Micro two-phase droplet generation device

Abstract

Provided is a micro two-phase liquid droplet generation device which does not require individual through holes corresponding to a plurality of flow channels for two-phase liquid droplet generation. The micro two-phase liquid droplet generation device according to the present invention comprises a row of a plurality of micro flow channels, a liquid transport port, and a slit, and is configured to form two-dispersed-phase parallel continuous streams at a first connection part between the plurality of micro flow channels through which a first dispersed phase flows and the slit through which a second dispersed phase flows. Furthermore, the micro two-phase liquid droplet generation device can be configured such that a continuous-phase liquid is sent to a second connection part between the plurality of micro flow channels through which the two-dispersed-phase parallel continuous streams flow and another liquid transport port that is preferably a second slit located downstream of the slit, the two-dispersed-phase parallel continuous streams are sheared at the second connection part to generate two-phase liquid droplets, in particular core-shell or Janus two-phase liquid droplets, and the product is collected from a discharge port.

Description

[Technical Field]

[0001] The present invention relates to a device for generating micro-two-phase droplets. [Background technology]

[0002] The inventors have developed an emulsion generation method that utilizes the intersection shape of microchannels as a method for generating microdroplets (emulsions) with excellent size uniformity (monodispersibility). This technology makes it possible to generate emulsions of uniform size, and the droplet diameter and generation rate of the emulsion can be flexibly controlled by manipulating the flow rate in the channels. The inventors have also developed an apparatus (Patent Document 1) consisting of a microchannel substrate with a large number of intersecting microchannels for droplet generation arranged in a row, and a holder for holding the microchannel substrate with a hierarchical structure for controlling the distribution of liquid to each microchannel, and further, a droplet generation apparatus (Patent Document 2) that three-dimensionally combines a row of multiple microchannels and slits arranged perpendicular to the row.

[0003] On the other hand, microdroplet generation technology has also been applied to the generation of emulsions in which microdroplets are composed of multiple dispersed phases. Specifically, for example, it is known that core-shell type or Janus type two-phase droplets can be generated by first forming a parallel continuous flow of two dispersed phases using a Y-shaped microchannel, and then shearing the parallel continuous flow of two dispersed phases with a continuous flow perpendicular to the parallel continuous flow of two dispersed phases in the same plane as the Y-shaped microchannel (Non-Patent Literature 1).

[0004] However, such two-phase droplet manufacturing equipment has a problem in that a single microchannel intersection structure has an upper limit on the flow rate at which droplets can be generated, resulting in a small processing capacity. On the other hand, when multiple microchannel structures for forming parallel continuous flows of two dispersed phases and generating two-phase droplets are arranged on a microchannel substrate with the aim of improving the processing capacity, it is necessary to provide multiple individual through-holes in the substrate that connect each channel inside the substrate to the outside of the substrate, serving as multiple inlets (liquid supply ports) for supplying the two dispersed and continuous phases from the outside of the substrate to each channel inside the microchannel substrate. Furthermore, it is necessary to use a microchannel substrate holder that has liquid supply paths corresponding to these multiple liquid supply ports on the substrate. Therefore, with conventional two-dimensionally arranged microchannels that utilize Y-shaped microchannels, a complex structure is required to generate a large quantity of two-phase droplets, and it is difficult to generate large quantities with a simple device. [Prior art documents] [Patent Documents]

[0005] [Patent Document 1] WO2007 / 026564 [Patent Document 2] WO2019 / 168130 [Non-patent literature]

[0006] [Non-Patent Document 1] Microfluidics and Nanofluidics (2010)9;427-437 [Overview of the project] [Problems that the invention aims to solve]

[0007] The present invention aims to solve the above problems and, unlike conventional two-phase droplet generation devices in which a Y-shaped channel for forming parallel continuous flow of two dispersed phases is arranged in a two-dimensional plane, to provide a micro two-phase droplet generation device that can be more easily implemented and managed than conventional devices by combining a slit and a microchannel array in a simple three-dimensional configuration, and in which the parallel continuous flow forming section of two dispersed phases is arranged at a high density. [Means for solving the problem]

[0008] This invention confirms that micro-two-phase droplets can be generated by a simple configuration that combines slits and a microfluidic array in three dimensions, and provides a device for generating micro-two-phase droplets that is easier to implement and manage than conventional devices, and in which two dispersed phase parallel continuous flow forming sections are densely arranged.

[0009] Preferred embodiments of the present invention are as follows. (Aspect 1) A row of multiple microchannels (16), The microchannel (16) has the following liquid transport ports arranged in the longitudinal direction: a first liquid transport port (11), a first slit (12), a second liquid transport port (13), and a third liquid transport port (14), A micro two-phase droplet generation device (100) comprising, Here, a "slit" is defined as having a linear end face with a width and an axis larger than the dimension of the width on a reference plane where the row of microchannels (16) exists, the row of microchannels (16) is located on the reference plane, the row of microchannels (16) is connected to the reference plane and the slit (12) which terminates on the reference plane, and the slit (12) extends transversely from the reference plane downwards from the reference plane, with the reference plane as its termination. The first slit (12) constitutes a part of the second dispersed phase supply port (12-1), and the second liquid transport port (13) constitutes a part of the continuous phase supply port or discharge port, and the first slit (12) and the second liquid transport port (13) terminate at the connection points with the plurality of microchannels (16). The plurality of microchannels (16) are arranged on the surface where the first slit (12) and the ends of the second liquid transport port (13) are present, connecting the end of the first liquid transport port (11) and the end of the first slit (12), connecting the end of the first slit (12) and the end of the second liquid transport port (13), and connecting the end of the second liquid transport port (13) and the end of the third liquid transport port (14). Here, the second liquid transport port (13) is either the end of the continuous phase supply port or the end of the discharge port. When the second liquid transport port (13) is the end of the continuous phase supply port, the third liquid transport port (14) is the discharge port. When the second liquid transport port (13) is the end of the discharge port, the third liquid transport port (14) is the continuous phase supply port. The first dispersed phase (1) is supplied from the first liquid transport port (11) to the plurality of microchannels (16), and the second dispersed phase (2) is supplied from the first slit (12) to the plurality of microchannels (16). Here, the first dispersed phase (1) and the second dispersed phase (2) are liquids that do not completely mix with each other. In the microchannel (16) connecting the end of the first slit (12) and the end of the second liquid transport port (13), the first dispersed phase (1) and the second dispersed phase (2) form a two-phase parallel continuous flow (4) which is a continuous flow containing the two phases of the first dispersed phase (1) and the second dispersed phase (2) in parallel. The continuous phase (3) is supplied from either the second liquid transport port (13) or the third liquid transport port (14) to the plurality of microchannels (16). At the connection point between the second liquid transport port (13) and the plurality of microchannels (16), two-phase droplets (5) formed by the first dispersed phase (1) and the second dispersed phase (2) are generated. The product (6) containing the two-phase droplets (5) is recovered from the other of the second liquid transport port (13) or the third liquid transport port (14). A micro two-phase droplet generation device configured as described above. (Aspect 2) The second liquid transport port (13) is a second slit, and the second slit (13) also satisfies the definition of the slit. At the connection location between the second liquid transport port (13) and the plurality of microchannels (16), the two-phase parallel continuous flow (4) is sheared using the flow of the continuous phase (3) as a driving force to generate the two-phase droplets (5). The micro two-phase droplet generation device according to Embodiment 1. (Embodiment 3) The micro two-phase droplet generation device according to Embodiment 1 or 2, wherein the two-phase droplets (5) are core-shell type two-phase droplets. (Embodiment 4) The micro two-phase droplet generation device according to Embodiment 1 or 2, wherein the two-phase droplets (5) are Janus type two-phase droplets. (Embodiment 5) The micro two-phase droplet generation device according to any one of Embodiments 1 to 4, wherein the terminal of the first liquid transport port (11), the terminal of the second liquid transport port (13), and / or the terminal of the third liquid transport port (14) are slit-shaped. (Embodiment 6) The micro two-phase droplet generation device according to any one of Embodiments 1 to 5, wherein the slit (11, 12, 13, 14) including the first slit (12) is a flat slit. (Embodiment 7) The micro two-phase droplet generation device according to any one of Embodiments 1 to 5, wherein the slit (11, 12, 13, 14) including the first slit (12) is an annular slit. (Embodiment 8) The micro two-phase droplet generation device according to Embodiment 6 or 7, which is configured by aligning a component (30, 41, 43) provided with the slit (12) and a flat component (20, 22, 24) having a plurality of rows of fine grooves (16, 16-2, 16-4) processed on its surface, and bonding the surface at the terminal of the plurality of slits (12, 13) and the surface on the side where the fine grooves (16, 16-2, 16-4) of the flat component (20, 22, 24) are processed. (Embodiment 9) A micro-two-phase droplet generating device according to embodiment 6 or 7, wherein a row of multiple micro-grooves (16) is machined onto the surface of a component (33, 42, 44) having the slit (12), and the row of multiple micro-channels is formed by sealing the micro-grooves (16-1, 16-3, 16-5) with another flat component (21, 23, 25). (Aspect 10) A micro two-phase droplet generating device according to any one of embodiments 1 to 9, wherein the inner wall of the microchannel (16) is composed of a hydrophilic surface, the first dispersed phase (1) is an organic phase, the second dispersed phase (2) is an organic phase, and the continuous phase is an aqueous phase, and core-shell type or Janus type microdroplets are generated. (Aspect 11) A micro two-phase droplet generating device according to any one of embodiments 1 to 9, wherein the inner wall of the second liquid transport port (13) is made of a hydrophilic surface, the first dispersed phase (1) is an organic phase, the second dispersed phase (2) is an organic phase, and the continuous phase is an aqueous phase, and core-shell type or Janus type microdroplets are generated. (Aspect 12) A micro two-phase droplet generating device according to any one of embodiments 1 to 9, wherein the inner wall of the microchannel (16) connecting the end of the first slit (12) and the end of the second liquid transport port (13) is made of a hydrophobic surface, and the inner wall of the microchannel (16) connecting the end of the second liquid transport port (13) and the end of the third liquid transport port (14) is made of a hydrophilic surface, and one of the first dispersed phase (1) and the second dispersed phase (2) is an aqueous phase and the other is an organic phase, and the continuous phase (3) is an aqueous phase, and the continuous phase (3) is supplied from the second liquid transport port (13) to the microchannel (16), generating a core-shell type microdroplet with the aqueous phase as the core and the organic phase as the shell. (Aspect 13) The inner wall of the microchannel (16) connecting the end of the first slit (12) and the end of the second liquid transport port (13) is composed of a hydrophobic surface, the inner wall of the second liquid transport port (13) is composed of a hydrophilic surface, either one of the first dispersed phase (1) and the second dispersed phase (2) is an aqueous phase, the other is an organic phase, the continuous phase (3) is an aqueous phase, the continuous phase (3) is supplied from the third liquid transport port (14) to the microchannel (16), and a core-shell type microdroplet having an aqueous phase as a core and an organic phase as a shell is generated. The micro two-phase droplet generation device according to any one of Aspects 1 to 9. (Aspect 14) The first dispersed phase is defined as phase 1, the continuous phase is defined as phase 2, the second dispersed phase is defined as phase 3, and the interfacial tension between phase 1 and phase 2 is γ i ; the interfacial tension between phase 1 and phase 3 is γ 13 ; the interfacial tension between phase 2 and phase 3 is γ 23 ; when expressed as such, γ 12 >γ 23 ; and S i =γ jk -(γ ij +γ ki ) [where i≠j≠k are 1, 2, 3], the spreading parameter S i is such that S1 < 0, S2 < 0, S3 > 0, and a core-shell type microdroplet is generated. The micro two-phase droplet generation device according to any one of Aspects 1 to 3, 5 to 13. (Aspect 15) The first dispersed phase is defined as phase 1, the continuous phase is defined as phase 2, the second dispersed phase is defined as phase 3, and the interfacial tension between phase 1 and phase 2 is γ 12 ; the interfacial tension between phase 1 and phase 3 is γ 13 ; the interfacial tension between phase 2 and phase 3 is γ 23 ; when expressed as such, γ 12 >γ 23 ; and S i =γ jk -(γ ij +γ ki ) [where i≠j≠k are 1, 2, 3], the spreading parameter S iA micro two-phase droplet generating device according to any one of embodiments 1, 2, 4 to 11, wherein S1 < 0, S2 < 0, and S3 < 0, and Janus-type microdroplets are generated. [Effects of the Invention]

[0010] The present invention provides a micro-two-phase droplet generation device that does not require individual through-holes corresponding to each channel for forming parallel continuous didispersed phases. Furthermore, unlike conventional devices in which Y-shaped channels for forming parallel continuous didispersed phases are arranged in a two-dimensional plane, the present invention provides a micro-two-phase droplet generation device that is easier to implement and manage than conventional devices, and in which the parallel continuous didispersed phases forming sections are arranged at a high density, through a simple configuration that combines slits and a microchannel array in three dimensions. [Brief explanation of the drawing]

[0011] [Figure 1] This is a schematic perspective view showing a micro two-phase droplet generation device according to Embodiment 1. [Figure 2] In the micro two-phase droplet generation device of Embodiment 1, (a) is an exploded perspective view of the micro-groove array substrate and the liquid distribution component, and (b) is a plan view and a cross-sectional view of the micro-groove array substrate and the liquid distribution component. [Figure 3] (a) is a schematic cross-section of the micro two-phase droplet generation device of Embodiment 1, showing how a two-phase parallel continuous flow is formed by the microchannel and slit, and how two-phase droplets are generated. (b) is a schematic cross-section of the micro two-phase droplet generation device of Embodiment 2, showing how a two-phase parallel continuous flow is formed by the microchannel and slit, and how two-phase droplets are generated. [Figure 4] This figure shows an example of the groove shape of a component having fine grooves that is joined to a liquid distribution device in the present invention. [Figure 5] In the micro two-phase droplet generation device of Embodiment 3, (a) is an exploded perspective view of the micro-groove sealing lid and the liquid distribution component with micro-grooves, and (b) is a plan view and a cross-sectional view of the micro-groove sealing lid and the liquid distribution component. [Figure 6](a) is a schematic cross-section of the micro-two-phase droplet generation device of Embodiment 3, showing how a two-phase parallel continuous flow is formed by the microchannel and slit, and how two-phase droplets are generated. (b) is a schematic cross-section of the micro-two-phase droplet generation device of Embodiment 4, showing how a two-phase parallel continuous flow is formed by the microchannel and slit, and how two-phase droplets are generated. [Figure 7] This figure shows an example of the shape of slits and micro-grooves on a liquid distribution device in the present invention. [Figure 8] In the micro two-phase droplet generation device of Embodiment 5, (a) is a partial cross-sectional perspective view of the annular liquid distribution device after the four components have been assembled, and (b) is a top view when the component having a fine groove is joined to the liquid distribution device. [Figure 9] (a) is a schematic cross-section of the micro-two-phase droplet generation device of Embodiment 5, showing how a two-phase parallel continuous flow is formed by the microchannel and slit, and how two-phase droplets are generated. (b) is a schematic cross-section of the micro-two-phase droplet generation device of Embodiment 6, showing how a two-phase parallel continuous flow is formed by the microchannel and slit, and how two-phase droplets are generated. [Figure 10] In the micro two-phase droplet generation device of Embodiment 7, (a) is a cross-sectional view of the annular liquid distribution device after the four components have been assembled, and (b) is a top view of the liquid distribution device with a lid attached to the liquid distribution device which has been processed with fine grooves. [Figure 11] (a) is a schematic cross-section of the micro-two-phase droplet generation device of Embodiment 7, showing how a two-phase parallel continuous flow is formed by the microchannel and slit, and how two-phase droplets are generated. (b) is a schematic cross-section of the micro-two-phase droplet generation device of Embodiment 8, showing how a two-phase parallel continuous flow is formed by the microchannel and slit, and how two-phase droplets are generated. [Figure 12] The diagram shows a perspective view including a cross-section of the annular liquid distribution device after the five components have been assembled in the micro two-phase droplet generation device of Embodiment 9 (joining the component with fine grooves to the liquid distribution device). [Figure 13]The image shows a perspective view of the micro two-phase droplet generation device of Embodiment 10, including a cross-section of the annular liquid distributor after the five components have been assembled (a lid is attached to the liquid distributor, which has been processed with fine grooves). [Figure 14] The image shows the formation of core-shell type two-phase droplets in Example 1 (didispersed phase flow rate (Qm) = (Qs) = 6 mL / h, continuous phase flow rate (Qc) = 30 mL / h). [Figure 15] The image shows a photograph of the core-shell type two-phase droplets produced in Example 1, taken outside the apparatus, along with their size distribution. [Figure 16-1] The image shows the formation of Janus-type two-phase droplets in Example 2 (didispersed phase flow rate (Qm) = (Qs) = 6 mL / h, continuous phase flow rate (Qc) = 30 mL / h). [Figure 16-2] The image shows a photograph of the Janus-type two-phase droplet produced in Example 2, taken outside the apparatus. [Figure 17] (a) shows a photograph of the Janus-type two-phase droplets produced in Example 3, taken outside the apparatus, and (b) shows the size distribution (didispersed phase flow rate (Qm) = 8 mL / h, (Qs) = 4 mL / h, continuous phase flow rate (Qc) = 30 mL / h). [Modes for carrying out the invention]

[0012] The present invention A row of multiple microchannels (16), The microchannel (16) has the following arrangement in the longitudinal direction: a first liquid transport port (11), a first slit (12), a second liquid transport port (13), and a third liquid transport port (14), A micro two-phase droplet generation device (100) comprising, Here, a "slit" is defined as having a linear end face with a width and an axis larger than the dimension of the width on a reference plane where the row of microchannels (16) exists, the row of microchannels (16) is located on the reference plane, the row of microchannels (16) is connected to the reference plane and the slit (12) which terminates on the reference plane, and the slit (12) extends transversely from the reference plane downwards from the reference plane, with the reference plane as its termination. The first slit (12) constitutes a part of the second dispersed phase supply port (12-1), the second liquid transport port (13) constitutes a part of the continuous phase supply port or discharge port, and the first slit (12) and the second liquid transport port (13) terminate at the connection points with the plurality of microchannels (16). The plurality of microchannels (16) are arranged such that, on the surface where the ends of the first slit (12) and the second liquid transport port (13) are located, the end of the first liquid transport port (11) connects the end of the first slit (12), the end of the first slit (12) connects the end of the second liquid transport port (13), and the end of the second liquid transport port (13) connects the end of the third liquid transport port (14), where the second liquid transport port (13) is either the end of a continuous phase supply port or the end of an outlet, and when the second liquid transport port (13) is the end of a continuous phase supply port, the third liquid transport port (14) is an outlet, and when the second liquid transport port (13) is the end of an outlet, the third liquid transport port (14) is a continuous phase supply port. A first dispersed phase (1) is supplied from the first liquid transport port (11) to the plurality of microchannels (16), and a second dispersed phase (2) is supplied from the first slit (12) to the plurality of microchannels (16), wherein the first dispersed phase (1) and the second dispersed phase (2) are liquids that do not completely mix with each other. In the microchannel (16) connecting the end of the first slit (12) and the end of the second liquid transport port (13), the first dispersed phase (1) and the second dispersed phase (2) form a two-phase parallel continuous flow (4) which is a continuous flow containing the two phases of the first dispersed phase (1) and the second dispersed phase (2) in parallel. The continuous phase (3) is supplied to the plurality of microchannels (16) from either the second liquid transport port (13) or the third liquid transport port (14). At the connection point between the second liquid transport port (13) and the plurality of microchannels (16), two-phase droplets (5) are generated from the first dispersed phase (1) and the second dispersed phase (2). The product (6) containing the two-phase droplet (5) is recovered from the other of the second liquid transport port (13) or the third liquid transport port (14). We provide a micro two-phase droplet generation device configured as described above.

[0013] The micro-two-phase droplet generation device of the present invention comprises a row of multiple microchannels and at least one slit. In addition, the present invention provides three liquid transport ports in addition to the one slit, and the ends of these three liquid transport ports can all be slits.

[0014] (Microfluidic channels) In the present invention, the size of the microchannel can be determined according to the purpose, but the width and height are usually selected from about 0.1 to 1000 μm, preferably about 1 to 500 μm, and more preferably about 10 to 100 μm. The cross-sectional shape of the microchannel is not particularly limited, but is preferably selected from rectangle, trapezoid, triangle, semicircle, circle, ellipse, and semi-ellipse according to the material to be processed and the processing method.

[0015] In the present invention, the length of the microchannel can be determined according to the purpose, but is usually selected from about 0.1 to 100 mm, preferably about 1 to 50 mm, and more preferably about 2 to 20 mm.

[0016] In the present invention, the arrangement of the rows of microchannels is not limited, but may be, for example, parallel (the spacing between channels does not need to be constant, and they are parallel without intersecting each other), parallel (the spacing between channels is constant), radial, etc.

[0017] In the present invention, the spacing between microchannels in a row of multiple microchannels can be determined according to the purpose, but at the narrowest point, it is usually selected from about 0.1 to 1000 μm, preferably about 1 to 500 μm, and more preferably about 10 to 200 μm.

[0018] In the present invention, the number of microchannels can be determined according to the purpose, but is usually selected from about 2 to 100,000, preferably about 10 to 50,000, and more preferably about 100 to 10,000.

[0019] (Slit, liquid transport port) In the present invention, the slit has a linear slit end face having a width and an axis (slit length) larger than the width on a reference surface (particularly a reference plane; a virtual surface, but may be an actual surface), the reference surface is a surface on which a plurality of rows of microchannels exist, and the slit extends transversely from the reference surface downwards, with the reference surface as its end point. The shape of the slit end face is not particularly limited and may be, for example, linear or annular. The transverse dimension of the slit can also be called the depth (height) of the slit. The transverse dimension of the slit is significantly larger than the dimension of the microchannel in the same direction, for example, it may be 3 times or more, 6 times or more, or 10 times or more than the above dimension of the microchannel.

[0020] The rows of microchannels lie on the reference plane, and the rows of microchannels are connected to the reference plane by slits that terminate at the reference plane. In other words, the rows of microchannels have connection points with the slits on the reference plane.

[0021] The micro two-phase droplet generation device of the present invention has a first dispersed phase supply port, a second dispersed phase supply port, a continuous phase supply port, and an outlet. The first dispersed phase supply port is a transport path that supplies the first dispersed phase to a plurality of microchannels. The second dispersed phase supply port is a transport path that supplies the second dispersed phase to a plurality of microchannels and has connection points with the plurality of microchannels. The continuous phase supply port is a transport path that supplies the continuous phase to a plurality of microchannels and has connection points with the plurality of microchannels. The outlet is a transport path that discharges droplet products generated from the plurality of microchannels and has connection points with the plurality of microchannels.

[0022] The first dispersed phase supply port, the second dispersed phase supply port, and the continuous phase supply port are connected to the first dispersed phase source, the second dispersed phase source, and the continuous phase source, respectively, for supplying the first dispersed phase, the second dispersed phase, and the continuous phase, such as tanks. The discharge port is connected to means for collecting and containing the generated two-phase droplet product.

[0023] In the present invention, the slit includes at least one slit (a first slit), the first slit being a slit for supplying the second dispersed phase. However, in the present invention, the slit may include, in addition to the first slit, slits as the end of a first liquid transport port (a liquid transport port for supplying the first dispersed phase), a second liquid transport port (a liquid transport port for supplying or discharging the continuous phase), and / or a third liquid transport port (a liquid transport port for discharging or supplying the continuous phase). In one particularly preferred embodiment, the slit includes at least a first slit for supplying the second dispersed phase and a second slit for supplying or discharging the continuous phase. In the case where there is a first dispersed phase supply slit (first liquid transport port), a second dispersed phase supply slit (first slit), a continuous phase supply or discharge slit (second liquid transport port, second slit), and a discharge or continuous phase supply slit (third liquid transport port), these slits each constitute a part of the first dispersed phase supply port (first liquid transport port), the second dispersed phase supply port, the continuous phase supply port or discharge port, and the discharge port or continuous phase supply port (third liquid transport port), and terminate at connection points with multiple microchannels.

[0024] In the micro-two-phase droplet generation device of the present invention, on a surface (particularly a plane) formed by a row of microchannels, the ends of the first liquid transport port (first dispersed phase supply port), the first slit (second dispersed phase supply slit), the second liquid transport port (continuous phase supply port or outlet, preferably the second slit), and the third liquid transport port (outlet or continuous phase supply port) are arranged in this order along the longitudinal direction of the microchannels. If the second liquid transport port (second slit) constitutes part of the continuous phase supply port, the end of the second liquid transport port (second slit) is followed by the end of the outlet, and if the second liquid transport port (second slit) constitutes part of the outlet, the end of the second liquid transport port (second slit) is followed by the end of the continuous phase supply port. Here, as described above, the first dispersed phase supply port, and / or the second liquid transport port and / or the third liquid transport port, which is the outlet and / or continuous phase supply port, may have a slit at its end.

[0025] Multiple microchannels are arranged to connect the end of a slit to an adjacent liquid transport port or slit (liquid supply port or discharge port) on a plane that crosses the slit (reference plane; particularly a plane perpendicular to the slit) where the end of the slit is located.

[0026] (Formation of a two-phase parallel continuous flow) In the present invention, in a micro two-phase droplet generation device having the above configuration, the first dispersed phase is supplied to a plurality of microchannels from a first liquid transport port (first dispersed phase supply port), the second dispersed phase is supplied to a plurality of microchannels from a first slit (second dispersed phase supply slit), the first dispersed phase and the second dispersed phase meet at the connection point between the first slit (second dispersed phase supply slit) and the microchannel, and a two-phase parallel continuous flow is formed in the microchannel connecting the end of the first slit and the end of the second liquid transport port (preferably the second slit), which is a continuous flow containing the two phases of the first dispersed phase and the second dispersed phase in parallel. In a microchannel connecting the end of the first slit and the end of the second liquid transport port (preferably the second slit), the formation of a two-phase parallel continuous flow between the first and second dispersed phases is basically made possible by the fact that the first and second dispersed phases do not completely mix with each other, and that when the first and second dispersed phases merge, neither of them forms a droplet in the other. However, it is preferable to adjust the flow velocity of the first and second dispersed phases, the wettability of the first and second dispersed phases with respect to the microchannel wall, etc.

[0027] Two-phase parallel flow refers to a flow where two phases are separated in the cross-section of the flow. For example, they may be separated vertically or horizontally (the orientation of the two phases is free, the sizes of the two phases may be different, and the boundary between the two phases may be curved rather than straight), or they may be separated concentrically, like inner and outer circles (even though they are separated concentrically, the outer phase may follow the cross-sectional shape of the microchannel, and the inner phase does not have to be a perfect circle). When the two phases are separated, parallel flow is also possible, where one phase is in the center and the other phase is parallel on both sides. Here, separation of two phases is not limited to the case where the first dispersed phase and the second dispersed phase do not mix at all. Parts of the first dispersed phase and the second dispersed phase may mix, or at least one may dissolve or diffuse into the other, but it means that two-phase flow can be observed macroscopically.

[0028] Furthermore, a two-phase parallel continuous flow refers to a situation where a two-phase parallel flow forms a continuous flow in the microchannel connecting the end of the first slit (second dispersed phase supply slit) and the end of the second liquid transport port. The two-phase parallel flow is formed near the connection point between the microchannel through which the first dispersed phase flows and the first slit (second dispersed phase supply slit), and flows within the microchannel. However, a two-phase parallel continuous flow specifically means that the two-phase parallel flow extends all the way to the connection point between the microchannel and the second liquid transport port. In this invention, the two-phase parallel continuous flow is a dispersed phase two-phase parallel continuous flow (two dispersed phases parallel continuous flow).

[0029] (Formation of two-phase droplets) In the present invention, a continuous phase is supplied to a plurality of microchannels from a continuous phase supply port, which is either a second liquid transport port or a third liquid transport port. Here, the second liquid transport port is either the end of the continuous phase supply port or the end of the discharge port. When the second liquid transport port is the end of the continuous phase supply port, the third liquid transport port is the discharge port, and when the second liquid transport port is the end of the discharge port, the third liquid transport port is the continuous phase supply port.

[0030] At this point, at the connection point between the microchannel and the second liquid transport port (let's call it connection point X), there is a first slit on one side of the microchannel and a third liquid transport port on the other side. At connection point X, the above-mentioned two-phase parallel continuous flow is supplied from the microchannel on the side of the first slit (let's call it microchannel A), and the continuous phase is supplied from the second liquid transport port or from the microchannel on the side of the third liquid transport port (let's call it microchannel B), so that the two-phase parallel continuous flow and the continuous phase meet. At connection point X, especially when the third liquid transport port is the second slit, the flow of the continuous phase acts as a driving force to shear the two-phase parallel continuous flow of the dispersed phase, and two-phase droplets such as core-shell type or Janus type droplets of the first and second dispersed phases are generated at the second liquid transport port or microchannel B. Whether the resulting two-phase droplet is core-shell, Janus-type, or something else, and in the case of a core-shell type, whether the first or second dispersed phase becomes the core and shell, is basically determined by the relationship of the interfacial tension between the first dispersed phase, the second dispersed phase, and the continuous phase.

[0031] Products containing two-phase droplets, such as core-shell or Janus droplets, are discharged and recovered from the outlet. When the second liquid transport port is the end of the continuous phase supply port, the outlet is connected to microchannel B, and when microchannel B is connected to the end of the continuous phase supply port, the second liquid transport port is the end of the outlet.

[0032] As described above, the second liquid transport port constitutes part of the continuous phase supply port or discharge port, but at the same time, at connection point X with the microchannels A and B on both sides, it also serves the function of generating two-phase droplets of the dispersed phase, such as core-shell type or Janus type, from the two-phase parallel continuous flow of the dispersed phase and the continuous phase.

[0033] In the micro two-phase droplet generation device of the present invention, the liquid transport ports other than the first slit (first dispersed phase supply port, continuous phase supply port, and discharge port) may have slits at the ends that connect to the microchannels. Therefore, in the micro two-phase droplet generation device of the present invention, there is at least one slit, but the number of slits may be two or more. For example, the ends of the first dispersed phase supply port, which is the first liquid transport port, the ends of the continuous phase supply port or discharge port, which is the second liquid transport port, and the ends of the continuous phase supply port or discharge port, which is the third liquid transport port, can be slits. However, the ends of the first, second, and third liquid transport ports do not have to be slits and may be cylindrical holes or the like. Each of the ends of the first, second, and third liquid transport ports only needs to be able to supply or discharge liquid to each of the multiple microchannels, and the number of such ends is not limited, but having one each is structurally simpler and preferable.

[0034] The first and second dispersed phases can be any combination that allows them to form a two-phase parallel continuous flow without completely mixing with each other, and may partially mix, dissolve, or diffuse with each other. Furthermore, the first and second dispersed phases meet the continuous phase after forming a two-phase parallel continuous flow, generating two-phase droplets. Therefore, a combination with a continuous phase capable of subsequently generating two-phase droplets is selected.

[0035] (Dispersed phase / Continuous phase) In the present invention, the liquid forming the dispersed phase and the continuous phase is preferably an organic compound or water. The organic compound is not particularly limited, but preferred examples include fluorinated oils, silicone oils, alkanes such as decane and octane, halogenated hydrocarbons such as liquid paraffin and chloroform, aromatic hydrocarbons such as toluene, and fatty acids such as oleic acid. Furthermore, in order to obtain solid or gel-like fine particles, it is also possible to use an aqueous or organic phase as the dispersed phase that can be cured by heat, photopolymerization, or crosslinking by ion exchange. Examples of usable materials include known polymerizable monomers, oligomers, or polymers, and preferred examples include acrylate monomers and styrene monomers.

[0036] The dispersed phase can be either an organic phase or an aqueous phase, and the combinations of the two dispersed phases can be organic phase / aqueous phase, aqueous phase / organic phase, or organic phase / organic phase. Furthermore, the continuous phase may be either an organic phase or an aqueous phase.

[0037] Preferably, when the continuous phase is an organic phase, the two-phase dispersed phase can be aqueous / organic, organic / organic, or organic / aqueous. When the continuous phase is an aqueous phase, the two-phase dispersed phase can be aqueous / organic or organic / organic. Preferred combinations of two-phase dispersed phase and continuous phase are (organic / organic) / aqueous and (aqueous / organic) / aqueous. Specific examples include combinations such as (acrylate monomer / silicone oil) / water and (water / alkanes) / water.

[0038] In order to generate micro-two-phase droplets, such as core-shell type or Janus type, in a continuous phase, it is preferable that the interfacial tension between the continuous phase and the two-phase dispersed phase is in a predetermined relationship.

[0039] While not limited to theory, if we define the first dispersed phase as phase 1, the continuous phase as phase 2, and the second dispersed phase as phase 3, and the interfacial tension between phase 1 and phase 2 as γ 12 The interfacial tension between phase 1 and phase 3 is γ 13 , the interfacial tension between phase 2 and phase 3 is γ23 Displayed as follows, γ 12 >γ 23 When S i =γ jk -(γ ij +γ ki Between the spreading parameter S defined by the equation (where i≠j≠k are 1,2,3), it is considered that (i) core-shell type (complete encapsulation) droplets are formed when S1<0, S2<0, S3>0, (ii) Janus type (partial encapsulation) droplets are formed when S1<0, S2<0, S3<0, and (iii) non-encapsulation (phase 1 and phase 3 form separate droplets) when S1<0, S2>0, S3<0. However, the interfacial tension (measured value) of the dispersed phase and continuous phase used depends on the apparatus and process conditions and is not necessarily maintained throughout the droplet generation process, and the interfacial tension (measured value) does not necessarily establish the droplet type according to the above relationship. Furthermore, the interfacial tension between the continuous phase and the channel wall of the microchannel or slit also has an effect.

[0040] Therefore, for example, when the continuous phase is an aqueous phase, it is preferable to hydrophilically treat the walls of the channel through which the continuous phase flows, especially the walls of the channel through which two-phase droplets are generated and flow. When the continuous phase is an organic phase, it is preferable to hydrophobicly treat the walls of the channel through which the continuous phase flows, especially the walls of the channel through which two-phase droplets are generated and flow. If the channel walls are made of organic resin, they are generally hydrophobic, and if they are made of metal or glass, they are generally hydrophilic. For hydrophilic treatment, for example, coating treatment with a hydrophilic polymer or plasma irradiation treatment can be used. For hydrophobic treatment, coating treatment with a hydrophobic polymer can be used.

[0041] In one preferred embodiment, to generate core-shell type microdroplets with an aqueous phase as the core and an organic phase as the shell, the inner wall of the microchannel (16) connecting the end of the first slit (12) and the end of the second liquid transport port (13) is made of a hydrophobic surface, and the inner wall of the microchannel (16) connecting the end of the second liquid transport port (13) and the end of the third liquid transport port (14) is made of a hydrophilic surface, the first dispersed phase (1) is the aqueous phase, the second dispersed phase (2) is the organic phase, and the continuous phase (3) is the aqueous phase, with the continuous phase (3) being supplied from the second liquid transport port (13) to the microchannel (16).

[0042] Similarly, in one preferred embodiment, the inner wall of the microchannel (16) connecting the end of the first slit (12) and the end of the second liquid transport port (13) may be made of a hydrophobic surface, and the inner wall of the second liquid transport port (13) may be made of a hydrophilic surface, with the first dispersed phase (1) being an aqueous phase, the second dispersed phase (2) being an organic phase, and the continuous phase (3) being an aqueous phase, and the continuous phase (3) being supplied from the third liquid transport port (14) to the microchannel (16) to generate core-shell type microdroplets with the aqueous phase as the core and the organic phase as the shell.

[0043] In another preferred embodiment, to generate microdroplets such as Janus type or core-shell type consisting of two phase-separated organic phases, the inner wall of the microchannel (16) may be made of a hydrophilic surface, the first dispersed phase (1) may be an organic phase, the second dispersed phase (2) may be an organic phase, and the continuous phase (3) may be an aqueous phase, with the continuous phase (3) being supplied to the microchannel (16) from the second liquid transport port (13).

[0044] Similarly, in one preferred embodiment, the inner wall of the second liquid transport port (13) may be made of a hydrophilic surface, and the first dispersed phase (1) may be an organic phase, the second dispersed phase (2) an organic phase, and the continuous phase (3) an aqueous phase. The continuous phase (3) may be supplied from the third liquid transport port (14) to the microchannel (16) to generate microdroplets such as Janus type or core-shell type, which consist of two organic phases that are phase-separated from each other.

[0045] Furthermore, surfactants can be added to each liquid to adjust the interfacial tension between dispersed phase 1, dispersed phase 2, and the continuous phase.

[0046] The flow rates of the first dispersed phase, second dispersed phase, and continuous phase per single microchannel are typically selected from approximately 0.001 mL to 100 mL / hour, preferably 0.01 mL to 10 mL / hour, and more preferably 0.1 mL to 5 mL / hour, depending on the type of microchannel. The flow rates of the first and second dispersed phases govern the ratio of the two-phase dispersed phases in the resulting two-phase droplets (core-shell type, Janus type, etc.), and can be selected from, for example, between 1:1000 and 1000:1, between 1:100 and 100:1, or even between 10:100 and 100:10.

[0047] The ratio of the total flow rate of the first and second dispersed phases (flow rate of the two-phase parallel continuous flow) to the flow rate of the continuous phase can be selected from, for example, between 1:100 and 100:1, between 2:100 and 100:2, or even between 5:100 and 100:5. However, for the purpose of shearing the two-phase parallel continuous flow with the flow of the continuous phase and generating two-phase droplets with excellent size uniformity, the Reynolds number should be sufficiently small (<10) so that the two-phase parallel continuous flow and the continuous phase flow each form a laminar flow. 3 It is preferable to set the flow rate so that ) occurs. Furthermore, although it largely depends on the physical properties of the liquid used, if the dispersed phase flow rate is too high compared to the continuous phase flow rate, or conversely, if the continuous phase flow rate is too high compared to the dispersed phase flow rate, two-phase droplets may not be sheared near the confluence point of the two phases, and phenomena such as the two-phase parallel continuous flow continuing further downstream or droplets being generated irregularly may occur. Therefore, it is preferable to adjust the flow rate appropriately so that two-phase droplets are generated near the second liquid transport port.

[0048] (Example of an embodiment) Hereinafter, examples of preferred embodiments of the present invention will be described with reference to the drawings. However, it should be noted that the present invention is not limited to these embodiments, and that the shape and dimensions of each embodiment are not limited and can be modified as appropriate.

[0049] (Embodiment 1) An example of a micro two-phase droplet generation device (100) according to one embodiment of the present invention is shown in Figures 1 and 2(a) and 2(b). In Figure 1, the micro two-phase droplet generation device (100) has, from top to bottom, a micro-groove array substrate (also called a microfluidic array) (20), a first member (31) and a second member (32) of a liquid distribution component (30). The micro-groove array substrate (20) has dimensions of, for example, 20 mm in width, 25 mm in length, and 4 mm in height. The first member (31) and the second member (32) each have dimensions of, for example, 30 mm in width, 33 mm in length, and 8 mm in height. These components and members are aligned with each other and liquid-tightly coupled to one another by fastening structures such as bolts.

[0050] Figure 2(a) is an exploded perspective view of the micro two-phase droplet generation device (100), showing, from top to bottom, the micro-groove array substrate (20), the first component (31) and the second component (32) of the liquid distribution component (30). Figure 2(b) shows a plan view of the micro-groove array substrate (20) and the first component (31) and the second component (32) of the liquid distribution component (30) of the micro two-phase droplet generation device (100), and cross-sectional views to the right and below the plan view. The cross-sectional views are taken from top to bottom along the line segments AA, BB, CC, and DD of the plan view. The fastening structure is omitted in the attached figures.

[0051] Referring to Figure 2(a), the micro-groove array substrate (20) has a row of microchannels (16) on its lower surface facing the liquid distribution component (30). The row of microchannels (16) consists of 16 parallel-arranged linear micro-grooves (16), specifically, linear micro-grooves (16) with a rectangular cross-section (width 100 μm, height 100 μm) and a length of 13 mm, with a gap of 100 μm between adjacent grooves. When the micro-groove array substrate (20) and the first member (31) of the liquid distribution component (30) are liquid-tightly coupled, the top surfaces of the micro-grooves (16-1) formed in the micro-groove array substrate (20) are sealed by the upper surface of the first member (31), forming microchannels (16).

[0052] The first member (31) of the liquid distribution component (30) has four slits, from left to right in Figures 2(a) and 2(b): a first dispersed phase supply slit (11), a second dispersed phase supply slit (12), a continuous phase supply slit (13), and a product discharge slit (14). In the definition of the present invention, the second dispersed phase supply slit (12) is the first slit, and the continuous phase supply slit (13) is the second slit as a preferred example of a second liquid transport port. Each slit has a slit end (opening) on ​​the main surface of the first member (31) with a longitudinal width (length) of 5 mm and a short-width (width) of 500 μm, and the spacing between slits is 3 mm. Each slit forms a flat plate-shaped (hereinafter simply referred to as plate-shaped) space (three-dimensional slit) that penetrates the first member (31) in the thickness direction. In the present invention, the first slit (12) is essential, but the first dispersed phase supply slit (11), the continuous phase supply slit (13), and the product discharge slit (14) do not need to be slits. They can be the first dispersed phase supply port, the continuous phase supply port, and the product discharge port (all liquid transport ports). For example, they may be large holes that open out at the main surface of the first member (31) and are connected to a plurality of microchannels (16).

[0053] The longitudinal direction of the rows of microchannels (16) in the microgroove array substrate (20) and the longitudinal direction of the slits (11, 12, 13, 14) in the first member (31) are arranged to intersect perpendicularly to each other.

[0054] The lower second member (32) of the liquid distribution component (30) has a first dispersed phase supply port (11-1), a second dispersed phase supply port (12-1), a continuous phase supply port (13-1), and a product discharge port (14-1), which are fluidly connected to the first dispersed phase supply slit (11), the second dispersed phase supply slit (12), the continuous phase supply slit (13), and the product discharge slit (14), respectively. The first dispersed phase supply port (11-1), the second dispersed phase supply port (12-1), the continuous phase supply port (13-1), and the product discharge port (14-1) have four cylindrical vertical holes on their upper surfaces at positions corresponding to the end faces of each slit, and these are continuous as spaces with cylindrical horizontal holes that extend to the four sides of the second member (32). The cylindrical lateral holes opening on the four sides of the second member (32) may have a female thread structure for liquid-tight connection with an external liquid supply or liquid discharge member.

[0055] Here, the first dispersed phase supply slit (11), the second dispersed phase supply slit (12), the continuous phase supply slit (13), and the product discharge slit (14) are functionally extensions or ends of the first dispersed phase supply port (11-1), the second dispersed phase supply port (12-1), the continuous phase supply port (13-1), and the product discharge port (14-1), respectively, and constitute a part of the first dispersed phase supply port (11-1), the second dispersed phase supply port (12-1), the continuous phase supply port (13-1), and the product discharge port (14-1). In the present invention, the first dispersed phase supply slit (11), the second dispersed phase supply slit (12), the continuous phase supply slit (13), and the product discharge slit (14) are referred to as the first dispersed phase supply port (11-1), the second dispersed phase supply port (12-1), the continuous phase supply port (13-1), and the product discharge port (14-1), respectively. In the following embodiments, depending on the drawings or context, the first dispersed phase supply slit (11), the second dispersed phase supply slit (12), the continuous phase supply slit (13), and the product discharge slit (14) may be excluded and referred to as the first dispersed phase supply port (11-1), the second dispersed phase supply slit (12), the continuous phase supply slit (13), and the product discharge slit (14) in a narrow sense.

[0056] In Embodiment 1, a first dispersed phase (1) is supplied to each of the multiple microchannels (16) from a first dispersed phase supply slit (11), and a second dispersed phase (2) is supplied from a second dispersed phase supply slit (12). As will be described below, a two-phase parallel continuous flow (4) is formed in the microchannel (16) between the first slit (12) and the second slit (13), and a continuous phase (3) is supplied from the continuous phase supply slit (13). Two-phase droplets (5), such as core-shell type or Janus type, are generated near the junction of the microchannel (16) with the second slit (13), and these two-phase droplets (5) are discharged through the product discharge slit (14) and the product discharge port (14-1).

[0057] Figure 3(a) is a schematic partial cross-sectional view of the micro-two-phase droplet generation device (100) of Figure 2, cut along the longitudinal direction of a single microchannel (16), schematically illustrating how two-phase droplets are generated. In Figure 3(a), the microchannel (16) is formed on the bonding surface (reference surface) between the micro-groove array substrate (20) and the liquid distribution component (30), and the slits (12, 13) extend vertically downward from the bonding surface (reference surface).

[0058] When the first dispersed phase (1) is supplied to the microchannel (16) from the left in Figure 3(a) to form a flow of the first dispersed phase (1), and the second dispersed phase (2) is supplied from the first slit (12) to form a flow of the second dispersed phase (2), the flows of the first dispersed phase (1) and the second dispersed phase (2) meet at the connection point between the microchannel (16) and the first slit (12), and a two-phase parallel continuous flow (4) of the first dispersed phase (1) and the second dispersed phase (2) is formed in the microchannel (16) between the first slit (12) and the second slit (13). A two-phase parallel continuous flow (4) means that the two phases, the first dispersed phase (1) and the second dispersed phase (2), do not completely mix with each other, but each forms a separate continuous flow. The two-phase parallel continuous flow (4) has a two-phase structure in which the first dispersed phase (1) and the second dispersed phase are separated but not completely mixed with each other in the cross-section of the microchannel (16).

[0059] When the continuous phase (3) is supplied to multiple microchannels (16) from the continuous phase supply slits (13), the flow of the two-phase parallel continuous flow (4) is sheared near the connection points between the multiple microchannels (16) and the continuous phase supply slits (13), with the flow of the continuous phase (3) acting as a driving force. This generates two-phase droplets (5) with a structure such as a core-shell type or a Janus type, consisting of the first dispersed phase (1) and the second dispersed phase (2). In Figure 3(a), two types of two-phase droplets, a core-shell type droplet (5-2) and a Janus type droplet (5-1), are depicted for illustrative purposes, but in reality, only one two-phase droplet (5), such as a core-shell type droplet (5-2) or a Janus type droplet (5-1), is generated. Whether a two-phase droplet (5) becomes a core-shell droplet (5-2) or a Janus-type droplet (5-1), and whether the first dispersed phase (1) or the second dispersed phase (2) becomes the core and shell when a core-shell droplet (5-2) is formed, is mainly determined by the relationship of the interfacial tensions between the first dispersed phase (1), the second dispersed phase (2), and the continuous phase (3). Also, although Figure 3(a) shows a core-shell droplet (5-2) with the second dispersed phase (2) as the core and the first dispersed phase (1) as the shell, it could also be a core-shell droplet with the first dispersed phase (1) as the core and the second dispersed phase (2) as the shell.

[0060] The product containing the two-phase droplet (5) is discharged through the product discharge slit (14) and the product discharge port (14-1).

[0061] (Embodiment 2) The micro two-phase droplet generation device (100) of Embodiment 2 of the present invention is similar to the micro two-phase droplet generation device (100) of Embodiment 1, but differs in that the continuous phase supply slit and the product discharge slit are interchangeable, and the continuous phase supply port and the product discharge port are interchangeable. As a result, in Figures 2(a) and 2(b), slit (13) is the product discharge slit, slit (14) is the continuous phase supply slit, liquid transport port (13-1) is the product discharge port, and liquid transport port (14-1) is the continuous phase supply port.

[0062] In Embodiment 2, the first dispersed phase (1) is supplied to the microchannel (16) from the first dispersed phase supply slit (11), and the second dispersed phase (2) is supplied from the second dispersed phase supply slit (12). As will be described below, a two-phase parallel continuous flow (4) is formed in the microchannel (16) between the first slit (12) and the second slit (13), and the continuous phase (3) is supplied from the continuous phase supply slit (14). Two-phase droplets (5-1, 5-2), such as core-shell type or Janus type, are generated near the junction of the microchannel (16) with the second slit (13), and these two-phase droplets (5-1, 5-2) are discharged through the product discharge slit (13) and the product discharge port (13-1).

[0063] Figure 3(b) is a schematic partial cross-sectional view of the micro-two-phase droplet generation device (100) of Embodiment 2, cut along the longitudinal direction of a single microchannel (16), schematically illustrating how two-phase droplets are generated. In Figure 3(b), the microchannel (16) is formed on the bonding surface (reference surface) between the micro-groove array substrate (20) and the first member (31) of the liquid distribution component (30), and the slits (12, 13) extend vertically downward from the bonding surface (reference surface).

[0064] When the first dispersed phase (1) is supplied to multiple microchannels (16) from the left in Figure 3(b) to form a flow of the first dispersed phase (1), and the second dispersed phase (2) is supplied from the first slit (12) to form a flow of the second dispersed phase (2), the flow of the first dispersed phase (1) and the flow of the second dispersed phase (2) meet at the connection point between the microchannels (16) and the first slit (12), and a two-phase parallel continuous flow (4) of the first dispersed phase (1) and the second dispersed phase (2) is formed in the microchannel (16) between the first slit (12) and the second slit (13) of the microchannel (16).

[0065] When the continuous phase (3) is supplied to multiple microchannels (16) from the continuous phase supply slit (14), the flow of the two-phase parallel continuous flow (4) is sheared near the connection point between the product discharge slit (13) and the microchannels (16), using the flow of the continuous phase (3) as a driving force. This allows the two phases, the first dispersed phase (1) and the second dispersed phase (2), to form a two-phase droplet (5) having a core-shell or Janus-type structure. In Figure 3(b), two types of two-phase droplets, a core-shell droplet (5-2) and a Janus-type droplet (5-1), are depicted for illustrative purposes, but in reality, only one two-phase droplet (5), such as a core-shell droplet (5-2) or a Janus-type droplet (5-1), is generated. Furthermore, in Figure 3(b), the core-shell droplet (5-2) is shown as having the second dispersed phase (2) as the core and the second dispersed phase (1) as the shell. However, it could also be a core-shell droplet with the second dispersed phase (1) as the core and the second dispersed phase (2) as the shell.

[0066] The product containing the two-phase droplet (5) is discharged through the product discharge slit (13) and the product discharge port (13-1).

[0067] In embodiments 1 and 2 of the present invention, Figure 4 shows examples of groove shapes for a component (20) having a micro-groove (16) joined to a liquid distribution component (30). Figure 4(a) shows a case where four slits (dashed lines) are bridged vertically by a row of linear microchannels (solid lines), Figure 4(b) shows a case where four slits (dashed lines) are bridged diagonally by a row of linear microchannels (solid lines), and Figure 4(c) shows a case where the width of the microchannels (solid lines) bridging the four slits changes continuously. Note that the width of the micro-groove may change discontinuously. Figures 4(d) to (f) show cases where the microchannel (solid line) connecting the sandwiched slit (dashed line) and the slits on both sides (dashed lines) is divided, with Figure 4(d) showing the case where the position and size match, Figure 4(e) showing the case where the position is misaligned, and Figure 4(f) showing the case where the number correspondence is not 1:1. Figure 4(g) also shows a case where some of the rows of bridging microchannels (solid lines) are connected to one another. The features in Figures 4(a) to 4(g) can be combined in any way.

[0068] In embodiments 1 and 2 of the present invention, the micro-groove array substrate (20) can be manufactured, for example, by transferring a pattern onto a silicone resin (PDMS: polydimethylsiloxane) from a mold made using SU-8 (Nippon Kayaku Co., Ltd.), a negative-type photoresist, on a Si substrate. The liquid distribution component (20) can be manufactured, for example, by machining a stainless steel material (SUS304). The slit-shaped through-holes of the liquid distribution component (20) can be manufactured, for example, by wire electrical discharge machining.

[0069] In embodiments 1 and 2 of the present invention, a core-shell type two-phase droplet is generated by delivering, for example, a first dispersed phase such as silicone oil (SO), a second dispersed phase such as 1,6-hexanediol diacrylate (HDDA), and a continuous phase such as an aqueous solution of polyvinyl alcohol (PVA). Alternatively, a Janus type two-phase droplet is generated by delivering a first dispersed phase such as 1,6-hexanediol diacrylate (HDDA), a second dispersed phase such as silicone oil with 1 wt% surfactant added (SO + surfactant), and a continuous phase such as an aqueous solution of polyvinyl alcohol (PVA). For delivering the dispersed and continuous phases, for example, a glass syringe and a syringe pump can be used. For observing droplet formation and measuring the size of the generated droplets, it is preferable to use, for example, an upright optical microscope and a high-speed video camera in combination.

[0070] (Embodiment 3) The micro two-phase droplet generation device (100) of Embodiment 3, as shown in Figures 5(a) and (b), has, from top to bottom, a lid (21) for sealing a micro-groove and a first member (34) and a second member (35) of a liquid distribution component (33). The sealing lid (21) has dimensions, for example, 20 mm in width, 20 mm in length, and 4 mm in height. The first member (34) and the second member (35) each have dimensions, for example, 30 mm in width, 33 mm in length, and 8 mm in height. These components and members are aligned with each other and liquid-tightly connected by fastening structures such as bolts. The fastening structures are omitted in the figures.

[0071] Figure 5(a) is an exploded perspective view of the micro two-phase droplet generation device (100), showing, from top to bottom, the sealing lid (21), the first component (34) and the second component (35) of the liquid distribution component (33). Figure 5(b) shows a plan view of the sealing lid (21), the first component (34) and the second component (35) of the liquid distribution component (33) of the micro two-phase droplet generation device (100), and cross-sectional views to the right and below the plan view. The cross-sectional views are, from top to bottom, cross-sectional views taken along line segments AA, BB, CC, and DD in the plan view.

[0072] Referring to Figures 5(a) and 5(b), the sealing lid (21) has a flat surface on its underside facing the liquid distribution component (33) that does not have microchannels.

[0073] The first member (34) of the liquid distribution component (33) has four slits, from left to right in Figures 5(a) and 5(b): a first dispersed phase supply slit (11), a second dispersed phase supply slit (12), a continuous phase supply slit (13), and a product discharge slit (14). In the definition of the present invention, the second dispersed phase supply slit (12) is the first slit, and the continuous phase supply slit (13) is the second slit as a preferred example of a liquid transport port for continuous phase supply. Each slit has a slit end portion (opening) on ​​the main surface of the first member (34) with a longitudinal width (length) of 5 mm and a short-width (width) of 500 μm, and the spacing between slits is 3 mm. Each slit forms a plate-like space (three-dimensional slit) that penetrates the first member (34) in the thickness direction.

[0074] The first member (34) of the liquid distribution component (33) has a total of 16 linear microgrooves (16-1) extending from the first dispersed phase supply slit (11) to the product discharge slit (14), each having a rectangular cross-section (width 100 μm, depth 100 μm), between the first dispersed phase supply slit (11), the second dispersed phase supply slit (12), the continuous phase supply slit (13), and the product discharge slit (14). Each of the 16 linear microgrooves (16-1) between the slits is formed in a straight line extending beyond the second dispersed phase supply slit (12) and the continuous phase supply slit (13). The longitudinal direction of the rows of microchannels (16-1) and the longitudinal direction of the slits (11, 12, 13, 14) of the first member (34) intersect each other perpendicularly.

[0075] When a sealing lid (21) is liquid-tightly bonded to the top surface of the first member (34) on which the fine grooves (16-1) of the liquid distribution component (33) are formed, the fine grooves (16-1) are sealed, forming a microchannel (16-1).

[0076] In the present invention, the first slit is essential, but the first dispersed phase supply slit (11), the continuous phase supply slit (13), and the product discharge slit (14) do not need to be slits. They may be the first dispersed phase supply port, the continuous phase supply port, and the product discharge port (liquid transport port), for example, large holes connected to a plurality of microchannels (16-1) formed on the main surface of the first member (34).

[0077] The lower second member (35) of the liquid distribution component (33) has a first dispersed phase supply port (11-1), a second dispersed phase supply port (12-1), a continuous phase supply port (13-1), and a product discharge port (14-1), which are fluidly connected to the first dispersed phase supply slit (11), the second dispersed phase supply slit (12), the continuous phase supply slit (13), and the product discharge slit (14), respectively. The first dispersed phase supply port (11-1), the second dispersed phase supply port (12-1), the continuous phase supply port (13-1), and the product discharge port (14-1) have four cylindrical vertical holes on their upper surfaces at positions corresponding to the end faces of each slit, and these are continuous as spaces with cylindrical horizontal holes that extend to the four sides of the second member (35). The cylindrical lateral holes opening on the four sides of the second member (35) may have a female thread structure for liquid-tight connection with an external liquid supply or liquid discharge member.

[0078] Here, the first dispersed phase supply slit (11), the second dispersed phase supply slit (12), the continuous phase supply slit (13), and the product discharge slit (14) are functionally extensions or ends of the first dispersed phase supply port (11-1), the second dispersed phase supply port (12-1), the continuous phase supply port (13-1), and the product discharge port (14-1), respectively, and constitute a part of the first dispersed phase supply port (11-1), the second dispersed phase supply port (12-1), the continuous phase supply port (13-1), and the product discharge port (14-1). In the definition of the present invention, the first dispersed phase supply port (11-1), the second dispersed phase supply port (12), the continuous phase supply port (13), and the product discharge port (14) are included, along with the first dispersed phase supply slit (11), the second dispersed phase supply slit (12), the continuous phase supply slit (13), and the product discharge slit (14). In the following embodiments, depending on the drawings or context, the first dispersed phase supply port (11-1), the second dispersed phase supply slit (12), the continuous phase supply slit (13), and the product discharge slit (14) may be indicated or referred to as the first dispersed phase supply port (11-1), the second dispersed phase supply slit (12), the continuous phase supply slit (13), and the product discharge slit (14) in a narrow sense.

[0079] In Embodiment 3, the first dispersed phase (1) is supplied to the microchannel (16-1) from the first dispersed phase supply slit (11), and the second dispersed phase (2) is supplied from the second dispersed phase supply slit (12). As will be described below, a two-phase parallel continuous flow (4) is formed in the microchannel (16-1) between the first slit (12) and the second slit (13), and the continuous phase (3) is supplied from the continuous phase supply slit (13). Two-phase droplets (5-1, 5-2), such as core-shell type or Janus type, are generated near the junction of the microchannel (16-1) with the second slit (13), and these two-phase droplets (5-1, 5-2) are discharged through the product discharge slit (14) and the product discharge port (14-1).

[0080] Figure 6(a) is a schematic partial cross-sectional view of a micro-two-phase droplet generation device (100) cut along the longitudinal direction of a single microchannel (16-1), schematically illustrating how two-phase droplets (5) are generated. In Figure 6(a), a microchannel (16-1) based on a fine groove is formed below the joint surface between the sealing lid (21) and the liquid distribution component (33), and the slits (12, 13) extend perpendicularly downward from the reference plane, with the plane connecting the bottom surface (lower surface) of the microchannel (16-1), i.e., the fine groove (16-1), serving as the reference plane.

[0081] When the first dispersed phase (1) is supplied to multiple microchannels (16-1) from the left in Figure 6(a) to form a flow of the first dispersed phase (1), and the second dispersed phase (2) is supplied from the first slit (12) to form a flow of the second dispersed phase (2), the flows of the first dispersed phase (1) and the second dispersed phase (2) meet at the connection point between the microchannels (16-1) and the first slit (12), and a two-phase parallel continuous flow (4) of the first dispersed phase (1) and the second dispersed phase (2) is formed in the microchannel (16-1) between the first slit (12) and the second slit (13) of the microchannel (16-1).

[0082] When a continuous phase (3) is supplied to multiple microchannels (16-1) from a continuous phase supply slit (13), the flow of the two-phase parallel continuous flow (4) is sheared near the connection point between the microchannels (16-1) and the continuous phase supply slit (13), driven by the flow of the continuous phase (3). This generates a two-phase droplet (5) having a core-shell or Janus-type structure, consisting of a first dispersed phase (1) and a second dispersed phase (2). In Figure 6(a), two types of two-phase droplets, a core-shell droplet (5-2) and a Janus-type droplet (5-1), are depicted for illustrative purposes. However, in reality, only one two-phase droplet, such as a core-shell droplet (5-2) or a Janus-type droplet (5-1), is generated. Furthermore, in Figure 6(a), the core-shell droplet (5-2) is shown as having the second dispersed phase (2) as the core and the first dispersed phase (1) as the shell. However, it could also be a core-shell droplet with the first dispersed phase (1) as the core and the second dispersed phase (2) as the shell.

[0083] The product containing the two-phase droplet (5) is discharged through the product discharge slit (14) and the product discharge port (14-1).

[0084] (Embodiment 4) The micro two-phase droplet generation device (100) of Embodiment 4 is similar to the micro two-phase droplet generation device (100) of Embodiment 3, but differs in that the continuous phase supply slit and the product discharge slit in Embodiment 1 are interchangeable, and the continuous phase supply port (13-1), the product discharge slit, and the product discharge port are interchangeable. As a result, in Figures 5(a) and 5(b), slit (13) is the product discharge slit, slit (14) is the continuous phase supply slit, liquid transport port (13-1) is the product discharge port, and liquid transport port (14-1) is the continuous phase supply port.

[0085] In Embodiment 4, the first dispersed phase (1) is supplied to the microchannel (16-1) from the first dispersed phase supply slit (11), and the second dispersed phase (2) is supplied from the second dispersed phase supply slit (12). As will be described below, a two-phase parallel continuous flow (4) is formed in the microchannel (16-1) between the first slit (12) and the second slit (13). The continuous phase (3) is supplied from the continuous phase supply port (14-1) and the continuous phase supply slit (14). Two-phase droplets (5-1, 5-2), such as core-shell type or Janus type, are generated near the junction of the microchannel (16-1) with the second slit (13), and these two-phase droplets (5-1, 5-2) are discharged through the product discharge slit (13) and the product discharge port (13-1).

[0086] Figure 6(b) is a schematic partial cross-sectional view of the micro-two-phase droplet generation device (100) of Embodiment 4, cut along the longitudinal direction of a single microchannel (16-1), schematically showing how two-phase droplets are generated. In Figure 6(b), a microchannel (16-1) based on a fine groove is formed below the joint surface between the sealing lid (21) and the first member (34) of the liquid distribution component (33). The slits (12, 13) extend perpendicularly downward from the reference plane, with the virtual plane connecting the bottom surfaces (lower surfaces) of the microchannel (16-1), i.e., the fine grooves, serving as the reference plane.

[0087] When the first dispersed phase (1) is supplied to the microchannel (16-1) from the left in Figure 6(b) to form a flow of the first dispersed phase (1), and the second dispersed phase (2) is supplied from the first slit (12) to form a flow of the second dispersed phase (2), the flow of the first dispersed phase (1) and the flow of the second dispersed phase (2) meet at the connection point between the microchannel (16-1) and the first slit (12), and a two-phase parallel continuous flow (4) of the first dispersed phase (1) and the second dispersed phase (2) is formed in the microchannel (16-1) between the first slit (12) and the second slit (13) of the microchannel (16-1).

[0088] When the continuous phase (3) is supplied to the microchannel (16-1) from the continuous phase supply slit (14), the flow of the two-phase parallel continuous flow (4) is sheared near the connection point between the continuous phase supply slit (14) and the microchannel (16-1), using the flow of the continuous phase (3) as a driving force. This generates two-phase droplets (5-1, 5-2) in which the first dispersed phase (1) and the second dispersed phase (2) have a core-shell or Janus-type structure. In Figure 6(b), two types of two-phase droplets, a core-shell droplet (5-2) and a Janus-type droplet (5-1), are depicted for illustrative purposes, but in reality, only one two-phase droplet, such as a core-shell droplet (5-2) or a Janus-type droplet (5-1), is generated. Furthermore, in Figure 6(b), the core-shell droplet (5-2) is shown as having the second dispersed phase (2) as the core and the first dispersed phase (1) as the shell. However, it could also be a core-shell droplet with the first dispersed phase (1) as the core and the second dispersed phase (2) as the shell.

[0089] The product containing the two-phase droplet (5) is discharged through the product discharge slit (13) and the product discharge port (13-1).

[0090] In embodiments 3 to 4 of the present invention, examples of the shapes of the micro-grooves processed in the liquid distribution component (33) are shown in Figure 7. Figure 7(a) shows the case where three slits are bridged by vertically intersecting linear micro-grooves, Figure 7(b) shows the case where they are bridged by diagonally intersecting linear micro-grooves, and Figure 7(c) shows the case where the width of the bridging micro-grooves changes continuously. Note that the width of the micro-grooves may change discontinuously. Figure 7(d) shows the case where there is a misalignment in the positions of the bridging micro-grooves, and Figure 7(e) shows the case where the correspondence of the number of bridging micro-grooves is not 1:1.

[0091] In embodiments 3 to 4 of the present invention, the sealing lid (21) is preferably made from a transparent material such as silicone resin (PDMS: polydimethylsiloxane), acrylic resin, or glass. The liquid distribution device is made from, for example, stainless steel (SUS304) by machining. The slit-shaped through holes in the liquid distribution device can be made by, for example, wire electrical discharge machining. The micro-grooves bridging the slits can be made by mechanical cutting, laser processing, etching, etc.

[0092] In embodiments 3 to 4 of the present invention, for example, core-shell type two-phase droplets are generated by delivering a first dispersed phase such as silicone oil (SO), a second dispersed phase such as 1,6-hexanediol diacrylate (HDDA), and a continuous phase such as an aqueous solution of polyvinyl alcohol (PVA). Alternatively, Janus type two-phase droplets are generated by delivering a first dispersed phase such as 1,6-hexanediol diacrylate (HDDA), a second dispersed phase such as silicone oil with 1 wt% surfactant added (SO + surfactant), and a continuous phase such as an aqueous solution of polyvinyl alcohol (PVA). For delivering the dispersed and continuous phases, for example, a glass syringe and a syringe pump can be used. For observing droplet formation and measuring the size of the generated droplets, it is preferable to use a combination of, for example, an upright optical microscope and a high-speed video camera.

[0093] (Embodiment 5) The micro two-phase droplet generation device (100) of Embodiment 5 consists of a micro-groove array substrate (22) on which micro-grooves (16-2) are formed, and a liquid distribution component (41) having three slits (11R, 12R, 13R) and a cylindrical hole (14H) (Figure 8(a)(b)). The micro-grooves (16-2) formed in the micro-groove array substrate (22) are formed radially from the central axis. The three slits (11R, 12R, 13R) formed in the liquid distribution component (41) are concentric annular shapes and have a cylindrical hole (14H) on their central axis.

[0094] The liquid distribution component (41) consists of four members (Figure 8(a)(b)). The liquid distribution component (41) is located below the component (22) having a fine groove (16-2) and is an uppermost first member (41-1) equipped with a first dispersed phase supply port (11-1); a second second member (41-2) from the top equipped with a second dispersed phase supply port (12-1) and, when combined with the first member (41-1), forms an annular slit (11R) for supplying the first dispersed phase (1); and a second member equipped with a continuous phase supply port (13-1) and a second The device comprises a third-stage second member (41-2) from the top, which, when combined with member (41-2), forms an annular slit (12R) for supplying a second dispersed phase (2); and a fourth-stage fourth member (41-4) from the top, which, when combined with the third member (41-3), forms an annular slit (13R) for supplying a continuous phase (3) and has a central cylindrical hole (14H) for product discharge and an outlet (14-1) (Figure 8(a)(b)).

[0095] Figure 8(a) shows a cross-sectional perspective view of the liquid distribution component (41) when the first to fourth members are combined. The supplied first dispersed phase (1), second dispersed phase (2), and continuous phase (3) flow from the lower layer through the annular slits (11R, 12R, 13R) and are supplied to the upper part of the liquid distribution component (41). Specifically, the first dispersed phase (1) is supplied from the first dispersed phase supply port (11-1) to the annular slit (11R) for supplying the first dispersed phase in the first member (41-1), the second dispersed phase (2) is supplied from the second dispersed phase supply port (12-1) to the annular slit (12R) for supplying the second dispersed phase in the second member (41-2), and the continuous phase (3) is supplied from the continuous phase supply port (13-1) to the annular slit (13R) for supplying the continuous phase in the third member (41-3), and the first dispersed phase (1), the second dispersed phase (2), and the continuous phase (3) are each pumped upward through their respective slits.

[0096] Here, in order to emphasize the shapes of the annular slits (11R, 12R, 13R) and cylindrical holes (14H), the parts excluding the annular slits (11R, 12R, 13R) and cylindrical holes (14H) are referred to as the first dispersed phase supply port (11-1), the second dispersed phase supply port (12-1), the continuous phase supply port (13-1), and the discharge port (14-1). However, as previously stated, in this disclosure, the annular slits (11R, 12R, 13R) and cylindrical holes (14H) are functionally part of the first dispersed phase supply port (11-1), the second dispersed phase supply port (12-1), the continuous phase supply port (13-1), and the discharge port (14-1) (in the following embodiments, the relationship between the annular slits and cylindrical holes and the first dispersed phase supply port, the second dispersed phase supply port, the continuous phase supply port, and the discharge port is the same, but will not be repeated).

[0097] Figure 8(a) shows a liquid distribution component (41) joined to a component (22) having three slits (i.e., a first dispersed phase supply slit (11R), a second dispersed phase supply slit (12R), and a continuous phase supply slit (13R)), and a cylindrical hole (14H) which is part of the outlet (14-1), with a fine groove (16-2). In Figure 8(a), the first dispersed phase is supplied to the outer annular slit (11R), the second dispersed phase is supplied to the middle annular slit (12R), and the continuous phase (3) is supplied to the inner slit (13R).

[0098] The first dispersed phase (1) and the second dispersed phase (2) are supplied to a microchannel (16-2) formed from a fine groove (16-2), and a two-phase parallel continuous flow (4) of the first dispersed phase (1) and the second dispersed phase (2) is formed in the microchannel (16-2) connecting the first dispersed phase supply slit (11R) and the second dispersed phase supply slit (12R). The continuous phase (3) is supplied to the microchannel (16-2), and two-phase droplets (5) generated near the connection point between the microchannel (16-2) through which the two-phase parallel continuous flow (4) flows and the continuous phase supply slit (13R) are discharged through the microchannel (16-2) and the central cylindrical discharge hole (14H).

[0099] Figure 9(a) illustrates how two-phase droplets are generated within the apparatus. When the first dispersed phase (1) is supplied to multiple microchannels (16-2) from the left in Figure 9(a), forming a flow of the first dispersed phase (1), and the second dispersed phase (2) is supplied from the first slit (12R), forming a flow of the second dispersed phase (2), the flows of the first dispersed phase (1) and the second dispersed phase (2) meet at the connection point between the microchannels (16-2) and the first slit (12R), and a two-phase parallel continuous flow (4) of the first dispersed phase (1) and the second dispersed phase (2) is formed in the microchannel (16-2) between the first slit (12R) and the second slit (13R) of the microchannel (16-2).

[0100] When the continuous phase (3) is supplied to multiple microchannels (16-2) from the continuous phase supply slit (13R), the flow of the two-phase parallel continuous flow (4) is sheared near the connection point between the microchannels (16-2) and the continuous phase supply slit (13R), driven by the flow of the continuous phase (3). This generates two-phase droplets (5-1, 5-2) in which the first dispersed phase (1) and the second dispersed phase (2) have a core-shell or Janus-type structure. In Figure 9(a), two types of two-phase droplets, a core-shell droplet (5-2) and a Janus-type droplet (5-1), are depicted for illustrative purposes, but in reality, only one two-phase droplet, such as a core-shell droplet (5-2) or a Janus-type droplet (5-1), is generated. Furthermore, in Figure 9(a), the core-shell droplet (5-2) is shown as having the second dispersed phase (2) as the core and the first dispersed phase (1) as the shell. However, it could also be a core-shell droplet with the first dispersed phase (1) as the core and the second dispersed phase (2) as the shell.

[0101] The product containing the two-phase droplet (5) is discharged through the cylindrical pore (14H) and the product outlet (14-1).

[0102] (Embodiment 6) The micro two-phase droplet generation device (100) of Embodiment 6 is similar to the micro two-phase droplet generation device (100) of Embodiment 5, but differs in that the slit for continuous phase supply and the cylindrical hole for product discharge are interchangeable, and the continuous phase supply port and the product discharge port are interchangeable. As a result, in Figures 8(a) and 8(b), the slit (13R) is the product discharge slit, the cylindrical hole (14H) is the cylindrical hole (opening) for continuous phase supply, the liquid transport port (13-1) is the product discharge port, and the liquid transport port (14-1) is the continuous phase supply port.

[0103] In Embodiment 6, the first dispersed phase (1) is supplied to the microchannel (16-2) from the first dispersed phase supply slit (11R), and the second dispersed phase (2) is supplied from the second dispersed phase supply slit (12R). As will be described below, a two-phase parallel continuous flow (4) is formed in the microchannel (16-2) between the first slit (12R) and the second slit (13R). The continuous phase (3) is supplied from the continuous phase supply port (14-1) and the cylindrical hole (14H) for continuous phase supply. Core-shell type or Janus type two-phase droplets (5) are generated near the junction with the second slit (13) of the microchannel (16-2), and these two-phase droplets (5) are discharged through the product discharge slit (13R) and the product discharge port (13-1).

[0104] Figure 9(b) is a schematic partial cross-sectional view of the micro-two-phase droplet generation device (100) of Embodiment 6, cut along the longitudinal direction of a single microchannel (16-2), schematically illustrating how two-phase droplets are generated. In Figure 9(b), the microchannel (16-2) is formed on the junction surface (reference surface) between the micro-groove array substrate (22) and the liquid distribution component (41), and the slits (12R, 13R) extend vertically downward from the reference surface.

[0105] When the first dispersed phase (1) is supplied to the microchannel (16-2) from the left in Figure 9(b) to form a flow of the first dispersed phase (1), and the second dispersed phase (2) is supplied from the first slit (12R) to form a flow of the second dispersed phase (2), the flow of the first dispersed phase (1) and the flow of the second dispersed phase (2) meet at the connection point between the microchannel (16-2) and the first slit (12R), and a two-phase parallel continuous flow (4) of the first dispersed phase (1) and the second dispersed phase (2) is formed in the microchannel (16-2) between the first slit (12R) and the second slit (13R).

[0106] When the continuous phase (3) is supplied to the microchannel (16-2) from the cylindrical hole (14H) for continuous phase supply, the flow of the two-phase parallel continuous flow (4) is sheared near the connection point between the discharge slit (13R) and the microchannel (16-2), driven by the flow of the continuous phase (3), thereby generating two-phase droplets (5-1, 5-2) having a core-shell or Janus-type structure, etc., of the first dispersed phase (1) and the second dispersed phase (2). In Figure 12, for illustrative purposes, two types of two-phase droplets, a core-shell droplet (5-2) and a Janus-type droplet (5-1), are depicted, but in reality, only one two-phase droplet, such as a core-shell droplet (5-2) or a Janus-type droplet (5-1), is generated. Furthermore, in Figure 9(b), the core-shell droplet (5-2) is shown as having the second dispersed phase (2) as the core and the first dispersed phase (1) as the shell. However, it could also be a core-shell droplet with the first dispersed phase (1) as the core and the second dispersed phase (2) as the shell.

[0107] The product containing the two-phase droplet (5) is discharged through the product discharge slit (13R) and the product discharge port (13-1).

[0108] (Embodiment 7) As shown in Figures 10(a) and 10(b), the micro two-phase droplet generation device (100) of Embodiment 7 has a liquid distribution component (42) having three slits (11R, 12R, 13R) and a cylindrical hole (14H), with a row of multiple micro grooves (16-2) formed on its top surface. Microchannels (16-2) are formed by sealing the top surfaces of these multiple micro grooves (16-2) with a lid (23). The lower surface of the lid (23) for sealing the micro grooves (16-2) is a flat plane. The micro grooves (16-2) formed on the liquid distribution component (42) are formed radially from the central axis. On the other hand, the three slits (11R, 12R, 13R) formed on the liquid distribution component (42) are concentric annular shapes and have a cylindrical hole (14H) on their central axis.

[0109] The liquid distribution component (42) consists of four members (Figure 10(a)(b)). The liquid distribution component (42) is located below a flat plate lid (23) for sealing the slits (11R, 12R, 13R), the cylindrical discharge hole (14H), and the fine groove (16-3), and is the uppermost first member (42-1) equipped with a first dispersed phase supply port (11-1); and the second second part from the top equipped with a second dispersed phase supply port (12-1) and, when combined with the first member (42-1), forms an annular slit (11R) for supplying the first dispersed phase (1). The device comprises: a material (42-2); a third-stage second member (42-2) from the top, which has a continuous phase supply port (13-1) and, when combined with the second member (42-2), forms an annular slit (12R) for supplying a second dispersed phase (2); and a fourth-stage fourth member (42-4) from the top, which, when combined with the third member (42-3), forms an annular slit (13R) for supplying a continuous phase (3) and has a cylindrical discharge hole (14H) in the center.

[0110] Furthermore, micro-grooves (16-3) are machined between the annular slits (11R, 12R, 13R) formed by combining the four components, and between the annular slit (13R) and the cylindrical hole (14H).

[0111] Figure 10(a) shows a cross-sectional perspective view of the liquid distribution component (42) when the first to fourth members are combined. The supplied first dispersed phase (1), second dispersed phase (2), and continuous phase (3) flow from the lower layer through the annular slits (11R, 12R, 13R) and are supplied to the upper part of the liquid distribution component (42). Specifically, the first dispersed phase (1) is supplied from the first dispersed phase supply port (11-1) to the annular slit (11R) for supplying the first dispersed phase in the first member (42-1), the second dispersed phase (2) is supplied from the second dispersed phase supply port (12-1) to the annular slit (12R) for supplying the second dispersed phase in the second member (42-2), and the continuous phase (3) is supplied from the continuous phase supply port (13-1) to the annular slit (13R) for supplying the continuous phase in the third member, with the first dispersed phase (1), the second dispersed phase (2), and the continuous phase (3) being pumped upward through each slit.

[0112] Figure 10(a) shows a liquid distribution component (42) joined to a component (42) having three slits (i.e., a slit for supplying the first dispersed phase (11R), a slit for supplying the second dispersed phase (12R), and a slit for supplying the continuous phase (13R)), and a cylindrical hole (14H) which is part of the outlet (14-1), with a fine groove (16-3). In Figure 10(a), the first dispersed phase is supplied to the outer annular slit (11R), the second dispersed phase is supplied to the middle annular slit (12R), and the continuous phase (3) is supplied to the inner slit (13R).

[0113] The first dispersed phase (1) and the second dispersed phase (2) are supplied to a microchannel (16-3) formed from a fine groove (16-3), and a two-phase parallel continuous flow (4) of the first dispersed phase (1) and the second dispersed phase (2) is formed in the microchannel (16-3) connecting the first dispersed phase supply slit (11R) and the second dispersed phase supply slit (12R). The continuous phase (3) is supplied to the microchannel (16-3), and two-phase droplets generated near the connection point between the microchannel (16-3) through which the two-phase parallel continuous flow (4) flows and the continuous phase supply slit (13R) are discharged through the microchannel (16-3) and the central cylindrical discharge hole (14H).

[0114] Figure 11(a) is a schematic partial cross-sectional view of the micro-two-phase droplet generation device (100) of Embodiment 7, cut along the longitudinal direction of a single microchannel (16-3), schematically illustrating how two-phase droplets are generated. In Figure 11(a), a microchannel (16-3) based on a fine groove is formed below the joint surface between the sealing lid (23) and the liquid distribution component (42), and the slits (12R, 13R) extend perpendicularly downward from the reference surface, with the bottom surface (lower surface) of the microchannel (16-3), i.e., the fine groove, as the reference surface.

[0115] When the first dispersed phase (1) is supplied to multiple microchannels (16-3) from the left in Figure 11(a) to form a flow of the first dispersed phase (1), and the second dispersed phase (2) is supplied from the first slit (12R) to form a flow of the second dispersed phase (2), the flow of the first dispersed phase (1) and the flow of the second dispersed phase (2) meet at the connection point between the microchannel (16-3) and the first slit (12R), and a two-phase parallel continuous flow (4) of the first dispersed phase (1) and the second dispersed phase (2) is formed in the microchannel (16-3) between the first slit (12R) and the second slit (13R) of the microchannel (16-3).

[0116] When the continuous phase (3) is supplied to multiple microchannels (16-3) from the continuous phase supply slit (13R), the flow of the two-phase parallel continuous flow (4) is sheared in the microchannels (16-3) near the connection point with the continuous phase supply slit (13R), using the flow of the continuous phase (3) as a driving force. This allows the two phases, the first dispersed phase (1) and the second dispersed phase (2), to form a two-phase droplet (5) having a core-shell or Janus-type structure. In Figure 11(a), two types of two-phase droplets, a core-shell droplet (5-2) and a Janus-type droplet (5-1), are depicted for illustrative purposes, but in reality, only one two-phase droplet (5), either a core-shell droplet (5-2) or a Janus-type droplet (5-1, etc.), is generated. Furthermore, in Figure 11(a), the core-shell droplet (5-2) is shown as having the second dispersed phase (2) as the core and the first dispersed phase (1) as the shell. However, it could also be a core-shell droplet with the first dispersed phase (1) as the core and the second dispersed phase (2) as the shell.

[0117] The product containing the two-phase droplet (5) is discharged through the cylindrical hole (14H) and the product outlet (14-1).

[0118] (Embodiment 8) The micro two-phase droplet generation device (100) of Embodiment 8 is similar to the micro two-phase droplet generation device (100) of Embodiment 7, but differs in that the continuous phase supply slit and the cylindrical hole for product discharge are interchangeable, and the continuous phase supply port and the product discharge port are interchangeable. As a result, in Figures 10(a) and 10(b), the slit (13R) is the product discharge slit, the cylindrical hole (14H) is the cylindrical hole for continuous phase supply, the liquid transport port (13-1) is the product discharge port, and the liquid transport port (14-1) is the continuous phase supply port.

[0119] In Embodiment 8, the first dispersed phase (1) is supplied to the microchannel (16-3) from the first dispersed phase supply slit (11R), the second dispersed phase (2) is supplied from the second dispersed phase supply slit (12R), and the continuous phase (3) is supplied from the continuous phase supply port (14-1) and the continuous phase supply cylindrical hole (14H). As will be described below, a two-phase parallel continuous flow (4) is formed in the microchannel (16-3) between the first slit (12R) and the second slit (13R), and two-phase droplets (5-1, 5-2), such as core-shell type or Janus type, are generated near the junction of the microchannel (16-3) with the second slit (13R), and these two-phase droplets (5-1, 5-2) are discharged through the product discharge slit (13R) and the product discharge port (13-1).

[0120] Figure 11(b) is a schematic partial cross-sectional view of the micro-two-phase droplet generation device (100) of Embodiment 8, cut along the longitudinal direction of a single microchannel (16-3), schematically illustrating how two-phase droplets are generated. In Figure 11(b), a microchannel (16-3) based on a fine groove is formed below the joint surface between the sealing lid (23) and the liquid distribution component (42). The slits (12R, 13R) extend perpendicularly downward from the reference plane, with the virtual plane connecting the bottom surfaces (lower surfaces) of the microchannel (16-3), i.e., the fine grooves, serving as the reference plane.

[0121] When the first dispersed phase (1) is supplied to multiple microchannels (16-3) from the left in Figure 11(b) to form a flow of the first dispersed phase (1), and the second dispersed phase (2) is supplied from the first slit (12R) to form a flow of the second dispersed phase (2), the flow of the first dispersed phase (1) and the flow of the second dispersed phase (2) meet at the connection point between the microchannel (16-3) and the first slit (12R), and a two-phase parallel continuous flow (4) of the first dispersed phase (1) and the second dispersed phase (2) is formed in the microchannel (16-3) between the first slit (12R) and the second slit (13R) of the microchannel (16-3).

[0122] When the continuous phase (3) is supplied to multiple microchannels (16-3) from the cylindrical hole (14H) for continuous phase supply, the flow of the two-phase parallel continuous flow (4) is sheared near the connection point between the product discharge slit (13R) and the microchannels (16-3), using the flow of the continuous phase (3) as a driving force. This allows the two phases, the first dispersed phase (1) and the second dispersed phase (2), to form a two-phase droplet (5) having a core-shell or Janus-type structure. In Figure 11(b), two types of two-phase droplets, a core-shell droplet (5-2) and a Janus-type droplet (5-1), are depicted for illustrative purposes, but in reality, only one two-phase droplet (5), such as a core-shell droplet (5-2) or a Janus-type droplet (5-1), is generated. Furthermore, in Figure 11(b), the core-shell droplet (5-2) is shown as having the second dispersed phase (2) as the core and the first dispersed phase (1) as the shell. However, it could also be a core-shell droplet with the first dispersed phase (1) as the core and the second dispersed phase (2) as the shell.

[0123] The product containing the two-phase droplet (5) is discharged through the product discharge slit (13R) and the product discharge port (13-1).

[0124] (Embodiment 9) In Embodiment 9, a liquid distribution component (43) is constructed using five members as shown in Figure 12, such that the central cylindrical hole (14H) of the apparatus used in Embodiments 5 and 6 is made into an annular slit (14R). By bonding this component with a component having fine grooves (fine groove array substrate) (24), it can be similarly used to generate liquid droplets.

[0125] The micro-groove array substrate (24) is a component having micro-grooves (16-4), and has four annular slits (11R, 12R, 13R, 14R), each connected to a supply port or discharge port (11-1, 12-1, 13-1, 14-1), and the liquid distribution component (43) is composed of a first member (43-1), a second member (43-2), a third member (43-3), a fourth member (43-4), and a fifth member (43-5).

[0126] (Embodiment 10) In Embodiment 10, a liquid distribution component (44) is constructed using five members as shown in Figure 13, so that the central cylindrical hole (14H) of the apparatus used in Embodiments 7 and 8 is made into an annular slit (14R), and by attaching it to a sealing lid (25), it can be used to generate droplets in the same way.

[0127] Here too, there are four annular slits (11R, 12R, 13R, 14R), each connected to a supply port or discharge port (11-1, 12-1, 13-1, 14-1), and the liquid distribution component (44) is composed of a first member (44-1), a second member (44-2), a third member (44-3), a fourth member (44-4), and a fifth member (44-5).

[0128] Furthermore, the present invention allows for the generation of micro-two-phase droplets using the micro-two-phase droplet generation device of the present invention. In other words, the present invention also provides a method for generating micro-two-phase droplets. [Examples]

[0129] The present invention will be described in more detail below with reference to examples.

[0130] (Example 1) A droplet generation device (Figure 2) consisting of a parallelized linear microfluidic substrate (fine groove array substrate) with a rectangular cross-section and a liquid distribution component was designed, fabricated, and used. The microfluidic substrate consisted of 16 linear microfluidic channels with a rectangular cross-section (width 100 μm, height 100 μm) and a length of 13 mm, with a gap of 100 μm between channels. The liquid distribution component, on the other hand, was constructed by stacking two members with a width of 30 mm, a length of 33 mm, and a height of 8 mm (Figure 2). The upper member had a total of four slits: a first dispersed phase supply slit, a second dispersed phase supply slit (first slit), a continuous phase supply slit (second slit), and a product discharge (liquid recovery) slit. The lower member had a first dispersed phase supply port, a second dispersed phase supply port, a continuous phase supply port, and a product discharge port, each connected to the slits of the upper member. Each slit had a width of 500 μm and a length of 5 mm, with a pitch of 3 mm between each slit (Figure 2(b)).

[0131] The microfluidic substrate was fabricated by transferring a pattern from a 100 μm high mold, made on a Si substrate using the negative photoresist SU-8 (Nippon Kayaku), to polydimethylsiloxane (PDMS). Silpot 184 (Toray Dow Corning) was used as the PDMS raw material. The two components of the liquid distribution part were fabricated by machining stainless steel material (SUS304). The slit-shaped through-holes of the liquid distribution part (30) were fabricated by wire electrical discharge machining. After bonding the microfluidic substrate and the liquid distribution part by oxygen plasma treatment, the channel walls were hydrophilized by alternately introducing aqueous solutions of the polymer electrolytes poly(allylamine hydrochloride) (PAH) and poly(sodium 4-styrenesulfonate) (PSS) into the channel.

[0132] As the introductory samples, a 2 wt% aqueous solution of polyvinyl alcohol (GL-03, Mitsubishi Chemical) was used as the continuous phase, silicone oil (SO, SH200-10CS, Toray Dow Corning) as the first dispersed phase, and 1,6-hexanediol diacrylate (HDDA, Shin Nakamura Chemical Industry) as the second dispersed phase. A 10 mL glass syringe (1000 series, Hamilton Company, USA) and a syringe pump (KDS200, KD Scientific, USA) were used to deliver the liquid to the liquid distribution component. An upright microscope (BX-51, Olympus) and a high-speed video camera (FASTCAM Mini AX50, Photron) were used in combination to observe droplet formation in the microchannel.

[0133] Continuous phase flow rate (Q c Figure 14 shows the formation of two-phase droplets in a parallelized microchannel when the flow rate of the first dispersed phase, SO (Qs), is set to 30 mL / h, the flow rate of the second dispersed phase, HDDA (Qm), is set to 6 mL / h. Two-phase droplets were observed to be formed near the connection point between the microchannel and the continuous phase supply slit. Figure 15 shows the results of collecting and observing the generated droplets outside the apparatus. The generated droplets had a core-shell structure with SO as the core and HDDA as the shell. The average diameter of the contained droplets was 87 μm with a coefficient of variation (CV value) of 3.1%, and the average diameter of the outer droplets was 108 μm with a CV value of 5.6%.

[0134] (Example 2) The experiment was conducted under the same conditions as in Example 1, using the same experimental apparatus as in Example 1, except that the first dispersed phase was HDDA and the second dispersed phase was SO (SH200-10CS, Toray Dow Corning) with a surfactant (BY11-030, Toray Dow Corning) added at a concentration of 0.1 wt%. Figure 16-1 shows the formation of two-phase droplets in the parallelized microchannel. Figure 16-2 shows the results of collecting and observing the generated droplets outside the apparatus. The generated droplets had a Janus structure in which SO and HDDA were phase-separated and both were partially exposed to the continuous phase.

[0135] (Example 3) The experiment was conducted using the same experimental apparatus as in Examples 1 and 2, under the same conditions as in Example 2, except that the flow rate (Qm) of the first dispersed phase, HDDA, was 8 mL / h, and the flow rate (Qs) of the second dispersed phase, SO with added surfactant, was 4 mL / h. The results of collecting the generated droplets outside the apparatus and observing them are shown in Figure 17. The generated droplets had a Janus structure in which SO and HDDA were phase-separated and both were partially exposed to the continuous phase. As shown in Figure 17, when the diameters of the SO and HDDA portions were measured, the average diameter of the HDDA portion was 109 μm with a CV value of 2.6%, and the average diameter of the SO portion was 91 μm with a CV value of 2.8%. [Industrial applicability]

[0136] According to the present invention, a micro two-phase droplet generation device can be provided that does not require individual through-holes corresponding to each of the two-phase parallel continuous flow forming channels and two-phase droplet generation channels in order to connect the liquid distribution channel with a plurality of two-phase parallel continuous flow forming channels and two-phase droplet generation channels. [Explanation of symbols]

[0137] 1 1st dispersed phase 2 Second dispersed phase 3 Continuous Phases 4. Two-phase parallel continuous flow 5 Two-phase droplet 5-1 Janus droplet 5-2 Core-shell droplets 6 products 11. First liquid transport port (slit) 11R First liquid transport port (annular slit) 11-1 1st dispersed phase supply port 12. First Slit Race 12, First Slit (Annular Slit) 12-1 2nd dispersed phase supply port 13. Second liquid transport port (slit) 13R Second liquid transport port (annular slit) 13-1 Continuous phase supply port or discharge port 14. Third liquid transport port (slit) 14R Second opening (slit) (annular slit) 14H Second opening (cylindrical hole) 14-1 Outlet or continuous phase supply port 16 Microchannels (rows) 16-1 Microgrooves or microchannels (arrangements thereof) 16-2 Microgrooves or microchannels (arrangements thereof) 16-3 Microgrooves or microchannels (rows) 16-4 Microgrooves or microchannels (rows) 16-5 Microgrooves or microchannels (rows) 20. Micro-groove array substrate (microfluidic array) 21. Sealing lid 22. Micro-groove array substrate (microfluidic array) 23. Sealing lid 24. Micro-groove array substrate (microfluidic array) 25. Sealing lid 30 Liquid distribution components 31 First Member 32 Second Member 33 Liquid distribution components 34. First component 35 Second Member 41 Liquid distribution components 41-1 Components constituting liquid distribution parts (first component) 41-2 Components constituting the liquid distribution part (second component) 41-3 Components constituting the liquid distribution part (third component) 41-4 Components constituting the liquid distribution part (fourth component) 42 Liquid distribution components 42-1 Components constituting the liquid distribution part (first component) 42-2 Components constituting the liquid distribution part (second component) 42-3 Components constituting the liquid distribution part (third component) 42-4 Components constituting the liquid distribution part (fourth component) 43 Liquid distribution components 43-1 Components constituting liquid distribution parts (first component) 43-2 Components constituting the liquid distribution part (second component) 43-3 Components constituting the liquid distribution part (third component) 43-4 Components constituting the liquid distribution part (fourth component) 43-5 Components constituting the liquid distribution part (5th component) 44 Liquid distribution components 44-1 Components constituting the liquid distribution part (first component) 44-2 Components constituting the liquid distribution part (second component) 44-3 Components constituting the liquid distribution part (third component) 44-4 Components constituting the liquid distribution part (fourth component) 44-5 Components constituting the liquid distribution part (5th component)

Claims

1. A row of multiple microchannels, The following slits are arranged in the longitudinal direction of the plurality of microchannels: a first slit, a second slit, a third slit, and a fourth slit, A method for generating micro two-phase droplets using a micro two-phase droplet generation device equipped with the following: The first dispersed phase is supplied from the first slit to the plurality of microchannels to form a flow of the first dispersed phase within the plurality of microchannels. The second dispersed phase is supplied from the second slit toward the plurality of microchannels to form a flow of the second dispersed phase within the second slit. The first dispersed phase and the second dispersed phase are liquids that do not completely mix with each other, and the flow of the first dispersed phase and the flow of the second dispersed phase meet at the connection points between the plurality of microchannels and the second slit, forming a two-phase parallel continuous flow which is a continuous flow containing the two phases of the first dispersed phase and the second dispersed phase in parallel within the plurality of microchannels connecting the end of the second slit and the end of the third slit. The continuous phase is supplied from either the third slit or the fourth slit toward the plurality of microchannels, forming a flow of the continuous phase in the third slit if one of them is the third slit, or in the plurality of microchannels connecting the end of the third slit and the end of the fourth slit if one of them is the fourth slit. At the connection point between the third slit and the plurality of microchannels, the two-phase parallel continuous flow and the continuous phase flow meet, and two-phase droplets of the first dispersed phase and the second dispersed phase are generated in the plurality of microchannels connecting the end of the third slit and the end of the fourth slit when one of them is the third slit, and in the third slit when one of them is the fourth slit. The product containing the two-phase droplet is recovered from the fourth slit if one of the two phases is the third slit, and from the third slit if one of the two phases is the fourth slit. A method for generating micro two-phase droplets, including the following.

2. A method for generating microtwo-phase droplets according to claim 1, wherein the inner walls of the plurality of microchannels and the inner wall of the third slit are composed of hydrophilic surfaces, the first dispersed phase is an organic phase, the second dispersed phase is an organic phase, and the continuous phase is an aqueous phase, thereby generating core-shell type or Janus type microdroplets.

3. A method for generating a micro two-phase droplet according to Claim 1, wherein the inner walls of the plurality of microchannels connecting the end of the second slit and the end of the third slit are made of hydrophobic surfaces, and the inner walls of the plurality of microchannels connecting the end of the third slit and the end of the fourth slit are made of hydrophilic surfaces, and either the first dispersed phase or the second dispersed phase is an aqueous phase and the other is an organic phase, the continuous phase is an aqueous phase, and the continuous phase is supplied from the third slit to the plurality of microchannels, thereby generating a core-shell type microdroplet with the aqueous phase as the core and the organic phase as the shell.

4. A method for generating a micro two-phase droplet according to claim 1, wherein the inner walls of the plurality of microchannels connecting the end of the second slit and the end of the third slit are made of hydrophobic surfaces, the inner wall of the third slit is made of hydrophilic surfaces, either the first dispersed phase or the second dispersed phase is an aqueous phase and the other is an organic phase, the continuous phase is an aqueous phase, the continuous phase is supplied to the plurality of microchannels from the fourth slit, and a core-shell type microdroplet is generated in which the aqueous phase is the core and the organic phase is the shell.

Images