Microfluidic device, droplet formation system, and droplet formation method

Abstract

This reduces the need for high processing precision, special materials, and special shapes in microfluidic devices, increasing the freedom to form droplets of the desired size. [Solution] A microfluidic device having a channel for forming droplets formed inside comprises a first channel through which a core fluid flows, a second channel through which a sheath fluid flows, a nozzle section where the first and second channels merge, and a third channel through which droplets formed in the nozzle section flow. The microfluidic device further includes a droplet diameter adjusting member disposed in the nozzle section or elsewhere, and the droplet diameter adjusting member is formed to be large enough to pass through the moving channel over a range from the opening where the moving channel opens to communicate with the outside of the microfluidic device to the nozzle section.

Description

Technical Field

[0001] The present disclosure relates to a microfluidic device, a droplet formation system including the microfluidic device, and a droplet formation method.

Background Art

[0002] Conventionally, various microfluidic devices for generating microdroplets have been proposed and are being considered for use in fields such as chemistry and biochemistry. In order to fabricate such microfluidic devices, generally, a technique called photolithography or the like is used, and expensive equipment, advanced techniques, and complicated processes are required. In order to change the size of the droplets generated in such a microfluidic device, a new microfluidic device with a changed size of the flow path in the device has been fabricated. Also, in order to change the size of the droplets generated in a microfluidic device, instead of fabricating a new microfluidic device with a changed flow path as described above, for example, a method of deforming a member constituting the microfluidic device such as a member constituting the flow path wall has also been proposed (for example, Patent Document 1 and Non-Patent Documents 1 and 2).

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Non-Patent Documents

[0004]

Non-Patent Document 1

Non-Patent Document 2

Summary of the Invention

[0005] However, to obtain smaller droplets, for example, it was necessary to improve the processing accuracy of microfluidic devices to create microfluidic devices with smaller channel diameters, or to fabricate microfluidic devices using special materials that could withstand high hydraulic pressure. Furthermore, when changing the size of the generated droplets by deforming the components that make up the channel walls, there was a problem that the materials of the components that make up the channel walls in the microfluidic device were limited to flexible materials. In particular, as in Non-Patent Document 2, when special mechanisms such as screw mechanisms were used, not only were the materials of the components limited, but the shape of the microfluidic device was also limited. Therefore, there was a need for a technology that would reduce the need to employ high processing accuracy, special materials, and special shapes to fabricate microfluidic devices, and increase the degree of freedom to form droplets of desired sizes, including smaller droplets, without having to prepare many variations of microfluidic devices with different channel diameters. [Means for solving the problem]

[0006] This disclosure can be implemented in the following forms: (1) According to one embodiment of the present disclosure, a microfluidic device is provided which has a channel for forming droplets formed inside. The microfluidic device has a first channel through which a core fluid for forming a dispersed phase flows, a second channel through which a sheath fluid for forming a continuous phase flows, a nozzle portion where the first channel and the second channel merge, and a third channel through which droplets formed in the nozzle portion flow. The microfluidic device further comprises a droplet diameter adjusting member disposed between or within the nozzle portion and at least one of the first channel, the second channel, and the third channel, the droplet diameter adjusting member being sized to pass through the moving channel, which is at least one of the first channel, the second channel, and the third channel, over a range from an opening in the moving channel that communicates with the outside of the microfluidic device to the nozzle portion. This form of microfluidic device allows a droplet size adjustment member to be introduced into the moving channel from its opening and moved to the nozzle within the channel. Therefore, by positioning the droplet size adjustment member near the nozzle, it becomes possible to adjust the droplet size formed by the microfluidic device. As a result, the need for high processing precision, special materials, or special shapes to fabricate the microfluidic device can be reduced, and the degree of freedom in forming droplets of a desired size can be increased without having to prepare many variations of microfluidic devices with different channel diameters. (2) In the microfluidic device of the above form, the droplet diameter adjusting member may be made of a magnetic material. With such a configuration, it becomes possible to move the droplet diameter adjusting member by applying a magnetic field to it. (3) Another embodiment of the present disclosure provides a droplet forming system. This droplet forming system comprises a microfluidic device as described in (1) and a droplet diameter adjusting member drive unit that moves the droplet diameter adjusting member from the opening to the nozzle within the moving channel. With this configuration, the droplet diameter formed by the microfluidic device can be adjusted by moving the droplet diameter adjusting member to the nozzle within the microfluidic device using the droplet diameter adjusting member drive unit. (4) In the droplet formation system of the above embodiment, the droplet diameter adjusting member may be made of a magnetic material, and the droplet diameter adjusting member drive unit may move the droplet diameter adjusting member by applying a magnetic field to the droplet diameter adjusting member. With such a configuration, the droplet diameter adjusting member can be moved to the nozzle by applying a magnetic field to the droplet diameter adjusting member by the droplet diameter adjusting member drive unit within the microfluidic device, thereby adjusting the droplet diameter formed in the microfluidic device. (5) In the droplet formation system of the above embodiment, the droplet diameter adjustment member drive unit may include a magnetic field source that generates a magnetic field, and may move at least one of the magnetic field source and the microfluidic device horizontally in two dimensions so that the droplet diameter adjustment member moves in the moving channel from the opening to the nozzle. With such a configuration, the droplet diameter adjustment member drive unit can move the droplet diameter adjustment member to the nozzle and adjust the droplet diameter formed by the microfluidic device by moving at least one of the magnetic field source and the microfluidic device horizontally in two dimensions. (6) In the droplet formation system of the above embodiment, the droplet diameter adjustment member drive unit may include a plurality of magnetic field sources capable of switching the generation of a magnetic field on and off, and the plurality of magnetic field sources are positioned to act on the moving channel over a range from the opening to the nozzle when the microfluidic device is placed in a predetermined location, and by sequentially switching the generation of a magnetic field on and off in each of the plurality of magnetic field sources, the location where the magnetic field acts in the moving channel over a range from the opening to the nozzle is sequentially changed, thereby moving the droplet diameter adjustment member from the opening to the nozzle in the moving channel. With such a configuration, the droplet diameter adjustment member drive unit can move the droplet diameter adjustment member to the nozzle by sequentially changing the location where the magnetic field acts in the moving channel over a range from the opening to the nozzle, thereby adjusting the droplet diameter formed by the microfluidic device. (7) A droplet formation method is provided according to yet another embodiment of the present disclosure. This droplet formation method provides a channel forming member having a first channel through which a core fluid for constituting a dispersed phase flows, a second channel through which a sheath fluid for constituting a continuous phase flows, a nozzle portion where the first channel and the second channel merge, and a third channel through which droplets formed in the nozzle portion flow. The position of the droplet diameter adjusting member is adjusted by moving the droplet diameter adjusting member between or within the nozzle portion and at least one of the first channel, the second channel, and the third channel in the channel forming member. The core fluid is supplied to the first channel and the sheath fluid is supplied to the second channel in the channel forming member where the droplet diameter adjusting member is located, thereby forming droplets in the nozzle portion. According to this droplet formation method, the position of the droplet diameter adjusting member is adjusted by moving the droplet diameter adjusting member near the nozzle portion within the flow channel forming member, and by supplying core fluid to the first flow channel and sheath fluid to the second flow channel, droplets of a desired size can be formed. (8) A droplet formation method is provided according to yet another embodiment of the present disclosure. This droplet formation method provides a channel forming member having a first channel through which a core fluid for forming a dispersed phase flows, a second channel through which a sheath fluid for forming a continuous phase flows, a nozzle portion where the first channel and the second channel merge, and a third channel through which droplets formed in the nozzle portion flow. The core fluid is supplied to the first channel in the channel forming member, and the sheath fluid is supplied to the second channel, while a droplet diameter adjusting member for adjusting the size of droplets is moved between or within the nozzle portion and at least one of the first channel, the second channel, and the third channel in the channel forming member. According to this droplet formation method, by supplying a core fluid to the first channel and a sheath fluid to the second channel, while moving a droplet diameter adjusting member near the nozzle portion within the channel forming member, droplets with a higher dispersion of particle size distribution can be formed. (9) According to yet another embodiment of the present disclosure, a method for manufacturing a microfluidic device is provided. This method for manufacturing a microfluidic device involves providing a channel forming member having a first channel through which a core fluid for forming a dispersed phase flows, a second channel through which a sheath fluid for forming a continuous phase flows, a nozzle portion where the first channel and the second channel merge, and a third channel through which droplets formed in the nozzle portion flow, and arranging a droplet diameter adjusting member for adjusting the size of droplets between at least one of the first channel, the second channel, and the third channel in the channel forming member and the nozzle portion, or within the nozzle portion. According to this method for manufacturing microfluidic devices, the droplet size adjustment member is positioned near the nozzle portion of a prepared channel forming member. Therefore, by utilizing an existing channel forming member and positioning the droplet size adjustment member near the nozzle portion within the channel forming member, the size of the droplets formed by the channel forming member can be adjusted without changing the shape of the channel forming member. The present disclosure can be realized in various forms, for example, in addition to a microfluidic device, it can be realized in forms such as a droplet formation system including a microfluidic device, a droplet formation method, a droplet diameter adjustment method, a method for manufacturing a microfluidic device, and the like.

Brief Description of the Drawings

[0007] [Figure 1] Plan view of a microfluidic device. [Figure 2] Cross-sectional view of a microfluidic device. [Figure 3] Plan view of three plate-like members constituting a microfluidic device. [Figure 4] Explanatory drawing showing the relationship between the location where a droplet diameter adjustment member is disposed and the size of droplets. [Figure 5] Explanatory drawing showing the relationship between the location where a droplet diameter adjustment member is disposed and the size of droplets. [Figure 6] Explanatory drawing showing the schematic configuration of a droplet formation system. [Figure 7] Explanatory drawing showing the schematic configuration of a droplet formation system. [Figure 8] Explanatory drawing showing an example of using a flow path forming member with different flow path shapes. [Figure 9] Explanatory drawing showing an example of using a flow path forming member with different flow path shapes. [Figure 10] Explanatory drawing showing an example of using a flow path forming member with different flow path shapes. [Figure 11] Explanatory drawing showing an example of using a flow path forming member with different flow path shapes. [Figure 12] Explanatory drawing showing an example of using a flow path forming member with different flow path shapes. [Figure 13] Explanatory drawing showing a droplet formation system including an optical tweezer. [Figure 14] Explanatory drawing showing a droplet formation system using the acoustic levitation method. [Figure 15] Explanatory drawing showing an example of a method for manufacturing a microfluidic device. [Figure 16] Explanatory drawing showing a method for manufacturing a droplet diameter adjustment member. [Figure 17]Explanatory drawing showing the state of imaging the droplet diameter adjustment member. [Figure 18] It is an explanatory drawing that images the state of forming droplets. [Figure 19] It is an explanatory drawing that images the state of forming droplets. [Figure 20] It is an explanatory drawing that images the state of forming droplets. [Figure 21] It is an explanatory drawing that images the state of forming droplets. [Figure 22] Explanatory drawing schematically showing the method of measuring the size of droplets. [Figure 23] Explanatory drawing showing the relationship between the position of the droplet diameter adjustment member and the droplet diameter. [Figure 24] Explanatory drawing showing the relationship between the flow rate ratio of the core fluid and the sheath fluid and the size of the droplets. [Figure 25] Explanatory drawing showing the influence of moving the droplet diameter adjustment member during droplet production.

Embodiments for Carrying Out the Invention

[0008] A. Configuration of the microfluidic device: Figures 1 to 3 are explanatory drawings showing the schematic configuration of the microfluidic device 10 as an embodiment of the present disclosure. Figure 1 is a plan view showing the microfluidic device 10 as seen from above, Figure 2 is a cross-sectional view taken along the 2-2 cross-section in Figure 1, and Figure 3 is a plan view showing the three plate-like members 10a to 10c constituting the microfluidic device 10 as seen from above. In Figures 1 to 3, and Figures 6 and 7 described later, in order to specify the directions, the XYZ axes orthogonal to each other are shown. The X-axis, Y-axis, and Z-axis shown in each figure represent the same directions. Note that Figures 1 to 3, and Figures 6 and 7 described later schematically represent the arrangement of each part, and do not accurately represent the ratio of the dimensions of each part.

[0009] The microfluidic device 10 of this embodiment is a plate-shaped member with microchannels formed inside. Multiple fluid channels are formed inside, and the device is designed to disperse one fluid into another by contact between different fluids to form droplets. Figures 1 to 3 show an example of a device in which two types of fluids are supplied as the microfluidic device 10.

[0010] The microfluidic device 10 includes a first channel 21 through which a core fluid for forming a dispersed phase flows, a second channel 23 through which a sheath fluid for forming a continuous phase flows, a nozzle section 27 where the first channel 21 and the second channel 23 merge, and a third channel 25 through which droplets formed in the nozzle section 27 flow. In Figures 1 to 3, the channels formed within the microfluidic device 10 are formed in a T-shape overall. In such a microfluidic device 10, the second channel 23 and the third channel 25 are connected at their ends in the nozzle section 27 and arranged in a straight line. The first channel 21 is connected to the second channel 23 and the third channel 25 at the nozzle section 27 so as to be perpendicular to them. In such a microfluidic device 10, the core fluid flowing through the first channel 21 and the sheath fluid flowing through the second channel 23 come into contact at the nozzle portion 27, and droplets of the core fluid constituting the dispersed phase are dispersed in the sheath fluid constituting the continuous phase, and these droplets flow through the third channel 25. The droplet formation will be explained in detail later.

[0011] Furthermore, the microfluidic device 10 is provided with a first opening 22 that opens to communicate with the outside of the microfluidic device 10 near the end of the first channel 21 that is spaced away from the nozzle portion 27. The first opening 22 is a structure for supplying core fluid into the first channel 21 from the outside. The microfluidic device 10 is also provided with a second opening 24 that opens to communicate with the outside of the microfluidic device 10 near the end of the second channel 23 that is spaced away from the nozzle portion 27. The second opening 24 is a structure for supplying sheath fluid into the second channel 23 from the outside. Furthermore, the microfluidic device 10 is provided with a third opening 26 that opens to communicate with the outside of the microfluidic device 10 near the end of the third channel 25 that is spaced away from the nozzle portion 27. The third opening 26 is a structure for discharging fluid containing droplets that have passed through the third channel 25 to the outside of the microfluidic device 10.

[0012] In the microfluidic device 10, the member on which the first channel 21, second channel 23, nozzle portion 27, and third channel 25 are formed is also called the "channel forming member 20". The constituent material of the channel forming member 20 is not particularly limited as long as it has processability that allows for the formation of microchannels. Examples of constituent materials for the channel forming member 20 include silicone resins such as polydimethylsiloxane (PDMS), cycloolefin resins, acrylic resins, or glass.

[0013] Figures 2 and 3 show a three-layer structure of plate-shaped members made of the above-described material, as an example of the configuration of the flow path forming member 20. Here, the flow path forming member 20 is constructed by stacking plate-shaped members 10a to 10c in this order. Plate-shaped member 10b has T-shaped through holes formed therein, which are shown in Figure 1 as the first flow path 21, the second flow path 23, the nozzle portion 27, and the third flow path 25. Plate-shaped member 10a is provided with three through holes, which are the first opening 22, the second opening 24, and the third opening 26. Plate-shaped member 10c does not have through holes. The flow path forming member 20 can be manufactured by stacking and joining such plate-shaped members 10a to 10c.

[0014] Alternatively, the flow path forming member 20 may be formed by laminating two plate-shaped members. In this case, for example, a T-shaped recess that will become the first flow path 21, the second flow path 23, the nozzle portion 27, and the third flow path 25 may be formed on the surface of one plate-shaped member, and through holes that will become the first opening 22, the second opening 24, and the third opening 26 may be formed in the other plate-shaped member. Then, the side of the plate-shaped member on which the recess is formed may be joined to the other plate-shaped member. Alternatively, a T-shaped recess that will become the first flow path 21, the second flow path 23, the nozzle portion 27, and the third flow path 25 may be formed on each of the two opposing surfaces of the two plate-shaped members, and the two plate-shaped members may be joined so that the recesses face each other. Alternatively, in the T-shaped flow path formed in the flow path forming member 20, at least one of the first flow path 21, the second flow path 23, and the third flow path 25 may extend to the outer circumference of the flow path forming member 20. In this case, the opening that communicates with the flow channel, which extends to the outer circumference of the flow channel forming member 20, may be provided on the side surface of the flow channel forming member 20, which is constructed by stacking plate-shaped members.

[0015] The microfluidic device 10 further includes a droplet diameter adjusting member 28, which is positioned between at least one of the first channel 21, the second channel 23, and the third channel 25 and the nozzle portion 27, or within the nozzle portion 27. Hereinafter, "between at least one of the first channel 21, the second channel 23, and the third channel 25 and the nozzle portion 27, or within the nozzle portion 27" will also be referred to as "the vicinity of the nozzle portion 27." The droplet diameter adjusting member 28 is a component for adjusting the size of droplets formed in the microfluidic device 10 by adjusting the location where the droplet diameter adjusting member 28 is positioned. By positioning the droplet diameter adjusting member 28 within the channel, it becomes possible to form smaller droplets compared to when it is not positioned. The adjustment of droplet diameter by the droplet diameter adjusting member 28 will be explained in detail later.

[0016] In this embodiment, a magnetic material is used as the droplet diameter adjusting member 28, and by applying a magnetic field to the droplet diameter adjusting member 28, the droplet diameter adjusting member 28 can be moved within the flow channel forming member 20. In this embodiment, at least one of the first flow channel 21, the second flow channel 23, and the third flow channel 25 is used as a "moving flow channel" for introducing the droplet diameter adjusting member 28 into the flow channel forming member 20 and moving it within the flow channel forming member 20. The droplet diameter adjusting member 28 is formed to be large enough to pass through the moving flow channel from the opening that opens to communicate with the outside of the microfluidic device (the opening provided in the moving flow channel among the first opening 22, the second opening 24, and the third opening 26) to the nozzle portion 27. Specifically, the droplet diameter adjusting member 28 is formed to be sufficiently small compared to the diameter of the cross-section of the moving flow channel so that the droplet diameter adjusting member 28 can pass through the range from the opening to the nozzle portion 27 in the moving flow channel. Therefore, when fabricating the microfluidic device 10, the droplet diameter adjusting member 28 is introduced into the moving channel from the opening of the moving channel, and by applying a magnetic field to the droplet diameter adjusting member 28, the droplet diameter adjusting member 28 is moved within the moving channel, and the position of the droplet diameter adjusting member 28 near the nozzle portion 27 can be adjusted. This makes it possible to form droplets of a desired size in the microfluidic device 10. The configuration for moving the droplet diameter adjusting member 28 within the moving channel will be explained in detail later.

[0017] The constituent material of the droplet diameter adjusting member 28 is not particularly limited as long as it is a magnetic material. It should be selected appropriately considering the stability with respect to the core fluid and sheath fluid used. The magnetic material constituting the droplet diameter adjusting member 28 is preferably a ferromagnetic or soft magnetic material. For example, metals such as nickel (Ni), cobalt (Co), and iron (Fe); alloys such as Ni-Fe alloy (permalloy), Fe-Co alloy, Fe-Ce-C martensitic stainless steel, MnAl magnets, Cu2MnAl (Whistler alloy); and intermetallic compounds such as SmCo5 (samarium cobalt magnet) and Nd2Fe 14Examples include B (neodymium magnet), oxides such as BaO·6Fe2O3 (Ba ferrite), CrO2, Fe3O4 (magnetite), γ-Fe2O3 (maghematite cubic crystal), and other transition metal compounds such as borides and phosphides.

[0018] The microfluidic device 10 of this embodiment can be used for various applications. For example, by using a fluorinated oil such as Novec7500, mineral oil, or vegetable oil as the sheath fluid constituting the continuous phase, and a culture medium such as DMEM or LB as the core fluid constituting the dispersed phase, droplets can be formed for isolating or culturing microorganisms such as cells or bacteria. Alternatively, by using a fluorinated oil such as Novec7500, mineral oil, or vegetable oil as the sheath fluid constituting the continuous phase, and using PCR reagents or LAMP reagents and a sample as the core fluid constituting the dispersed phase, digital PCR or digital LAMP for DNA or RNA analysis can be performed. As described above, in addition to forming droplets (oil-based) as a w / o emulsion with an oil-based continuous phase and a water-based dispersed phase, droplets (water-based) as an o / w emulsion with an oil-based continuous phase and an oil-based dispersed phase may also be formed. For example, when used in the manufacture of cosmetics, the w / o emulsion can be used for lotion production, and the o / w emulsion can be used for emulsion production. Furthermore, as will be described later, when forming droplets using three or more fluids, the technique of using a droplet size adjusting member 28 can also be applied. In this case, for example, droplets as w / o / w emulsions or w / w / o emulsions can be formed. For example, in a wow system, by using an aqueous solution as the inner solution, an octanol lipid solution as the outer solution, and a buffer such as HEPES as the outermost solution, liposomes covered with a lipid bilayer can be produced and used in pharmaceuticals, cosmetics, and cell-free expression systems for membrane proteins.

[0019] B. Arrangement of droplet diameter adjusting members and droplet size: Figure 4 is an explanatory diagram showing the relationship between the location of the droplet size adjustment member 28 in the microfluidic device 10 and the size of the droplets formed. Figure 4 shows a magnified view of each channel near the nozzle section 27. Here, an oil-based fluid is used as the sheath fluid constituting the continuous phase, and a water-based fluid is used as the core fluid constituting the dispersed phase, showing how droplets are formed as a w / o emulsion. In Figure 4, the flow direction of the core fluid flowing through the first channel 21 and the sheath fluid flowing through the second channel 23 is indicated by white arrows. Figure 4(A) shows three arrangement examples of the droplet size adjustment member 28 near the nozzle section 27, from position 1 to position 3. Position 1 shows the location near the boundary with the nozzle section 27 in the first channel 21, position 2 shows the location near the boundary with the nozzle section 27 in the third channel 25, and position 3 shows the location near the boundary with the nozzle section 27 in the second channel 23. Figure 4(B) shows the droplet diameter adjustment member 28 positioned at position 3, and Figure 4(C) shows the droplet diameter adjustment member 28 positioned at position 2. The size of the droplets formed can be changed by positioning the droplet diameter adjustment member 28 near the nozzle portion 27. As shown in Figures 4(B) and 4(C), smaller droplets can be formed by positioning the droplet diameter adjustment member 28 at position 2 compared to position 3. As will be described later, when the droplet diameter adjustment member 28 is positioned at position 1, droplets of an intermediate size between those formed at position 2 and position 3 can be formed. In Figure 4(A), positions 1 to 3 are shown as examples of locations for positioning the droplet diameter adjustment member 28, but the location for positioning the droplet diameter adjustment member 28 is not limited to these. The droplet diameter adjustment member 28 can be positioned at any position near the nozzle portion 27, for example, a position closer to the center of the nozzle portion 27 or a position closer to the flow path wall.

[0020] Thus, when using the microfluidic device 10, prior to droplet formation, the droplet diameter adjusting member 28 is introduced into the moving channel within the channel forming member 20, and the droplet diameter adjusting member 28 is moved to the vicinity of the nozzle portion 27 to adjust the position of the droplet diameter adjusting member 28. In this way, by subsequently supplying sheath fluid to the first channel 21 and core fluid to the second channel 23, droplets of the desired size can be formed by the nozzle portion 27.

[0021] Figure 5 is an explanatory diagram showing the relationship between the location where the droplet diameter adjustment member 28 is placed and the size of the droplet formed, similar to Figure 4. Figure 5(A) shows how the droplet diameter adjustment member 28 is fixed at a specific location near the nozzle portion 27 to form a droplet, and as an example, it shows how the droplet diameter adjustment member 28 is placed at position 2, similar to Figure 4(C). In contrast, Figure 5(B) shows how the position of the droplet diameter adjustment member 28 is moved during the process of forming a droplet using the microfluidic device 10. That is, in Figure 5, core fluid is supplied to the first channel 21 and sheath fluid is supplied to the second channel 23, while the droplet diameter adjustment member 28 is moved near the nozzle portion 27. Such movement of the droplet diameter adjustment member 28 can be performed at any position near the nozzle portion 27, such as positions 1 to 3 shown in Figure 4(A). Figure 5(B) shows, as an example, how the droplet diameter adjustment member 28 is moved between position 2 and position 3. As shown in Figure 5, by moving the droplet diameter adjusting member 28 while forming droplets, it is possible to form droplets exhibiting a polydisperse particle size distribution compared to when the position of the droplet diameter adjusting member 28 is fixed while forming droplets.

[0022] C. Method of moving the droplet diameter adjustment member: Figure 6 is an explanatory diagram illustrating the schematic configuration of a droplet formation system 40 equipped with the microfluidic device 10 of this embodiment. In addition to the microfluidic device 10, the droplet formation system 40 includes a droplet diameter adjustment member drive unit 50, which is a device for moving the droplet diameter adjustment member 28 from the opening to the nozzle portion 27 within the moving channel. The droplet diameter adjustment member drive unit 50 moves the droplet diameter adjustment member 28, which is made of a magnetic material, within the moving channel by applying a magnetic field to the droplet diameter adjustment member 28. As shown in Figure 6, the droplet diameter adjustment member drive unit 50 of the droplet formation system 40 includes a magnetic field source 52 that generates a magnetic field, and a moving mechanism 54 that moves the magnetic field source 52 relative to the microfluidic device 10. Note that in Figure 6, the specific configuration of the microfluidic device 10 is omitted, and only the arrangement of the droplet diameter adjustment member 28 inside the channel forming member 20 is schematically shown.

[0023] The magnetic field generated by the magnetic field source 52 may be an alternating current (AC) magnetic field or a direct current (DC) magnetic field. Figure 6 shows the magnetic field source 52 as an AC electromagnet that generates an AC magnetic field. In this case, the magnetic field source 52 may be composed of a coil, or a coil and a magnetic core. The droplet formation system 40 may further include an AC current supply unit (not shown) that supplies an AC current to the magnetic field source 52 for generating the magnetic field. The AC current supplied from the AC current supply unit to the magnetic field source 52 can be, for example, a sinusoidal AC, a square wave AC, or a pulse signal. If the magnetic field source 52 is a DC electromagnet that generates a DC magnetic field, the droplet formation system 40 may be equipped with a DC current supply unit instead of the AC current supply unit. Alternatively, the magnetic field source 52 may be composed of a permanent magnet that generates a DC magnetic field.

[0024] The moving mechanism 54 is a device for horizontally moving at least one of the magnetic field source 52 and the microfluidic device 10 in two dimensions. That is, the moving mechanism 54 may move the stage supporting the microfluidic device 10 horizontally in the XY plane while the magnetic field source 52 is fixed, or it may move the magnetic field source 52 horizontally while the microfluidic device 10 is fixed, or it may move both the magnetic field source 52 and the microfluidic device 10 horizontally in the XY plane. By moving the magnetic field source 52 relatively along a position that overlaps with the moving channel in the microfluidic device 10 in the Z-axis direction, the moving mechanism 54 can move the droplet diameter adjusting member 28 within the moving channel and guide the droplet diameter adjusting member 28 to the vicinity of the nozzle portion 27.

[0025] Figure 7 is an explanatory diagram showing the schematic configuration of a droplet formation system 140, which is a modified example of the droplet formation system 40 shown in Figure 6, and is equipped with a droplet diameter adjustment member drive unit 150 instead of the droplet diameter adjustment member drive unit 50. The droplet diameter adjustment member drive unit 150 is a device that moves the droplet diameter adjustment member 28, which is made of a magnetic material, within a moving channel by applying a magnetic field to the droplet diameter adjustment member 28, and includes a magnetic field source array 53. The magnetic field source array 53 is composed of a plurality of magnetic field sources 52 arranged two-dimensionally on the XY plane. The magnetic field sources 52 only need to be able to switch the generation of a magnetic field on and off, and for example, they can be devices that generate an alternating magnetic field by being supplied with alternating current from an alternating current supply unit. The plurality of magnetic field sources 52 constituting the magnetic field source array 53 are arranged along a position that overlaps with the moving channel in the microfluidic device 10 in the Z-axis direction. In other words, the multiple magnetic field sources 52 constituting the magnetic field source array 53 are positioned to generate a magnetic field over the range from the opening of the moving channel to the nozzle portion 27 when the microfluidic device 10 is placed in a predetermined location in the droplet formation system 140. By sequentially switching the on / off of magnetic field generation in each of the multiple magnetic field sources 52, the droplet formation system 140 can sequentially change the location where the magnetic field acts within the moving channel from the opening to the nozzle portion 27, thereby moving the droplet diameter adjusting member from the opening to the nozzle portion 27 within the moving channel.

[0026] For example, in Figure 7, when the magnetic field generation at the first magnetic field source 52a, which is positioned close to the droplet diameter adjustment member 28 introduced into the moving channel, is turned on, the droplet diameter adjustment member 28 moves to a position where it overlaps with the first magnetic field source 52a in the Z-axis direction. Subsequently, the magnetic field generation at the first magnetic field source 52a is turned off, and the magnetic field generation at the second magnetic field source 52b, which is positioned adjacent to the nozzle section 27 side along the moving channel relative to the first magnetic field source 52a, is turned on. As a result, the droplet diameter adjustment member 28 moves to a position where it overlaps with the second magnetic field source 52b in the Z-axis direction. By sequentially repeating this operation, the droplet diameter adjustment member 28 can be moved to the vicinity of the nozzle section 27 within the moving channel.

[0027] As described above, the microfluidic device 10, droplet formation system, and droplet formation method of this embodiment are configured such that a droplet diameter adjustment member 28 is placed near the nozzle portion 27 within the microfluidic device 10 to adjust the diameter of the generated droplets. Therefore, it is possible to reduce the need for high processing precision, special materials, or special shapes to fabricate the microfluidic device, and to increase the degree of freedom in forming droplets of a desired size without having to prepare many variations of microfluidic devices with different flow path diameters. As a result, for example, it becomes easier to form smaller droplets. At this time, the size of the generated droplets can be easily changed by the simple operation of adjusting the position of the droplet diameter adjustment member 28.

[0028] In other words, in general, in microfluidic devices, smaller droplets are more likely to form with smaller channel diameters, and larger droplets are more likely to form with larger channel diameters. Also, in droplet generation, generally, increasing the flow rate of the sheath fluid constituting the continuous phase makes it easier to form smaller droplets. According to this embodiment, even without changing the shape of the channel forming member 20, the size of the channel can be changed by arranging the droplet diameter adjusting member 28 near the nozzle portion 27, thereby generating droplets with a diameter corresponding to the size of the channel. Furthermore, since the droplet size can be reduced by arranging the droplet diameter adjusting member 28, the flow rate of the sheath fluid can be reduced, thereby reducing the amount of fluid used for droplet formation. This is because, by arranging the droplet diameter adjusting member 28, the channel at the location where the core fluid forms droplets in the nozzle portion 27 becomes narrower, reducing the pressure and shear stress required for droplet formation, and thus reducing the flow rate of the sheath fluid. In this way, the size of the droplets generated can be adjusted by the arrangement of the droplet diameter adjusting member 28. Therefore, it is not necessary to change the shape of the flow path forming member 20 to change the size of the droplets, and even when the flow rate of the fluid used for droplet generation is kept the same, it becomes possible to form droplets of various sizes.

[0029] Furthermore, in the microfluidic device 10 of this embodiment, a droplet diameter adjustment member 28 is introduced into the channel forming member 20 from the outside, and the droplet diameter adjustment member 28 is moved within the channel forming member 20 to adjust the position of the droplet diameter adjustment member 28 within the channel forming member 20. Therefore, for example, an existing component commercially available as a microfluidic device can be used as the channel forming member 20, and the size of the generated droplets can be adjusted.

[0030] Furthermore, since the droplet diameter adjustment member 28 can be moved non-contact within the flow path forming member 20, the droplet diameter adjustment member 28 can be moved while performing the droplet formation operation. As a result, droplets exhibiting a more polydisperse particle size distribution can be formed.

[0031] D. Variations in the arrangement of flow path shape and droplet diameter adjusting members: Figures 4 and 5 show an example where the vicinity of the nozzle portion 27 has a T-shaped flow path. However, the configuration for adjusting the droplet diameter using a droplet diameter adjustment member can also be applied to different flow path shapes. Below, we will describe an example of applying the droplet diameter adjustment member to a flow path forming member with a flow path shape other than T-shaped.

[0032] Figure 8 is an explanatory diagram illustrating an example of droplet formation by flow focusing, where the flow path shape near the nozzle portion 227 is cross-shaped. Here, an oil-based fluid is used as the sheath fluid flowing through the second flow paths 223 and 224, and a water-based fluid is used as the core fluid flowing through the first flow path 221, showing how droplets are formed as a w / o emulsion. Figure 8 shows four examples of placement of the droplet diameter adjustment member near the nozzle portion 227, shown as positions 1 to 4. Position 1 is near the boundary with the nozzle portion 227 in the third flow path 225, position 2 is near the boundary with the nozzle portion 227 in the first flow path 221, position 3 is near the boundary with the nozzle portion 227 in the second flow path 223, and position 4 is near the boundary with the nozzle portion 227 in the second flow path 223. Including positions 1 to 4 shown in Figure 8, the size of the formed droplets can be adjusted by adjusting the position of the droplet diameter adjustment member near the nozzle portion 227.

[0033] Figure 9 is an explanatory diagram illustrating an example of droplet formation using a flow channel shaped like two connected cross-shaped channels. The flow channel shown in Figure 9 is equipped with two nozzle sections 327 and 367. Here, an oil-based fluid is used as the first sheath fluid flowing through the second flow channels 323 and 324, and a water-based fluid is used as the core fluid flowing through the first flow channel 321 and the second sheath fluid flowing through the second flow channels 363 and 364 to form droplets as a w / o / w emulsion. Figure 9 shows four arrangement examples of the droplet diameter adjusting member near the nozzle section 327, shown as positions 1 to 4. Position 1 shows the position near the boundary with the nozzle section 327 in the first flow channel 321, position 2 shows the position near the boundary with the nozzle section 327 in the intermediate flow channel 325, position 3 shows the position near the boundary with the nozzle section 327 in the second flow channel 323, and position 4 shows the position near the boundary with the nozzle section 327 in the second flow channel 324. Furthermore, Figure 9 shows four examples of arrangements of the droplet diameter adjusting member near the nozzle portion 367, specifically positions 5 to 8. Position 5 indicates a position near the boundary with the nozzle portion 367 in the intermediate flow path 325, position 6 indicates a position near the boundary with the nozzle portion 367 in the third flow path 365, position 7 indicates a position near the boundary with the nozzle portion 367 in the second flow path 363, and position 8 indicates a position near the boundary with the nozzle portion 367 in the second flow path 364.

[0034] In the nozzle section 327, the core fluid flowing through the first channel 321 disperses in the first sheath fluid to form droplets 30, and the formed droplets 30 flow through the intermediate channel 325. In the nozzle section 367, the fluid containing the droplets 30 flowing through the intermediate channel 325 disperses in the second sheath fluid to form two-layered droplets 330, and the formed droplets 330 flow through the third channel 365. Thus, focusing on droplet formation in the nozzle section 327, the intermediate channel 325 can be called the "third channel" through which the droplets formed in the nozzle section flow, and focusing on droplet formation in the nozzle section 367, the intermediate channel 325 can be called the "first channel" through which the core fluid for forming the dispersed phase flows. The size of the droplets 30 can be adjusted by adjusting the position of the droplet diameter adjustment member near the nozzle section 327, including positions 1 to 4 shown in Figure 9. Furthermore, the size of the droplet 330 can be adjusted by adjusting the position of the droplet diameter adjusting member near the nozzle portion 367, including positions 5 to 8 shown in Figure 9.

[0035] Figure 10 is an explanatory diagram illustrating an example in which, in the nozzle section 427, two first channels 421 and 422, through which the first core fluid and the second core fluid flow respectively, are connected to a second channel, forming a droplet 430 in which the two types of core fluids are mixed. Here, a water-based fluid is used as the first and second core fluids flowing through the first channels 421 and 422, and an oil-based fluid is used as the sheath fluid flowing through the second channel 423, showing how a droplet is formed as a w / o emulsion. Figure 10 shows four arrangement examples of the droplet diameter adjusting member near the nozzle section 427, shown as positions 1 to 4. Position 1 shows the position near the boundary with the nozzle section 427 in the second channel 423, position 2 shows the position near the boundary with the nozzle section 427 in the first channel 421, position 3 shows the position near the boundary with the nozzle section 427 in the first channel 422, and position 4 shows the position near the boundary with the nozzle section 427 in the third channel 425. The size of the formed droplet 430 can be adjusted by adjusting the position of the droplet diameter adjusting member near the nozzle portion 427, including positions 1 to 4 shown in Figure 10.

[0036] Figure 11 shows an example where the flow path shape near the nozzle section 227 is cross-shaped, similar to Figure 8, and the same reference numerals are used for parts common to Figure 8. Here, similar to Figure 8, an oil-based fluid is used as the sheath fluid flowing through the second flow paths 223 and 224, and a water-based fluid is used as the core fluid flowing through the first flow path 221, showing how droplets are formed as a w / o emulsion. In Figure 11, position 1 is shown as an example of the arrangement of the droplet diameter adjustment member near the nozzle section 227. By arranging the droplet diameter adjustment member at a position that divides the core fluid flowing from the first flow path 221 into the nozzle section 227, as shown at position 1 in Figure 11, the droplets can be divided to form double droplets (droplets arranged in two rows) 230. At this time, the size of the formed droplets 230 can be adjusted by adjusting the position of the droplet diameter adjustment member near position 1 in Figure 11. Furthermore, by adjusting the position of the droplet diameter adjustment member near the nozzle portion 27, it is possible to switch between a state in which a double droplet 230 is formed, as shown in Figure 11, and a state in which a single droplet 30 is formed, as shown in Figure 8.

[0037] Figure 12, similar to Figure 10, shows an example in which two first channels 421 and 422, through which different core fluids flow, are connected to a second channel in the nozzle section 427, and the same reference numerals are used for parts common to Figure 12. Here, similar to Figure 10, a water-based fluid is used as the first and second core fluids flowing through the first channels 421 and 422, and an oil-based fluid is used as the sheath fluid flowing through the second channel 423, showing how droplets are formed as a w / o emulsion. In Figure 12, position 1 is shown as an example of the arrangement of the droplet diameter adjusting member near the nozzle section 427. As shown in position 1 in Figure 12, by arranging the droplet diameter adjusting member at a position that divides the first core fluid flowing from the first channel 421 into the nozzle section 427 and the second core fluid flowing from the first channel 422 into the nozzle section 427, droplets 431 originating from the first core fluid and droplets 432 originating from the second core fluid can be formed independently. At this time, the size of the formed droplets 431 and 432 can be adjusted by adjusting the position of the droplet diameter adjusting member near position 1 in Figure 12. Furthermore, by adjusting the position of the droplet diameter adjusting member near the nozzle portion 427, it is possible to switch between a state in which different types of droplets are formed independently, as shown in Figure 12, and a state in which droplets mixed with the first core fluid and the second core fluid are formed, as shown in Figure 10.

[0038] E. Modified materials and movement methods for the droplet diameter adjusting member: In Figures 6 and 7, the droplet diameter adjustment member drive unit of the droplet formation system moves the droplet diameter adjustment member by applying a magnetic field to it, but other configurations are also possible. Below, we will describe an example of a configuration in which a force or energy other than a magnetic field is applied from outside the flow path forming member to move the droplet diameter adjustment member within the moving flow path.

[0039] Figure 13 is an explanatory diagram illustrating a droplet formation system 540 in which the droplet diameter adjustment member drive unit, which moves the droplet diameter adjustment member 28 within the moving channel of the channel forming member 20, is equipped with optical tweezers that use laser light. Optical tweezers are devices that use focused laser light to capture and move dielectric nanoparticles on the order of micrometers at the point of focus. In this case, the channel forming member 20 can be formed from a material that sufficiently transmits laser light, and the droplet diameter adjustment member 28 can be formed from dielectric particles such as metal microparticles or resin microparticles. By moving the laser light source of the optical tweezers relative to the microfluidic device 10, the point of focus of the laser light can be moved along the moving channel of the channel forming member 20, thereby moving the droplet diameter adjustment member 28 within the moving channel.

[0040] Figure 14 is an explanatory diagram illustrating a droplet formation system 640 that utilizes acoustic levitation, in which a droplet diameter adjustment member drive unit 650 moves a droplet diameter adjustment member 28 within a moving channel of a flow channel forming member 20. Acoustic levitation is a non-contact material control technology using sound, and the droplet diameter adjustment member drive unit 650 comprises a vibrator (sound source) 662 and a reflecting plate 664 positioned opposite each other with the flow channel forming member 20 in between. Sound generated by the vibrator 662 is reflected by the reflecting plate 664 to generate standing waves, and by positioning the droplet diameter adjustment member 28, which is a fine particle, in the trough of the standing wave, the droplet diameter adjustment member 28 is captured by sound. Furthermore, by changing the direction of the sound, the captured droplet diameter adjustment member 28 can be moved. By using such a device, the droplet diameter adjustment member 28 can be moved within the moving channel. In this case, the droplet diameter adjusting member 28 can be made of various materials, for example, metal microparticles or resin microparticles made of PET resin, acrylic resin, styrene resin, etc.

[0041] F. Other variations: In the microfluidic device of the embodiment described above, the droplet diameter adjustment member 28 was placed at a specific location near the nozzle to form droplets of a desired size, and then the position of the droplet diameter adjustment member 28 could be changed to further change the size of the generated droplets. However, a different configuration is also possible. That is, the droplet diameter adjustment member 28 may be placed at a specific location near the nozzle within the flow channel forming member 20, and the droplet diameter adjustment member 28 may be fixed to the flow channel forming member 20 at that location. Even with such a configuration, the need for high processing precision, special materials, or special shapes to manufacture the microfluidic device can be reduced, and a similar effect can be obtained in that the degree of freedom to form droplets of a desired size can be increased without having to prepare many variations of microfluidic devices with different flow channel diameters.

[0042] Figure 15 is an explanatory diagram illustrating an example of a method for manufacturing such a microfluidic device, namely, a method for forming a droplet diameter adjusting member 728 that is fixed in the vicinity of the nozzle portion 27 within the flow path forming member 20. Figure 15 shows an example in which the flow path shape near the nozzle portion 27 is T-shaped, similar to Figure 4, and the same reference numerals are used for parts common to Figure 4.

[0043] In Figure 15, a photocurable material is used as the constituent material of the droplet diameter adjustment member 728. Specifically, first, an uncured liquid photocurable resin material 720 is poured into the moving channel and guided to the vicinity of the nozzle portion 27 (Figure 15(A)). Then, light irradiation is performed to cure the photocurable resin material 720 in the range of position and shape in which the droplet diameter adjustment member 728 is to be formed (Figure 15(B)). After that, by discharging the uncured liquid photocurable resin material 720 from the channel, a droplet diameter adjustment member 728 of the desired shape is formed at the desired position near the nozzle portion 27 (Figure 15(C)). As the photocurable resin to be used, for example, a type that uses radical polymerization of unsaturated double bonds, such as acrylic resin, or a type that uses cationic polymerization, such as epoxy resin, can be used. [Examples]

[0044] <Fabrication of channel forming members> As a channel forming member, a channel forming member 20 having a three-layer structure and a T-shaped channel was fabricated as shown in Figures 1 to 3. The plate-like members 10a to 10c were all made from acrylic plates measuring 300 mm x 300 mm. For plate-like member 10a, a 2 mm thick material was used, and three through holes of 1.5 mm diameter were provided to form the first opening 22, the second opening 24, and the third opening 26. For plate-like member 10b, a 500 μm thick material was used, and two linear through holes with a width of 500 μm and a length of 200 mm were punched out using a laser processing machine to form a T-shaped through hole. For plate-like member 10c, a 500 μm thick material was used. These plate-like members were aligned and bonded together to form the channel forming member 20. A droplet size adjusting member 28, described later, was introduced into the second channel 23 from the second opening 24 of the channel forming member 20. Subsequently, PTFE tubes for supplying and discharging fluid were fixed to the first opening 22, second opening 24, and third opening 26 that open on the surface of the flow channel forming member 20 using adhesive (High Super 5, manufactured by Cemedyne Co., Ltd.).

[0045] <Fabrication of droplet diameter adjustment member> Figure 16 is an explanatory diagram showing the manufacturing method of the droplet diameter adjusting member 28. Figure 17 is an explanatory diagram showing an image of the fabricated droplet diameter adjusting member 28. To fabricate the droplet diameter adjusting member 28, first, a first mold 70 was fabricated using a 3D printer (Form3, manufactured by Formlabs) (Figure 16(A)). The first mold 70 was provided with a bullet-shaped projection 71 with a height H of 500 μm and a diameter D of 400 μm, which corresponds to the shape of the droplet diameter adjusting member 28. Subsequently, SILPOT 184 (manufactured by Toray Dow Corning Co., Ltd.) as polydimethylsiloxane (PDMS) was poured into the first mold 70 and heated at 75°C for 90 minutes to fabricate a second mold 72 having a recess 73 which is the inverse shape of the projection 71 (Figure 16(B)). A liquid mixture of iron(II,III) oxide powder (5 μm or smaller) and a photocurable resin (Norland optical adhesive 63) was poured into the recess 73 of the second mold 72 as the material for the droplet diameter adjusting member 28. A curing reaction was carried out at 50% intensity for 10 minutes using a light curing unit (LIGHTNINGDUBE LC8, manufactured by Hamamatsu Photonics K.K.) to produce a droplet diameter adjusting member 28 as a magnetic material (Figure 16(C)). The obtained droplet diameter adjusting member 28 was removed from the recess 73 of the second mold 72 using tweezers.

[0046] <Droplet formation using microfluidic devices> After inserting the droplet diameter adjustment member 28 into the flow channel forming member 20, a neodymium magnet measuring 5 × 5 × 3 mm was placed on the surface of the flow channel forming member 20 so as to be in contact with the surface on the plate-shaped member 10C side. By manually moving the neodymium magnet, the droplet diameter adjustment member 28 was moved to the vicinity of the nozzle portion 27 and fixed in place, completing the microfluidic device 10. The droplet diameter adjustment member 28 was fixed at one of the positions 1 to 3 shown in Figure 4, and droplet formation was performed. Also, as shown in Figure 5(B), droplet formation was performed while repeatedly moving the droplet diameter adjustment member 28 between positions 2 and 3. Water was used as the core fluid to constitute the dispersed phase, and oil was used as the sheath fluid to constitute the continuous phase. A syringe pump (Gemini 88 plus, manufactured by KD Scientific) was used to deliver the core fluid and sheath fluid, and the respective fluids were supplied from the first opening 22 or the second opening 24 via the PTFE tube described above.

[0047] Figures 18 to 21 are explanatory diagrams showing the process of forming droplets using the microfluidic device 10. In Figure 8, a neodymium magnet, indicated by a dashed line, is used to fix the droplet diameter adjustment member 28, which is a magnetic material, to position 2 in Figure 4, and a droplet is formed. Figure 19 shows the process when the droplet diameter adjustment member 28 is fixed to position 1 shown in Figure 4 and a droplet is formed. Figure 20 shows the process when the droplet diameter adjustment member 28 is fixed to position 2 and a droplet is formed. Figure 21 shows the process when the droplet diameter adjustment member 28 is fixed to position 3 and a droplet is formed. In each of Figures 19 to 21, the process of droplet formation is shown in chronological order.

[0048] <Measuring droplet size> Figure 22 is a schematic diagram illustrating the method for measuring droplet size. The droplet diameter was measured using the image analysis software ImageJ, by measuring the distance from one end to the other of the droplet 30 in a direction parallel to the fluid flow direction containing the droplet 30 in the third channel 25. Regarding the volume of the droplet 30, after measuring the droplet diameter as described above, for droplets 30 in contact with the channel wall, the total volume was calculated by assuming that the droplet 30 is composed of a rectangular parallelepiped and a pair of hemispheres with a diameter equal to the diameter of a circle with the same area as the cross-section of the rectangular parallelepiped. For droplets 30 not in contact with the channel wall, the volume was calculated by assuming that the droplet 30 is a perfect sphere with the droplet diameter measured as described above as its diameter.

[0049] <Relationship between the position of the droplet diameter adjusting member and the droplet diameter> Figure 23 is an explanatory diagram showing the relationship between the position where the droplet diameter adjustment member 28 is placed and the diameter of the formed droplet. In Figure 23, the average value calculated by measuring the diameters of 20 droplets is shown as the droplet diameter. As shown in Figure 23, when comparing positions 1 to 3, the droplet diameter was smallest when the droplet diameter adjustment member 28 was placed at "position 2" near the boundary with the nozzle portion 27 in the third flow path 25, and the droplet diameter was largest when the droplet diameter adjustment member 28 was placed at "position 3" near the boundary with the nozzle portion 27 in the second flow path 23. Thus, it was confirmed that the size of the formed droplet can be adjusted by the position of the droplet diameter adjustment member 28 placed near the nozzle portion 27.

[0050] <Relationship between flow rate ratio and droplet size> Figure 24 is an explanatory diagram showing the relationship between the flow rate ratio of the core fluid (water) and the sheath fluid (oil) and the size of the formed droplet. In Figure 24, the horizontal axis represents the flow rate ratio, and the vertical axis represents the volume of the droplet. Here, the relationship between the flow rate ratio and the size of the droplet was investigated for both cases: when the droplet diameter adjustment member 28 is placed near the nozzle portion 27 (with droplet diameter adjustment member) and when the droplet diameter adjustment member 28 is not used (without droplet diameter adjustment member). In the case with "droplet diameter adjustment member," as an example, the result of placing the droplet diameter adjustment member at position 2 in Figure 4(A) is shown. When measuring the size of the droplet, the water flow rate was fixed at 30.8 μL / min, and the flow rate ratio, which is the ratio of the oil flow rate to the water flow rate, was changed by adjusting the oil flow rate.

[0051] As shown in Figure 24, under the flow rate ratio of 1, the volume of the droplets generated when the "droplet diameter adjustment member is present" is approximately 16,000,000 μm³. 3 As a result, the volume of the droplets could be reduced to approximately 1 / 5 compared to the case without the droplet diameter adjustment member. Furthermore, it was shown that in order to achieve the same droplet volume as with the droplet diameter adjustment member under a flow rate of 1 with the droplet diameter adjustment member, the flow rate ratio would need to be approximately 40, requiring approximately 40 times the amount of oil (sheath fluid).

[0052] Under conditions where the flow rate ratio is larger, the amount of sheath fluid flowing through the channel increases, which raises the internal pressure within the channel. As a result, the likelihood of damage to the components constituting the channel due to the high internal pressure increases. In contrast, it was confirmed that when a droplet size adjustment component is used, the amount of sheath fluid can be suppressed even when relatively small droplets are formed, and as a result, damage to components caused by increased internal pressure can be suppressed.

[0053] Specifically, in the microfluidic device used for the measurement shown in Figure 24, when the water flow rate was fixed at 30.8 μL / min and the flow rate ratio was changed by the oil flow rate, it was found that when the flow rate ratio was greater than 80, the connection between the second opening 24 of the flow channel forming member and the PTFE tube bonded to the second opening 24 broke. Therefore, it was confirmed that by placing the droplet diameter adjusting member 28 near the nozzle portion 27 during droplet formation, even small droplets that would be difficult to form due to the durability of the microfluidic device if the droplet diameter adjusting member were not used could be formed without any problems.

[0054] <Droplet formation when the droplet diameter adjustment member is moved> Figure 25 is an explanatory diagram showing the results of an investigation into the effect of moving the droplet diameter adjustment member 28 during droplet formation. Figure 25(A) shows the results of collecting droplets formed when the droplet diameter adjustment member 28 was fixed at position 2 in Figure 4, as shown in Figure 5(A), and observing them under a microscope. Figure 25(B) shows the results of collecting droplets formed when the droplet diameter adjustment member 28 was repeatedly moved between position 2 and position 3 in Figure 4, as shown in Figure 5(B), and observing them under a microscope. As shown in Figure 25(A), when droplets are formed with the droplet diameter adjustment member 28 fixed, the dispersion of the formed droplets is relatively small. In contrast, as shown in Figure 25(B), when droplets are formed while moving the droplet diameter adjustment member 28, droplets of various sizes are formed, and it was confirmed that the dispersibility of the particle size distribution is improved.

[0055] This disclosure is not limited to the embodiments described above, and can be implemented in various configurations without departing from its spirit. For example, the technical features in the embodiments corresponding to the technical features in each form described in the summary of the invention can be replaced or combined as appropriate in order to solve some or all of the above-mentioned problems, or to achieve some or all of the above-mentioned effects. Furthermore, if a technical feature is not described as essential in this specification, it can be deleted as appropriate.

[0056] This disclosure can also be implemented in the following forms: [Application Example 1] A microfluidic device in which a channel for forming droplets is formed inside, A first channel through which the core fluid for forming the dispersed phase flows, A second channel through which the sheath fluid for forming the continuous phase flows, A nozzle section where the first flow path and the second flow path merge, A third channel through which the droplet formed in the nozzle flows, A structure has been formed, The microfluidic device further includes a droplet diameter adjusting member disposed between at least one of the first, second, and third channels and the nozzle portion, or within the nozzle portion. The droplet diameter adjusting member is formed in a moving channel, which is at least one of the first, second, and third channels, to be large enough to pass through the moving channel, from the opening where the moving channel opens to communicate with the outside of the microfluidic device, to the nozzle portion. Microfluidic devices. [Application Example 2] The microfluidic device described in Application Example 1, The aforementioned droplet diameter adjusting member is made of a magnetic material. Microfluidic devices. [Application Example 3] A droplet forming system for forming droplets, The microfluidic device described in Application Example 1 or 2, A droplet diameter adjusting member drive unit moves the droplet diameter adjusting member from the opening to the nozzle portion within the aforementioned moving channel, Equipped with Droplet formation system. [Application Example 4] The droplet formation system described in Application Example 3, The aforementioned droplet diameter adjusting member is made of a magnetic material. The droplet diameter adjustment member drive unit moves the droplet diameter adjustment member by applying a magnetic field to the droplet diameter adjustment member. Droplet formation system. [Application Example 5] The droplet formation system described in Application Example 4, The aforementioned droplet diameter adjusting member drive unit is Equipped with a magnetic field source that generates a magnetic field, The magnetic field source and the microfluidic device are moved horizontally in two dimensions so that the droplet diameter adjusting member moves within the moving channel from the opening to the nozzle. Droplet formation system. [Application Example 6] The droplet formation system described in Application Example 4, The aforementioned droplet diameter adjusting member drive unit is A plurality of magnetic field sources capable of switching the generation of a magnetic field on and off, comprising a plurality of magnetic field sources positioned so as to act on the moving channel over a range from the opening to the nozzle when the microfluidic device is placed in a predetermined location, By sequentially switching the magnetic field generation on and off in each of the multiple magnetic field sources, the location where the magnetic field acts within the moving channel from the opening to the nozzle is sequentially changed, thereby moving the droplet diameter adjusting member from the opening to the nozzle within the moving channel. Droplet formation system. [Application Example 7] A method for forming droplets, A channel forming member is provided, which has a first channel through which a core fluid for forming a dispersed phase flows, a second channel through which a sheath fluid for forming a continuous phase flows, a nozzle section where the first channel and the second channel merge, and a third channel through which droplets formed in the nozzle section flow. Between at least one of the first, second, and third channels in the channel forming member and the nozzle portion, or within the nozzle portion, the position of the droplet diameter adjusting member for adjusting the size of the droplet is adjusted by moving the droplet diameter adjusting member. The core fluid is supplied to the first channel and the sheath fluid is supplied to the second channel in the channel forming member on which the droplet diameter adjusting member is arranged, thereby forming droplets in the nozzle portion. Droplet formation method. [Application Example 8] A method for forming droplets, A channel forming member is provided, which has a first channel through which a core fluid for forming a dispersed phase flows, a second channel through which a sheath fluid for forming a continuous phase flows, a nozzle section where the first channel and the second channel merge, and a third channel through which droplets formed in the nozzle section flow. The core fluid is supplied to the first channel in the channel forming member, and the sheath fluid is supplied to the second channel, while a droplet diameter adjusting member for adjusting the size of droplets is moved between at least one of the first channel, the second channel, and the third channel in the channel forming member and the nozzle portion, or within the nozzle portion. Droplet formation method. [Application Example 9] A method for manufacturing a microfluidic device having a channel formed inside that forms a droplet, A channel forming member is provided, which has a first channel through which a core fluid for forming a dispersed phase flows, a second channel through which a sheath fluid for forming a continuous phase flows, a nozzle section where the first channel and the second channel merge, and a third channel through which droplets formed in the nozzle section flow. A droplet diameter adjusting member for adjusting the size of a droplet is positioned between at least one of the first, second, and third channels in the channel forming member and the nozzle portion, or within the nozzle portion. A method for manufacturing microfluidic devices. [Explanation of symbols]

[0057] 10... Microfluidic devices 10a, 10b, 10c... Plate-shaped members 20... Flow channel forming member 21,221,321,421,422…First channel 22...First opening 23,223,323,324,363,364,423…Second channel 24…Second opening 25,225,425… Third channel 26,365... Third opening 27,227,327,367,427… Nozzle section 28... Droplet diameter adjustment member 30,230,330,430,431,432…Droplets 40, 140, 540, 640… Droplet formation systems 50, 150, 650… Droplet diameter adjustment member drive unit 52… Magnetic field source 52a...First magnetic field source 52b...Second magnetic field source 53…Magnetic field source array 54...Movement mechanism 70...First mold 71...protrusion 72...Second mold 73…recess 325...Intermediate channel 662…Oscillator 664... Reflective plate 720…Photocurable resin material 728... Droplet diameter adjustment member

Claims

1. A microfluidic device in which a channel for forming droplets is formed inside, A first channel through which the core fluid for forming the dispersed phase flows, A second channel through which the sheath fluid for forming the continuous phase flows, A nozzle section where the first flow path and the second flow path merge, A third channel through which the droplet formed in the nozzle flows, A structure has been formed, The microfluidic device further includes a droplet size adjusting member disposed between at least one of the first channel, the second channel, and the third channel and the nozzle portion, or within the nozzle portion. The droplet diameter adjusting member is formed in a moving channel, which is at least one of the first, second, and third channels, to be large enough to pass through the moving channel, from the opening where the moving channel opens to communicate with the outside of the microfluidic device, to the nozzle portion. Microfluidic devices.

2. A microfluidic device according to claim 1, The aforementioned droplet diameter adjusting member is made of a magnetic material. Microfluidic devices.

3. A droplet forming system for forming droplets, The microfluidic device according to claim 1, A droplet diameter adjusting member drive unit moves the droplet diameter adjusting member from the opening to the nozzle portion within the aforementioned moving channel, Equipped with Droplet formation system.

4. A droplet formation system according to claim 3, The aforementioned droplet diameter adjusting member is made of a magnetic material. The droplet diameter adjustment member drive unit moves the droplet diameter adjustment member by applying a magnetic field to the droplet diameter adjustment member. Droplet formation system.

5. A droplet formation system according to claim 4, The aforementioned droplet diameter adjusting member drive unit is Equipped with a magnetic field source that generates a magnetic field, The magnetic field source and the microfluidic device are moved horizontally in two dimensions so that the droplet diameter adjusting member moves within the moving channel from the opening to the nozzle. Droplet formation system.

6. A droplet formation system according to claim 4, The aforementioned droplet diameter adjusting member drive unit is A plurality of magnetic field sources capable of switching the generation of a magnetic field on and off, comprising a plurality of magnetic field sources positioned so as to act on the moving channel over a range from the opening to the nozzle when the microfluidic device is placed in a predetermined location, By sequentially switching the magnetic field generation on and off in each of the multiple magnetic field sources, the location where the magnetic field acts within the moving channel from the opening to the nozzle is sequentially changed, thereby moving the droplet diameter adjusting member from the opening to the nozzle within the moving channel. Droplet formation system.

7. A method for forming droplets, A channel forming member is prepared, which has a first channel through which a core fluid for forming a dispersed phase flows, a second channel through which a sheath fluid for forming a continuous phase flows, a nozzle section where the first channel and the second channel merge, and a third channel through which droplets formed in the nozzle section flow. Between at least one of the first, second, and third channels in the channel forming member and the nozzle portion, or within the nozzle portion, the position of the droplet diameter adjusting member for adjusting the size of the droplet is adjusted by moving the droplet diameter adjusting member. The core fluid is supplied to the first channel and the sheath fluid is supplied to the second channel in the channel forming member on which the droplet diameter adjusting member is arranged, thereby forming droplets in the nozzle portion. Droplet formation method.

8. A method for forming droplets, A channel forming member is prepared, which has a first channel through which a core fluid for forming a dispersed phase flows, a second channel through which a sheath fluid for forming a continuous phase flows, a nozzle section where the first channel and the second channel merge, and a third channel through which droplets formed in the nozzle section flow. The core fluid is supplied to the first channel in the channel forming member, and the sheath fluid is supplied to the second channel, while a droplet diameter adjusting member for adjusting the size of droplets is moved between at least one of the first channel, the second channel, and the third channel in the channel forming member and the nozzle portion, or within the nozzle portion. Droplet formation method.

9. A method for manufacturing a microfluidic device having a channel formed inside that forms a droplet, A channel forming member is prepared, which has a first channel through which a core fluid for forming a dispersed phase flows, a second channel through which a sheath fluid for forming a continuous phase flows, a nozzle section where the first channel and the second channel merge, and a third channel through which droplets formed in the nozzle section flow. A droplet diameter adjusting member for adjusting the size of a droplet is positioned between at least one of the first, second, and third channels in the channel forming member and the nozzle portion, or within the nozzle portion. A method for manufacturing microfluidic devices.

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