Mixing device for microchannel and microchannel device

Abstract

To provide a mixing device for improving mixing efficiency in a wider flow rate range with a comparatively simple shape, and a micro flow channel device using the same.SOLUTION: A mixing device mixes a plurality of fluids in a mixing region 8. The mixing region has first and second wall surfaces 21 and 22 that face each other, a first obstacle structure 6 that projects toward the second wall surface from the first wall surface and functions as an obstacle against a flow of a fluid, and a second obstacle structure 7 which projects toward the first wall surface from the second wall surface, and functions as an obstacle against the flow of the fluid. The first obstacle structure is composed of a plurality of first obstacle structure constitution parts 61, ..., 64 that are arranged side by side, and the second obstacle structure is composed of a plurality of second obstacle structure constitution parts 71, ..., 77 that are arranged side by side. The first obstacle structure constitution parts and the second obstacle structure constitution parts are arranged in a mutually asymmetrical state with a center line X of a single flow channel as an axis.SELECTED DRAWING: Figure 3

Description

[Technical Field]

[0001] The present invention relates to a mixer for mixing a plurality of fluids flowing down a microchannel, and a microchannel device having this mixer. [Background technology]

[0002] Mixing devices for microchannels have been developed as so-called micromixers. Generally, fluid flow in microchannels is laminar due to a low Reynolds number (typically Re = 0.1 to 10), making it difficult to mix multiple fluids. Therefore, in the field of micro-total analysis systems (μTAS), much research has been conducted on fluid mixing.

[0003] Micromixers are broadly classified into "active mixers" and "passive mixers" based on their operating principles. Active mixers use external energy (such as electric or magnetic fields) to induce forced convection, while passive mixers are configured to increase the mixing interface of fluids by devising the shape of the microchannel (see Non-Patent Documents 1 and 2).

[0004] However, because the active mixer utilizes external energy such as an electric field or a magnetic field, it requires an external power source to provide the external energy (see Patent Document 1). Therefore, the external power source and other accessories inevitably increase the overall size of the device, leading to high costs. In particular, when used as a microchannel chip, disposable devices are required. However, when electrodes or other components are required, disposable devices are expensive and therefore unsuitable. Furthermore, large devices have portability issues, making them unsuitable for use at the analysis site (on-site analysis) or point-of-care testing (POCT).

[0005] Therefore, passive mixers are suitable for miniaturizing devices and enabling disposable use. Therefore, numerous research efforts are being conducted on flow path shapes suitable for use as passive mixers. A typical passive mixer is one in which the bottom surface of the flow path is provided with raised obstacles at appropriate intervals (see Non-Patent Documents 3 and 4). This technology involves placing elongated raised obstacles at appropriate intervals on the bottom surface of the flow path, oriented transversely to the direction of the fluid flow. The longitudinal direction of these obstacles is angled (obliquely) to cause the fluid in the flow path to flow downward in a spiral, resulting in mixing. Other passive mixers that have been developed include those with a spiral flow path (see Patent Document 2) and those with a fluid storage section (see Patent Document 3). [Prior art documents] [Patent documents]

[0006] [Patent Document 1] Japanese Patent Application Laid-Open No. 2008-062190 [Patent Document 2] Japanese Patent Application Laid-Open No. 2014-198324 [Patent Document 3] Japanese Patent Application Laid-Open No. 2014-134476 [Non-patent literature]

[0007] [Non-Patent Document 1] Chia Yen Lee, Chin-Lung Chang, Yao-Nan Wang and Lung-Ming Fu, “International Journal of Molecular Sciences” 2011,12(5), pp.3263-pp.3287 [Non-patent document 2] Morteza Bayareh, Mohse Nazami Ashani and Azam Usefian, “Chemical Engineering and Processing - Process Inensification”, 2020, Vol.147, pp.107771 [Non-patent document 3] Abraham D. Stroock, Stephan KW Dertinger, Armand Ajdari, Igor Mezic, Howard A. Stone and George M. Whitesides, “Science”, Vol.295(5555), 2002, pp.647-pp.651 [Non-patent document 4] Daigo Natsuhara, Keisuke Takishita, Kisuke Tanaka, Azusa Kage, Ryoji Suzuki, Yuko Mizukami, Norikuni Saka, Moeto Nagai and Takayuki Shibata, “Micromachines”, 11(6), 2020, pp.540 Summary of the Invention [Problem to be solved by the invention]

[0008] The typical passive mixer described above induces a spiral flow using a raised obstacle on the bottom surface of the channel. However, this raised obstacle is difficult to fabricate because it requires varying the channel depth. Generally, soft lithography is used to fabricate microchannels (and microchannel chips). To vary the microchannel depth, the height of the channel components in the mold must be varied. This mold is typically fabricated using semiconductor manufacturing processes (e.g., MEMS: Micro Electro Mechanical Systems) by patterning photoresist using photolithography to form a mold with a concave and convex shape. However, to partially vary the channel depth, the patterning must be performed twice to apply two types of photoresist, one for the deep region and one for the shallow region. However, fabricating the photoresist twice requires a long manufacturing process, which reduces the reproducibility of film thickness control (dimensions) during the two film depositions, potentially resulting in poor accuracy of the finished mold.

[0009] Therefore, in order to form a mold with only one patterning, it is preferable to provide obstacle components that protrude from the wall surface rather than providing a protruding structure on the bottom of the channel, but in this case, it is necessary to devise the shape and arrangement of the obstacle components that protrude from the wall surface.In other words, since the main purpose is to intentionally increase the surface area of ​​the interface where multiple fluids come into contact, thereby promoting mutual diffusion and improving mixing efficiency, a shape that would exert this effect had to be designed.

[0010] However, in order to promote interdiffusion, the flow channel shape becomes complex, and the patterning using photoresist also becomes complicated, which increases the manufacturing cost and reduces the reproducibility of dimensions according to the fine shape.In addition, as the shape becomes more complex, the mixing efficiency becomes greatly affected by the flow rate (Reynolds number), and there has been a strong demand for a mixer that can maintain high mixing efficiency over a wide range of flow rates (inlet flow rates).

[0011] The present invention has been made in consideration of the above points, and its object is to provide a mixing device that has a relatively simple shape and improves mixing efficiency over a wide flow rate range, and a microchannel device that uses the same. [Means for solving the problem]

[0012] Therefore, the present invention, which relates to a mixing device, is a mixing device for a microchannel comprising a plurality of supply flow paths, a single flow path where these supply flow paths converge, and a mixing region formed within an appropriate range of this single flow path, and which mixes a plurality of fluids in the mixing region, wherein the mixing region comprises first and second wall surfaces facing each other, a first obstacle structure that protrudes from the first wall surface toward the second wall surface and functions as an obstacle to the flow of fluids, and a second obstacle structure that protrudes from the second wall surface toward the first wall surface and functions as an obstacle to the flow of fluids, wherein the first obstacle structure is composed of a plurality of first obstacle structure-composing parts arranged in parallel, and the second obstacle structure is composed of a plurality of second obstacle structure-composing parts arranged in parallel, and the first obstacle structure-composing part and the second obstacle structure-composing part are arranged asymmetrically with respect to each other with the center line of the single flow path as an axis.

[0013] According to the above configuration, when multiple fluids simultaneously flow down through the mixing region of a single flow path, the flow patterns of the fluids flowing down along the first wall surface and the fluids flowing down along the second wall surface are different from each other, and within the mixing region, the fluids flowing down along the first and second wall surfaces influence each other's flows, thereby increasing the surface area of ​​the interface where the fluids to be mixed come into contact.

[0014] Here, the asymmetric state of the first and second obstacle structure components can be defined as being different from each other in at least one of the protrusion length, adjacent spacing, and total number of individual obstacle structure components.

[0015] That is, although the obstacle structure components used in conventional general mixing devices are asymmetric in the strict sense, for example, when they are protruded in a staggered pattern, some are configured in a state where they become symmetric when one side is moved axially along the symmetry axis (this is sometimes called "approximate symmetry" to distinguish it from strict symmetry), but in the present invention, such approximately symmetric cases are defined as being included in the symmetric state, and the construction of an asymmetric state (complete asymmetry) that excludes the approximately symmetry is meant. Therefore, by creating a completely asymmetric state as described above, that is, a state where they do not become symmetric when one side is moved axially along the center line that serves as the symmetry axis, such as when at least one or more of the protrusion length, adjacent interval, and total number of the two are different from each other, the fluids flowing down near the first and second wall surfaces can generate flows of different states from each other, and as a result of the two fluids influencing each other's flows, the surface area of ​​the interface where the two fluids come into contact can be increased.

[0016] By providing the first and second obstacle structure components in a completely asymmetric state as in the above configuration, it is preferable that the flow path spaces formed on the first wall surface side and the second wall surface side with the center line of the single flow path as a boundary have different capacities within the range where the mixing region is formed. Since the formation of the flow path space is a space through which a fluid can flow down, by forming the flow path space in different states on both sides of the center line of the single flow path as a boundary, it is possible to generate different flows for the fluid flowing down along both wall surfaces.

[0017] In previous mixing devices, the obstacle structures (obstacle structure components) were configured symmetrically (including approximately symmetrically). This meant that the fluid flowing through the flow channel tended to flow in a regular pattern, necessitating a long flow path to promote mixing. Therefore, to achieve a sufficient mixing state (e.g., a mixing state of 80% or more), it was necessary to provide a very long mixing channel (single channel) or to change the flow rate (Reynolds number) of the supply fluid. In contrast, with the present invention configured as described above, the fluids flowing near the first wall surface and the second wall surface can be prevented from flowing in a regular pattern as they flow down the mixing region. This allows the fluids to continuously influence each other's flow, achieving high mixing efficiency within a relatively short range. At the same time, the effect of the flow rate (Reynolds number) of the supply fluid on the mixing state can be reduced.

[0018] In order to create a specific asymmetric state in the invention of the above configuration, some of the first obstacle structure components are configured as cross-border barrier portions that protrude to a position beyond the center line of the single flow path and induce the fluid to flow down beyond the center line.

[0019] In this configuration, part or all of the first obstacle structure component is configured to extend beyond the center line of the single flow path (transboundary barrier component), so that the fluid flowing down along the first wall surface meanders significantly and is guided to the vicinity of the second wall surface. In contrast, the second obstacle structure component is configured to be asymmetric with the transboundary barrier component (e.g., with a short protrusion length), so that the fluid flowing down near the second wall surface is guided in a manner different from that near the first wall surface. Furthermore, the first obstacle structure component that extends beyond the center line causes the fluid to meander significantly again and be guided to the second wall surface, thereby continuing the irregular flow. This increases the interfacial surface area of ​​the fluids to be mixed, thereby promoting mixing.

[0020] Furthermore, in the invention having the above configuration, the second obstacle structure component that is arranged on the extension line of the cross-border barrier section may be composed of a cross-border area flow path component that forms a flow path of a predetermined width together with the cross-border barrier section.

[0021] In the above configuration, the cross-border obstacle component induces a meandering flow of fluid near the first wall, and the fluid is guided to the cross-border region flow path component together with the fluid near the second wall. In other words, the fluids flowing downstream in the mixing region can be concentrated in the cross-border region flow path component. Because the cross-border region flow path component is formed at a position offset from the centerline of the single flow path, all of the various fluids to be mixed temporarily flow downstream in a position offset from the centerline of the single flow path. Then, the downstream cross-border flow diversion component simultaneously induces the fluids to be mixed toward the first wall, causing all of the fluids to pass near both walls, providing an opportunity for them to mix in an appropriate ratio.

[0022] In such a configuration, it is preferable that the second obstacle structure component, which is located downstream of the flow path of a predetermined width formed by the cross-border barrier component and the cross-border area flow path component, is configured as a cross-border flow detour component that protrudes with a longer protrusion length than the cross-border area flow path component and detours the flow of fluid that flows downstream across the center line.

[0023] According to the above configuration, the presence of the cross-border obstacle component and the cross-border region flow path component creates a flow path of a predetermined width offset from the centerline of the single flow path. The entire fluid flowing down the single flow path meanders significantly as it passes through the flow path of the predetermined width. However, the presence of the cross-border flow detour component causes the fluid that has passed through the flow path of the predetermined width to detour in the opposite direction. That is, because the cross-border flow detour component protrudes from the second wall by a length longer than the cross-border region flow path component, the fluid that is guided near the second wall by the flow path of the predetermined width is detoured by the presence of the cross-border flow detour component, and the flow is guided toward the first wall. This series of fluid flows results in a steep flow of the fluid down the flow path of the predetermined width, while it is slow in other regions. Furthermore, because the flow is different on both sides of the centerline of the single flow path, the imbalance in the flow is maintained and is not corrected to a balanced state. As a result, the fluids flowing down the mixing region (within a single flow path) continuously increase the interfacial surface area of ​​the fluids to be mixed due to the above-mentioned flow imbalance, making it possible to quickly increase the mixing efficiency.

[0024] In this case, the cross-border flow detouring section is preferably disposed between adjacent cross-border region flow-path components. Because the cross-border flow detouring section protrudes from the second wall surface by a length longer than the cross-border region flow-path components, it acts as an obstacle to the fluid flowing down the flow path of a predetermined width formed by the cross-border obstacle component and the cross-border region flow-path component, guiding the fluid to the tip of the cross-border flow detouring section. The length of the protrusion of the cross-border flow detouring section can be adjusted so that the gap formed between its tip and the first wall surface is wider than the predetermined width of the flow path formed by the cross-border obstacle component and the cross-border region flow-path component, thereby slowing the flow in the detouring region. This configuration, in other words, alternates between the flow path of a predetermined width formed by the cross-border obstacle component and the cross-border region flow-path component and the cross-border flow detouring section. This creates variations in the overall flow of the fluids to be mixed, promoting mixing of the fluids.

[0025] The mixing area may be formed to an appropriate length, and a plurality of mixing areas may be formed in the single flow path, and these mixing areas may be configured to be arranged in series. In this case, the plurality of mixing areas may all have the same configuration, or may be configured to be arranged with the arrangement of obstacle structures changed.

[0026] With this configuration, fluids can basically be mixed in a mixing region formed over a predetermined length. However, multiple mixing regions can be formed depending on the type of fluid to be mixed and the flow rate of the fluids to be supplied to improve the mixing state of the fluids. In particular, while a phenomenon in which the liquid initially flowing down near the first wall and the liquid flowing down near the second wall are partially reversed as the mixing progresses, forming a mixing region of sufficient length allows the mixing state to progress further. Naturally, each mixing region is provided with a sufficient number of obstacle structure components, and the single flow path for this purpose is also provided with an appropriate length. Note that multiple mixing regions formed in series do not all need to have the same configuration, but simply swapping the first obstacle structure and the second obstacle structure is not preferable. This is because simply swapping the obstacle structures would result in the mixing region being approximately symmetrical as a whole.

[0027] The present invention relating to a microchannel device comprises a mixing device having any one of the above-described configurations within a microchannel chip, and is characterized in that the mixing device comprises a plurality of supply channels and a single channel that constitute the mixing device, the mixing region formed within an appropriate range of the single channel, a fluid injection part that injects a fluid into the supply channels, a reaction region that is provided contiguous to the single channel, and a discharge part that discharges the fluid at the end of the channel that has passed through the reaction region.

[0028] According to the above configuration, a specimen or the like can be immobilized in a reaction region provided in a microchannel chip, and reagents or the like can be mixed and supplied. Since the reagent or the like can be a mixture of multiple fluids as described above, it is not necessary to supply a premix of the reagent or the like to the microchannel chip. By appropriately selecting the fluids to be mixed, it is possible to supply the required amount of reagent or the like in a minimal amount. Furthermore, by using the dispensing device disclosed in Japanese Patent Application No. 2020-190959 by the applicant of the present application in the reaction region, it is possible to dispense the mixed reagent or the like into multiple reaction vessels, and it is also possible to cause different reactions in each of the multiple reaction vessels. [Effects of the Invention]

[0029] According to the present invention, the first and second obstacle structure components that constitute the first and second obstacle structures are each configured to protrude from the first or second wall surface toward the other wall surface, and therefore can be configured with a relatively simple shape. As a result, when forming a mold using photolithography technology, it is not necessary to partially change the depth of the flow path, and therefore easy manufacturing is possible with a single patterning.

[0030] Furthermore, the obstacle structure configured as described above allows the multiple fluids to mix appropriately as they flow downstream, and the mixed state of the fluids at that time is less dependent on the fluid flow rate (Reynolds number), thereby improving the mixing efficiency over a wide range of flow rates.

[0031] Furthermore, since the mixing device having the above configuration can be constructed at the same time as the microchannel chip is manufactured, it can be easily incorporated into the microchannel device, and the incorporated microchannel device can supply reagents, etc. to the reaction region while mixing multiple liquids. Also, since there is no need to mix multiple fluids in advance to prepare reagents, etc., storage of reagents, etc. is unnecessary. Moreover, since it is only necessary to supply the minimum amount of fluid required to be supplied to the reaction region, reagents, etc. (mixed fluid) can be used while being conserved. [Brief explanation of the drawings]

[0032] [Figure 1] FIG. 1 is an explanatory diagram showing an embodiment of a microchannel device. [Figure 2] FIG. 1 is an explanatory view showing a first embodiment of a mixing device. [Figure 3] FIG. 10 is an explanatory diagram showing details of a mixed region. [Figure 4] FIG. 2 is an explanatory diagram showing the flow of a fluid flowing down in a mixing region. [Figure 5]FIG. 2 is an explanatory diagram showing the shape of a mixing structure used in Experimental Example 1. [Figure 6] FIG. 1 is an explanatory diagram showing the results of Experimental Example 1. [Figure 7] FIG. 10 is an explanatory diagram showing the shape and dimensions of a mixing region used in Experimental Example 2. [Figure 8] 10 is a graph showing the results of Experimental Example 2. [Figure 9] 10 is a graph showing the results of Experimental Example 3. [Figure 10] FIG. 10 is an explanatory diagram showing a modified example of the embodiment of the mixing device. [Figure 11] FIG. 10 is an explanatory diagram showing another modified example of the mixing device. [Figure 12] FIG. 10 is an explanatory diagram showing another modified example of the mixing device. [Figure 13] 10 is a graph showing some results of Experimental Example 4. [Figure 14] 10 is a graph showing the remaining results of Experimental Example 4. [Figure 15] FIG. 4 is an explanatory view showing a second embodiment of the mixing device. [Figure 16] FIG. 10 is an explanatory diagram showing a mixing device used in Experimental Example 5. [Figure 17] FIG. 10 is an explanatory diagram showing the results of Experimental Example 5. [Figure 18] FIG. 10 is an explanatory diagram showing a mixing device used in Experimental Example 6. [Figure 19] 10 is a graph showing the results of Experimental Example 6. [Figure 20] 10 is a graph showing the results of Experimental Example 7. [Figure 21] 10 is a graph showing the results of Experimental Example 8. DETAILED DESCRIPTION OF THE INVENTION

[0033] DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The following describes embodiments of the present invention with reference to the accompanying drawings. For convenience of explanation, the microchannel will be described first in general, and then the mixing device according to the present invention will be described.

[0034] <Microfluidic Device> FIG. 1 shows an outline of a microchannel device. FIG. 1(a) is a perspective view showing the overall outline, and FIG. 1(b) is a cross-sectional view taken along line BB. As shown in these figures, the microchannel device 1 has a configuration in which a plurality of microchannels are provided in a microchannel chip. The microchannels generally have a diameter of 0.005 to 2.0 mm. 2 This refers to a flow channel with a cross-sectional area of ​​about 1000 microliters, which is used to transport microfluids (very small amounts of liquid fluid, about 1 to 500 microliters).

[0035] The microfluidic device 1 of this embodiment has a configuration in which two layers are laminated together, with a flow channel forming substrate 12 laminated on a bottom plate (base) 11. Specifically, as shown in detail in FIG. 1(b), the flow channel forming substrate 12, on which a flow channel forming region has been formed in advance by soft lithography, is laminated to the upper surface of the bottom plate 11 having a smooth flat surface, with an adhesive member 10. Note that the lamination is not limited to the case where the adhesive member 10 is used, and direct bonding by plasma bonding or the like may also be used, as long as the bottom plate (base) 11 and the flow channel forming substrate 12 are laminated together by any of various methods.

[0036] In this embodiment, the bottom plate 11 is made of a glass substrate, the flow path forming substrate 12 is made of silicone resin (PDMS: polydimethylsiloxane), and double-sided tape is used as the adhesive member 10. The flow path forming substrate 12 is produced by soft lithography by patterning the shape of the flow path portion on a silicon substrate, and using this as a mold (casting die), providing silicone resin with a cavity of a predetermined shape such as a flow path.

[0037] As shown in FIGS. 1(a) and 1(b), the multiple microchannels formed on the channel-forming substrate 12 include a fluid delivery section 2 and a main channel 3 connected to the fluid delivery section 2. The fluid delivery section 2 is connected to injection sections 13 and 14, which open onto the surface of the channel-forming substrate 12, and delivers fluids injected from the injection sections 13 and 14. The main channel 3 also constitutes a part of the reaction region 100 and discharges excess fluid at its end. The reaction region 100 illustrated in the microchannel device 1 of this embodiment is configured with a branching device that branches off from the main channel 3. Therefore, the ends of the channels are the end of the main channel 3 and the end of the discharge channel 4 after passing through the branching device, and are connected to discharge sections 15 and 16, respectively. These discharge sections 15 and 16 are configured to open on the surface of the channel-forming substrate 12 and can discharge fluids from the openings as well as function to exhaust internal air within each channel. The fluid supplied to the channels may be a liquid or a suspension containing fine particles.

[0038] The liquid delivery section 2 delivers fluids supplied from the injection sections 13 and 14 to the reaction area 100. When multiple different types of fluids (two types shown in the figure) are supplied simultaneously, as shown in the figure, a mixing device is provided to mix the multiple fluids using a single flow path upstream of the liquid delivery section 2.

[0039] The embodiment of the microchannel device 1 has the above-described configuration, and therefore can mix multiple types of fluids in a part of the fluid delivery section 2 in the process of delivering the fluid to the reaction region 100, and then supply the mixed fluid to the reaction region 100. In this embodiment, a dispensing device is used in the reaction region 100, and a branch channel 31 branching from the main channel 3 is provided, and a chamber region 32 is provided in the branch channel, and a reaction vessel 33 is provided in this chamber region 32, so that the reaction state of the target substance in the reaction vessel 33 can be confirmed. Also, by branching into multiple channels, a device that can simultaneously process multiple reactions is exemplified.

[0040] <First embodiment of the mixing device> Next, a first embodiment of the mixing device will be described in detail. Fig. 2 is a plan view showing the channel structure constituting the mixing device 5 of this embodiment. As shown in this figure, the mixing device 5 is configured to include a plurality of (two in the figure) supply channels 51, 52 and a single channel 53 where these supply channels 51, 52 join together, and this single channel 53 is formed in a part of the liquid delivery section 2. In addition, injection channels 54, 55 continuous with the injection sections 13, 14 when the microchannel device 1 (Fig. 1) is constructed are provided at the base ends of the supply channels 51, 52, and a desired liquid can be supplied to the supply channels 51, 52 from the injection sections 13, 14 at a predetermined flow rate (injection pressure).

[0041] The single flow path 53 has the same flow path shape as the liquid delivery section 2, which is basically rectangular in cross section, and is structured such that a first wall surface 21 and a second wall surface 22 are provided on both sides of the bottom surface 20. A mixing region 8 is formed by providing obstacle structures 6, 7 that protrude from the walls 21, 22 of such a rectangular flow path in an appropriate range toward the other side. The mixing region 8 shown in FIG. 2 is provided in one location in a part of the liquid delivery section 2, but it is also possible to configure the liquid delivery section 2 to have multiple mixing regions 8 at multiple locations.

[0042] Next, the obstacle structures 6 and 7 will be described. Figure 3 is a partial enlarged view of the mixing region 8, focusing on the structure of the obstacle structures 6 and 7. Figure 3(a) is a diagram showing a channel structure with a groove-like channel, and Figure 3(b) is a diagram showing only the channel portion; both diagrams show the same state. Note that for convenience of explanation, the diagram shows a small number of obstacle structures 6 and 7, making the mixing region 8 short. In reality, however, a long mixing region 8 is formed by a large number of obstacle structures 6 and 7. Furthermore, the channel shown in Figure 3(a) is shown with the bottom surface 20 integrated with the wall surfaces 21 and 22, but when forming the microchannel device 1 (Figure 1), the bottom surface 20 may be formed by the bottom plate (base) 11. Furthermore, Figure 3(a) shows the channel as a groove, so the top is shown open; however, the microchannel has a structure in which the top is also closed, as shown in Figure 3(b).

[0043] The obstacle structures 6 and 7 provided in the mixing region 8 are asymmetric with respect to each other, as shown in Fig. 3. That is, they are not arranged in a state of line symmetry when the center line X of the single flow path 53 (liquid delivery section 2) is taken as the axis of symmetry. This asymmetric state means that when one of them is moved in the axial direction of the axis of symmetry (center line) X, they are not in a symmetric state (approximately symmetric) (this is sometimes referred to as complete asymmetry).

[0044] More specifically, in order to configure the two obstacle structures 6, 7 so that they are not symmetrical (including approximately symmetrical), in this embodiment, one obstacle structure (first obstacle structure) 6 is provided so as to protrude from one wall surface (first wall surface) 21 of the single flow path 53 (liquid delivery section 2) toward the other wall surface (second wall surface) 22, and the other obstacle structure (second obstacle structure) 7 is provided so as to protrude from the second wall surface 22 toward the first wall surface 21 in the opposite direction to the first obstacle structure 6. In addition, the first obstacle structure 6 is made up of a plurality of first obstacle structure components 61,...,64, and the second obstacle structure 7 is also made up of a plurality of second obstacle structure components 71,...,77, but the numbers, lengths, and adjacent intervals of these are all provided so as to be different from each other.

[0045] In this way, the number, length, and adjacent spacing of the obstacle structure components 61,...,64, 71,...,77 on both sides can all be different from each other. Alternatively, even if only one of these is different, the structure can be asymmetric (including approximately symmetric). In a mixing region 8 of a predetermined length, if only the number or adjacent spacing is different, the obstacle structure components on the side with fewer or narrower spacing can be divided into multiple groups. In this case, regions without obstacle structure components are formed between the multiple groups, thereby varying the fluid flow. Furthermore, if only the lengths are different, the fluid flowing near the two wall surfaces 21, 22 will be asymmetric. Various modifications will be described later. Here, an embodiment in which the number, length, and adjacent spacing of the obstacle structure components are all different from each other is illustrated.

[0046] <Obstacle structure component> Therefore, the details of the obstacle structure components will be described. In the embodiment shown in Fig. 3, the first obstacle structure components 61,...,64 are configured to protrude to positions beyond the center line X of the single flow path 53 (liquid delivery section 2). When these obstacle structure components 61,...,64 protrude beyond the center line X, the fluid flowing through the single flow path 53 is guided to make a large detour from the first wall surface 21 and flow down beyond the center line X (the boundary line between the spaces near both wall surfaces 21, 22). In this sense, these obstacle structure components 61,...,64 can serve as cross-border barriers that cross the central boundary.

[0047] On the other hand, the second obstacle structure components 71,...,77 are provided with a shorter protrusion length than the first obstacle structure components 61,...,64. Furthermore, these second obstacle structure components 71,...,77 are arranged alternately with different lengths, with adjacent intervals that are half that of the first obstacle structure components 61,...,64. The short obstacle structure components 71, 73, 75, 77 are provided in positions facing the first obstacle structure components 61,...,64, and the long obstacle structure components 72, 74, 76 are arranged in between them.

[0048] Therefore, the short obstacle structure-composing portions 71, 73, 75, 77 are provided to narrow the width of the flow path to a predetermined width (narrow width) together with the first obstacle structure-composing portions 61,...,64, and constitute the flow path at the tip of the cross-border barrier portions 61,...,64, and in that sense, they function as cross-border area flow path-composing portions. Also, by being arranged downstream of the first obstacle structure-composing portions (cross-border barrier portions) 61,...,64, the long obstacle structure-composing portions 72, 74, 76 guide the flow of fluid that leaves the first wall surface 21 and flows down across the center line X, returning it to the first wall surface 21 and diverting it, and in that sense, they can function as cross-border flow diverting portions.

[0049] Furthermore, by setting the protruding length of the long second obstacle structure components (cross-border flow detouring sections) 72, 74, 76 to be approximately the same as or shorter than the protruding length of the first obstacle structure components (cross-border barrier sections) 61,...,64, for example, to be approximately the same as the distance from the tip of the cross-border barrier sections 61,...,64 to the second wall surface 22, an appropriate flow path space A is formed between the tip of the cross-border flow detouring sections 72, 74, 76 and the first wall surface 21. By forming this flow path space A, the speed of the liquid flowing down at high speed is slowed by the cross-border barrier sections 61,...,64, and convection due to slight changes in flow speed when flowing down at high speed can be promoted.

[0050] <Fluid flow> The above state will be explained based on Figure 4. Figure 4(a) mainly shows the state of the mixing region 8. Note that, with respect to the flow path width H (the distance between the first wall surface 21 and the second wall surface 22) of the single flow path 53 (liquid delivery section 2), the protrusion length H1 of the first obstacle structure components (hereinafter sometimes referred to as cross-boundary barrier components) 61,...,64 exceeds half of the flow path width H, and the protrusion length H2 of the long second obstacle structure components (hereinafter sometimes referred to as cross-boundary flow detour components) 72, 74,76 is set to H2 = H - H1. Note that the protrusion length H3 of the short second obstacle structure components (hereinafter sometimes referred to as cross-boundary region flow path components) 71, 73, 75,77 is approximately half of the protrusion length H2, even though it is long. The predetermined width H4 of the flow path B formed between the cross-border region flow path constituent portions 71 and the cross-border barrier portions 61 is H4 = H - H1 - H3, which is a sufficiently narrow width. In addition, the gap H5 from the tip of the cross-border flow detour portion 72 that forms the flow path space A to the first wall surface 21 is H5 = H - H2, which is equal to the protrusion length H1 of the cross-border barrier portions 61.

[0051] 4(a), for example, when two types of liquids L1 and L2 are supplied to a single flow path 53 while being separated into both sides of the first wall surface 21 and the second wall surface 22, the liquids pass through a narrow flow path (hereinafter, may be referred to as a narrow flow path) B formed by the cross-border barrier section 61 and the cross-border region flow path forming section 71 immediately after joining, and then flow into an appropriate flow path space A. At this time, among the liquids passing through the narrow flow path B, the liquid (first liquid) L1 supplied from the first wall surface 21 side is largely detoured, and is concentrated in the narrow flow path B together with the liquid (second liquid) L2 supplied from the second wall surface 22 side, and passes through at an increased speed.

[0052] The fluid that has passed through narrow flow path B is prevented from flowing smoothly downward by the cross-boundary flow detouring section 72 provided downstream, and is guided to flow path space A formed between the cross-boundary flow detouring section 72 and the first wall surface 21. At this time, the vicinity of the tip of the cross-boundary flow detouring section 72 is located close to the narrow flow path B, so the fluid passing near this tip can pass through the next narrow flow path B relatively quickly, but the fluid that has moved to the vicinity of the first wall surface 21 flows relatively slowly, and therefore moves to the next narrow flow path B with a delay.

[0053] Furthermore, the fluid passing near the second wall surface 22 (near the second obstacle structure components 71, 72...) moves in a meandering manner due to the two types of obstacle structure components 71, 72... with different protrusion lengths, causing the flow direction to change considerably. A narrow flow path space C is formed between these two types of obstacle structure components 71, 72..., but because it is formed close to the narrow flow path B, it cannot be expected that the fluid will remain in this narrow flow path space C. As a result, an irregular flow occurs between the first wall surface 21 and the fluid passing through the flow path space A.

[0054] In this way, the surface area of ​​the interface between the fluid passing near the first wall surface 21 (in the above example, centered on the first liquid L1) and the fluid passing near the second wall surface 22 (in the above example, centered on the second liquid L2) can be increased, thereby improving the mixing efficiency.

[0055] When considering the flow of fluids in the configuration of the above-described embodiment, if the first obstacle structure-constituting portions 61,... and the second obstacle structure-constituting portions 71,... are arranged in a substantially symmetrical manner as shown in Fig. 4(b), the fluid flowing near the first wall surface 21 and the fluid flowing near the second wall surface 22 will simply alternate between fast and slow states. Therefore, although a detour flow path is formed by both obstacle structure-constituting portions 61, 71,... and the flow direction changes, the surface area of ​​the interface where the two fluids come into contact may only increase gradually.

[0056] The obstacle structure components 61, 71, ... shown in Figure 4(b) protrude to a length that exceeds the center line X of the single flow path 53. However, if the obstacle structure components 61, 71, ... do not reach the center line X of the single flow path 53, as shown in Figure 4(c), there is nothing to obstruct the flow near the center line X of the single flow path 53, so the fluid flows down more regularly. In addition, the fluid flowing down near both wall surfaces 21, 22 is less likely to flow beyond the center line X and into the other side, which may make it unsuitable for promoting a mixed state.

[0057] <Experimental Example 1> To confirm the above points, an experiment was conducted to analyze the streamlines. For the computational fluid analysis, commercially available finite element analysis software was used, specifically COMSOL (registered trademark) Multiphysics (version 5.4) manufactured by COMSOL AB. As shown in Figure 5, the analysis experiment was conducted for three types of structures: a simple periodic structure (see Figure 5(a)), an alternating arrangement symmetric structure (see Figure 5(b)), and an alternating arrangement asymmetric structure (see Figure 5(c)), which are symmetrical with respect to the obstacle structure. The results are shown in Figure 6.

[0058] As is clear from the results shown in Figure 6, in the case of a flow path in which obstacle structures are arranged symmetrically (see Figures 6(a) and (b)), the fluid flow is concentrated on the center line and is in a regular state, but in the case of an asymmetrical flow path (see Figure 6(c)), the flow meanders significantly and is irregular overall.

[0059] <Experimental Example 2> From the above results, it is expected that the irregular flow in the mixing region 8 due to the shape shown in Figure 5(c) (alternately arranged asymmetric structure) will also improve the mixing efficiency, so an experiment was conducted to confirm the change in mixing efficiency due to the same shape. As shown in Figure 7, the experimental mixing region 8 had an asymmetrical, alternating structure in which the first and second obstacle structures 6 and 7 were asymmetric. The single flow path 53 (liquid delivery section 2) had a flow path width of 200 μm. The cross-boundary barrier sections 61,..., constituting the first obstacle structure 6, had a width of 50 μm and a protrusion length of 120 μm. The cross-boundary region flow path components 71,..., constituting the second obstacle structure 7, had a width of 50 μm and a protrusion length of 40 μm, and the cross-boundary flow detour sections 72,..., had a width of 50 μm and a protrusion length of 80 μm. The entire mixing region 8 was counted as one barrier group, with the area between the centers of the two cross-boundary barrier sections 61,..., located on either side of the cross-boundary flow detour section 72,..., as the center. 100 barrier groups were installed, with cross-boundary barrier sections 61,..., located at the base and terminal ends, respectively. As a result, the overall length of the mixed region 8 is 20.05 mm.

[0060] In the experiment, in order to confirm the mixed state, a fluorescent reagent (fluorescein solution) and pure water were mixed and observed. Two supply flow paths 51 and 52 upstream of the flow path were used to supply the mixture at a flow rate of 5 μL / min, respectively, and the mixture was mixed in a single flow path 53 at a total flow rate of 10 μL / min (Reynolds number (Re) = 1.3).

[0061] The mixing efficiency was observed at intervals of several millimeters, starting from a point 270 μm before the point where the single flow channel 53 first enters the mixing region 8 (point 0 mm). Specifically, the evaluation was performed for every five sets of barrier groups (every 1.0 mm) of the aforementioned number of sets. The evaluation of the mixing efficiency was calculated as the standard deviation of the fluorescence intensity profile at the observation point. The calculation method for the mixing efficiency was the same as that described in Non-Patent Document 4.

[0062] The results are shown in Figure 8. From these results, it was confirmed that the mixing efficiency exceeded 80% when the fluid had passed through a range of approximately 4 mm (equivalent to 20 pairs) from the starting point. The temporary decrease in mixing efficiency after this is thought to be a reversal phenomenon of the mixed fluid, which will be discussed later. Furthermore, from an examination of the subsequent mixing efficiency, it was found that the mixing efficiency was at least 80% after passing through a range of 8 mm (equivalent to 40 pairs) from the starting point, and that the fluid flowing down a range of 13 mm (equivalent to 65 pairs) stabilized at a mixing efficiency of 90%.

[0063] <Experimental Example 3> As shown in Experimental Example 2 above, the mixing efficiency was favorable for a fluid with a flow rate of 10 μL / min (Reynolds number (Re) = 1.3). Therefore, experiments were also conducted with other flow rates. The mixing region 8 used in the experiment had the same configuration as in Experimental Example 2, as shown in Figure 7. Two types of flow rates were used for the supplied fluid: a total flow rate of 1 μL / min (Reynolds number (Re) = 0.13), which was significantly smaller than the flow rate in Experimental Example 2, and a total flow rate of 100 μL / min (Reynolds number (Re) = 13), which was significantly larger than the flow rate in Experimental Example 2. The results are shown in Figure 9.

[0064] For comparison, Figure 9 also shows the change in mixing efficiency in Experimental Example 2. As is clear from these results, when the flow rate is low, the mixing efficiency exceeds 80% at a point where the flow path length is approximately 10 mm, and the change in mixing efficiency also increases smoothly. On the other hand, even when the flow rate is high, the mixing efficiency exceeds 80% at a point where the flow path length is approximately 15 mm. Note that the experiment was conducted at flow rates that vary greatly around 10 μL / min, but for flow rates between these, it can be expected that the changes in the results graph will be intermediate.

[0065] From the above experimental results, it was found that when the mixing region 8 is formed by asymmetrically arranging the obstacle structures 6 and 7 as shown in Figure 7 (alternately arranged asymmetric structure), suitable mixing efficiency can be achieved even when fluids are supplied at a wide range of flow rates.

[0066] <Modification> Based on the results of the above experiments, we will now explain possible modifications of this embodiment. First, as shown in Figure 10(a), the tips of the cross-border barrier sections 61,..., protruding from the first wall surface 21, are extended until they reach the vicinity of the second wall surface 22, thereby forming a narrow flow path B between the first wall surface 21 and the cross-border barrier sections 61,.... In this configuration, the protruding length H2 of the cross-border flow detour sections 72,... is made shorter than the protruding length H1 of the cross-border barrier sections 61,... so that H2 = H - H1 is satisfied. This makes the gap H5 between the tips of the cross-border flow detour sections 72,... and the first wall surface 21 larger than the flow path width of the narrow flow path B. Therefore, the flow path spaces A and C formed at the tip ends of the cross-border flow detour sections 72,..., have different widths, which can produce the irregular changes described above.

[0067] To summarize the above configuration, the gap formed between the tip of the cross-border barrier section 61,... protruding from the first wall surface 21 and the second wall surface 22 (and the flow path space C formed between adjacent obstacle structure components) and the gap formed between the tip of the cross-border flow detour section 72,... protruding from the second wall surface 22 and the first wall surface 21 (and the flow path space A formed between adjacent obstacle structure components) can be said to be arranged so as to be asymmetrical with respect to each other.

[0068] 10(b), in another modified example, the protrusion length H2 of the cross-border flow detouring sections 72,... is set to about half the flow path width H. Naturally, the cross-border barrier sections 61,... have a protrusion length that exceeds the center line X, and the cross-border region flow path forming sections 71,... are provided at positions opposite their tips, so that the flow path space A formed in the first wall surface 21 and the flow path space C formed in the second wall surface 22 are in a significantly different state.

[0069] In this way, by increasing the protrusion length H2 of the cross-boundary flow detour sections 72,..., it is possible to reduce the flow velocity of the fluid that has passed through the narrow flow path B, and it is also possible to guide a large amount of fluid into the flow path space A, which is expected to generate convection in the flow path space A. Note that even if no clear convection occurs in the flow path space A, it is possible that an irregular flow may occur because the flow path spaces A and C formed near both wall surfaces 21 and 22 are different in width.

[0070] 11, the protrusion length H2 of the cross-boundary flow detour sections 72,... can be further increased. For example, as shown in FIG. 11(a), the protrusion length H2 of the cross-boundary flow detour sections 72,... may be configured to exceed half the flow path width H and be approximately the same as the protrusion length H1 of the cross-boundary barrier sections 61,... (H2 = H1). Even in this case, the gap H5 from the tip of the cross-boundary flow detour section 72,... to the first wall surface 21 is larger than the flow path width H4 of the narrow flow path B, and therefore the flow path space A formed on the side of the first wall surface 21 can be configured to be larger than the flow path space C formed on the side of the second wall surface 22.

[0071] 11(b), even when the protrusion length H2 of the cross-boundary flow detour sections 72,... is configured to be longer, the protrusion length may be changed as long as the gap H5 from the tip of the cross-boundary flow detour section 72,... to the first wall surface 21 is within a range larger than the flow path width H4 of the narrow flow path B (H5>H4). This is because the flow path space A formed on the side of the first wall surface 21 is larger than the flow path space C formed on the side of the second wall surface 22, and therefore it is possible to create a difference in the speed of the flow on both sides to a certain extent.

[0072] Furthermore, conversely, the protrusion length H2 of the cross-boundary flow detouring sections 72,... can also be shortened. For example, as shown in FIG. 12(a), the tips of the cross-boundary flow detouring sections 72,... can be protruded to the point where they are positioned in the middle of the narrow flow path B. That is, the protrusion length H2 of the cross-boundary flow detouring sections 72,... is set to H2 = H3 + 0.5H4. Even in this state, the cross-boundary flow detouring sections 72,... can function as an obstacle to the fluid flowing down the narrow flow path B, thereby guiding the fluid to detour. In this modification, adjustment protrusions 65, 66, and 67 are provided to prevent the gap H5 between the tips of the cross-boundary flow detouring sections 72,... and the first wall surface 21 from becoming excessively large. The protrusion length H6 of this adjustment protrusion 65,... is adjusted so that the gap H5 between the tip of the cross-border flow detour section 72,... and the first wall surface 21 is approximately the same as the protrusion length H1 of the cross-border barrier section 61,... (H4 = H1).

[0073] 12(b), it is also possible to set the protrusion length H2 of the cross-border flow detouring sections 72,... to be extremely short, so that it is approximately the same as the protrusion length H3 of the cross-border area flow path forming sections 71,... (H2 = H3). Even in this case, the adjustment protrusions 65,... are provided so that the gap H5 between the tip of the cross-border flow detouring section 72,... and the first wall surface 21 is approximately the same as the protrusion length H1 of the cross-border barrier sections 61,... (H4 = H1). In this case, the protruding lengths H2, H3 of the second obstacle structure components (both the cross-boundary flow detour components and the cross-boundary area flow path components) 71,... that protrude from the second wall surface 22 are the same, and the cross-boundary flow detour components 72,... are not able to become obstacles to the fluid flowing down the narrow flow path B, but a mixing effect can be expected because the flow path space A is formed on the side of the first wall surface 21. In particular, because the narrow flow paths B are continuous, the flow of the fluid is likely to become regular in the narrow flow paths B, but because these paths are located at a position offset from the center line X of the single flow path 53, the fluid as a whole is expected to detour and try to flow along the center line X.

[0074] <Experimental Example 4> Next, we conducted an experiment to confirm the mixing efficiency when the protrusion length of the cross-boundary flow diversion sections 72,... was changed while the basic configuration of the mixing region 8 was an alternating asymmetric structure. The experiment used the mixing device (see Figure 7) used in Experimental Example 2 as the basic configuration, and the dimensions of each component were changed by changing the protrusion length of the cross-boundary flow diversion sections 72,.... The state of change in protrusion length is as described below for each experimental device. Similar to Experimental Example 2, the fluorescent reagent and pure water were supplied from two supply flow paths 51, 52. To change the flow rate, the same amount of both liquids was mixed per minute, and three flow rates in a single flow path were used: 1 μL / min (Reynolds number (Re) = 0.13), 10 μL / min (Reynolds number (Re) = 1.3), and 100 μL / min (Reynolds number (Re) = 13). The observation of the mixing efficiency was also the same as in Experimental Example 2, with the point 270 μm before the point where the flow enters the first mixing region 8 in the single flow path being set as 0 mm (starting point), and the mixing efficiency was measured at intervals of several mm. Specifically, evaluation was performed for every five sets (every 1.0 mm) of the above number of barrier groups. The method of measuring the mixing efficiency was also the same as in Experimental Example 2.

[0075] The experimental apparatuses, from apparatus 5-1 to apparatus 5-5, were designed with several different protrusion lengths for the transboundary flow detour sections 72,... Apparatus 5-1 is a modified example shown in Figure 10(b), in which the protrusion length H2 of the transboundary flow detour sections 72,... is set to the center of the single flow path, H2 = 0.5H (= 100 μm). Apparatus 5-2 is a modified example shown in Figure 11(a), in which the protrusion length H2 of the transboundary flow detour sections 72,... is set to the same length as the transboundary barrier sections 61,..., H2 = H1 (= 120 μm). Apparatus 5-3 is a modified example shown in Figure 11(b), in which the protrusion length H2 of the transboundary flow detour sections 72,... is longer than the transboundary barrier sections 61,..., H2 = H1 + 0.5H4 (= 140 μm). Device 5-4 is a modified example shown in Figure 12(a), in which the protrusion length H2 of the cross-border flow detour sections 72,... is shortened to H2 = H3 + 0.5H4 (= 60 μm), and the protrusion length H6 of the adjusting protrusions 65,... is set to H6 = 0.5H4 (= 20 μm). Device 5-5 is a modified example shown in Figure 12(b), in which the protrusion length H2 of the cross-border flow detour sections 72,... is further shortened to H2 = H3 (= 40 μm), and the protrusion length H6 of the adjusting protrusions 65,... is set to H6 = H4 (= 40 μm).

[0076] Figure 13 shows the mixing efficiency of the devices 5-1 to 5-3, in which the protrusion length H2 of the transboundary flow diversion sections 72,... was longer than the standard (see Figure 7), and Figure 14 shows the mixing efficiency of the devices 5-4 and 5-5, in which the protrusion length H2 was shorter. As is clear from these figures, effective mixing is possible even when the protrusion length H2 of the transboundary flow diversion sections 72,... was varied. In particular, when the protrusion length H2 was set to the same extent as the transboundary barrier sections 61,... (see Figure 13(b)), mixing was favorable over a wide range of flow rates (1 μL / min to 100 μL / min), reaching a mixing efficiency of over 80% and approximately 90% at approximately 10 mm. Furthermore, even when the protrusion length H2 of the transboundary flow diversion sections 72,... was shortened (see Figure 14), favorable mixing efficiency was achieved at flow rates below medium speed (10 μL / min), except for high speeds (100 μL / min).

[0077] <Second embodiment of the mixing device> Next, a second embodiment of the present invention relating to a mixing device will be described. An overview of this embodiment is shown in Fig. 15. As shown in Fig. 15, this embodiment has a configuration including multiple mixing regions 8a, 8b, 8c... in which the obstacle structures 6, 7 are asymmetrical as described above. Specifically, in an appropriate flow path length, an obstacle structure 6 having multiple first obstacle structure components 61... corresponding to the flow path length, and an obstacle structure 7 similarly having multiple second obstacle structure components 71, 72... constitute one section of mixing region 8 (8a, 8b, 8c...), and these multiple sections of mixing regions 8a, 8b, 8c... are connected in series.

[0078] Furthermore, the mixing regions 8a, 8b, 8c, etc., each having a plurality of compartments, have a structure (inverted structure) in which the first obstacle structures 6 and the second obstacle structures 7 are mutually inverted between adjacent ones of them. The inverted structure is a state in which the protruding state from the first wall surface 21 (the configuration of the first obstacle structures 6) and the protruding state from the second wall surface (the configuration of the second obstacle structures 7) are mutually interchanged with each other, with the center line X of the single flow path 53 as the boundary.

[0079] More specifically, in the mixing region 8a of the most upstream section (first section), the first obstacle structure-constituting parts 61,... protrude from the first wall surface 21 and the second obstacle structure-constituting parts 71,... protrude from the second wall surface 22 (the same as in the first embodiment), but in the mixing flow path 8b of the next section (second section), the first obstacle structure-constituting parts 61,... protrude from the second wall surface 22 and the second obstacle structure-constituting parts 72,... protrude from the first wall surface 21. Furthermore, in the mixing region 8c of the next section in series (third section), the state is again reversed to be the same as the mixing region 8a of the first section. Since each mixing flow path 8a, 8b, 8c, etc. is recognized as an independent mixing region, a flat flow path S without obstacle structures 6, 7 is provided between each mixing region 8a, 8b, 8c, etc., and the liquid delivery section 2 (single flow path 53) is returned to a downward flowing state just before the flow into and just after the flow out of each mixing region 8a, 8b, 8c, etc.

[0080] According to the results of Experimental Example 2, it was confirmed that the mixing efficiency of the fluid that entered the mixing region peaked at an initial flow path length of approximately 4 mm (corresponding to 20 barrier groups), and then decreased. After various investigations into the cause of this, it was found that, as mentioned above, the fluid that passed through the narrow flow path B due to the cross-boundary barrier section 61,... was disturbed by the cross-boundary flow detour section 72 provided downstream, and the fluid flowing down near the first wall surface 21 became a relatively slow flow, while the fluid flowing down near the second wall surface 22 became a relatively steep flow (see FIG. 4(a)). As a result, a steeply flowing liquid is more likely to flow into the flow path space A formed on the side of the first wall surface 21, while a slower flow is more likely to flow down with a delay and approach the second wall surface 22.The inventors have confirmed through experiments that by repeating the above flow, a reversal phenomenon can occur in which the fluid that was initially flowing down near the first wall surface 21 after being supplied moves to the vicinity of the second wall surface 22, and the fluid that was flowing down near the second wall surface 22 moves to the vicinity of the first wall surface 21.

[0081] Therefore, by providing a plurality of mutually inverted mixing regions 8a, 8b, 8c, etc. in series as described above, it is expected that the reversal phenomenon can be quickly reversed. In particular, since the change in mixing efficiency immediately after being supplied to the mixing region 8 is significantly improved, the mixing state is promoted by flowing the fluid into the next mixing channel 8 via the flat channel S. The state in which the fluid reversal phenomenon occurs is a state in which at least the mixing of the liquids has progressed, so it is not a complete reversal state but rather a reversal tendency, and when this reversal tendency appears, mixing has already progressed moderately.

[0082] In this way, by providing multiple compartments of mixing regions 8a, 8b, 8c, etc. to reverse the reversal phenomenon, even if a fluid reversal phenomenon occurs, the multiple fluids will ultimately be mixed as a whole without being biased toward either the first or second wall surface.

[0083] When a plurality of mixing regions 81,... are provided, the individual mixing regions 81,... may all have the same configuration. The above-mentioned fluid reversal phenomenon occurs at a point after passing through an appropriate length (an appropriate number of barrier groups) of the mixing region 8, so the mixing efficiency increases immediately after flowing into the mixing region 8. Therefore, by sequentially flowing down through a plurality of independent mixing regions 8a, 8b, 8c,..., it is possible to improve the mixing efficiency while appropriately reversing the reversal phenomenon.

[0084] <Experimental Example 5> To confirm the above-mentioned state, we observed the state of a mixture of a fluorescent reagent (fluorescein solution) and pure water. For the experiment, as shown in Figure 16, multiple mixing regions 8a, 8b, and 8c were connected in series, and the second (second section) mixing region 8b had an inverted structure in which the first obstacle structure 6 and the second obstacle structure 7 were simply swapped. Furthermore, two upstream supply channels 51 and 52 supplied 5 μL / min each, resulting in a total of 10 μL / min (Reynolds number (Re) = 1.3) of fluid being mixed in a single channel 53. The mixed state was observed.

[0085] The dimensions of each part of the mixing device are as shown in the figure, and each mixing region 8a, 8b, 8c has 25 barrier groups, and each channel length is 5.05 mm. Furthermore, flat channels S with a length of 0.5 mm were formed between each mixing channel 8a, 8b, 8c.

[0086] Figure 17 shows the mixed state at seven locations P0, P1a, P1b, P1c, P1d, P2a, and P2b, which are enclosed by rectangles in Figure 16. Note that the mixed state at each location was obtained by capturing an image of the fluorescent state of the fluorescent reagent, but because it is difficult to distinguish the fluorescent color when the image is binarized, Figure 17 shows the image converted into a model diagram. Note that the fluorescent reagent is shown with shading, and the concentration of the fluorescent reagent is represented by changing the density of the shading.

[0087] As shown in FIG. 17, immediately after supplying the fluorescent reagent from one supply channel 51 and the pure water from the other supply channel 52, the two do not mix within the single channel 53 and are clearly separated into two layers (P0). As they flow down from here through the mixing region 8a of the first section, the fluorescent reagent and pure water gradually mix, and the concentration of the fluorescent reagent decreases overall (P1a-P1d). Here, the fluorescent reagent initially flows down near the first wall surface 21 (P1a). However, the pure water gradually flows into the vicinity of the first wall surface 21, decreasing the concentration in the channel space A. At the same time, the fluorescent reagent flows into the vicinity of the second wall surface 22, and mixing progresses (P1b, P1c). Furthermore, near the end of the mixing region 8a of the first section, the concentration of the fluorescent reagent increases near the second wall surface 22 (P1d). This is the fluid reversal phenomenon. Even in the state where this reversal phenomenon occurs, the concentration distribution is in a state where mixing has progressed to a moderate degree compared to the initial state (P1a).

[0088] In this experiment, the arrangement of the first obstacle structure 6 and the second obstacle structure 7 was swapped in the mixing region 8b of the second section. When the fluid in which the above-mentioned reversal phenomenon occurred passed through the mixing region 8b of the second section, the flow pattern in the entire single flow channel (multiple mixing regions 8a-8c) changed, resulting in the reversal phenomenon occurring again (P2a). Although it is possible to achieve favorable mixing efficiency by repeating the reversal and re-reversal phenomena sequentially when forming a reversal structure using 100 consecutive barrier groups (Fig. 7), the above results demonstrated that sufficient mixing is also possible by forming an inverted structure using a moderate number of barrier groups (25 groups).

[0089] <Experimental Example 6> Based on the above results, in order to determine the suitability of the inverted structure, in Experimental Example 6, we decided to observe the mixing efficiency when the number of sets of barrier groups (channel length) constituting the multiple channel regions 8a, 8b, 8c, etc. was changed. This experiment was carried out using two types of mixing devices, as shown in Figure 18. One of them had the same configuration (and similar dimensions) as the one used in Experimental Example 5, with each mixing region being composed of 25 sets of barrier groups (channel length of 5.05 mm), and a total of four sections connected in series (total channel length of 22.5 mm), but with the first and second obstacle structures 6, 7 in the odd-numbered and even-numbered sections reversed relative to each other (see Figure 18(a)). The other was a system in which the mixing region of each compartment was composed of five barrier groups (with a channel length of 1.05 mm), with a total of 16 compartments connected in series (total channel length of 24.82 mm), and similarly the configuration of odd-numbered and even-numbered compartments was reversed (see Figure 18(b)).In both experimental devices, a flat channel S (a channel with a straight structure without obstacles) with a channel length of 0.5 mm was provided at the joints between each compartment, and the basic channel dimensions were the same as those in Experimental Example 5.

[0090] As in Experimental Example 2, the fluid to be supplied was a mixture of a fluorescent reagent (fluorescein solution) and pure water, which was then observed to confirm the mixed state. The fluids were supplied from two supply flow paths 51 and 52 upstream of the flow path at a flow rate of 5 μL / min each, and mixed in a single flow path 53 at a total flow rate of 10 μL / min (Reynolds number (Re) = 1.3). As in Experimental Example 2, the mixing efficiency was also evaluated by calculating the standard deviation of the fluorescence intensity profile at the observation point.

[0091] The results of this experiment are shown in Figure 19. In addition, for comparison with Experimental Example 2, the graph showing the experimental results also shows the results of Experimental Example 2 when 100 sets were connected together, along with the label "1 section." Furthermore, "4 sections" refers to four sections connected together, with 25 sets of barrier groups as shown in Figure 18(a) as one section, and "16 sections" refers to 16 sections connected together, with 5 sets of barrier groups as shown in Figure 18(b).

[0092] As is clear from the experimental results, in the case of a mixer with 25 barrier groups in one compartment and 4 connected compartments, results were almost the same as those of a mixer with 100 barrier groups in one compartment, but in the case of 5 barrier groups in one compartment and 16 connected compartments, the mixing efficiency was significantly inferior. In particular, when there were 25 barrier groups in 4 compartments, there was less fluctuation after the mixing efficiency reached 80% or more than when there were 100 barrier groups in one compartment.

[0093] From these results, it is estimated that the fewer the barrier groups constituting one section (below 25), the earlier the timing of reversal will be, resulting in a state approaching a symmetrical state. Therefore, when using an inverted structure, it is preferable to have a configuration with approximately 10 or more barrier groups so as not to approximate symmetry as a whole, and preferably more than the 25 barrier groups at which the reversal phenomenon occurs initially. However, this number of barrier groups is for the case where the shape and dimensions are as exemplified in Figure 18. If the shape and dimensions of the barrier groups constituting each section are individually changed or the supply flow rate is changed, the appropriate number of groups may differ.

[0094] <Experimental Example 7> Next, a comparative experiment was conducted between a mixer that is thought to be in a suitable state when using an inverted structure (the same structure as that used in Experimental Example 6, with 25 sets of barrier groups installed in four sections) and a conventional symmetrical structure. For the experiment, a simple periodic structure (see Figure 5(a)) and an alternating symmetrical structure (see Figure 5(b)) were used as the conventional symmetrical structure, and both had a mixing region with a total flow path length of 22.5 mm. As this was a comparative experiment, the other conditions were the same as in Experiment 6.

[0095] The above results are shown in Figure 20. As is clear from these experimental results, when mixing regions were formed using a simple periodic structure and an alternating symmetrical structure for comparison, the mixing efficiency tended to increase slightly as the flow passed through each mixing region, but even when the flow reached a distance of approximately 20 mm, the mixing efficiency was still less than 50%. Figure 20 also shows the mixing efficiency in a simple rectangular flow channel without obstacle structures 6 and 7, and in this case the maximum mixing efficiency was approximately 10%.

[0096] <Experimental Example 8> Furthermore, an experiment was conducted to confirm the relationship between the flow rate (Reynolds number (Re)) of the supplied fluid and the mixing efficiency for a mixing device (similar to Experimental Example 7) that was considered to be in a favorable state for an inverted structure. The experiment was conducted using the same mixing device (25 barrier groups divided into four compartments) as in Experimental Example 7, with the same dimensions and shape. To change the flow rate, the same amount of both fluids was mixed per minute, and the total flow rate was varied. The flow rates in the single channel were 1 μL / min (Reynolds number (Re) = 0.13), 10 μL / min (Reynolds number (Re) = 1.3), and 100 μL / min (Reynolds number (Re) = 13). The other conditions were the same as those used in the previous measurement of mixing efficiency. The results are shown in Figure 21. Note that the graph for a flow rate of 10 μL / min (Re = 1.3) in Figure 21 differs slightly from that in Figure 20, but this is due to the different experimental date and does not significantly affect the overall trend.

[0097] As shown in Figure 21, the experimental results indicate that a mixing efficiency of 80% or higher can be achieved at any position beyond approximately 15 mm over a wide range of flow rates (Reynolds numbers). Furthermore, focusing only on the end of the mixing region 8a (5.05 mm) in the first section, the results show that the mixing efficiency increases favorably regardless of the flow rate (Reynolds number). Furthermore, although the mixing efficiency is low at high flow rates (100 μL / min (Re = 13)), favorable mixing efficiency can be achieved early at medium flow rates (10 μL / min (Re = 1.3)) or less. It takes approximately 22.5 mm (at the point of passing through the fourth section) for the mixing efficiency to reach 90%. In other words, this result indicates that a channel length of approximately 22.5 mm is sufficient to achieve effective mixing.

[0098] <Summary> The following conclusions can be drawn from the above experimental examples. In the mixing region that constitutes the mixer, the mixing efficiency is improved by configuring the first and second obstacle structures asymmetrically. Furthermore, although multiple asymmetric mixing channels may be configured in series, simply reversing the installation state of the obstacle structures requires that the number of barrier groups that constitute one section be at least an appropriate number. These various configurations enable fluid mixing with favorable mixing efficiency regardless of the flow rate (Reynolds number).

[0099] <Other variations> The embodiments and experimental examples of the present invention are as described above, but the present invention is not limited to the configurations described in the above embodiments, etc. Therefore, the configurations of the above embodiments, etc. may be partially modified or other elements may be added.

[0100] For example, while the above-described embodiments of the mixing device all have a configuration including two supply flow paths 51, 52, this is an example of mixing the minimum number of fluids, and when mixing three or more fluids, a configuration including three or more supply flow paths is possible. Even in such a configuration, by configuring a similar mixing region 8, the fluids flowing down both sides of the single flow path 53 (near the first and second wall surfaces 21, 22) are interchanged to the extent that a mutual reversal phenomenon occurs, so that even three or more fluids can be mixed in the same way.

[0101] Furthermore, when three or more types of fluids are to be mixed, the single flow path 53 of the above embodiment can be branched into supply flow paths 51 and 52, and two types of fluids, for example, can be mixed upstream of each of the branched paths, making it possible to mix a total of four types of fluids.

[0102] Furthermore, the spacing between the obstacle structure components 61,... that make up the obstacle structure 6 shown solely as an experimental example is 150 μm, and the spacing between the obstacle structure components 71, 72,... that make up the other obstacle structure 7 is 50 μm, but this was determined to balance with the fact that the width dimension of each component 61, 71,... is 50 μm; the spacing and width dimension may also be unbalanced, and each dimension, including that of the other components, can be changed as appropriate.

[0103] Although only a rectangular protruding configuration is illustrated for the obstacle structure-constituting portions 61,...,71,..., this shape is not limited to a rectangle and may be changed as appropriate. In this case, the concept of asymmetrical configuration with respect to the center line X of the single flow path 53 does not include asymmetry due solely to the shape of the obstacle structure-constituting portion, but does include asymmetry achieved by appropriately changing the shape of the flow path spaces A and C to change the width of the space. By changing the shape of the flow path spaces A and C in this way, for example, if a cross-border barrier portion is formed by the protruding length to the center line X using the first obstacle structure-constituting portion 61,... of an appropriate shape, the obstacle structure-constituting portion of that shape may function as the cross-border barrier portion. [Explanation of symbols]

[0104] 1. Microfluidic Device 2. Liquid delivery section 3 Mainstream section 4 Exhaust channel 5 Mixing device 6. First Obstacle Structure 7 Secondary Obstacle Structure 8,8a,8b,8c mixed area 11 Bottom plate (board) 12 Flow path configuration board 13,14 Injection part 15,16 Discharge section 20 Bottom surface of the liquid delivery section (single flow path) 21 First wall surface of the liquid delivery section (single flow path) 22 Second wall surface of the liquid delivery section (single flow path) 31 Branch channel 32 Chamber area 33 Reaction vessel 51,52 Supply channel 53 Single Channel 61, 62, 63, 64 First obstacle structure component (cross-border barrier section) 71, 73, 75, 77 Second obstacle structure component (cross-border area flow channel component) 72, 74, 76 Second obstacle structure component (cross-border flow diversion section) A, C flow path space B Narrow channel L1 First liquid L2 Second liquid S Flat flow path X Single channel centerline

Claims

1. A microchannel mixing device comprising a plurality of supply channels, a single channel at which these supply channels converge, and a mixing region formed within an appropriate range of the single channel, wherein the device mixes a plurality of fluids in the mixing region, The mixing region includes first and second wall surfaces facing each other, a first obstacle structure protruding from the first wall surface toward the second wall surface to function as an obstacle to the flow of the fluid, and a second obstacle structure protruding from the second wall surface toward the first wall surface to function as an obstacle to the flow of the fluid, the first obstacle structure is configured by arranging a plurality of first obstacle structure components in parallel in the downstream direction of the fluid, and the second obstacle structure is configured by arranging a plurality of second obstacle structure components in parallel in the downstream direction of the fluid, a part or all of the first obstacle structure component is constituted by an over-boundary barrier portion that protrudes to a position beyond the center line of the single flow path and induces the fluid to flow down beyond the center line; By configuring all of the second obstacle structure components with a protrusion length shorter than the protrusion length of the cross-border barrier portion, the first obstacle structure components and the second obstacle structure components are arranged in a state where they are not symmetrical in a plan view with the center line of the single flow path as an axis, A mixing device characterized in that a flow path space formed on the first wall surface side of the center line between adjacent first obstacle structure components and a flow path space formed on the second wall surface side of the center line between adjacent first obstacle structure components are configured to have different volumes due to differences in flow path widths.

2. The mixing device described in claim 1, wherein the first obstacle structure component and the second obstacle structure component are arranged in a state where they are different from each other in at least one of the adjacent spacing and total number, so that the flow path space formed on the first wall surface side of the center line between adjacent first obstacle structure components and the flow path space formed on the second wall surface side of the center line between adjacent first obstacle structure components have different volumes.

3. A mixing device as described in claim 1 or 2, wherein the second obstacle structure component, which is arranged on the extension line of the cross-border barrier section, is composed of a cross-border area flow path component that forms a flow path of a predetermined width together with the cross-border barrier section.

4. The mixing device described in claim 3, wherein the second obstacle structure component, which is located downstream of the flow path of a predetermined width formed by the cross-border barrier component and the cross-border area flow path component, is configured as a cross-border flow detour component that protrudes by a longer protrusion length than the cross-border area flow path component and detours the flow of fluid that flows downstream across the center line.

5. The mixing device according to claim 4 , wherein the cross-border flow detouring portion is disposed between adjacent cross-border region flow path forming portions.

6. A microchannel mixing device comprising a plurality of supply channels, a single channel at which these supply channels converge, and a mixing region formed within an appropriate range of the single channel, wherein the device mixes a plurality of fluids in the mixing region, The mixing region includes first and second wall surfaces facing each other, a first obstacle structure protruding from the first wall surface toward the second wall surface to function as an obstacle to the flow of the fluid, and a second obstacle structure protruding from the second wall surface toward the first wall surface to function as an obstacle to the flow of the fluid, the first obstacle structure is configured by arranging a plurality of first obstacle structure components in parallel in the downstream direction of the fluid, and the second obstacle structure is configured by arranging a plurality of second obstacle structure components in parallel in the downstream direction of the fluid, the entire first obstacle structure component is constituted by an over-boundary barrier portion that protrudes beyond the center line of the single flow path and induces the fluid to flow down beyond the center line; the second obstacle structure component is configured to include a cross-border area flow path component that is disposed on an extension line of the cross-border barrier component and that, together with the cross-border barrier component, forms a flow path of a predetermined width at a position offset from the center line of the single flow path, and a cross-border flow detour component that is disposed between adjacent cross-border area flow path components and is longer than the cross-border area flow path component, and that protrudes at its tip with a protrusion length that forms a flow path width between the tip and the first wall surface that is larger than the flow path of the predetermined width, thereby detouring the flow of fluid that flows down beyond the center line, A mixing device characterized in that a flow path space formed on the first wall surface side of the center line of the single flow path between adjacent first obstacle structure components and a flow path space formed on the second wall surface side of the center line between adjacent first obstacle structure components are configured to have different volumes due to differences in flow path widths.

7. A microchannel mixing device comprising a plurality of supply channels, a single channel at which these supply channels converge, and a mixing region formed within an appropriate range of the single channel, wherein the device mixes a plurality of fluids in the mixing region, The mixing region includes first and second wall surfaces facing each other, a first obstacle structure protruding from the first wall surface toward the second wall surface to function as an obstacle to the flow of the fluid, and a second obstacle structure protruding from the second wall surface toward the first wall surface to function as an obstacle to the flow of the fluid, the first obstacle structure is configured by arranging a plurality of first obstacle structure components in parallel in the downstream direction of the fluid, and the second obstacle structure is configured by arranging a plurality of second obstacle structure components in parallel in the downstream direction of the fluid, The first obstacle structure component is composed of an overflow barrier portion that protrudes beyond the center line of the single flow path and guides the fluid to flow down beyond the center line, and an adjustment protrusion that is disposed between adjacent overflow barrier portions, All of the second obstacle structure components are configured with a protrusion length shorter than the protrusion length of the crossing barrier section, Among the second obstacle structure components, the obstacle structure component arranged on the extension line of the crossing barrier section is composed of a crossing region flow path component that forms a flow path of a predetermined width together with the crossing barrier section, Among the second obstacle structure components, the obstacle structure component arranged downstream of the flow path of a predetermined width formed by the cross-border barrier component and the cross-border area flow path component is composed of a cross-border flow detour component that detours the flow of fluid that flows down across the center line, A mixing device characterized in that the flow path formed by the cross-border barrier portion and the cross-border area flow path forming portion is located at a position offset from the center line of the single flow path toward the second wall surface.

8. 8. The mixing device according to claim 1, wherein a plurality of the mixing regions are formed, and the plurality of mixing regions are arranged in series in the single flow path.

9. A microchannel device comprising the mixing device according to any one of claims 1 to 8 in a microchannel chip, A microchannel device comprising: a plurality of supply channels, a single channel, and the mixing region that constitute the mixing apparatus; a fluid injection unit that injects a fluid into the supply channels; a reaction region that is provided continuously with the single channel; and a discharge unit that discharges the fluid at an end of the channel that has passed through the reaction region.

Images