIG. 2(b), the cells CE will change from the state shown in FIG. 1(b) to the state shown in FIG. 1(c).
[0045] Therefore, from the experimental results, it was found that by configuring the microchannel 1 shown in Fig. 1 and adjusting the flow rate, a vortex L2a as shown in Fig. 1(a) is generated. Therefore, it was found that the intervals between the cells CE can be made equal by simply configuring the microchannel 1 as described above and adjusting the flow rate.
[0046] <Description of Modifications> However, the shapes and the like shown in this embodiment are merely examples, and various modifications and changes are possible within the scope of the gist of the present invention described in the claims. For example, the microchannel 1 exemplified in this embodiment can be modified as shown in FIG. 4. The microchannel 1A shown in FIG. 4 will be described below. Note that the same components as those in the microchannel 1 shown in FIG. 1 are denoted by the same reference numerals, and description thereof will be omitted.
[0047] The only difference between the microchannel 1A shown in Fig. 4 and the microchannel 1 shown in Fig. 1 is whether or not there is a first guide member 2a having a semicircular cross-sectional shape and a second guide member 2b having a circular cross-sectional shape, and the rest is the same. Therefore, only the difference will be described below.
[0048] As shown in FIG. 4, on the inner wall surface on the upper wall surface 1d side of the microchannel 1A, a first guide member 2a is provided at a position facing the protrusion 1b, and a second guide member 2b is provided at a position facing the recessed hole 1c.
[0049] Thus, if the first guide member 2a and the second guide member 2b as shown in Fig. 4 are provided, when the sample liquid L2 is caused to flow at a high flow rate (e.g., 0.5 m / s), the cells CE will come into contact with the first guide member 2a and / or the second guide member 2b and move downward as shown in Fig. 4. This makes it easier for the cells CE to be caught in the vortex L2a, so that the cells CE can be guided into the recessed hole 1c. Therefore, this makes it possible to more reliably capture the cells CE one by one in the recessed hole 1c.
[0050] On the other hand, the microchannel 1 illustrated in Fig. 1 can be modified as shown in Fig. 5. The microchannel 1B illustrated in Fig. 5 will be described below. Note that the same components as those in the microchannel 1 illustrated in Fig. 1 are denoted by the same reference numerals, and description thereof will be omitted.
[0051] The only difference between the microchannel 1B shown in Fig. 5 and the microchannel 1 shown in Fig. 1 is whether or not there is a guide path 3 having a vertically elongated cylindrical shape in cross section, and the rest is the same. Therefore, only this difference will be described below.
[0052] As shown in Fig. 5, a guide path 3 having a vertically long cylindrical shape in a cross-sectional view is integrally provided on the left side of the upper wall surface 1d of the microchannel 1B. As shown in Fig. 5, a liquid L3 different from the sample liquid L2 is caused to flow in the guide path 3. As a result, the liquid L3 flows through the guide path 3 into the microchannel 1B shown in Fig. 5.
[0053] Thus, if a guide path 3 as shown in Fig. 5 is provided, when sample liquid L2 is caused to flow at a high flow rate (e.g., 0.5 m / s), cells CE are moved downward as shown in Fig. 5 by liquid L3 that has flowed into microchannel 1B through guide path 3. This makes it easier for cells CE to be caught in vortex L2a, so that cells CE can be guided into recessed hole 1c. Therefore, even in this way, cells CE can be more reliably captured one by one in recessed hole 1c.
[0054] On the other hand, the microchannels 1, 1A, and 1B described above all show examples in which the protrusions 1b and the recesses 1c are provided on the lower wall surface 1a side, but this is not limiting, and the protrusions 1b and the recesses 1c may be provided on the upper wall surface 1d side as long as the intervals between the cells CE can be made equal.
[0055] On the other hand, in this embodiment, the microchannels 1, 1A, and 1B are exemplified as the flow channel structure, but the present invention is not limited thereto, and may be applied to a liquid feed tube 1C that feeds a sample liquid L2 from a predetermined container Y into a microchannel 102, as shown in Fig. 6. That is, the liquid feed tube 1C may be changed to a configuration similar to the microchannels 1, 1A, and 1B described above.
[0056] Meanwhile, the liquid sending tube 1C as described above can be manufactured as follows, which will be specifically described with reference to Figs.
[0057] As shown in FIG. 7(a), a base material K made of a stretchable elastic body is prepared. For example, the material of the base material K may be a silicone rubber material ELITE DOUBLE manufactured by Zhermack or a silicone rubber material AR-G1 series for 3D printers manufactured by KEYENCE. Such a base material K includes a base material body Ka formed in a rectangular shape as shown in FIG. 7(a). As shown in FIG. 7(a), acute-angled mountain-shaped protrusions Kb extending in the front-rear direction are integrally provided at regular intervals on the surface Ka1 of the base material body Ka in the left-right direction in the figure. As a result, as shown in FIG. 7(a), recesses Kc are provided between the protrusions Kb, and the recesses Kc are also provided at regular intervals in the left-right direction in the figure.
[0058] On the other hand, as shown in FIG. 7(a), rectangular projections Kd extending in the front-rear direction in the figure are integrally provided at regular intervals on the rear surface Ka2 of the base body Ka in the left-right direction in the figure.
[0059] Thus, when manufacturing the liquid-feeding tube 1C using such a base material K, first, the base material K is stretched by pulling it in the direction of the arrow Y10 (left-right direction in the figure) shown in Fig. 7(a). In this state, the stretched base material K is rolled in the direction of the arrow Y11 (front-back direction in the figure) shown in Fig. 7(a), and the front side surface Ka3 and the rear side surface Ka4 of the base material main body Ka shown in Fig. 7(a) are joined by an adhesive or the like. In this way, a tubular liquid-feeding tube 1C can be manufactured as shown in Fig. 7(b).
[0060] Therefore, by using such a base material K, it is possible to simply and easily manufacture a tubular liquid delivery pipe 1C as shown in FIG. 7(b).
[0061] Thus, the liquid-transfer tube 1C manufactured in this manner has recesses Kc at regular intervals on the inner wall surface as shown in FIG. 7(b). Therefore, the same effect as the microchannels 1, 1A, and 1B described above can be obtained. In addition, since the liquid-transfer tube 1C shown in FIG. 7(b) has protrusions Kd at regular intervals on the outer peripheral wall surface, these protrusions Kd act as ribs, and thereby the liquid-transfer tube 1C can be reinforced. In addition, FIG. 7(a) shows an example in which acute-angled mountain-shaped protrusions Kb extending in the front-rear direction are integrally provided at regular intervals on the surface Ka1 of the base body Ka toward the left-right direction in the figure, but the length in the front-rear direction in the figure may be shortened (e.g., halved). In this way, when the tube-shaped liquid-transfer tube 1C is manufactured as shown in FIG. 7(b), the recesses Kc are not provided on the entire inner wall surface, and if it is halved, for example, it will appear only on 180° of the inner wall surface. Therefore, simply by shortening the length of the projection Kb in the front-rear direction, it is possible to arbitrarily change the angle of the recessed hole Kc appearing on the inner wall surface.
[0062] On the other hand, the liquid sending tube 1C can also be manufactured as shown in FIG. 8. That is, first, a base material K identical to the base material K shown in FIG. 7(a) is prepared as shown in FIG. 8(a). Then, the base material K is stretched by pulling it in the direction of the arrow Y10 shown in FIG. 8(a) (horizontal direction in the figure). In this state, the stretched base material K is rolled in the direction of the arrow Y11 shown in FIG. 8(a) (front-back direction in the figure) to form a semi-cylindrical arc shape as shown in FIG. 8(b). Then, a predetermined plate I shown in FIG. 8(c) is bonded to the front side Ka3 and the rear side Ka4 of the base material body Ka shown in FIG. 8(b) by adhesive or the like. This makes it possible to manufacture the liquid sending tube 1C as shown in FIG. 8(c). The predetermined plate I plays a role of maintaining the base material K in an arc shape and preventing leakage when the sample liquid L2 flows through it.
[0063] Therefore, by using such a base material K, it is possible to simply and easily manufacture the liquid delivery tube 1C as shown in FIG. 8(c).
[0064] Thus, the liquid-feeding tube 1C manufactured in this manner also has recesses Kc at regular intervals on its inner wall surface, as shown in Fig. 8(c). Therefore, the same effect as the microchannels 1, 1A, and 1B described above can be obtained. Note that the liquid-feeding tube 1C shown in Fig. 8(c) also has protrusions Kd at regular intervals on its outer peripheral wall surface, and these protrusions Kd act as ribs, thereby reinforcing the liquid-feeding tube 1C. [Industrial Applicability]
[0065] Incidentally, in the present embodiment, the particles are described by way of example as cells, but the present invention is not limited thereto and can also be applied to particles such as pollen.
[0066] In addition, although the present embodiment shows an example of application to a flow cytometer device, the present invention is not limited to this, and can also be applied to devices that measure larger particles such as pollen using a flow system and devices that use the microdroplet method. [Explanation of symbols]
[0067] 1, 1A, 1B Microchannel (channel) 1C Liquid delivery pipe (flow path) 1c recessed hole 2a First guide member (guiding member) 2b Second guide member (guiding member) 3 Taxiway L2 Sample liquid (fluid) L3 Liquid (specified fluid) CE cells (particles) K base material Ka1 surface Kc concave hole Kd protrusion I Prescribed board
Claims
1. The flow channel has an inner wall surface through which a fluid containing particles to be measured flows, and has recesses provided at regular intervals on the inner wall surface of the flow channel, A flow path structure in which the particles can enter the recesses and in which vortices can be generated within the recesses by changing the flow rate of the fluid.
2. 2. The flow path structure according to claim 1, wherein a guide member for guiding the particles into the recesses is provided on an inner wall surface of the flow path opposite to the recesses provided at regular intervals on the inner wall surface of the flow path.
3. A guide path is provided on an inner wall surface of the flow path opposite to the recesses provided at regular intervals on the inner wall surface of the flow path, 2. The flow path structure according to claim 1, wherein the particles are guided into the recesses by flowing a predetermined fluid into the guide path.
4. The flow channel structure according to claim 1 , wherein the flow channel through which the fluid containing the particles to be measured flows is a micro flow channel.
5. 2. The flow path structure according to claim 1, wherein the flow path through which the fluid containing the particles to be measured flows is formed in a tubular shape.
6. 2. The flow path structure according to claim 1, wherein the flow path through which the fluid containing the particles to be measured flows is formed in an arc shape and has a predetermined plate installed on the upper surface.
7. The flow channel structure according to claim 5 , wherein protrusions are provided at regular intervals on an outer peripheral wall surface of the flow channel formed in a tubular shape.
8. The flow path structure according to claim 6 , wherein protrusions are provided at regular intervals on an outer peripheral wall surface of the flow path formed in an arc shape.
9. 7. A method for manufacturing a flow path in the flow path structure according to claim 5 or 6, in which a flow path through which a fluid containing particles to be measured flows is provided, by stretching a base material made of a stretchable elastic body having recesses at regular intervals on at least one surface in a predetermined direction to form the base material into a tube shape or an arc shape, thereby manufacturing a flow path through which a fluid containing particles to be measured flows.